Etiology of hepatocellular carcinoma in Latin America: a prospective, multicenter, international study

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EHMC, EHBC patient groups." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mehmet Buyukberber, Irfan Koruk, Oztekin Cýkman, Mehmet Koruk, Mehmet Emin Küçükoglu, Abdullah Sakman, Omer Demir, Saime Sahinoz" "autores" => array:8 [ 0 => array:3 [ "preGrado" => "Dr." "nombre" => "Mehmet" "apellidos" => "Buyukberber" ] 1 => array:2 [ "nombre" => "Irfan" "apellidos" => "Koruk" ] 2 => array:2 [ "nombre" => "Oztekin" "apellidos" => "Cýkman" ] 3 => array:2 [ "nombre" => "Mehmet" "apellidos" => "Koruk" ] 4 => array:2 [ "nombre" => "Mehmet" "apellidos" => "Emin Küçükoglu" ] 5 => array:2 [ "nombre" => "Abdullah" "apellidos" => "Sakman" ] 6 => array:2 [ "nombre" => "Omer" "apellidos" => "Demir" ] 7 => array:2 [ "nombre" => "Saime" "apellidos" => "Sahinoz" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119316801?idApp=UINPBA00004N" "url" => "/16652681/0000000900000001/v1_201906230851/S1665268119316801/v1_201906230851/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "titulo" => "Etiology of hepatocellular carcinoma in Latin America: a prospective, multicenter, international study" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "63" "paginaFinal" => "69" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Eduardo Fassio, Solangel Díaz, Catalina Santa, María Elisa Reig, Yamila Martínez Artola, Angelo Alves de Mattos, Carlos Míguez, Joao Galizzi, Rodrigo Zapata, Ezequiel Ridruejo, Francisco Carlos de Souza, Nelia Hernández, Leonardo Pinchuk" "autores" => array:14 [ 0 => array:5 [ "preGrado" => "Dr." "nombre" => "Eduardo" "apellidos" => "Fassio" "email" => array:1 [ 0 => "efassio@intramed.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "Solangel" "apellidos" => "Díaz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "†" "identificador" => "aff2" ] ] ] 2 => array:3 [ "nombre" => "Catalina" "apellidos" => "Santa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "‡" "identificador" => "aff3" ] ] ] 3 => array:3 [ "nombre" => "María" "apellidos" => "Elisa Reig" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "§" "identificador" => "aff4" ] ] ] 4 => array:3 [ "nombre" => "Yamila" "apellidos" => "Martínez Artola" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "||" "identificador" => "aff5" ] ] ] 5 => array:3 [ "nombre" => "Angelo" "apellidos" => "Alves de Mattos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "¶" "identificador" => "aff6" ] ] ] 6 => array:3 [ "nombre" => "Carlos" "apellidos" => "Míguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "**" "identificador" => "aff7" ] ] ] 7 => array:3 [ "nombre" => "Joao" "apellidos" => "Galizzi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "††" "identificador" => "aff8" ] ] ] 8 => array:3 [ "nombre" => "Rodrigo" "apellidos" => "Zapata" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "#" "identificador" => "aff9" ] ] ] 9 => array:3 [ "nombre" => "Ezequiel" "apellidos" => "Ridruejo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "§§" "identificador" => "aff10" ] ] ] 10 => array:3 [ "nombre" => "Francisco" "apellidos" => "Carlos de Souza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "|| ||" "identificador" => "aff11" ] ] ] 11 => array:3 [ "nombre" => "Nelia" "apellidos" => "Hernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "¶¶" "identificador" => "aff12" ] ] ] 12 => array:3 [ "nombre" => "Leonardo" "apellidos" => "Pinchuk" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "***" "identificador" => "aff13" ] ] ] 13 => array:1 [ "colaborador" => "Multicenter Group for the Study of Hepatocarcinoma in Latin America, on behalf of the Asociación Latinoamericana para el Estudio del Hígado (ALEH)." ] ] "afiliaciones" => array:13 [ 0 => array:3 [ "entidad" => "Hospital Nacional Prof. A. Posadas, Buenos Aires, Argentina" "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Policlínica Metropolitana, Caracas, Venezuela" "etiqueta" => "†" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Hospital P. Tobón Uribe, Universidad de Antioquia, Medellin, Colombia" "etiqueta" => "‡" "identificador" => "aff3" ] 3 => array:3 [ "entidad" => "Hospital Italiano, Buenos Aires, Argentina" "etiqueta" => "§" "identificador" => "aff4" ] 4 => array:3 [ "entidad" => "Hospital Dr J. Méndez, Buenos Aires, Argentina" "etiqueta" => "||" "identificador" => "aff5" ] 5 => array:3 [ "entidad" => "Santa Casa de Misericordia, Porto Alegre, Brazil" "etiqueta" => "¶" "identificador" => "aff6" ] 6 => array:3 [ "entidad" => "Hospital Dr B. Udaondo, Buenos Aires, Argentina" "etiqueta" => "**" "identificador" => "aff7" ] 7 => array:3 [ "entidad" => "Hospital Felício Rocho, Belo Horizonte, Brazil" "etiqueta" => "††" "identificador" => "aff8" ] 8 => array:3 [ "entidad" => "Clínica Alemana, Santiago de Chile, Chile" "etiqueta" => "‡‡" "identificador" => "aff9" ] 9 => array:3 [ "entidad" => "Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno, Buenos Aires, Argentina" "etiqueta" => "§§" "identificador" => "aff10" ] 10 => array:3 [ "entidad" => "Hospital Mater Dei, Belo Horizonte, Brazil" "etiqueta" => "||||" "identificador" => "aff11" ] 11 => array:3 [ "entidad" => "Hospital de Clínicas, Montevideo, Uruguay" "etiqueta" => "¶¶" "identificador" => "aff12" ] 12 => array:3 [ "entidad" => "Hospital de Clínicas J. de S. Martín, Buenos Aires, Argentina" "etiqueta" => "***" "identificador" => "aff13" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "textoCompleto" => "IntroductionHepatocellular carcinoma (HCC) is a malignant tumor that usually emerges in cirrhotic patients, mostly associated with hepatitis B, hepatitis C and chronic alcohol intake. The incidence of HCC is highly variable across the world, depending on the relative presence of the underlying liver diseases at each region.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>,<a class="elsevierStyleCrossRef" href="#bib0010">2</a> It especially depends on the prevalence of chronic carriers of hepatitis B virus (HBV). Therefore, annual incidence is very high (greater than 30/ 100.000 individuals) in some Asian (China, Mongolia, Korea) and African countries (Gambia, Guinea, Congo) with high endemicity of hepatitis B.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>,<a class="elsevierStyleCrossRef" href="#bib0010">2</a> In contrast, in areas where the rate of chronic carriers of HBsAg is low, like Australia, European countries and North America, the annual incidence of HCC is much lower (consistently under 10/100.000 individuals) and main underlying diseases are hepatitis C and alcoholic cirrhosis.<a class="elsevierStyleCrossRefs" href="#bib0015">3</a>-<a class="elsevierStyleCrossRef" href="#bib0040">8</a> In 1989, with the introduction of the first-generation enzyme-immunoassay, it was found that most of patients with HCC studied in tertiary centers from Spain and Italy had antibodies to HCV.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>,<a class="elsevierStyleCrossRef" href="#bib0025">5</a> More recent studies performed in Italian tertiary centers also showed that hepatitis C was the leading cause of HCC in that setting.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> However, Donato et al, in Brescia, North of Italy, found that heavy alcohol intake accounted for 45% of cases of HCC, chronic HCV infection for 36%, and chronic HBV infection for another 22%.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> In Australia, chronic alcoholism seems to be the leading risk factor.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> In the United States of North America, two recently published single-center studies have shown differing results, with predominance of alcoholic cirrhosis in one<a class="elsevierStyleCrossRef" href="#bib0040">8</a> and hepatitis C in the other.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Furthermore, there may be synergistic effects between alcohol and hepatitis C in the development of HCC,<a class="elsevierStyleCrossRefs" href="#bib0035">7</a>,<a class="elsevierStyleCrossRef" href="#bib0050">10</a> between alcohol and hepatitis B,<a class="elsevierStyleCrossRef" href="#bib0035">7</a> and also between alcohol and diabetes.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>In Latin America, no prospective study has been performed analyzing epidemiological aspects of HCC patients. In the medical literature, there is no publication on the incidence or the ranking of HCC as a cause of death in Latin American countries. A few retrospective studies performed in our countries have been published, approaching the aspect of the relative contribution of different etiologies. In Brazil, a large retrospective study included 287 patients followed in 19 sites from 8 different States.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> Complete medical history and serological information about the 3 main causes of HCC was available in only 132 out of 287 cases. Among them, chronic alcoholism was present in 36%, chronic hepatitis B in 35% and hepatitis C in 25% (as the sole risk factors or in different combinations).<a class="elsevierStyleCrossRef" href="#bib0055">11</a> In Mexico, a single-center retrospective study analyzed epidemiological features of 127 patients.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> However, the full serological results on HBV and HCV were completed in only 71 out of 127 cases. Among them, HCV was shown in 73% (alone in 45%, associated with alcohol in 15% and with HBV in 13%).<a class="elsevierStyleCrossRef" href="#bib0060">12</a> In contrast, two studies from Peru have found that HBV was the more frequent etiology in patients with HCC in that country (present in 44% and in 63% of cases, respectively).<a class="elsevierStyleCrossRef" href="#bib0065">13</a>,<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Another small study was performed in Chile, showing predominance of hepatitis C, present in 48% of 50 cases of HCC.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> A multicenter, retrospective study including 551 patients with HCC completed in Argentina during 2005 evidenced that alcoholic cirrhosis and hepatitis C (present in 76% of cases) were the more frequent etiologies in the series.