Treatment of HCV in patients with renal failure
ABSTRACT There continues to be a high prevalence of hepatitis C virus infection in patients with chronic kidney disease (CKD) on maintenance hemodialysis, despite screening of blood products and precautions to prevent the transmission of viral hepatitis within dialysis units. In addition, an increased rate of mortality from liver disease has been observed in infected patients on long-term dialysis, despite the frequent absence of biochemical dysfunction. Hepatitis C-infected renal transplant recipients have diminished patient and graft survivals compared to uninfected controls. Treatment with interferon in renal transplant candidates has resulted in sustained viral responses that have been long lasting even after subsequent renal transplant. A major concern limiting the use of interferon following renal transplant is graft dysfunction due to rejection. Ribavirin's induction of hemolytic anemia is the major reason why it is avoided in patients with CKD. Cautious use of reduced-dose ribavirin in small studies has been promising in these patients with close monitoring of hematocrit and additional measures to enhance compensatory erythropoiesis.
- SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Patients with chronic hepatitis C virus (HCV) infection and disease-related complications - among them cirrhosis and liver failure - pose a particular management challenge. Some of these patients may fail to respond to current therapy (non-responders), and some are affected so severely that treatment puts them at an unacceptable risk for complications. Treatment with pegylated interferon (peg-IFN) plus ribavirin improves hepatic enzyme levels and eradicates the virus in approximately 50% of patients; however, a significant number of patients do not respond to therapy or relapse following treatment discontinuation. Several viral, hepatic and patient-related factors influence response to IFN therapy; many of these factors cannot be modified to improve long-term outcomes. Identifying risk factors and measuring viral load early in the treatment can help to predict response to IFN therapy and determine the need to modify or discontinue treatment. Retreatment options for patients who have failed therapy are limited. Retreatment with peg-IFN has been successful in some patients who exhibit an inadequate response to conventional IFN treatment, particularly those who have relapsed. Consensus IFN, another option in treatment-resistant patients, has demonstrated efficacy in the retreatment of non-responders and relapsers. Although the optimal duration of retreatment and the benefits and safety of maintenance therapy have not been determined, an extended duration is likely needed. This article reviews the risk factors for HCV treatment resistance and discusses the assessment and management of difficult-to-treat patients.Liver international: official journal of the International Association for the Study of the Liver 01/2008; 27(10):1297-310. DOI:10.1111/j.1478-3231.2007.01613.x · 4.41 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: At least five groups have evaluated treatment for patients with decompensated cirrhosis preliminary to liver transplantation.330–334 In the earliest reported study, 32 patients awaiting liver transplantation were considered for antiviral treatment, but over one-half were found ineligible because of cytopenias.330 Among those treated with standard or low doses of interferon alfa-2b or low doses of both interferon alfa-2b and ribavirin, 33% became HCV RNA negative. Almost all developed adverse effects, most of which was graded as severe. In a second study, 30 patients with HCV-related cirrhosis destined for liver transplantation (half graded as CTP class A) were treated with interferon alfa-2b, 3 mU daily and ribavirin, 800 mg/day if their presumed time to liver transplantion was less than 4 months.331 After a median treatment duration of 12 weeks, 30% responded to treatment and then underwent liver transplantation, 2/3 of whom remained HCV RNA negative over a median follow-up period of 46 weeks. Sixty percent developed neutropenia. Reported in the same year was a study of 20 patients, most with genotype 1 infection, who were treated before transplantation for a mean of 14 months with interferon alfa-2b in a dose of 5 mU daily.332 At transplantation, 60% were HCV RNA negative, but only 20% remained negative after transplantation. A fourth study involved 124 patients with advanced cirrhosis (CTP classes A, B and C) treated mainly with interferon alfa-2b plus ribavirin, and less frequently, with pegylated interferon plus ribavirin.333 Treatment began with half doses that were increased incrementally as tolerated at 2 week intervals (referred to as a low accelerating dose regimen), and growth factors were used as needed. An SVR developed in 13% of patients with genotype 1 and in 50% with non-genotype 1 infections. Adverse events were frequent, requiring dose reductions or treatment termination, but among those who did become HCV RNA negative before transplantation, 80% remained negative 6 or more months after transplantation. The most recent study is the only one to include non-treated controls but these consisted of patients unwilling to participate in the study.334 The treatment administered was peginterferon alfa-2b, 1.0 μg/kg body weight given weekly and ribavirin, 800 to 1000 mg daily for 24 weeks. An SVR developed in 44% of the patients with HCV genotypes 2 or 3, and in 7% of those with genotypes 1 or 4. Treatment had to be discontinued in 20%, was reduced in 39%, and was tolerated in 41%. Over a 30-month follow-up period, decompensated events occurred in 83% of the controls, 62% of the non-responders, and in 23% of the patients who had developed an SVR. The conclusion of this study was that antiviral therapy can be life-saving, improves hepatic function, and that treatment seems appropriate for persons with genotype 2 and 3 infections particularly in those with cirrhosis, CTP classes A and B.Hepatology 04/2009; 49(4):1335-74. DOI:10.1002/hep.22759 · 11.19 Impact Factor