Hepatitis C and hepatocellular carcinoma
Eduardo Fassio
,
Corresponding author
* Hospital Nacional Prof. A. Posadas El Palomar, Buenos Aires, Argentina.
Read
2751
Timeswas read the article
373
Total PDF
2378
Total HTML
Share statistics
array:24 [ "pii" => "S1665268119317363" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31736-3" "estado" => "S300" "fechaPublicacion" => "2010-01-01" "aid" => "71398" "copyright" => "Fundación Clínica Médica Sur, A.C." "copyrightAnyo" => "2010" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2010;9 Supl 1:S119-22" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 63 "formatos" => array:3 [ "EPUB" => 12 "HTML" => 24 "PDF" => 27 ] ] "itemSiguiente" => array:19 [ "pii" => "S1665268119317375" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31737-5" "estado" => "S300" "fechaPublicacion" => "2010-01-01" "aid" => "71399" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2010;9 Supl 1:S123-31" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 65 "formatos" => array:3 [ "EPUB" => 11 "HTML" => 27 "PDF" => 27 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "On the cusp of change: New therapeutic modalities for HCV" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S123" "paginaFinal" => "S131" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0030" "etiqueta" => "Figure 6." "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 847 "Ancho" => 2078 "Tamanyo" => 218722 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Kwo P, et al, (Easl Abstract 995) J Hepatol 2008; 48(Supl. 2): S1-375.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Maribel Rodríguez-Torres" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Maribel" "apellidos" => "Rodríguez-Torres" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317375?idApp=UINPBA00004N" "url" => "/16652681/00000009000000S1/v1_201906221034/S1665268119317375/v1_201906221034/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119317351" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31735-1" "estado" => "S300" "fechaPublicacion" => "2010-01-01" "aid" => "71397" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2010;9 Supl 1:S112-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 57 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 16 "PDF" => 31 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Insulin resistance, hepatic steatosis and hepatitis C: A complex relationship with relevant clinical implications" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S112" "paginaFinal" => "S118" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 1:</span></span>" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 911 "Ancho" => 1000 "Tamanyo" => 104275 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Relationships between metabolic and viral factors and hepatic steatosis in the setting of chronic hepatitis C. Insulin resistance is the major determinant of steatosis and in turn is aggravated by several genotype-independent mechanisms probably related to the presence of viral proteins in the hepatocyte and due to the inflammatory response linked to viral infection. Several specific steatogenic mechanisms operate in genotype 3 infection. Alcohol consumption can also contribute to steatosis development.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Marco Arrese, Arnoldo Riquelme, Alejandro Soza" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Marco" "apellidos" => "Arrese" ] 1 => array:2 [ "nombre" => "Arnoldo" "apellidos" => "Riquelme" ] 2 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Soza" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317351?idApp=UINPBA00004N" "url" => "/16652681/00000009000000S1/v1_201906221034/S1665268119317351/v1_201906221034/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "titulo" => "Hepatitis C and hepatocellular carcinoma" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S119" "paginaFinal" => "S122" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Eduardo Fassio" "autores" => array:1 [ 0 => array:4 [ "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" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "Hospital Nacional Prof. A. Posadas El Palomar, Buenos Aires, Argentina." "etiqueta" => "*" "identificador" => "aff1" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0005" class="elsevierStylePara elsevierViewall">Chronic hepatitis C virus (HCV) infection is a well-recognized risk factor for hepatocellular carcinoma (HCC). HCC is a malignant tumor that usually emerges in patients with chronic liver disease and hepatitis B, hepatitis C and alcoholic cirrhosis are the more frequent predisposing conditions.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">The incidence of HCC is highly variable across the world and it runs a parallel course with the prevalence of chronic carriers of hepatitis B virus (HBV) at each region.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Thus, in areas with high endemicity of HBV, like sub-Saharan Africa or Eastern Asia, the highest annual incidence rates of HCC are found (greater than 30/100.000 individuals) and most of patients are young adults who became infected with the virus very early at their lives, either through vertical (mother to newborn) or horizontal (between siblings) transmission. More than 80% of world cases of HCC occur in these 2 regions and China alone accounts for more than 50%.