Treatment of hepatitis C before and after liver transplantation
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"documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2006;5 Supl 1:S60-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 55 "formatos" => array:3 [ "EPUB" => 12 "HTML" => 20 "PDF" => 23 ] ] "en" => array:8 [ "idiomaDefecto" => true "titulo" => "Treatment of hepatitis C virus infection in drug addicts" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S60" "paginaFinal" => "S62" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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/S1665268119319763?idApp=UINPBA00004N" "url" => "/16652681/00000005000000S1/v1_201906280857/S1665268119319763/v1_201906280857/en/main.assets" ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "Treatment of hepatitis C before and after liver transplantation" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S63" "paginaFinal" => "S66" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Rosalba Moreno Alcantar" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Rosalba" "apellidos" => "Moreno Alcantar" "email" => array:1 [ 0 => "rosalba_moreno@yahoo.com.mx" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "Departamento de Gastroenterologia, IMSS Hospital de Especialidades Bernardo Sepúlveda CMN Siglo XXI, México, D.F. México" "etiqueta" => "1" "identificador" => "aff1" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Address for correspondence:" ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0005" class="elsevierStylePara elsevierViewall">Liver cirrhosis secondary to chronic hepatitis C virus (HCV) infection is the primary reason for transplantations in most centers. Despite a reduction in the incidence of hepatitis C, the number of HCV-positive individuals with end-stage liver disease is expected to increase. Factors responsible for this trend include the development of cirrhosis in one third of HCV patients after 25-35 years of infection, the high prevalence of HCV in people aged 30-50 years, and the lack of an effective treatment for hepatitis C.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Infection or viremia recurs in all patients after transplantation, but not all patients develop significant histological lesions. The survival rates of HCV-positive liver transplant patients and grafts 5-8 years after transplantation is similar to that of transplant patients not infected with HCV.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> On the other hand, recurrence of hepatitis or disease on the graft is variable. In some patients, accelerated progression to cirrhosis results in loss of the graft; in others, recurrence is minimal and not progressive. However, two lines of evidence suggest that recurrent hepatitis C is aggressive and should be treated. Firstly, the number of cases of chronic hepatitis who progress to cirrhosis, graft failure, and retransplantation has increased. Some studies have shown that 30% of patients develop graft cirrhosis<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> years after transplantation. Secondly, in HCV patients, the rate of progression to fibrosis is faster than that in immunocompetent patients, which suggests that cirrhosis develops more rapidly in HCV patients than in immunocompetent patients.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">There are three forms of recurrence, which differ in clinical presentation, pathophysiology, prognosis, and their treatment.</p><p id="p0020" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0005"><li class="elsevierStyleListItem" id="list0005"><span class="elsevierStyleLabel">1.</span><p id="p0025" class="elsevierStylePara elsevierViewall">Chronic hepatitis C of grafts has a higher rate of progression to fibrosis than that of HCV patients who have not received transplants. Because fibrogenesis is more aggressive in transplanted patients than in immunocompetent patients, advanced fibrosis or cirrhosis develops faster (9-12 years vs 20-50 years).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In 80% of patients, the degree of hepatitis 1 year after the transplantation is compatible with that of chronic hepatitis patients.</p></li></ul><ul class="elsevierStyleList" id="li0010"><li class="elsevierStyleListItem" id="list0010"><span class="elsevierStyleLabel">2.</span><p id="p0030" class="elsevierStylePara elsevierViewall">Fibrotic cholestatic hepatitis occurs in less than 10% of cases, but it is a serious condition. It causes graft failure within a few months in 50% of cases afflicted by it. It is characterized by biochemical cholestasis, marked jaundice, very high viremia titers, and histological inflammation.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p></li></ul><ul class="elsevierStyleList" id="li0015"><li class="elsevierStyleListItem" id="list0015"><span class="elsevierStyleLabel">3.