Challenges of recurrent hepatitis C in the liver transplant patient (original) (raw)
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Therapeutic management of recurrent hepatitis C after liver transplantation
Liver International, 2007
Recurrent hepatitis C ranges from minimal damage to cirrhosis developing in a few months or years in a substantial proportion of transplant recipients. Different virus, host and donor factors are involved in the pathogenesis of recurrence, but many are poorly understood. Therapeutic strategies can be utilized in the pre-, peri-or posttransplantation setting. Antiviral therapy using interferon and ribavirin and modifying immunosuppression are the main strategies to prevent progression disease. The efficacy of interferon and ribavirin is limited and side effects, reduction/withdrawal are frequent. Current sustained virological response rates are approximately 28%. An optimal immunosupppression regimen has not been established. The choice of calcineurin inhibitors has not clearly been shown to affect histological hepatitis C virus (HCV) but higher cumulative exposure to corticosteroids to treat acute rejection is associated with more severe recurrence. The manner in which the doses of immunosuppression are modified has more influence on HCV recurrence than the use of a specific drug per se. Debate about the influence of immunosuppressive regimens on HCV recurrence is ongoing. Potential antifibrotic therapy and new agents targeting HCV infection and replication are emerging and are anticipated to be added to our armentarium in battling recurrent HCV post-LT.
Treatment of recurrent hepatitis C following liver transplantation
Current gastroenterology reports
Cirrhosis due to hepatitis C virus infection is now the most common indication for liver transplantation in Western Europe and the United States. In the absence of effective prophylaxis, recurrent hepatitis C virus infection is almost inevitable. Although the natural history and intermediate-term outcome of recurrent infection with hepatitis C virus are now better documented, factors that may influence the recurrence of hepatitis and consequent progression of graft disease remain unclear. Interferon used as a single agent for the treatment of recurrent infection has proven unsatisfactory. Early intervention for recurrent infection with the combination of interferon and ribavirin appears promising, and this approach may prevent or delay progression of hepatitis C virus-related graft disease after liver transplantation.
Transplantation Proceedings, 2006
Background. Hepatitis C virus (HCV) reinfection after liver transplantation is a virtually constant finding and leads to chronic hepatitis and cirrhosis in variable proportions. This study aimed to assess the safety and efficacy of ␣-interferon (IFN) plus ribavirin for recurrent HCV following liver transplantation. Patients and Methods. Thirty of 55 patients (54.5%) with histologically proven HCV recurrence after liver transplantation were given antiviral therapy (␣-IFN at a dose of 6 MU ϫ 3 ϫ week IM associated with oral ribavirin 1 g/d for 12 months) and followed up for a further 12 months after the end of the treatment. Liver and renal function tests, hemocytometric values, and HCV-RNA were assessed every 3 months throughout the therapy and follow-up. Liver biopsy was performed before and after the treatment and after another 12 months of follow-up. Results. Eight patients (26.7%) were withdrawn from the treatment due to adverse events and another 8 (26.7%) needed a dosage reduction. Eleven patients (36.7%) had a biochemical and virological response, becoming aminotransferase and HCV-RNA negative at the end of the treatment; 6 patients (20%) still had a sustained response after 12 months of follow-up. All 6 patients are clinically stable at 6 years after completing the antiviral therapy. A low viral load before therapy was a positive predictor of sustained response. No histologically significant improvement was seen at the end of the therapy or after the follow-up. Conclusions. The combination of ␣-IFN plus ribavirin induced a sustained virologic response in 20% of liver transplant recipients with recurrent HCV, but intolerance of the therapy prompted its discontinuation or a dosage reduction in a large proportion of patients. However, we have observed a long-term efficacy of the antiviral therapy in the sustained responders.
Treatment for Recurrent Hepatitis C Virus Infection After Liver Transplantation
Transplantation Proceedings, 2009
Cirrhosis due to hepatitis C virus (HCV) infection is the current leading indication for orthotopic liver transplantation (OLT) in the world. This series reports our program's experience with the treatment of HCV infection after the development of histological hepatitis. Between March 2002 and June 2008, patients with recurrent HCV were selected for treatment if the liver biopsy showed at least the F2 degree of Metavir score. HCV viral load was measured at 4, 12 and 24 weeks as well as at the end of treatment and at 6 months thereafter for patients who became HCV RNA negative (sustained virological response [SVR]). In this period, we performed 287 liver transplantations in 279 patients, including 117 (42%) who had HCV cirrhosis as the indication for OLT of whom 25 were eligible for antiviral treatment. Twelve patients completed treatment, 7 remain on treatment, and 6 were discontinued. The principal collateral effect was anemia. Only 1 patient had an episode of acute cellular rejection, which responded to adjustment of immunosuppression. Antiviral treatment in transplanted patients was feasible and did not seem to induce severe immunological effects. Adjuvant therapies to reduce cytopenias are frequently required, principally erythropoietin. The best results were observed with the pegylated interferon alfa (PEG) plus ribavirin (RBV) group: 38.9% of SVR. We recommend antiviral treatment of eligible patients with confirmed HCV recurrence using PEG plus RBV.