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In contrast, intermediate annual incidence rates (5-20/ 100.000 individuals) are observed in Southern European countries (Italy, Spain, Greece) and low annual incidence rates (lower than 5/100.000 individuals) in Northern European countries, Oceania and North and South America, where the rates of chronic carriers of HBV are coincidently low. In all these regions, chronic hepatitis C and alcoholic cirrhosis are the main risk factors for HCC.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">There is a difference also in the incidence trends of HCC between the Asian and some of the occidental countries. A decreasing incidence of HCC has been reported in Taiwan as a consequence of the ins-tauration of universal hepatitis B vaccination pro-grams;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and in China, due to a government program promoting dietetic changes and then a reduced exposure to the hepatocarcinogen aflatoxin B<span class="elsevierStyleInf">1</span>.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> In contrast, many studies performed in indus-trialized countries (USA, United Kingdom, Italy, France and Canada) have been showing a significant increase of the incidence.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> A recently published study showed that the age-adjusted HCC incidence rates tripled between 1975 and 2005 in USA.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> In that country, available studies suggest that HCV infection acquired 2-4 decades ago accounts at least 50% of the observed increase in HCC.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">In Latin America, a few published studies have also showed the importance of hepatitis C and chronic alcoholism as risk factors for HCC.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Small retrospective series of patients with HCC from Mexico and Chile reported that chronic HCV infection was present in 73% and 48% of them, respectively.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> A multicenter series from Brazil including 287 HCC cases (but with full serological studies available in only 132 out of them), found that hepatitis C accounted for 25%.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In Argentina, a retrospective multicenter study analyzed the etiology among 551 patients with HCC and showed that alcoholic cirrhosis and chronic hepatitis C were present in 76% of cases (hepatitis C in 40.5%).<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Recently, the first prospective study aimed in investigating etiology of HCC in Latin America was performed.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Most of the patients were included by colleagues from Argentina, Brazil, Venezuela and Colombia. Hepatitis C was shown to be the leading risk factor for HCC, present in 38% out of 240 cases<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> (without significant differences between the countries).</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Risk Factors for Hcc Among Patients with Chronic Hepatitis C</span><p id="p0025" class="elsevierStylePara elsevierViewall">The main risk factor for occurrence of HCC in patients with hepatitis C is the presence of cirrhosis. Almost all the patients with HCC associated with HCV have cirrhosis at the time of diagnosis. Among patients with HCV-related cirrhosis, the annual incidence of HCC ranges between 2-8%.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> The rate is higher in Japan (4-8%),<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> intermediate in Italy (2-4%),<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> and lower in USA (1.4%).<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> The 5-year cumulative risk for HCC in patients with cirrhosis was 17% in Europe and 30% in Japan.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Furthermore, studies from Italy have shown that HCC was the main cause of death and the first complication to develop among compensated cirrhotic patients;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> and, also in Japan, the development of HCC was more frequent than that of hepatic failure.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="p0030" class="elsevierStylePara elsevierViewall">The risk for HCC is much lower in patients with noncirrhotic hepatitis C. In a Japanese study, the incidence per 100 person years increased from 0.4 among those with stage F0-F1 to 1.5 in stage F2, 5.1 in stage F3 and to 6.9 in stage F4.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> In a multicen-ter study from USA, that included 1005 patients, the cumulative 5-year HCC incidence was 7.0% among patients with cirrhosis and 4.1% in those with bridging fibrosis in the baseline liver biopsy. In 18% of patients with occurrence of HCC during follow-up, serial biopsies did not show progression to cirrho-sis.