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> All of these studies have been retrospective and most of them share the problem of etiological results not being completely assessed. Less frequent diseases such as hereditary hemochromatosis have not been investigated in many cases. As a consequence, the prevalence of cryptogenic cirrhosis as a cause of HCC is also unknown in our countries. Another possible bias in some of these studies is that they were performed in tertiary referral centers and percentages of alcoholic cirrhosis as a cause of HCC might have been underestimated in those settings, because alcoholic patients with HCC are many times diagnosed in general hospitals and they are not usually referred for specific therapies like liver transplantation.In order to increase the knowledge of the disease in this area of the world, the Governing Board of the Asociación Latinoamericana para el Estudio del Hígado (ALEH) [in English, Latin American Association for the Study of the Liver (LAASL)] decided to organize and support a prospective study aimed in knowing epidemiological aspects of HCC. The primary aim of this prospective, multicenter, international and observational study was to analyze the etiology of the underlying chronic liver disease in patients with HCC from Latin America. Secondary aims were to evaluate: a. Staging of HCC by using two systems: the historical Okuda classification<a class="elsevierStyleCrossRef" href="#bib0085">17</a> and the BCLC system,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> recommended by the AASLD Guidelines for the management of HCC; b. Percentage of patients receiving specific treatment for HCC and types of therapy.Patients and MethodsAll members of ALEH received an e-mail inviting them to participate in this prospective study. During the period of patient inclusion, they were sent reminder e-mails. A database was constructed and a specific link was placed at the web page of ALEH. Through this link, members and non-members of ALEH could firstly register, read the text of the protocol, revise the Okuda and BCLC classifications, and upload the patient data. Enrollment of cases could be performed in two or more times: in the first time, the main results concerning the primary objective of the study (gender, dates of birth and diagnosis of HCC, countries of birth and diagnosis, etiology of chronic liver disease, presence or absence of cirrhosis, number and diameter of nodules, diagnosis performed through a surveillance program or not) were loaded. In the following times, data about the staging systems (Okuda and BCLC classifications)<a class="elsevierStyleCrossRef" href="#bib0085">17</a>,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> and type of treatment that patients received could be completed. However, if only demographical and etiological data were loaded and results about staging and type of treatment were lacking, the case was still included because our main objective was to know the etiology of HCC in Latin America.Inclusion of patients was allowed during a period of 18 months, from September 01, 2006 to March 31, 2008. Participants were asked to include in the study only incident cases (new and consecutive diagnoses of HCC during the 18 month period) or cases with a diagnosis previous to the starting date but with an active follow-up or treatment during the study period. The definition of case of HCC was according the EASL and AASLD guidelines.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>,<a class="elsevierStyleCrossRef" href="#bib0100">20</a> In completing the “etiology” field, participants could choose among the following fixed categories: alcohol; HCV; HBV; HCV plus alcohol; HBV plus alcohol; HCV plus HBV; HCV plus HBV plus alcohol; hemochromatosis; primary biliary cirrhosis; autoimmune hepatitis; nonalcoholic steatohepatitis; cryptogenic cirrhosis; other. The etiology of the chronic liver disease was defined according to conventional and international criteria.<a class="elsevierStyleCrossRefs" href="#bib0105">21</a>-<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Alcohol was considered as the etiological factor when there was a history of ethanol intake greater than 80 g/day for more than 10 years.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Anti-HCV antibodies were assessed by using third-generation enzyme-immunoassay and anti-HBc and HBsAg were also analyzed using enzyme-immunoassay. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki.During the study period, 120 colleagues from 14 Latin American countries completed their registration at the web site: 34 from Brazil, 28 from Argentina, 24 from Venezuela, 10 from Peru, 5 from Chile, 4 from Colombia, 3 from Uruguay, 3 from Dominican Republic, 2 from Mexico, 2 from Ecuador, 2 from Paraguay, 1 each from Bolivia, Costa Rica and Cuba. Among them, 27 participants from 9 different countries uploaded all the cases of HCC included in this report.Statistical analysis: Mean ± standard deviation, median, interquartile range, minimal and maximal values were used to describe quantitative variables; frequencies and proportions were used to describe categorical variables. In the comparison of quantitative variables, test t Student and ANOVA were used, whereas Chi square test was used to compare qualitative variables. A p value < 0.05 was considered as statistically significant.ResultsDuring the study period, 240 patients with HCC were uploaded in the database: 174 were male (72.5%), 66 were female (27.5%). Median age was 64 years old, interquartile range 57-72, minimal 19, maximal 92 years old. In 205 out of 240 (85.4%) cases, patients had underlying cirrhosis. The number of cases diagnosed by country was: 90 in Argentina, 44 in Brazil, 43 in Venezuela, 32 in Colombia, 10 in Chile, 8 in Uruguay, 6 in Mexico, 4 in Antigua and Barbuda (treated and uploaded in Argentina), 3 in Ecuador.<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a> shows the etiology of chronic liver disease in the 240 patients with HCC. The main etiological groups were: HCV in 74 patients (30.8%), alcohol in 49 (20.4%), cryptogenic cirrhosis in 35 (14.6%), HBV in 26 (10.8%), HCV plus alcohol in 14 (5.8%).<elsevierMultimedia ident="t0005"></elsevierMultimedia><a class="elsevierStyleCrossRef" href="#t0010">Table 2</a> shows mean ± SD age at diagnosis time in the main etiological groups. There were no significant differences between the groups. <a class="elsevierStyleCrossRef" href="#t0015">Table 3</a> shows that percentages of male and female gender in the main etiological groups were significantly different (p <0.001). Although the majority of patients were male in all categories, percentages were higher in groups of alcohol (93.9%), HCV plus alcohol (92.9%) and HBV (84.6%) than in cryptogenic cirrhosis (60%) and HCV (59.5%).<elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="t0015"></elsevierMultimedia>Considering the different combinations, chronic hepatitis C was shown in 91 patients (37.9%): as the sole risk factor in 74, associated with chronic alcoholism in 14, associated with hepatitis B in 2, and with hepatitis B and alcoholism in 1; history of chronic alcoholism was present in 68 patients (28.3%): as the sole risk factor in 49, associated with HCV in 14, associated with HBV in 4, and with HCV plus HBV in 1; chronic hepatitis B was shown in 33 patients (13.8%): as the sole risk factor in 26, associated with chronic alcoholism in 4, associated with HCV in 2, and with HCV plus alcohol in 1.Regarding tumor extension, in 152 cases (63.3%), only one nodule was detected; in 30 (12.5%) and in 16 (6.7%) patients, two and three lesions, respectively, were shown. In 32 cases (13.3%), more than 3 nodules were detected. Finally, in 10 patients (4.2%), a massive pattern of growth was described. The mean ± SD diameter of the major (or the only) nodule was 48.9 ± 31 mm (interquartile range 25-69 mm). Among the 240 patients with HCC, 124 (51.7%) were diagnosed being involved in a surveillance program. There was a significant difference in the tumor diameter between HCC cases diagnosed through a surveillance program and those who were not involved in an early detection program (43.5 ± 28.9 versus 54.8 ± 32.3 mm, respectively) (p = 0.004).Information on staging systems was answered in 188 out of 240 HCC cases. In respect to Okuda classification, 117 cases corresponded to stage I, 59 to stage II, and 12 to stage III. In the BCLC system, 105, 54, 19 and 10 cases were classified in stages A, B, C and D, respectively. Among the 188 cases of HCC with data fully completed on staging, 102 had been diagnosed through a surveillance program and 86 had not. <a class="elsevierStyleCrossRef" href="#t0020">Table 4</a> shows that there were significant differences in the proportions of patients being diagnosed in stages A, B, C and D among both groups (p < 0.01). Patients diagnosed through a screening strategy were in stages A and B in 69.6 and 17.6%, respectively; compared to 39.5 and 41.9% in patients diagnosed without a screening program.<elsevierMultimedia ident="t0020"></elsevierMultimedia>Specific treatments for HCC were indicated in 164 out of 240 (68.3%) patients: surgical resection in 21, liver transplantation in 21, percutaneous ethanol injection in 23, radiofrequency ablation in 19, transarterial chemoembolization in 87, sorafenib in 5, other systemic therapies in 2. Eleven more patients were allocated to the local waiting list for liver transplants. Among patients with diagnosis through a surveillance program, 77% received specific therapies, compared to 59% in patients without diagnosis by that strategy (p = 0.002).DiscussionThis report shows the results of the first prospective study performed in Latin America analyzing epidemiological features of 240 patients with HCC. Regarding demographical aspects, we found that our population was similar to that described in occidental countries, with a male predominance (72.5% of cases), a male:female ratio of 2.6 and a median age of 64 years old at diagnosis time. Another finding that resembles results from European countries was that HCC had emerged on underlying cirrhosis in 205 out of 240 (85.4%) cases. In respect to the etiology, we found that hepatitis C was the more frequent cause of HCC, shown in 91 patients (37.9%), either as the sole risk factor (in 74 cases) or in different combinations. Following to HCV, the second risk factor was chronic alcoholism, present in 68 patients (28.3%) (as the only risk factor in 49, and with different combinations in other 19). The third more frequent etiology was the cryptogenic cirrhosis, diagnosed in 35 cases (14.6%).As shown in <a class="elsevierStyleCrossRef" href="#t0010">table 2</a>, we did not find significant differences between the main groups in the age of presentation and the interquartile range observed (57-71 years old) suggests that most of the patients were in their sixties. In contrast, we found some differences in the gender relationship between etiological groups. The male:female ratio was 1.5 in pure hepatitis C and cryptogenic cirrhosis whereas it was 15.3 in alcoholic cirrhosis and 5.5 in pure hepatitis B. Interestingly, the group of patients with HCV plus alcohol was in this aspect very similar to that with only chronic alcoholism (with 93% of males and a male:female ratio of 13). It has been shown in case-control studies that the intake of alcohol greater than 80 gr/day for more than 10 years increases the risk for HCC.