</span><p id="p0035" class="elsevierStylePara elsevierViewall">Hepatitis that progresses slowly during the first decade occurs in some patients. Histological damage is scarce or absent despite a high viral load. About 25% (8%–44%) of patients develop cirrhosis of the graft 5 years after transplantation. The results of recent studies indicate that the rate of graft cirrhosis is higher now than several years ago.</p></li></ul></p><p id="p0040" class="elsevierStylePara elsevierViewall">Cirrhosis is more aggressive in transplant patients than in patients who have not received transplants. The median of the first episode of decompensation is 8 months after diagnosis of cirrhosis of the graft. Transplant patients with decompensated cirrhosis experience episodes of ascites and, less frequently, encephalopathy. The accrued rate of decompensation in liver transplant patients with cirrhosis is 42% per year and 63% in 3 years; in patients with cirrhosis who have not received liver transplants, decompensation is only 3% per year and 18% in 5 years. The following indices are predictive of decompensation: a Child score greater than A, albumin levels less than 3.4 g/dL, and an interval of less than 1 year between transplantation and diagnosis of decompensated cirrhosis. The survival rate of HCV patients with these conditions is less than 10% in 3 years; the survival rate of HCV patients who have not undergone transplantation is 60%).<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="p0045" class="elsevierStylePara elsevierViewall">Factors affecting the development of hepatitis in liver transplant patients are the same as those for immunocompetent hosts:</p><p id="p0050" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0020"><li class="elsevierStyleListItem" id="list0020"><span class="elsevierStyleLabel">•</span><p id="p0055" class="elsevierStylePara elsevierViewall">host factors (demography, immune status, comorbidity, liver function at the time of transplantation),</p></li></ul><ul class="elsevierStyleList" id="li0025"><li class="elsevierStyleListItem" id="list0025"><span class="elsevierStyleLabel">•</span><p id="p0060" class="elsevierStylePara elsevierViewall">viral factors (genotype, viral load, quasispecies), and</p></li></ul><ul class="elsevierStyleList" id="li0030"><li class="elsevierStyleListItem" id="list0030"><span class="elsevierStyleLabel">•</span><p id="p0065" class="elsevierStylePara elsevierViewall">factors associated with the transplant status:</p></li></ul><ul class="elsevierStyleList" id="li0035"><li class="elsevierStyleListItem" id="list0035"><span class="elsevierStyleLabel">•</span><p id="p0070" class="elsevierStylePara elsevierViewall">donor factors (age, extent of liver steatosis, liver volume, live donor or corpse),</p></li></ul><ul class="elsevierStyleList" id="li0040"><li class="elsevierStyleListItem" id="list0040"><span class="elsevierStyleLabel">•</span><p id="p0075" class="elsevierStylePara elsevierViewall">surgical factors (duration of ischemia), and</p></li></ul><ul class="elsevierStyleList" id="li0045"><li class="elsevierStyleListItem" id="list0045"><span class="elsevierStyleLabel">•</span><p id="p0080" class="elsevierStylePara elsevierViewall">environmental factors (immunosuppression, ingestion of alcohol, viral coinfections).</p></li></ul></p><p id="p0085" class="elsevierStylePara elsevierViewall">Of these factors, those that promote accelerated progression of fibrogenesis are a low immunosuppression status induced by antirejection treatment or HIV coinfection, elevated secondary viral load, previous liver damage, and ischemia during surgery. It is assumed that greater drug-induced immunodepression and decreased quality of transplant organs because of the increasing age of donors are responsible for the recent increase in the incidence of recurrent hepatitis C.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Antiviral treatment</span><p id="p0090" class="elsevierStylePara elsevierViewall">There are several potential strategies for management of liver transplant patients, each of which has advantages and disadvantages.</p><p id="p0095" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0050"><li class="elsevierStyleListItem" id="list0050"><span class="elsevierStyleLabel">1.</span><p id="p0100" class="elsevierStylePara elsevierViewall">Antiviral treatment during the pretransplantation phase. This strategy is associated with a risk of precipitating liver failure, complications of the HCV infections, or severe cytopenias. The benefit of this practice is that it reduces the aggressiveness of the recurrence.</p></li></ul><ul class="elsevierStyleList" id="li0055"><li class="elsevierStyleListItem" id="list0055"><span class="elsevierStyleLabel">2.</span><p id="p0105" class="elsevierStylePara elsevierViewall">Antiviral treatment shortly after transplantation and before histological damage is incurred. In theory, this alternative is convenient but its use is limited by difficulties associated with the administration of antiviral drugs during a period of high immunosuppression and frequent cytopenias.