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> However, most of experts think that severe liver fibrosis secondary to long-lasting chronic inflammation and liver regeneration resulting from immune-mediated cell death are factors contributing to HCC development; and that a direct oncogenic role of HCV remains to be determined.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="p0035" class="elsevierStylePara elsevierViewall">Among patients with cirrhosis associated with HCV, risk factors for developing HCC can be separated in host-related, virus-related and external ones. Some host-related factors that have been independently associated with progression to HCC are older age at infection (> 50 years), male gender, decreased platelet count, esophageal varices;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> and presence of comorbid conditions, including porphyria cutanea tarda,<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> liver steatosis <a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> and diabetes.</p><p id="p0040" class="elsevierStylePara elsevierViewall">Regarding viral-related factors, there is no evidence that viral load influences the risk for developing HCC. Considering that previous research had produced controversial results, a recent meta-analy-sis was performed to investigate whether genotype 1b was associated with a higher risk of HCC.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Authors focused on 21 studies that presented age-adjusted risk estimates for genotype 1b versus other genotypes and found that patients infected with HCV-1b had almost double the risk to develop HCC than those infected with the others [Relative Risk (95% Confidence Intervals) = 1.78 (1.36-2.32)].<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p><p id="p0045" class="elsevierStylePara elsevierViewall">Cohort studies from Italy and China have shown that cirrhotic patients coinfected with HCV and HBV had a 2-to 6-fold higher risk of developing HCC compared with those infected with only one vi-rus;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> and a meta-analysis of 32 case-control studies found a synergistic effect between HBV and HCV infections in causing HCC.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> Interestingly, patients with chronic hepatitis C and an occult HBV infection (presence of HBV DNA in the liver or in serum but HBsAg negative) had also a higher risk of HCC during follow-up than those with HCV infection alone;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> and HBV DNA was frequently detected in liver tissue of Japanese patients with a sustained virologic response to antiviral treatment for hepatitis C who developed a HCC.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> In contrast, recent studies have shown that a past HBV infection (anti-HBc seropositivity with HBsAg negative) does not mean an additional risk for HCC, when multivariate analysis are performed.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p><p id="p0050" class="elsevierStylePara elsevierViewall">Coinfection with HIV may also modify the natural history of chronic hepatitis C and a faster progression to cirrhosis has been described. A retrospective study showed that anti-HIV positive patients with HCC were younger at the diagnosis time than anti-HIV negative ones; and the estimated time from HCV infection to HCC was significantly shorter in the coinfected patients than in monoinfec-ted ones (26.1 <span class="elsevierStyleItalic">vs.</span> 33.8 years, respectively) (p 0.002).<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a></p><p id="p0055" class="elsevierStylePara elsevierViewall">In respect to external factors, chronic alcoholism and hepatitis C seem to have a synergistic effect in increasing risk for HCC. Case-control studies have shown that among patients with chronic hepatitis C, there is an approximately 2-fold increased risk for HCC in heavy drinkers as compared to non-drinkers;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</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.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> Another external factor that modifies the incidence of HCC in patients with chronic hepatitis C is the effect of antiviral treatment based on interferon. A recently published meta-analysis including 20 studies (4.700 patients) showed that the risk of HCC had been reduced in treatment groups (interferon alone in 18 studies, in association with ribavirin in 2) as compared to controls [Relative Risk (95% CI), 0.43 (0.33-0.56)].<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> As expected, risk was significantly lower in patients with a sustained virologic response versus nonresponders [Relative Risk (95% CI), 0.35 (0.26-0.46)].<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> However, another recent meta-analysis (including 3.246 patients) concluded that interferon treatment prevented the development of HCC in chronic hepatitis C, even in nonresponders.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Surveillance for Hepatocellular Carcinoma</span><p id="p0060" class="elsevierStylePara elsevierViewall">Patients with hepatitis C and cirrhosis should undergo surveillance for HCC. In those with bridging fibrosis, the cost-efficacy of this strategy has not been evaluated.