<a class="elsevierStyleCrossRefs" href="#bib0040">8</a>,<a class="elsevierStyleCrossRefs" href="#bib0050">10</a>,<a class="elsevierStyleCrossRef" href="#bib0130">26</a> In patients with alcoholic cirrhosis, the risk for HCC is approximately 1% per year.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> Furthermore, case-control studies have shown that among patients with chronic hepatitis C, there is an approximately 2-fold increased risk for HCC in those who drink heavily alcohol as compared to nondrinkers;<a class="elsevierStyleCrossRef" href="#bib0140">28</a>,<a class="elsevierStyleCrossRef" href="#bib0145">29</a> and longitudinal studies performed in Japan have found that lifetime alcohol use was independently associated with risk for HCC in patients with hepatitis C.<a class="elsevierStyleCrossRef" href="#bib0150">30</a>,<a class="elsevierStyleCrossRef" href="#bib0155">31</a> It has been suggested that hepatitis C and chronic alcoholism have not only an additive but a synergistic effect in increasing risk for HCC.<a class="elsevierStyleCrossRefs" href="#bib0035">7</a>,<a class="elsevierStyleCrossRef" href="#bib0050">10</a>Cryptogenic cirrhosis has increasingly been recognized as a risk factor for HCC in recent studies. In a large series from Italy, including 641 cases of HCC, the etiology of cirrhosis was considered as cryptogenic in 6.9%.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> A similar percentage (9.2%) was found in the retrospective series of 551 patients studied in Argentina.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> In a recent single-center study from USA, cryptogenic cirrhosis was the second most frequent etiology among patients with HCC, accounting for 29% of cases.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Patients with cryptogenic cirrhosis described in these HCC series usually have features of the so-called metabolic syndrome: obesity has been observed in 41-58% of cases,<a class="elsevierStyleCrossRefs" href="#bib0030">6</a>,<a class="elsevierStyleCrossRefs" href="#bib0045">9</a>,<a class="elsevierStyleCrossRef" href="#bib0160">32</a>,<a class="elsevierStyleCrossRef" href="#bib0165">33</a> and diabetes, in 47 to 88%.<a class="elsevierStyleCrossRefs" href="#bib0030">6</a>,<a class="elsevierStyleCrossRefs" href="#bib0045">9</a>,<a class="elsevierStyleCrossRef" href="#bib0160">32</a>,<a class="elsevierStyleCrossRef" href="#bib0165">33</a> In USA, insulin resistance syndrome manifestating as obesity and diabetes is now emerging as a risk factor for HCC.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> In fact, both obesity and diabetes are recognized as independent risk factors for HCC.<a class="elsevierStyleCrossRef" href="#bib0175">35</a>,<a class="elsevierStyleCrossRef" href="#bib0180">36</a> In a recent study from USA, the relative risk of dying from liver cancer was 4.52 times higher for men with a body mass index ≥ 35 kg/m2 compared with the reference groups (body mass index from 18.5 to 24.9).<a class="elsevierStyleCrossRef" href="#bib0185">37</a> In another large study, 173,643 patients with diabetes and without a concomitant liver disease and 650.620 control individuals without diabetes were followed-up.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> The risk of developing HCC was approximately 2 times higher among diabetics compared to nondiabetics (the highest risk was among patients with a longer than 10 year follow-up).<a class="elsevierStyleCrossRef" href="#bib0180">36</a> Most of the experts suggest that the link between metabolic syndrome and HCC is through the sequence insulin resistance syndrome → NAFLD → cirrhosis → HCC. In a prospective study, Sanyal, et al. have shown that patients with cirrhosis due to nonalcoholic steatohepatitis do develop HCC although their risk is significantly lower compared with patients with cirrhosis due to hepatitis C.<a class="elsevierStyleCrossRef" href="#bib0190">38</a> However, recent reports have also suggested that HCC may even emerge in patients with metabolic syndrome and fatty liver in the absence of cirrhosis<a class="elsevierStyleCrossRef" href="#bib0195">39</a> or significant liver fibrosis.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> In our study, 35 patients (14.6% of the studied population) were defined as having a cryptogenic cirrhosis. Unfortunately, participants were not asked to load data about metabolic syndrome features. Therefore, we cannot infer any conclusion on the possible origin of the cryptogenic cirrhosis in our patients. Besides, the etiology of cirrhosis in 11 patients with HCC (4.6%) of our series was defined as NASH, because there was a previous histological diagnosis of this disease.Regarding the secondary objectives of the study, we observed that the majority of patients in this HCC series had only one nodule (63%), were in early or intermediate stages in the BCLC classification (85%) and were given a specific treatment (68%). These figures are rather satisfactory and much better than those described in a general population-based study from USA, performed among Medicare recipients.<a class="elsevierStyleCrossRef" href="#bib0205">41</a> There is an explanation for this discrepancy: although all the members of ALEH were invited to participate in the study, most of whom finally did so are hepatologists working in tertiary centers and as a consequence, our study is not a population based one. However, treatments considered as curative (surgical resection, liver transplant or percutaneous ablation) were applied in only 84 patients (35%) and many patients (n 87, 36.2%) received transarterial chemoembolization, a palliative therapy, probably reflecting some difficulties in performing liver transplants or resections in our Latin American countries.An interesting percentage of patients (52%) was diagnosed as having a HCC while they were involved in a surveillance program to detect tumors at early stages, as usually recommended in clinical Guidelines.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>,<a class="elsevierStyleCrossRef" href="#bib0100">20</a> Compared with those who were not involved in a surveillance program, these patients presented a significantly lower tumor diameter and a significantly higher percentage of them were at early stage of BCLC classification (70 vs. 39%, respectively) and were given a specific treatment for HCC (77 versus 59%, respectively).One of the main limitations of the study is the possible selection bias. Trying to avoid this bias, the Governing Board of ALEH decided not to restrict the enrollment of patients to a few Latin American well-recognized experts but to invite all their members to participate. In fact, many of the participants in the survey are young investigators. However, most of them deal with Hepatology and work in tertiary centers. Thus, although they uploaded in the database all the consecutive cases of HCC diagnosed in their hospitals during the period study, some selection bias cannot be discarded. Another weakness is that 87% of cases were enrolled by participants from 4 countries (Argentina, Brazil, Venezuela and Colombia) and only a few patients were included from other ones. Therefore, some caution is warranted when interpreting our results and further larger and more extended studies will be necessary to expand the knowledge on epidemiology of HCC in Latin America.In conclusion, this first prospective study analyzing epidemiological features of HCC in Latin American countries showed that chronic hepatitis C is also the more frequent etiology in our area, followed by alcoholic cirrhosis. Demographical results were very similar to that described in occidental countries, with a male predominance (male:female ratio 2.6) and an important proportion of patients being diagnosed at their sixties.Abbreviations<ul class="elsevierStyleList" id="li0005"><li class="elsevierStyleListItem" id="list0005">•HCC: Hepatocellular carcinoma.</li><li class="elsevierStyleListItem" id="list0010">•HBV: Hepatitis B virus.</li><li class="elsevierStyleListItem" id="list0015">•HBsAg: Hepatitis B surface antigen.</li><li class="elsevierStyleListItem" id="list0020">•HCV: Hepatitis C virus.</li><li class="elsevierStyleListItem" id="list0025">•ALEH: Asociación Latinoamericana para el Estudio del Hígado.</li><li class="elsevierStyleListItem" id="list0030">•LAASL: Latin American Association for the Study of the Liver.</li><li class="elsevierStyleListItem" id="list0035">•BCLC: Barcelona Clínic Liver Cancer.</li><li class="elsevierStyleListItem" id="list0040">•AASLD: American Association for the Study of Liver Diseases.</li><li class="elsevierStyleListItem" id="list0045">•EASL: European Association for the Study of the Liver.</li><li class="elsevierStyleListItem" id="list0050">•USA: United States of America.</li><li class="elsevierStyleListItem" id="list0055">•NAFLD: Nonalcoholic fatty liver disease.</li><li class="elsevierStyleListItem" id="list0060">•NASH: Nonalcoholic steatohepatitis.</li></ul>Financial DisclosureAuthors have nothing to declare.Other Participants of the Multicenter Group For The Study of Hepatocarcinoma in Latin America:Daniel Zamora Valdez, Veracruz, Mexico; Raúl Adrover, La Plata, Argentina; Lucy Dagher, Caracas, Venezuela; Eduardo Marriott Díaz, Guayaquil, Ecuador; José Trevizoli, Brasilia DF, Brazil; Eric Bassetti Soares, Belo Horizonte, Brazil; María Ponce, Tucumán, Argentina; Carlos Brodersen, Buenos Aires, Argentina; Francisco Souto, Cuiabá, Brazil; Johanel Wanderlinder, Caracas, Venezuela; Luciana Kikuchi, Sao Paulo, Brazil; Nancy Vera Lagos, San Cristobal, Venezuela; Frederico Marinho, Recife, Brazil; Daniel Camps, Córdoba, Argentina; Graciela Perelstein, Buenos Aires, Argentina." "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1210985" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1127269" "titulo" => "Key words" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients and Methods" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Abbreviations" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Financial Disclosure" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2010-01-05" "fechaAceptado" => "2010-01-25" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec1127269" "palabras" => array:5 [ 0 => "Hepatitis C" 1 => "Alcoholic cirrhosis" 2 => "Cryptogenic cirrhosis" 3 => "Hepatitis B" 4 => "BCLC staging system" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Background/aims. No prospective study has been published investigating etiology of HCC in Latin America. The primary aim of this prospective study was to analyze the etiology of liver disease in patients with HCC from our area. Secondary aims were to evaluate staging using Okuda and BCLC classifications; and percentage of patients receiving treatment.Methods. The Governing Board of the Latin American Association for the Study of the Liver designed the protocol. During a 18 month period, all members were invited to load their incident HCC cases on line.Results. 