</p></li></ul><ul class="elsevierStyleList" id="li0060"><li class="elsevierStyleListItem" id="list0060"><span class="elsevierStyleLabel">3.</span><p id="p0110" class="elsevierStylePara elsevierViewall">Antiviral treatment of established hepatitis, either during the acute phase or during the chronic phase.</p></li></ul><ul class="elsevierStyleList" id="li0065"><li class="elsevierStyleListItem" id="list0065"><span class="elsevierStyleLabel">4.</span><p id="p0115" class="elsevierStylePara elsevierViewall">Antiviral treatment of patients who received retransplants because of graft failure. This option is much debated.</p></li></ul></p><p id="p0120" class="elsevierStylePara elsevierViewall">Pretransplantation treatment of patients on the waiting list for donor organs should be restricted to patients with compensated cirrhosis, because treatment of patients with decompensated cirrhosis may cause serious complications. The objectives of treatment during this phase are to achieve a sustained virological response (SVR) to prevent the recurrence of cirrhosis after the transplant or to stabilize the progression of the disease. The treatment of choice for HCV patients with compensated cirrhosis is a combination of pegylated interferon and ribavirin. Despite the improvement evident after this therapy, the SVR seems to be lower in patients with compensated cirrhosis (43%–50%) than in patients without cirrhosis (57%–65%; 11% in patients with genotype 1 HCV and 50% in patients with HCV genotypes other than genotype 1). Responses of patients with severe cirrhosis are low because of a high prevalence of patients with genotype 1 HCV, an inability to maintain full treatment doses because of cytopenias, particularly neutropenia, which is most frequent with pegylated interferon treatment, and the risk of complications that affect the liver function. Growth factors such as erythropoietin and the stimulating factor of neutrophils may be useful to avoid having to reduce dosages of drugs or discontinue medication. As the optimal doses have not been defined for transplant patients with HCV, the recommended doses and durations of treatment are mainly based on the genotype present. Some authors support the practice of progressive increases of an initially low dose according to the patient’s tolerance and others recommend treatment with the full dose from the beginning.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>, If the transplantation is done when viremia is negative, infection of the graft can be prevented in up to 65% of cases.</p><p id="p0125" class="elsevierStylePara elsevierViewall">Early posttransplantation treatment refers to the first 2-6 weeks after transplantation when reinfection has already appeared but signs of hepatocyte injury are not evident. The SVR rate is 0%–11% with interferon monotherapy, 8% with pegylated interferon and 18%–33% with interferon in combination with ribavirin. Maintenance of antiviral treatment during this phase of transplantation is problematic because of comorbidities (poor resilience of recently transplanted patients, graft rejection, cytopenia, and infections) and poor tolerance of side effects.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Because of these limitations, this treatment should be reserved for patients who have a high risk of aggressive relapse (patients coinfected with HIV, those who have undergone retransplantation, and those who have received transplant organs from live donors), provided that there are no contraindications.</p><p id="p0130" class="elsevierStylePara elsevierViewall">The results of treatment of recurrent hepatitis C (established disease) with interferon or ribavirin monotherapy are not encouraging. SVR rates are 18% for pegylated interferon monotherapy, 22% for standard interferon plus ribavirin and 28% for pegylated interferon plus ribavirin. The most common adverse effect of treatment of recurrent hepatitis C is anemia caused by hemolysis, which occurs mainly in patients with renal failure. In general, positive virological responses are associated with histological improvement.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> The results of antiviral treatment are worse in liver transplant patients than in immunocompetent patients because the former group has:</p><p id="p0135" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0070"><li class="elsevierStyleListItem" id="list0070"><span class="elsevierStyleLabel">1.</span><p id="p0140" class="elsevierStylePara elsevierViewall">an elevated prevalence of HCV genotype 1,</p></li></ul><ul class="elsevierStyleList" id="li0075"><li class="elsevierStyleListItem" id="list0075"><span class="elsevierStyleLabel">2.</span><p id="p0145" class="elsevierStylePara elsevierViewall">high levels of viremia,</p></li></ul><ul class="elsevierStyleList" id="li0080"><li class="elsevierStyleListItem" id="list0080"><span class="elsevierStyleLabel">3.