Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation☆
Introduction
Hepatitis C virus (HCV) infection is the leading cause of cirrhosis and hepatocellular carcinoma in the Western world and Japan and HCV-related liver disease accounts for more than half of the indications of liver transplantation in most transplant programs [1]. Regretfully, infection of the liver graft with HCV occurs almost universally after transplantation and chronic hepatitis and cirrhosis develop in a significant proportion of patients a few years after transplantation [2], [3], [4]. Recent studies have shown that graft and patient survival are significantly lower in patients undergoing transplantation for HCV-related cirrhosis compared to patients undergoing LT for other causes [5], [6]. Therefore, prevention of hepatitis C recurrence in the liver graft has become one of the major goals of most transplant programs.
Treatment of HCV infection is usually initiated after liver transplantation, but the optimal timing for initiation of antiviral therapy is unknown. Early treatment initiated a few weeks after LT does not appear to be the best approach given the rapid increase in viral load that follows graft reperfusion [7], [8], [9]. Antiviral therapy is commonly initiated a few months (or years) after LT, when follow-up liver biopsies demonstrate disease progression. Most studies, however, indicate that the efficacy of antiviral therapy in liver transplant recipients is low; sustained virological response occurs in less than 20% of treated patients and adverse effects force treatment interruption in a significant proportion of cases [10], [11], [12].
A different strategy to prevent HCV disease recurrence in the liver graft is eradication of HCV before LT. Most clinical trials using combination therapy have shown that the response rates in patients with significant fibrosis is quite high, exceeding 40% when pegilated interferon and ribavirin are used [13], [14]. Advanced cirrhosis, however, is considered a contraindication for antiviral therapy, due to the numerous and potentially severe side effects caused by interferon and ribavirin administration. For these reasons very few studies have analyzed the efficacy of antiviral therapy in HCV-infected patients awaiting liver transplantation [15], [16].
We have analyzed the safety and efficacy of interferon and ribavirin therapy in a cohort of 30 patients with HCV-related cirrhosis on the waiting list for liver transplantation. Our results show that virological response occurs in one third of these patients and, although adverse effects are very common, a close clinical follow-up might prevent life-threatening complications.
Section snippets
Patients
Thirty patients with HCV-related cirrhosis awaiting liver transplantation were included in the study. The study was approved by the Ethical Committee of our Institution and by the Spanish Health Ministry. All patients gave their written informed consent before entering the study. The inclusion criteria were: a positive anti-HCV test, positive HCV-RNA in serum, platelet count >50×109/l (or 75×109/l if prothrombin activity was <40%), neutrophil count >1.2×109/l, hemoglobin >9 g/dl, and expected
Patients’ baseline characteristics
From June 2001 to September 2002, 50 patients who were not participating in other ongoing clinical trials were evaluated for this study. Nineteen patients (38%) were excluded due to laboratory abnormalities (thrombocytopenia and/or neutropenia in 17 and renal failure in two) and one (2%) refused to participate. Therefore, 30 patients comprised the final study cohort. Eligibility to participate in this study for patients included in other clinical trials was similar (50%). The demographic,
Discussion
The increasing incidence and severity of HCV recurrence after LT has prompted our and other groups to analyze all possible strategies to prevent HCV infection of the graft. One of these strategies is to initiate antiviral therapy before liver transplantation. In our study, interferon was administered daily to avoid the peaks and valleys of serum interferon concentrations that occur with standard therapy regimen and therefore to improve its pharmacokinetics [18], [19]. Although pegilated
Acknowledgements
This study was supported in part by grants from the Fondo de Investigación Sanitaria (FIS 01/1483), Instituto de Salut Carlos III (CO3/02) and La Fundació Marató de TV3 (2000). M.G.-R. is a recipient of a grant from Instituto de Salut Carlos III (BEFI 01/9201) and A.F. is a recipient of a grant from IDIBAPS.
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2016, The Lancet Infectious Diseases
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The authors declare that they received funding from Schering Plough in order to carry out their research.