240 cases from 9 countries were uploaded, 174 were male (72.5%), median age was 64 years, interquartile range 57-72. In 85.4% of cases, patients had underlying cirrhosis. Main etiological factors were: HCV in 74 patients (30.8%), alcohol in 49 (20.4%), cryptogenic cirrhosis in 35 (14.6%), HBV in 26 (10.8%), HCV plus alcohol in 14 (5.8%). Considering the combinations, hepatitis C was shown in 91 patients (38%); chronic alcoholism in 68 patients (28%); and hepatitis B in 33 patients (14%). There were no significant differences between the groups in the age at diagnosis. Percentage of male gender was higher in groups of alcohol (94%), HCV plus alcohol (93%) and HBV (85%) than in cryptogenic cirrhosis (60%) and HCV (59%) (p<0.001).Conclusions. Our prospective study showed that hepatitis C is the more frequent etiology of HCC in Latin America, followed by alcoholic cirrhosis. Demographical results showed a male predominance (male:female ratio 2.6) with an important proportion of patients being diagnosed at their sixties." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "HCC: Hepatocellular carcinoma. HCV: Hepatitis C virus. HBV: Hepatitis B virus. NASH: Nonalcoholic steatohepatitis. AIH: Autoimmune hepatitis. PBC: Primary biliary cirrhosis." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Etiology \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">n \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Percentage \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HCV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">30.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Alcohol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">20.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Cryptogenic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">14.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HBV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">10.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HCV + alcohol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">5.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Other \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">5.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">NASH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">4.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HBV + alcohol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">AIH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Hemochromatosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HCV + HBV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">0.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">PBC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">0.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HCV + HBV + alcohol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">0.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2067274.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Etiology of chronic liver disease in 240 patients with diagnosis of HCC." ] ] 1 => array:7 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Etiology \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Mean \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HCV<a class="elsevierStyleCrossRef" href="#tbl2fn0020">**</a> (n 74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">64.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">9.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Alcohol<a class="elsevierStyleCrossRef" href="#tbl2fn0020">**</a> (n 49) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">64.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">8.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Cryptogenic (n 35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">62.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">16.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HBV<a class="elsevierStyleCrossRef" href="#tbl2fn0020">**</a> (n 26) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">62.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">11.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HCV + alcohol (n 14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">60.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">11.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2067275.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tbl2fn0015" "etiqueta" => "*" "nota" => "There were no significant differences." ] 1 => array:3 [ "identificador" => "tbl2fn0020" "etiqueta" => "**" "nota" => "As the only risk factor present. HCC: Hepatocellular carcinoma; HCV, hepatitis C virus; HBV, hepatitis B virus." ] ] ] "descripcion" => array:1 [ "en" => "Age at diagnosis time in the main etiological groups of patients with HCC (in years).<a class="elsevierStyleCrossRef" href="#tbl2fn0015">*</a>" ] ] 2 => array:7 [ "identificador" => "t0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" scope="col">Etiology \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">n \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Male gender (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">Female gender (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HCV<a class="elsevierStyleCrossRef" href="#tblfn0020">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">59.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">40.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Alcohol<a class="elsevierStyleCrossRef" href="#tblfn0020">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">93.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">6.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">Cryptogenic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">60.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">40.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HBV<a class="elsevierStyleCrossRef" href="#tblfn0020">**</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">84.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">15.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="middle">HCV + alcohol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">92.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">7.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2067273.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "*" "nota" => "Differences are significantly different (p < 0.001)." ] 1 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "**" "nota" => "As the only risk factor present. HCC: Hepatocellular carcinoma. HCV: Hepatitis C virus. HBV: Hepatitis B virus." ] ] ] "descripcion" => array:1 [ "en" => "Percentages of male and female genders in the main etiological groups in patients with HCC.<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a>" ] ] 3 => array:7 [ "identificador" => "t0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">BCLC stages \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="middle" scope="col">Surveillance program (n 102)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="middle" scope="col">No survei llance program (n 86)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">n \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">% \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">n \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="middle" scope="col">% \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">69.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">39.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">17.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">41.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">7.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">12.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">4.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="middle">5.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2067272.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tab3tfn0005" "etiqueta" => "a" "nota" => "Differences are statistically significant among both groups (p < 0.01). HCC: Hepatocellular carcinoma. BCLC: Barcelona Clinic Liver Cancer." ] ] ] "descripcion" => array:1 [ "en" => "Staging of HCC patients by BCLC classification according to diagnosis with or without a surveillance program.<a class="elsevierStyleCrossRef" href="#tab3tfn0005">a</a>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:41 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatocellular carcinoma: epidemiology, risk factors, and screening" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Sherman M." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Semin Liv Dis" "fecha" => "2005" "volumen" => "25" "paginaInicial" => "143" "paginaFinal" => "154" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." 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"referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Survival in hepatocellular carcinoma: impact of screening and etiology of liver disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Kemp W." 1 => "Pianko S." 2 => "Nguyen S." 3 => "Bailey M.J." 4 => "Roberts SK." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1440-1746.2005.03844.x" "Revista" => array:6 [ "tituloSerie" => "J Gastroenterol Hepatol" "fecha" => "2005" "volumen" => "20" "paginaInicial" => "873" "paginaFinal" => "881" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15946134" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of antibodies to hepatitis C virus in Spanish patients with hepatocellular carcinoma and hepatic cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Bruix J." 1 => "Barrera J.M." 2 => "Calvet X." 3 => "Ercilla G." 4 => "Costa J." 5 => "Sanchez Tapias J.M." 6 => "Ventura M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0140-6736(89)91015-5" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1989" "volumen" => "2" "paginaInicial" => "1004" "paginaFinal" => "1006" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2572739" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." 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Eduardo Fassio