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Surveillance should be performed using ultrasonography, at 6 month intervals. If nodules are detected on ultrasound, patients should undergo diagnostic algorithms suggested by recent HCC Guidelines.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:3 [ "identificador" => "xres1210326" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1126743" "titulo" => "Key words" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Risk Factors for Hcc Among Patients with Chronic Hepatitis C" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Surveillance for Hepatocellular Carcinoma" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2010-03-20" "fechaAceptado" => "2010-04-20" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec1126743" "palabras" => array:6 [ 0 => "Hepatocarcinoma" 1 => "Risk factors for hepatocarcinoma" 2 => "Cirrhosis" 3 => "Incidence of hepatocarcinoma" 4 => "Interferon" 5 => "Coinfection" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abs0005" class="elsevierStyleSection elsevierViewall"><p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Chronic hepatitis C virus infection is a well-recognized risk factor for occurrence of hepatocellular carcinoma (HCC). In Europe, Oceania and America, chronic hepatitis C and alcoholic cirrhosis are the main risk factors for HCC. In Latin America, a few retrospective and one prospective study have also shown the pre-dominant role played by hepatitis C in this setting. Furthermore, the incidence of HCC has been increasing in industrialized countries in the last decades; partially as a consequence of the increase in HCV-related cirrhosis (as the long-term sequel of the peak of infections occurring 2-4 decades ago). The main risk factor for HCC development in patients with hepatitis C is the presence of cirrhosis. Among patients with hepatitis C and cirrhosis, the annual incidence rate of HCC ranges between 1-8%, being higher in Japan (4-8%) intermediate in Italy (2-4%) and lower in USA (1.4%). Some studies have also found that HCC may be the first complication to develop and the more frequent cause of death in the compensated HCV-associated cirrhosis. Other risk factors for HCC occurrence are older age at infection, male gender, decreased platelet count, esophageal varices, presence of porphyria cutanea tarda, liver steatosis or diabetes, infection with genotype 1b, coinfection with hepatitis B virus or with HIV and chronic alcoholism. Many studies and also meta-analysis have reported that antiviral therapy based on interferon may reduce the incidence of HCC in chronic hepatitis C, especially in patients with sustained virologic response. Patients with HCV-related cirrhosis should undergo surveillance for HCC.</p></span>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:49 [ 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." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary liver cancer: worldwide incidence and trends." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Bosch FX" 1 => "Ribes J" 2 => "Díaz M" 3 => "Cléries R" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2004" "volumen" => "127" "paginaInicial" => "S5" "paginaFinal" => "S16" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15508102" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatocellular carcinoma in cirrhosis: incidence and risk factors." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Fattovich G" 1 => "Stroffolini T" 2 => "Zagni I" 3 => "Donato F" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2004" "volumen" => "127" "paginaInicial" => "S35" "paginaFinal" => "S50" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15508101" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatocellular carcinoma: epidemiology and molecular carcinogenesis." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "El-Serag HB" 1 => "Rudolph KL" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2007.04.061" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2007" "volumen" => "132" "paginaInicial" => "2557" "paginaFinal" => "2576" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17570226" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." "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:3 [ 0 => "Bruix J" 1 => "Barrera JM" 2 => "Calvet X" ] ] ] ] ] "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" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Colombo M" 1 => "Kuo G" 2 => "Choo QL" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0140-6736(89)91016-7" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1989" "volumen" => "2" "paginaInicial" => "1006" "paginaFinal" => "1008" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2572740" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Bugianesi E" 1 => "Leone N" 2 => "Vanni E" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2002" "volumen" => "123" "paginaInicial" => "134" "paginaFinal" => "140" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12105842" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Donato F" 1 => "Tagger A" 2 => "Chiesa R" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.510260308" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "1997" "volumen" => "26" "paginaInicial" => "579" "paginaFinal" => "584" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9303486" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9." "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" => true "autores" => array:3 [ 0 => "Kemp W" 1 => "Pianko S" 2 => "Nguyen S" ] ] ] ] ] "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" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primitive liver cancers: epidemiology and geographical study in France." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Borie F" 1 => "Trétarre B" 2 => "Bouvier AM" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MEG.0b013e3283293783" "Revista" => array:6 [ "tituloSerie" => "Eur J Gastroenterol Hepatol" "fecha" => "2009" "volumen" => "21" "paginaInicial" => "984" "paginaFinal" => "989" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19357522" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Chang MH" 1 => "Chen CJ" 2 => "Lai MS" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199706263362602" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1997" "volumen" => "336" "paginaInicial" => "1855" "paginaFinal" => "1859" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9197213" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary prevention of hepatocellular carcinoma." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Yu SZ" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Gastroenterol Hepatol" "fecha" => "1995" "volumen" => "10" "paginaInicial" => "674" "paginaFinal" => "682" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8580413" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rising incidence of hepatocellular carcinoma in the Uinted States." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "El-Serag HB" 1 => "Mason AC" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199903113401001" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1999" "volumen" => "340" "paginaInicial" => "745" "paginaFinal" => "750" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10072408" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increase in primary liver cancer in the UK, 1979-94." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Taylor-Robinson SD" 1 => "Foster GR" 2 => "Arora S" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(05)63789-0" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1997" "volumen" => "350" "paginaInicial" => "1142" "paginaFinal" => "1143" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9343506" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cancer mortality in Europe, 1995-1999, and overview of trends since 1960." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Levi F" 1 => "Lucchini F" 2 => "Negri E" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ijc.20097" "Revista" => array:6 [ "tituloSerie" => "Int J Cancer" "fecha" => "2004" "volumen" => "110" "paginaInicial" => "155" "paginaFinal" => "169" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15069676" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Review article: the changing epidemiology of hepatocellular carcinoma in Canada." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Dyer Z" 1 => "Peltekian K" 2 => "van Zanten SV" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2036.2005.02504.x" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2005" "volumen" => "22" "paginaInicial" => "17" "paginaFinal" => "22" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15963075" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatocellular carcinoma incidence, mortality and survival trends in the United States from 1975 to 2005." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Altekruse SF" 1 => "McGlynn KA" 2 => "Reichman ME" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2008.20.7753" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2009" "volumen" => "27" "paginaInicial" => "1485" "paginaFinal" => "1491" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19224838" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors for the rising rates of primary liver cancer in the United States." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "El-Serag HB" 1 => "Mason AC" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "2000" "volumen" => "160" "paginaInicial" => "3227" "paginaFinal" => "3230" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11088082" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatocellular carcinoma: recent trends in the United States." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "El-Serag HB" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2004" "volumen" => "127" "paginaInicial" => "S27" "paginaFinal" => "S34" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15508094" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatocellular carcinoma in Brazil: report of a national survey (Florianopolis, SC, 1995)." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Goncalves CS" 1 => "Pereira FE" 2 => "Gayotto LC" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1590/s0036-46651997000300008" "Revista" => array:7 [ "tituloSerie" => "Rev Inst Med Trop Sao Paulo" "fecha" => "1997" "volumen" => "39" "paginaInicial" => "165" "paginaFinal" => "170" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9460258" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1529943014001090" "estado" => "S300" "issn" => "15299430" ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatocellular carcinoma and hepatitis C in Mexico." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Mondragon-Sanchez R" 1 => "Garduno-López AL" 2 => "Hernández-Castillo E" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hepatogastroenterology" "fecha" => "2005" "volumen" => "52" "paginaInicial" => "1159" "paginaFinal" => "1162" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16001652" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence and genotypes of hepatitis C virus in blood donors and in patients with chronic liver disease and hepatocarcinoma in a Chilean population." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Muñoz G" 1 => "Velazco M" 2 => "Thiers V" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Med Chil" "fecha" => "1998" "volumen" => "126" "paginaInicial" => "1035" "paginaFinal" => "1042" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9922505" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Etiology of hepatocellular carcinoma in Argentina: results of a multicenter retrospective study." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Fassio E" 1 => "Míguez C" 2 => "Soria S" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Acta Gastroenterol Latinoamer" "fecha" => "2009" "volumen" => "39" "paginaInicial" => "47" "paginaFinal" => "52" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Etiology of hepatocellular carcinoma in Latin America: a prospective, multicenter, international study." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Fassio E" 1 => "Díaz S" 2 => "Santa C" 3 => "Reig ME" 4 => "Martínez Artola Y" 5 => "Alves de Mattos A" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Hepatol" "fecha" => "2010" "volumen" => "9" "paginaInicial" => "63" "paginaFinal" => "69" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20332549" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of hepatocellular carcinoma." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Bruix J" 1 => "Sherman M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.20933" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2005" "volumen" => "42" "paginaInicial" => "1208" "paginaFinal" => "1236" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16250051" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Ikeda K" 1 => "Saitoh S" 2 => "Koida I" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "1993" "volumen" => "18" "paginaInicial" => "47" "paginaFinal" => "53" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7686879" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Yoshida H" 1 => "Shiratori Y" 2 => "Moriyama M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-131-3-199908030-00003" "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "1999" "volumen" => "131" "paginaInicial" => "174" "paginaFinal" => "181" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10428733" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The natural history of compensated cirrhosis due to hepatitis C virus: a 17-year cohort study of 214 patients." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Sangiovanni A" 1 => "Prati GM" 2 => "Fasani P" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.21176" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2006" "volumen" => "43" "paginaInicial" => "1303" "paginaFinal" => "1310" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16729298" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Fattovich G" 1 => "Pantalena M" 2 => "Zagni I" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1572-0241.2002.07057.x" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol" "fecha" => "2002" "volumen" => "97" "paginaInicial" => "2886" "paginaFinal" => "2895" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12425564" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Lok AS" 1 => "Seef LB" 2 => "Morgan TR" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2008.09.014" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2009" "volumen" => "136" "paginaInicial" => "138" "paginaFinal" => "148" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18848939" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lower incidence of hepatic failure than hepatocellular carcinoma in Japanese patients with chronic hepatitis C." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Imazeki F" 1 => "Yokosuka O" 2 => "Fukai K" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1478-3231.2005.01062.x" "Revista" => array:6 [ "tituloSerie" => "Liver Int" "fecha" => "2005" "volumen" => "25" "paginaInicial" => "772" "paginaFinal" => "778" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15998428" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virusinduced hepatocarcinogenesis." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Bartosch B" 1 => "Thimme R" 2 => "Blum HE" 3 => "Zoulim F" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2009.05.008" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2009" "volumen" => "51" "paginaInicial" => "810" "paginaFinal" => "820" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19545926" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Degos F" 1 => "Christidis C" 2 => "Ganne-Carrie N" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.47.1.131" "Revista" => array:6 [ "tituloSerie" => "Gut" "fecha" => "2000" "volumen" => "47" "paginaInicial" => "131" "paginaFinal" => "136" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10861275" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liver cancer risk is increased in patients with porphyria cutanea tarda in comparison to matched control patients with chronic liver disease." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Fracanzani AL" 1 => "Taioli E" 2 => "Sampietro M" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2001" "volumen" => "35" "paginaInicial" => "498" "paginaFinal" => "503" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11682034" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C virus infection." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Ohata K" 1 => "Hamasaki K" 2 => "Toriyama K" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cncr.11427" "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "2003" "volumen" => "97" "paginaInicial" => "3036" "paginaFinal" => "3043" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12784339" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Raimondi S" 1 => "Bruno S" 2 => "Mondelli MU" 3 => "Maisonneve P" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2009.01.019" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2009" "volumen" => "50" "paginaInicial" => "1142" "paginaFinal" => "1154" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19395111" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Chiaramonte M" 1 => "Stroffolini T" 2 => "Vian A" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "1999" "volumen" => "85" "paginaInicial" => "2132" "paginaFinal" => "2137" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10326690" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of hepatitis C and B virus infection on risk of hepatocellular carcinoma: a prospective study." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Tsai JF" 1 => "Jeng JE" 2 => "Ho MS" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/bjc.1997.493" "Revista" => array:6 [ "tituloSerie" => "Br J Cancer" "fecha" => "1997" "volumen" => "76" "paginaInicial" => "968" "paginaFinal" => "974" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9328161" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A meta-analysis of epide-miological studies on the combined effect of hepatitis B and C virus infections on causing hepatocellular carcinoma." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Donato F" 1 => "Boffetta P" 2 => "Puoti M" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int J Cancer" "fecha" => "1998" "volumen" => "75" "paginaInicial" => "347" "paginaFinal" => "354" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9455792" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Occult hepatitis B virus infection is associated with the development of hepatocellular carcinoma in chronic hepatitis C patients." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Squadrito G" 1 => "Pollicino T" 2 => "Cacciola I" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cncr.21702" "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "2006" "volumen" => "106" "paginaInicial" => "1326" "paginaFinal" => "1330" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16453330" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Frequent detection of hepatitis B virus DNA in hepatocellular carcinoma of patients with sustained virologic response for hepatitis C virus." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Tamori A" 1 => "Hayashi T" 2 => "Shinzaki M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jmv.21488" "Revista" => array:6 [ "tituloSerie" => "J Med Virol" "fecha" => "2009" "volumen" => "81" "paginaInicial" => "1009" "paginaFinal" => "1014" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19382258" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence of anti-HBc seropositivity on the risk of hepatocellular carcinoma in HCV-infected patients after adjusting for confounding factors." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Ohki T" 1 => "Tateishi R" 2 => "Goto E" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2893.2009.01152.x" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2010" "volumen" => "17" "paginaInicial" => "91" "paginaFinal" => "97" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19566786" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lack of correlation between serum anti-HBcore detectability and hepatocellular carcinoma in patients with HCV-related cirrhosis." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Stroffolini T" 1 => "Almasio PL" 2 => "Persico M" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1572-0241.2008.01912.x" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol" "fecha" => "2008" "volumen" => "103" "paginaInicial" => "1966" "paginaFinal" => "1972" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18637087" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.