</span><p id="p0150" class="elsevierStylePara elsevierViewall">a high prevalence of nonresponders,</p></li></ul><ul class="elsevierStyleList" id="li0085"><li class="elsevierStyleListItem" id="list0085"><span class="elsevierStyleLabel">4.</span><p id="p0155" class="elsevierStylePara elsevierViewall">a high incidence of patients for whom antiviral doses are reduced because of low tolerance to treatment, mainly to ribavirin, and</p></li></ul><ul class="elsevierStyleList" id="li0090"><li class="elsevierStyleListItem" id="list0090"><span class="elsevierStyleLabel">5.</span><p id="p0160" class="elsevierStylePara elsevierViewall">reduced sensitivity to interferon.</p></li></ul></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Recommendations of the consensus panel</span><p id="p0165" class="elsevierStylePara elsevierViewall">Does the course of HCV infection in transplant patients differ from that in patients who have not undergone transplants?</p><p id="p0170" class="elsevierStylePara elsevierViewall">The progression of hepatitis C is faster in transplant patients than in patients who have not undergone transplants.</p><p id="p0175" class="elsevierStylePara elsevierViewall">Evidence quality: 1</p><p id="p0180" class="elsevierStylePara elsevierViewall">Should liver transplants be conducted in patients with HCV infection?</p><p id="p0185" class="elsevierStylePara elsevierViewall">There is no formal contraindication against the eligibility of patients with chronic HCV infection for transplantation.</p><p id="p0190" class="elsevierStylePara elsevierViewall">Evidence quality: 1</p><p id="p0195" class="elsevierStylePara elsevierViewall">Do immunosuppressive regimens have an influence on the post-transplantation progression of hepatitis C? Yes.</p><p id="p0200" class="elsevierStylePara elsevierViewall">Evidence quality: 2</p><p id="p0205" class="elsevierStylePara elsevierViewall">What is the ideal time to initiate posttransplantation antiviral treatment?</p><p id="p0210" class="elsevierStylePara elsevierViewall">Most panelists recommended that treatment be initiated after liver damage is proven; 62% were in favor of initiating treatment after the presence of lobular hepatitis is established, and 38% suggested initiating treatment when the presence of chronic hepatitis with fibrosis is established.</p><p id="p0215" class="elsevierStylePara elsevierViewall">Evidence quality: 3</p><p id="p0220" class="elsevierStylePara elsevierViewall">What is the treatment of choice for posttransplantation treatment of HCV?</p><p id="p0225" class="elsevierStylePara elsevierViewall">Pegylated interferon and ribavirin.</p><p id="p0230" class="elsevierStylePara elsevierViewall">Evidence quality: 2</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Antiviral treatment" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Recommendations of the consensus panel" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:35 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 0 | 5 |
| 2024 October | 38 | 4 | 42 |
| 2024 September | 59 | 3 | 62 |
| 2024 August | 43 | 3 | 46 |
| 2024 July | 41 | 5 | 46 |
| 2024 June | 48 | 3 | 51 |
| 2024 May | 33 | 14 | 47 |
| 2024 April | 31 | 2 | 33 |
| 2024 March | 31 | 2 | 33 |
| 2024 February | 58 | 5 | 63 |
| 2024 January | 46 | 3 | 49 |
| 2023 December | 38 | 8 | 46 |
| 2023 November | 39 | 6 | 45 |
| 2023 October | 78 | 9 | 87 |
| 2023 September | 37 | 6 | 43 |
| 2023 August | 40 | 5 | 45 |
| 2023 July | 63 | 16 | 79 |
| 2023 June | 65 | 8 | 73 |
| 2023 May | 81 | 5 | 86 |
| 2023 April | 46 | 3 | 49 |
| 2023 March | 51 | 1 | 52 |
| 2023 February | 30 | 3 | 33 |
| 2023 January | 29 | 4 | 33 |
| 2022 December | 33 | 6 | 39 |
| 2022 November | 52 | 10 | 62 |
| 2022 October | 35 | 4 | 39 |
| 2022 September | 31 | 5 | 36 |
| 2022 August | 36 | 9 | 45 |
| 2022 July | 22 | 5 | 27 |
| 2022 June | 22 | 8 | 30 |
| 2022 May | 26 | 6 | 32 |
| 2022 April | 30 | 10 | 40 |
| 2022 March | 40 | 4 | 44 |
| 2022 February | 42 | 8 | 50 |
| 2022 January | 81 | 8 | 89 |
| 2021 December | 40 | 7 | 47 |
| 2021 November | 42 | 11 | 53 |
| 2021 October | 62 | 14 | 76 |
| 2021 September | 53 | 14 | 67 |
| 2021 August | 56 | 11 | 67 |
| 2021 July | 62 | 11 | 73 |
| 2021 June | 44 | 12 | 56 |
| 2021 May | 53 | 11 | 64 |
| 2021 April | 147 | 30 | 177 |
| 2021 March | 83 | 5 | 88 |
| 2021 February | 48 | 13 | 61 |
| 2021 January | 74 | 16 | 90 |
| 2020 December | 49 | 15 | 64 |
| 2020 November | 50 | 12 | 62 |
| 2020 October | 26 | 8 | 34 |
| 2020 September | 36 | 13 | 49 |
| 2020 August | 23 | 4 | 27 |
| 2020 July | 23 | 4 | 27 |
| 2020 June | 27 | 6 | 33 |
| 2020 May | 20 | 4 | 24 |
| 2020 April | 15 | 3 | 18 |
| 2020 March | 6 | 0 | 6 |
| 2020 February | 5 | 4 | 9 |
| 2020 January | 5 | 3 | 8 |
| 2019 December | 6 | 8 | 14 |
| 2019 November | 3 | 0 | 3 |
| 2019 October | 2 | 2 | 4 |
| 2019 September | 0 | 2 | 2 |
| 2019 August | 1 | 0 | 1 |
| 2019 July | 2 | 3 | 5 |
| 2019 June | 2 | 6 | 8 |
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