Management of recurrent hepatitis C after liver transplantation
Journal of Viral Hepatitis, 2001
Hepatitis C virus (HCV) reinfection is almost universal in patients transplanted for HCV-related cirrhosis. The medium-term survival after orthotopic liver transplantation (OLT) is similar to other transplanted patients, but the long-term survival remains uncertain. The prevention and an effective treatment of progressive liver disease are the primary aims in HCV recurrence. Interferon and ribavirin, as monotherapy or in combination, have been tried to treat or prevent HCV recurrence. Preliminary studies suggest a better chance of initial HCV clearance and better results in preventing HCV recurrence with combination therapy. IFN or ribavirin, as monotherapy, may normalize liver enzymes, but only gives rise to a transient virological response, without histological improvement. Combination IFN and ribavirin may be able to prevent progression of HCV-related graft disease, but indications and duration of treatment need further evaluation.
RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION: OUTCOME AND ROLE OF RETRANSPLANTATION
Transplantation Journal, 2004
Cirrhosis due to hepatitis C is now the commonest indication for liver transplantation in Western Europe and in the United States. Graft reinfection is almost universal. The natural history of recurrent hepatitis C ranges from minimal damage to cirrhosis in a few months or years. Different virus and host immune factors are involved in the pathogenesis of hepatitis and are determinants of the outcome. The association between immunosuppression and severity of HCV recurrence is conflicting and remains to be evaluated fully. The treatment of recurrent HCV disease with IFN or ribavirin, as monotherapy, is ineffective. Preliminary results from combination therapy, however, are encouraging. Currently, a reasonable approach would be to treat patients with histological and clinical disease progression. New approaches for the prophylaxis of recurrent hepatitis C are under evaluation but whether this treatment will influence the severity of liver disease or the outcome of recurrence is still unknown.
Gastroenterology, 2007
Patients with mild hepatitis C recurrence (fibrosis stage F0 to F2, n ؍ 54) were randomized to no treatment (group A, n ؍ 27) or peginterferon alfa-2b/ ribavirin for 48 weeks (group B, n ؍ 27). Patients with severe recurrence (F3 to F4, cholestatic hepatitis) were treated (group C, n ؍ 27). All patients (n ؍ 81) underwent a liver biopsy at baseline and after followup; paired hepatic venous pressure gradient (HVPG) measurements were available in 51 patients. Results: Thirteen (48%) patients of group B and 5 (18.5%) of group C achieved sustained virological response. Liver fibrosis progressed >1 stage in 40 (49%) of 81 patients: 19 (70%) of group A versus 7 (26%) of group B (P ؍ .001) and in 14 (54%) of group C. HVPG increased (6.5 to 13 mm Hg, P < .01) in patients in whom fibrosis worsened, whereas it decreased (5 to 3.5 mm Hg, P ؍ .017) or remained unchanged in those with fibrosis improvement or stabilization, respectively. The only variable independently associated with fibrosis improvement/stabilization was treatment (odds ratio [OR] ,7.3؍ 95% confidence interval [CI] 1.3 to 10, P ؍ .009). Among treated patients, alanine aminotransferase (ALT) normalization and viral clearance were independently associated with histological or hemodynamic improvement/stabilization (OR 5.3, 95% CI 1.5 to 18, P < .01; OR 7.4, 95% CI 1.4 to 38, P ؍ .01; respectively). Conclusions: Our data demonstrate that in liver transplantation recipients, antiviral therapy slows disease progression (particularly in sustained virological responders), as shown by its effects on liver histology and on HVPG.
Drug Design, Development and Therapy
Background: Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) has been a frequent and relevant problem in the past two decades. This analysis evaluated the efficacy and safety of new interferon (IFN)-free direct-acting antiviral (DAA) therapies in a large real-world cohort of HCV patients after LT. Methods: We retrospectively analyzed a cohort of 157 patients infected with HCV who underwent deceased donor LT between 1997 and 2014. Patient survival, outcome, and side effects of antiviral therapy were assessed. Results: Survival with recurrent HCV genotype 1 (GT1) infection was inferior to other HCV GTs (P=0.01). The overall sustained virological response (SVR) rate with new DAA therapy was 94.6% (n=37). Patients with both GT1 and other GTs reached SVR rates .90%. We noticed a few side effects, mainly caused by ribavirin, and only one discontinuation in DAA-treated patients. Conclusion: DAA therapy was effective and safe in previous hard-to-treat patients after LT in this real-world cohort.