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efassio@intramed.net

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, Solangel Díaz†, Catalina Santa‡, María Elisa Reig§, Yamila Martínez Artola||, Angelo Alves de Mattos¶, Carlos Míguez**, Joao Galizzi††, Rodrigo Zapata#, Ezequiel Ridruejo§§, Francisco Carlos de Souza|| ||, Nelia Hernández¶¶, Leonardo Pinchuk***, Multicenter Group for the Study of Hepatocarcinoma in Latin America, on behalf of the Asociación Latinoamericana para el Estudio del Hígado (ALEH).

* Hospital Nacional Prof. A. Posadas, Buenos Aires, Argentina

† Policlínica Metropolitana, Caracas, Venezuela

‡ Hospital P. Tobón Uribe, Universidad de Antioquia, Medellin, Colombia

§ Hospital Italiano, Buenos Aires, Argentina

|| Hospital Dr J. Méndez, Buenos Aires, Argentina

¶ Santa Casa de Misericordia, Porto Alegre, Brazil

** Hospital Dr B. Udaondo, Buenos Aires, Argentina

†† Hospital Felício Rocho, Belo Horizonte, Brazil

‡‡ Clínica Alemana, Santiago de Chile, Chile

§§ Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno, Buenos Aires, Argentina

|||| Hospital Mater Dei, Belo Horizonte, Brazil

¶¶ Hospital de Clínicas, Montevideo, Uruguay

*** Hospital de Clínicas J. de S. Martín, Buenos Aires, Argentina

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Hepatocellular carcinoma &#40;HCC&#41; is a malignant tumor that usually emerges in cirrhotic patients&#44; mostly associated with hepatitis B&#44; hepatitis C and chronic alcohol intake&#46; The incidence of HCC is highly variable across the world&#44; depending on the relative presence of the underlying liver diseases at each region&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It especially depends on the prevalence of chronic carriers of hepatitis B virus &#40;HBV&#41;&#46; Therefore&#44; annual incidence is very high &#40;greater than 30&#47; 100&#46;000 individuals&#41; in some Asian &#40;China&#44; Mongolia&#44; Korea&#41; and African countries &#40;Gambia&#44; Guinea&#44; Congo&#41; with high endemicity of hepatitis B&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In contrast&#44; in areas where the rate of chronic carriers of HBsAg is low&#44; like Australia&#44; European countries and North America&#44; the annual incidence of HCC is much lower &#40;consistently under 10&#47;100&#46;000 individuals&#41; and main underlying diseases are hepatitis C and alcoholic cirrhosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3</span></a>-<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In 1989&#44; with the introduction of the first-generation enzyme-immunoassay&#44; it was found that most of patients with HCC studied in tertiary centers from Spain and Italy had antibodies to HCV&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> More recent studies performed in Italian tertiary centers also showed that hepatitis C was the leading cause of HCC in that setting&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> However&#44; Donato et al&#44; in Brescia&#44; North of Italy&#44; found that heavy alcohol intake accounted for 45&#37; of cases of HCC&#44; chronic HCV infection for 36&#37;&#44; and chronic HBV infection for another 22&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In Australia&#44; chronic alcoholism seems to be the leading risk factor&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In the United States of North America&#44; two recently published single-center studies have shown differing results&#44; with predominance of alcoholic cirrhosis in one<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and hepatitis C in the other&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Furthermore&#44; there may be synergistic effects between alcohol and hepatitis C in the development of HCC&#44;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> between alcohol and hepatitis B&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and also between alcohol and diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">In Latin America&#44; no prospective study has been performed analyzing epidemiological aspects of HCC patients&#46; In the medical literature&#44; there is no publication on the incidence or the ranking of HCC as a cause of death in Latin American countries&#46; A few retrospective studies performed in our countries have been published&#44; approaching the aspect of the relative contribution of different etiologies&#46; In Brazil&#44; a large retrospective study included 287 patients followed in 19 sites from 8 different States&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Complete medical history and serological information about the 3 main causes of HCC was available in only 132 out of 287 cases&#46; Among them&#44; chronic alcoholism was present in 36&#37;&#44; chronic hepatitis B in 35&#37; and hepatitis C in 25&#37; &#40;as the sole risk factors or in different combinations&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In Mexico&#44; a single-center retrospective study analyzed epidemiological features of 127 patients&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> However&#44; the full serological results on HBV and HCV were completed in only 71 out of 127 cases&#46; Among them&#44; HCV was shown in 73&#37; &#40;alone in 45&#37;&#44; associated with alcohol in 15&#37; and with HBV in 13&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> In contrast&#44; two studies from Peru have found that HBV was the more frequent etiology in patients with HCC in that country &#40;present in 44&#37; and in 63&#37; of cases&#44; respectively&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Another small study was performed in Chile&#44; showing predominance of hepatitis C&#44; present in 48&#37; of 50 cases of HCC&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> A multicenter&#44; retrospective study including 551 patients with HCC completed in Argentina during 2005 evidenced that alcoholic cirrhosis and hepatitis C &#40;present in 76&#37; of cases&#41; were the more frequent etiologies in the series&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> All of these studies have been retrospective and most of them share the problem of etiological results not being completely assessed&#46; Less frequent diseases such as hereditary hemochromatosis have not been investigated in many cases&#46; As a consequence&#44; the prevalence of cryptogenic cirrhosis as a cause of HCC is also unknown in our countries&#46; Another possible bias in some of these studies is that they were performed in tertiary referral centers and percentages of alcoholic cirrhosis as a cause of HCC might have been underestimated in those settings&#44; because alcoholic patients with HCC are many times diagnosed in general hospitals and they are not usually referred for specific therapies like liver transplantation&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">In order to increase the knowledge of the disease in this area of the world&#44; the Governing Board of the Asociaci&#243;n Latinoamericana para el Estudio del H&#237;gado &#40;ALEH&#41; &#91;in English&#44; Latin American Association for the Study of the Liver &#40;LAASL&#41;&#93; decided to organize and support a prospective study aimed in knowing epidemiological aspects of HCC&#46; The primary aim of this prospective&#44; multicenter&#44; international and observational study was to analyze the etiology of the underlying chronic liver disease in patients with HCC from Latin America&#46; Secondary aims were to evaluate&#58; a&#46; Staging of HCC by using two systems&#58; the historical Okuda classification<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> and the BCLC system&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> recommended by the AASLD Guidelines for the management of HCC&#59; b&#46; Percentage of patients receiving specific treatment for HCC and types of therapy&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Patients and Methods</span><p id="p0020" class="elsevierStylePara elsevierViewall">All members of ALEH received an e-mail inviting them to participate in this prospective study&#46; During the period of patient inclusion&#44; they were sent reminder e-mails&#46; A database was constructed and a specific link was placed at the web page of ALEH&#46; Through this link&#44; members and non-members of ALEH could firstly register&#44; read the text of the protocol&#44; revise the Okuda and BCLC classifications&#44; and upload the patient data&#46; Enrollment of cases could be performed in two or more times&#58; in the first time&#44; the main results concerning the primary objective of the study &#40;gender&#44; dates of birth and diagnosis of HCC&#44; countries of birth and diagnosis&#44; etiology of chronic liver disease&#44; presence or absence of cirrhosis&#44; number and diameter of nodules&#44; diagnosis performed through a surveillance program or not&#41; were loaded&#46; In the following times&#44; data about the staging systems &#40;Okuda and BCLC classifications&#41;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and type of treatment that patients received could be completed&#46; However&#44; if only demographical and etiological data were loaded and results about staging and type of treatment were lacking&#44; the case was still included because our main objective was to know the etiology of HCC in Latin America&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">Inclusion of patients was allowed during a period of 18 months&#44; from September 01&#44; 2006 to March 31&#44; 2008&#46; Participants were asked to include in the study only incident cases &#40;new and consecutive diagnoses of HCC during the 18 month period&#41; or cases with a diagnosis previous to the starting date but with an active follow-up or treatment during the study period&#46; The definition of case of HCC was according the EASL and AASLD guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In completing the &#8220;etiology&#8221; field&#44; participants could choose among the following fixed categories&#58; alcohol&#59; HCV&#59; HBV&#59; HCV plus alcohol&#59; HBV plus alcohol&#59; HCV plus HBV&#59; HCV plus HBV plus alcohol&#59; hemochromatosis&#59; primary biliary cirrhosis&#59; autoimmune hepatitis&#59; nonalcoholic steatohepatitis&#59; cryptogenic cirrhosis&#59; other&#46; The etiology of the chronic liver disease was defined according to conventional and international criteria&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21</span></a>-<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Alcohol was considered as the etiological factor when there was a history of ethanol intake greater than 80 g&#47;day for more than 10 years&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Anti-HCV antibodies were assessed by using third-generation enzyme-immunoassay and anti-HBc and HBsAg were also analyzed using enzyme-immunoassay&#46; The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki&#46;</p><p id="p0030" class="elsevierStylePara elsevierViewall">During the study period&#44; 120 colleagues from 14 Latin American countries completed their registration at the web site&#58; 34 from Brazil&#44; 28 from Argentina&#44; 24 from Venezuela&#44; 10 from Peru&#44; 5 from Chile&#44; 4 from Colombia&#44; 3 from Uruguay&#44; 3 from Dominican Republic&#44; 2 from Mexico&#44; 2 from Ecuador&#44; 2 from Paraguay&#44; 1 each from Bolivia&#44; Costa Rica and Cuba&#46; Among them&#44; 27 participants from 9 different countries uploaded all the cases of HCC included in this report&#46;</p><p id="p0035" class="elsevierStylePara elsevierViewall">Statistical analysis&#58; Mean &#177; standard deviation&#44; median&#44; interquartile range&#44; minimal and maximal values were used to describe quantitative variables&#59; frequencies and proportions were used to describe categorical variables&#46; In the comparison of quantitative variables&#44; test t Student and ANOVA were used&#44; whereas Chi square test was used to compare qualitative variables&#46; A p value &#60; 0&#46;05 was considered as statistically significant&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="p0040" class="elsevierStylePara elsevierViewall">During the study period&#44; 240 patients with HCC were uploaded in the database&#58; 174 were male &#40;72&#46;5&#37;&#41;&#44; 66 were female &#40;27&#46;5&#37;&#41;&#46; Median age was 64 years old&#44; interquartile range 57-72&#44; minimal 19&#44; maximal 92 years old&#46; In 205 out of 240 &#40;85&#46;4&#37;&#41; cases&#44; patients had underlying cirrhosis&#46; The number of cases diagnosed by country was&#58; 90 in Argentina&#44; 44 in Brazil&#44; 43 in Venezuela&#44; 32 in Colombia&#44; 10 in Chile&#44; 8 in Uruguay&#44; 6 in Mexico&#44; 4 in Antigua and Barbuda &#40;treated and uploaded in Argentina&#41;&#44; 3 in Ecuador&#46;</p><p id="p0045" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#t0005">Table 1</a> shows the etiology of chronic liver disease in the 240 patients with HCC&#46; The main etiological groups were&#58; HCV in 74 patients &#40;30&#46;8&#37;&#41;&#44; alcohol in 49 &#40;20&#46;4&#37;&#41;&#44; cryptogenic cirrhosis in 35 &#40;14&#46;6&#37;&#41;&#44; HBV in 26 &#40;10&#46;8&#37;&#41;&#44; HCV plus alcohol in 14 &#40;5&#46;8&#37;&#41;&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0050" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#t0010">Table 2</a> shows mean &#177; SD age at diagnosis time in the main etiological groups&#46; There were no significant differences between the groups&#46; <a class="elsevierStyleCrossRef" href="#t0015">Table 3</a> shows that percentages of male and female gender in the main etiological groups were significantly different &#40;p &#60;0&#46;001&#41;&#46; Although the majority of patients were male in all categories&#44; percentages were higher in groups of alcohol &#40;93&#46;9&#37;&#41;&#44; HCV