-Canadian multicenter study." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Bräu N" 1 => "Fox RK" 2 => "Xiao P" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2007.06.010" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2007" "volumen" => "47" "paginaInicial" => "527" "paginaFinal" => "537" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17692986" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association between hepatitis C virus antibodies and hepatocellular carcinoma in Taiwan." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Yu MW" 1 => "You SL" 2 => "Chang CJ" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Cancer Res" "fecha" => "1991" "volumen" => "51" "paginaInicial" => "5621" "paginaFinal" => "5625" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1655259" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1529943014001181" "estado" => "S300" "issn" => "15299430" ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C and hepatitis B in the etiology of hepatocellular carcinoma in the Japanese population." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Tanaka K" 1 => "Hirohata T" 2 => "Koga S" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cancer Res" "fecha" => "1991" "volumen" => "51" "paginaInicial" => "2842" "paginaFinal" => "2847" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1851661" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of factors affecting the appearance of hepatocellular carcinoma in patients with chronic hepatitis C. A long term follow up study after histologic diagnosis." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Aizawa Y" 1 => "Shibamoto Y" 2 => "Takagi I" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "2000" "volumen" => "89" "paginaInicial" => "53" "paginaFinal" => "59" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10897000" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Singal AK" 1 => "Singh A" 2 => "Jaganmoham S" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cgh.2009.10.026" "Revista" => array:6 [ "tituloSerie" => "Clin Gastroenterol Hepatol" "fecha" => "2010" "volumen" => "8" "paginaInicial" => "192" "paginaFinal" => "199" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19879972" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0245" "etiqueta" => "49." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Meta-analysis: reduced incidence of hepatocellular carcinoma in patients not responding to interferon therapy of chronic hepatitis C." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Miyake Y" 1 => "Iwasaki Y" 2 => "Yamamoto K" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Int J Cancer" "fecha" => "2010" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/00000009000000S1/v1_201906221034/S1665268119317363/v1_201906221034/en/main.assets" "Apartado" => array:4 [ "identificador" => "78185" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Module XVIII" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/00000009000000S1/v1_201906221034/S1665268119317363/v1_201906221034/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317363?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 0 | 11 |
| 2024 October | 79 | 6 | 85 |
| 2024 September | 129 | 7 | 136 |
| 2024 August | 120 | 5 | 125 |
| 2024 July | 138 | 6 | 144 |
| 2024 June | 129 | 5 | 134 |
| 2024 May | 141 | 7 | 148 |
| 2024 April | 120 | 7 | 127 |
| 2024 March | 111 | 2 | 113 |
| 2024 February | 133 | 15 | 148 |
| 2024 January | 180 | 9 | 189 |
| 2023 December | 89 | 12 | 101 |
| 2023 November | 118 | 16 | 134 |
| 2023 October | 120 | 9 | 129 |
| 2023 September | 76 | 11 | 87 |
| 2023 August | 69 | 5 | 74 |
| 2023 July | 73 | 7 | 80 |
| 2023 June | 64 | 5 | 69 |
| 2023 May | 45 | 1 | 46 |
| 2023 April | 50 | 6 | 56 |
| 2023 March | 50 | 6 | 56 |
| 2023 February | 20 | 1 | 21 |
| 2023 January | 41 | 5 | 46 |
| 2022 December | 14 | 8 | 22 |
| 2022 November | 10 | 2 | 12 |
| 2022 October | 23 | 8 | 31 |
| 2022 September | 7 | 10 | 17 |
| 2022 August | 7 | 4 | 11 |
| 2022 July | 9 | 8 | 17 |
| 2022 June | 9 | 4 | 13 |
| 2022 May | 10 | 5 | 15 |
| 2022 April | 11 | 5 | 16 |
| 2022 March | 14 | 5 | 19 |
| 2022 February | 6 | 4 | 10 |
| 2022 January | 7 | 4 | 11 |
| 2021 December | 5 | 7 | 12 |
| 2021 November | 4 | 7 | 11 |
| 2021 October | 6 | 9 | 15 |
| 2021 September | 5 | 13 | 18 |
| 2021 August | 6 | 5 | 11 |
| 2021 July | 10 | 11 | 21 |
| 2021 June | 9 | 9 | 18 |
| 2021 May | 11 | 6 | 17 |
| 2021 April | 14 | 4 | 18 |
| 2021 March | 3 | 5 | 8 |
| 2021 February | 15 | 10 | 25 |
| 2021 January | 3 | 6 | 9 |
| 2020 December | 3 | 3 | 6 |
| 2020 November | 2 | 4 | 6 |
| 2020 October | 2 | 2 | 4 |
| 2020 September | 6 | 7 | 13 |
| 2020 August | 4 | 6 | 10 |
| 2020 July | 3 | 0 | 3 |
| 2020 June | 3 | 2 | 5 |
| 2020 May | 1 | 4 | 5 |
| 2020 April | 1 | 2 | 3 |
| 2020 March | 3 | 3 | 6 |
| 2020 February | 4 | 1 | 5 |
| 2020 January | 1 | 2 | 3 |
| 2019 December | 9 | 6 | 15 |
| 2019 November | 2 | 3 | 5 |
| 2019 October | 3 | 1 | 4 |
| 2019 September | 3 | 2 | 5 |
| 2019 August | 1 | 1 | 2 |
| 2019 July | 2 | 7 | 9 |
| 2019 June | 1 | 5 | 6 |
Show all