plus alcohol &#40;92&#46;9&#37;&#41; and HBV &#40;84&#46;6&#37;&#41; than in cryptogenic cirrhosis &#40;60&#37;&#41; and HCV &#40;59&#46;5&#37;&#41;&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="t0015"></elsevierMultimedia><p id="p0055" class="elsevierStylePara elsevierViewall">Considering the different combinations&#44; chronic hepatitis C was shown in 91 patients &#40;37&#46;9&#37;&#41;&#58; as the sole risk factor in 74&#44; associated with chronic alcoholism in 14&#44; associated with hepatitis B in 2&#44; and with hepatitis B and alcoholism in 1&#59; history of chronic alcoholism was present in 68 patients &#40;28&#46;3&#37;&#41;&#58; as the sole risk factor in 49&#44; associated with HCV in 14&#44; associated with HBV in 4&#44; and with HCV plus HBV in 1&#59; chronic hepatitis B was shown in 33 patients &#40;13&#46;8&#37;&#41;&#58; as the sole risk factor in 26&#44; associated with chronic alcoholism in 4&#44; associated with HCV in 2&#44; and with HCV plus alcohol in 1&#46;</p><p id="p0060" class="elsevierStylePara elsevierViewall">Regarding tumor extension&#44; in 152 cases &#40;63&#46;3&#37;&#41;&#44; only one nodule was detected&#59; in 30 &#40;12&#46;5&#37;&#41; and in 16 &#40;6&#46;7&#37;&#41; patients&#44; two and three lesions&#44; respectively&#44; were shown&#46; In 32 cases &#40;13&#46;3&#37;&#41;&#44; more than 3 nodules were detected&#46; Finally&#44; in 10 patients &#40;4&#46;2&#37;&#41;&#44; a massive pattern of growth was described&#46; The mean &#177; SD diameter of the major &#40;or the only&#41; nodule was 48&#46;9 &#177; 31 mm &#40;interquartile range 25-69 mm&#41;&#46; Among the 240 patients with HCC&#44; 124 &#40;51&#46;7&#37;&#41; were diagnosed being involved in a surveillance program&#46; There was a significant difference in the tumor diameter between HCC cases diagnosed through a surveillance program and those who were not involved in an early detection program &#40;43&#46;5 &#177; 28&#46;9 versus 54&#46;8 &#177; 32&#46;3 mm&#44; respectively&#41; &#40;p &#61; 0&#46;004&#41;&#46;</p><p id="p0065" class="elsevierStylePara elsevierViewall">Information on staging systems was answered in 188 out of 240 HCC cases&#46; In respect to Okuda classification&#44; 117 cases corresponded to stage I&#44; 59 to stage II&#44; and 12 to stage III&#46; In the BCLC system&#44; 105&#44; 54&#44; 19 and 10 cases were classified in stages A&#44; B&#44; C and D&#44; respectively&#46; Among the 188 cases of HCC with data fully completed on staging&#44; 102 had been diagnosed through a surveillance program and 86 had not&#46; <a class="elsevierStyleCrossRef" href="#t0020">Table 4</a> shows that there were significant differences in the proportions of patients being diagnosed in stages A&#44; B&#44; C and D among both groups &#40;p &#60; 0&#46;01&#41;&#46; Patients diagnosed through a screening strategy were in stages A and B in 69&#46;6 and 17&#46;6&#37;&#44; respectively&#59; compared to 39&#46;5 and 41&#46;9&#37; in patients diagnosed without a screening program&#46;</p><elsevierMultimedia ident="t0020"></elsevierMultimedia><p id="p0070" class="elsevierStylePara elsevierViewall">Specific treatments for HCC were indicated in 164 out of 240 &#40;68&#46;3&#37;&#41; patients&#58; surgical resection in 21&#44; liver transplantation in 21&#44; percutaneous ethanol injection in 23&#44; radiofrequency ablation in 19&#44; transarterial chemoembolization in 87&#44; sorafenib in 5&#44; other systemic therapies in 2&#46; Eleven more patients were allocated to the local waiting list for liver transplants&#46; Among patients with diagnosis through a surveillance program&#44; 77&#37; received specific therapies&#44; compared to 59&#37; in patients without diagnosis by that strategy &#40;p &#61; 0&#46;002&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discussion</span><p id="p0075" class="elsevierStylePara elsevierViewall">This report shows the results of the first prospective study performed in Latin America analyzing epidemiological features of 240 patients with HCC&#46; Regarding demographical aspects&#44; we found that our population was similar to that described in occidental countries&#44; with a male predominance &#40;72&#46;5&#37; of cases&#41;&#44; a male&#58;female ratio of 2&#46;6 and a median age of 64 years old at diagnosis time&#46; Another finding that resembles results from European countries was that HCC had emerged on underlying cirrhosis in 205 out of 240 &#40;85&#46;4&#37;&#41; cases&#46; In respect to the etiology&#44; we found that hepatitis C was the more frequent cause of HCC&#44; shown in 91 patients &#40;37&#46;9&#37;&#41;&#44; either as the sole risk factor &#40;in 74 cases&#41; or in different combinations&#46; Following to HCV&#44; the second risk factor was chronic alcoholism&#44; present in 68 patients &#40;28&#46;3&#37;&#41; &#40;as the only risk factor in 49&#44; and with different combinations in other 19&#41;&#46; The third more frequent etiology was the cryptogenic cirrhosis&#44; diagnosed in 35 cases &#40;14&#46;6&#37;&#41;&#46;</p><p id="p0080" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#t0010">table 2</a>&#44; we did not find significant differences between the main groups in the age of presentation and the interquartile range observed &#40;57-71 years old&#41; suggests that most of the patients were in their sixties&#46; In contrast&#44; we found some differences in the gender relationship between etiological groups&#46; The male&#58;female ratio was 1&#46;5 in pure hepatitis C and cryptogenic cirrhosis whereas it was 15&#46;3 in alcoholic cirrhosis and 5&#46;5 in pure hepatitis B&#46; Interestingly&#44; the group of patients with HCV plus alcohol was in this aspect very similar to that with only chronic alcoholism &#40;with 93&#37; of males and a male&#58;female ratio of 13&#41;&#46; It has been shown in case-control studies that the intake of alcohol greater than 80 gr&#47;day for more than 10 years increases the risk for HCC&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#44;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> In patients with alcoholic cirrhosis&#44; the risk for HCC is approximately 1&#37; per year&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Furthermore&#44; case-control studies have shown that among patients with chronic hepatitis C&#44; there is an approximately 2-fold increased risk for HCC in those who drink heavily alcohol as compared to nondrinkers&#59;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> and longitudinal studies performed in Japan have found that lifetime alcohol use was independently associated with risk for HCC in patients with hepatitis C&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> It has been suggested that hepatitis C and chronic alcoholism have not only an additive but a synergistic effect in increasing risk for HCC&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="p0085" class="elsevierStylePara elsevierViewall">Cryptogenic cirrhosis has increasingly been recognized as a risk factor for HCC in recent studies&#46; In a large series from Italy&#44; including 641 cases of HCC&#44; the etiology of cirrhosis was considered as cryptogenic in 6&#46;9&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> A similar percentage &#40;9&#46;2&#37;&#41; was found in the retrospective series of 551 patients studied in Argentina&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In a recent single-center study from USA&#44; cryptogenic cirrhosis was the second most frequent etiology among patients with HCC&#44; accounting for 29&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Patients with cryptogenic cirrhosis described in these HCC series usually have features of the so-called metabolic syndrome&#58; obesity has been observed in 41-58&#37; of cases&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> and diabetes&#44; in 47 to 88&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> In USA&#44; insulin resistance syndrome manifestating as obesity and diabetes is now emerging as a risk factor for HCC&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> In fact&#44; both obesity and diabetes are recognized as independent risk factors for HCC&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> In a recent study from USA&#44; the relative risk of dying from liver cancer was 4&#46;52 times higher for men with a body mass index &#8805; 35 kg&#47;m<span class="elsevierStyleSup">2</span> compared with the reference groups &#40;body mass index from 18&#46;5 to 24&#46;9&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> In another large study&#44; 173&#44;643 patients with diabetes and without a concomitant liver disease and 650&#46;620 control individuals without diabetes were followed-up&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> The risk of developing HCC was approximately 2 times higher among diabetics compared to nondiabetics &#40;the highest risk was among patients with a longer than 10 year follow-up&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Most of the experts suggest that the link between metabolic syndrome and HCC is through the sequence insulin resistance syndrome &#8594; NAFLD &#8594; cirrhosis &#8594; HCC&#46; In a prospective study&#44; Sanyal&#44; <span class="elsevierStyleItalic">et al&#46;</span> have shown that patients with cirrhosis due to nonalcoholic steatohepatitis do develop HCC although their risk is significantly lower compared with patients with cirrhosis due to hepatitis C&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> However&#44; recent reports have also suggested that HCC may even emerge in patients with metabolic syndrome and fatty liver in the absence of cirrhosis<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> or significant liver fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> In our study&#44; 35 patients &#40;14&#46;6&#37; of the studied population&#41; were defined as having a cryptogenic cirrhosis&#46; Unfortunately&#44; participants were not asked to load data about metabolic syndrome features&#46; Therefore&#44; we cannot infer any conclusion on the possible origin of the cryptogenic cirrhosis in our patients&#46; Besides&#44; the etiology of cirrhosis in 11 patients with HCC &#40;4&#46;6&#37;&#41; of our series was defined as NASH&#44; because there was a previous histological diagnosis of this disease&#46;</p><p id="p0090" class="elsevierStylePara elsevierViewall">Regarding the secondary objectives of the study&#44; we observed that the majority of patients in this HCC series had only one nodule &#40;63&#37;&#41;&#44; were in early or intermediate stages in the BCLC classification &#40;85&#37;&#41; and were given a specific treatment &#40;68&#37;&#41;&#46; These figures are rather satisfactory and much better than those described in a general population-based study from USA&#44; performed among Medicare recipients&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> There is an explanation for this discrepancy&#58; although all the members of ALEH were invited to participate in the study&#44; most of whom finally did so are hepatologists working in tertiary centers and as a consequence&#44; our study is not a population based one&#46; However&#44; treatments considered as curative &#40;surgical resection&#44; liver transplant or percutaneous ablation&#41; were applied in only 84 patients &#40;35&#37;&#41; and many patients &#40;n 87&#44; 36&#46;2&#37;&#41; received transarterial chemoembolization&#44; a palliative therapy&#44; probably reflecting some difficulties in performing liver transplants or resections in our Latin American countries&#46;</p><p id="p0095" class="elsevierStylePara elsevierViewall">An interesting percentage of patients &#40;52&#37;&#41; was diagnosed as having a HCC while they were involved in a surveillance program to detect tumors at early stages&#44; as usually recommended in clinical Guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Compared with those who were not involved in a surveillance program&#44; these patients presented a significantly lower tumor diameter and a significantly higher percentage of them were at early stage of BCLC classification &#40;70 <span class="elsevierStyleItalic">vs&#46;</span> 39&#37;&#44; respectively&#41; and were given a specific treatment for HCC &#40;77 versus 59&#37;&#44; respectively&#41;&#46;</p><p id="p0100" class="elsevierStylePara elsevierViewall">One of the main limitations of the study is the possible selection bias&#46; Trying to avoid this bias&#44; the Governing Board of ALEH decided not to restrict the enrollment of patients to a few Latin American well-recognized experts but to invite all their members to participate&#46; In fact&#44; many of the participants in the survey are young investigators&#46; However&#44; most of them deal with Hepatology and work in tertiary centers&#46; Thus&#44; although they uploaded in the database all the consecutive cases of HCC diagnosed in their hospitals during the period study&#44; some selection bias cannot be discarded&#46; Another weakness is that 87&#37; of cases were enrolled by participants from 4 countries &#40;Argentina&#44; Brazil&#44; Venezuela and Colombia&#41; and only a few patients were included from other ones&#46; Therefore&#44; some caution is warranted when interpreting our results and further larger and more extended studies will be necessary to expand the knowledge on epidemiology of HCC in Latin America&#46;</p><p id="p0105" class="elsevierStylePara elsevierViewall">In conclusion&#44; this first prospective study analyzing epidemiological features of HCC in Latin American countries showed that chronic hepatitis C is also the more frequent etiology in our area&#44; followed by alcoholic cirrhosis&#46; Demographical results were very similar to that described in occidental countries&#44; with a male predominance &#40;male&#58;female ratio 2&#46;6&#41; and an important proportion of patients being diagnosed at their sixties&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Abbreviations</span><p id="p0110" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0005"><li class="elsevierStyleListItem" id="list0005"><span class="elsevierStyleLabel">&#8226;</span><p id="p0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HCC&#58;</span> Hepatocellular carcinoma&#46;</p></li><li class="elsevierStyleListItem" id="list0010"><span class="elsevierStyleLabel">&#8226;</span><p id="p0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HBV&#58;</span> Hepatitis B virus&#46;</p></li><li class="elsevierStyleListItem" id="list0015"><span class="elsevierStyleLabel">&#8226;</span><p id="p0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HBsAg&#58;</span> Hepatitis B surface antigen&#46;</p></li><li class="elsevierStyleListItem" id="list0020"><span class="elsevierStyleLabel">&#8226;</span><p id="p0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HCV&#58;</span> Hepatitis C virus&#46;</p></li><li class="elsevierStyleListItem" id="list0025"><span class="elsevierStyleLabel">&#8226;</span><p id="p0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ALEH&#58;</span> Asociaci&#243;n Latinoamericana para el Estudio del H&#237;gado&#46;</p></li><li class="elsevierStyleListItem" id="list0030"><span class="elsevierStyleLabel">&#8226;</span><p id="p0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">LAASL&#58;</span> Latin American Association for the Study of the Liver&#46;</p></li><li class="elsevierStyleListItem" id="list0035"><span class="elsevierStyleLabel">&#8226;</span><p id="p0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">BCLC&#58;</span> Barcelona Cl&#237;nic Liver Cancer&#46;</p></li><li class="elsevierStyleListItem" id="list0040"><span class="elsevierStyleLabel">&#8226;</span><p id="p0150" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">AASLD&#58;</span> American Association for the Study of Liver Diseases&#46;</p></li><li class="elsevierStyleListItem" id="list0045"><span class="elsevierStyleLabel">&#8226;</span><p id="p0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">EASL&#58;</span> European Association for the Study of the Liver&#46;</p></li><li class="elsevierStyleListItem" id="list0050"><span class="elsevierStyleLabel">&#8226;</span><p id="p0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">USA&#58;</span> United States of America&#46;</p></li><li class="elsevierStyleListItem" id="list0055"><span class="elsevierStyleLabel">&#8226;</span><p id="p0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">NAFLD&#58;</span> Nonalcoholic fatty liver disease&#46;</p></li><li class="elsevierStyleListItem" id="list0060"><span class="elsevierStyleLabel">&#8226;</span><p id="p0170" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">NASH&#58;</span> Nonalcoholic steatohepatitis&#46;</p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Financial Disclosure</span><p id="p0175" class="elsevierStylePara elsevierViewall">Authors have nothing to declare&#46;</p><p id="p0180" class="elsevierStylePara elsevierViewall">Other Participants of the Multicenter Group For The Study of Hepatocarcinoma in Latin America&#58;</p><p id="p0185" class="elsevierStylePara elsevierViewall">Daniel Zamora Valdez&#44; Veracruz&#44; Mexico&#59; Ra&#250;l Adrover&#44; La Plata&#44; Argentina&#59; Lucy Dagher&#44; Caracas&#44; Venezuela&#59; Eduardo Marriott D&#237;az&#44; Guayaquil&#44; Ecuador&#59; Jos&#233; Trevizoli&#44; Brasilia DF&#44; Brazil&#59; Eric Bassetti Soares&#44; Belo Horizonte&#44; Brazil&#59; Mar&#237;a Ponce&#44; Tucum&#225;n&#44; Argentina&#59; Carlos Brodersen&#44; Buenos Aires&#44; Argentina&#59; Francisco Souto&#44; Cuiab&#225;&#44; Brazil&#59; Johanel Wanderlinder&#44; Caracas&#44; Venezuela&#59; Luciana Kikuchi&#44; Sao Paulo&#44; Brazil&#59; Nancy Vera Lagos&#44; San Cristobal&#44; Venezuela&#59; Frederico Marinho&#44; Recife&#44; Brazil&#59; Daniel Camps&#44; C&#243;rdoba&#44; Argentina&#59; Graciela Perelstein&#44; Buenos Aires&#44; Argentina&#46;</p></span></span>"
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          "identificador" => "xres1210985"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abs0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1127269"
          "titulo" => "Key words"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        3 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Patients and Methods"
        ]
        4 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Results"
        ]
        5 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Discussion"
        ]
        6 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Abbreviations"
        ]
        7 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Financial Disclosure"
        ]
        8 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2010-01-05"
    "fechaAceptado" => "2010-01-25"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Key words"
          "identificador" => "xpalclavsec1127269"
          "palabras" => array:5 [
            0 => "Hepatitis C"
            1 => "Alcoholic cirrhosis"
            2 => "Cryptogenic cirrhosis"
            3 => "Hepatitis B"
            4 => "BCLC staging system"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abs0005" class="elsevierStyleSection elsevierViewall"><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Background&#47;aims&#46;</span> No prospective study has been published investigating etiology of HCC in Latin America&#46; The primary aim of this prospective study was to analyze the etiology of liver disease in patients with HCC from our area&#46; Secondary aims were to evaluate staging using Okuda and BCLC classifications&#59; and percentage of patients receiving treatment&#46;</p><p id="sp0026" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Methods&#46;</span> The Governing Board of the Latin American Association for the Study of the Liver designed the protocol&#46; During a 18 month period&#44; all members were invited to load their incident HCC cases on line&#46;</p><p id="sp0027" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Results&#46;</span> 240 cases from 9 countries were uploaded&#44; 174 were male &#40;72&#46;5&#37;&#41;&#44; median age was 64 years&#44; interquartile range 57-72&#46; In 85&#46;4&#37; of cases&#44; patients had underlying cirrhosis&#46; Main etiological factors were&#58; HCV in 74 patients &#40;30&#46;8&#37;&#41;&#44; alcohol in 49 &#40;20&#46;4&#37;&#41;&#44; cryptogenic cirrhosis in 35 &#40;14&#46;6&#37;&#41;&#44; HBV in 26 &#40;10&#46;8&#37;&#41;&#44; HCV plus alcohol in 14 &#40;5&#46;8&#37;&#41;&#46; Considering the combinations&#44; hepatitis C was shown in 91 patients &#40;38&#37;&#41;&#59; chronic alcoholism in 68 patients &#40;28&#37;&#41;&#59; and hepatitis B in 33 patients &#40;14&#37;&#41;&#46; There were no significant differences between the groups in the age at diagnosis&#46; Percentage of male gender was higher in groups of alcohol &#40;94&#37;&#41;&#44; HCV plus alcohol &#40;93&#37;&#41; and HBV &#40;85&#37;&#41; than in cryptogenic cirrhosis &#40;60&#37;&#41; and HCV &#40;59&#37;&#41; &#40;p&#60;0&#46;001&#41;&#46;</p><p id="sp0028" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Conclusions&#46;</span> Our prospective study showed that hepatitis C is the more frequent etiology of HCC in Latin America&#44; followed by alcoholic cirrhosis&#46; Demographical results showed a male predominance &#40;male&#58;female ratio 2&#46;6&#41; with an important proportion of patients being diagnosed at their sixties&#46;</p></span>"
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        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="npara0005" class="elsevierStyleSimplePara elsevierViewall">HCC&#58; Hepatocellular carcinoma&#46; HCV&#58; Hepatitis C virus&#46; HBV&#58; Hepatitis B virus&#46; NASH&#58; Nonalcoholic steatohepatitis&#46; AIH&#58; Autoimmune hepatitis&#46; PBC&#58; Primary biliary cirrhosis&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Etiology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Percentage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HCV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">30&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Alcohol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">20&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Cryptogenic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">14&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HBV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">10&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HCV &#43; alcohol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">5&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">5&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">NASH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">4&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HBV &#43; alcohol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">AIH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Hemochromatosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HCV &#43; HBV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">PBC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HCV &#43; HBV &#43; alcohol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Etiology of chronic liver disease in 240 patients with diagnosis of HCC&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Etiology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HCV<a class="elsevierStyleCrossRef" href="#tbl2fn0020"><span class="elsevierStyleSup">&#42;&#42;</span></a> &#40;n 74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">64&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">9&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Alcohol<a class="elsevierStyleCrossRef" href="#tbl2fn0020"><span class="elsevierStyleSup">&#42;&#42;</span></a> &#40;n 49&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">64&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">8&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Cryptogenic &#40;n 35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">62&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">16&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HBV<a class="elsevierStyleCrossRef" href="#tbl2fn0020"><span class="elsevierStyleSup">&#42;&#42;</span></a> &#40;n 26&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">62&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">11&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HCV &#43; alcohol &#40;n 14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">60&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">11&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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            1 => array:3 [
              "identificador" => "tbl2fn0020"
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              "nota" => "<p class="elsevierStyleNotepara" id="npara2115">As the only risk factor present&#46; HCC&#58; Hepatocellular carcinoma&#59; HCV&#44; hepatitis C virus&#59; HBV&#44; hepatitis B virus&#46;</p>"
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          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Age at diagnosis time in the main etiological groups of patients with HCC &#40;in years&#41;&#46;<a class="elsevierStyleCrossRef" href="#tbl2fn0015"><span class="elsevierStyleSup">&#42;</span></a></p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Etiology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Male gender &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Female gender &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HCV<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">59&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">40&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Alcohol<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">93&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">6&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Cryptogenic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">60&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">40&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HBV<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">84&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">15&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">HCV &#43; alcohol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">92&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">7&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            1 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "&#42;&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npara0115">As the only risk factor present&#46; HCC&#58; Hepatocellular carcinoma&#46; HCV&#58; Hepatitis C virus&#46; HBV&#58; Hepatitis B virus&#46;</p>"
            ]
          ]
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          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Percentages of male and female genders in the main etiological groups in patients with HCC&#46;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#42;</span></a></p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">BCLC stages&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="middle" scope="col">Surveillance program &#40;n 102&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="middle" scope="col">No survei llance program &#40;n 86&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">69&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">39&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">17&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">41&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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Article information

ISSN: 16652681
Original language: English

DOI:10.1016/S1665-2681(19)31681-3

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Year/Month	Html	Pdf	Total

2024 October	15	3	18
2024 September	19	8	27
2024 August	18	4	22
2024 July	18	5	23
2024 June	15	3	18
2024 May	12	2	14
2024 April	22	2	24
2024 March	18	3	21
2024 February	10	4	14
2024 January	19	12	31
2023 December	16	6	22
2023 November	17	6	23
2023 October	23	11	34
2023 September	13	5	18
2023 August	17	4	21
2023 July	10	7	17
2023 June	31	2	33
2023 May	38	2	40
2023 April	29	3	32
2023 March	25	1	26
2023 February	9	1	10
2023 January	10	5	15
2022 December	7	2	9
2022 November	13	2	15
2022 October	7	6	13
2022 September	6	6	12
2022 August	8	3	11
2022 July	10	8	18
2022 June	6	4	10
2022 May	5	3	8
2022 April	6	9	15
2022 March	6	10	16
2022 February	4	4	8
2022 January	16	6	22
2021 December	13	20	33
2021 November	28	7	35
2021 October	15	7	22
2021 September	10	5	15
2021 August	6	5	11
2021 July	6	8	14
2021 June	3	7	10
2021 May	6	7	13
2021 April	25	6	31
2021 March	9	5	14
2021 February	3	13	16
2021 January	6	5	11
2020 December	13	13	26
2020 November	5	10	15
2020 October	12	6	18
2020 September	15	5	20
2020 August	9	4	13
2020 July	2	1	3
2020 June	4	1	5
2020 May	3	2	5
2020 April	1	3	4
2020 March	4	4	8
2020 February	2	1	3
2020 January	3	2	5
2019 December	4	3	7
2019 November	5	1	6
2019 October	0	1	1
2019 September	4	3	7
2019 August	1	1	2
2019 July	1	5	6
2019 June	1	6	7

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