Treatment of patients with decompensated post-hepatitis C cirrhosis before liver transplantation: strategy to prevent hepatitis C virus (HCV) recurrence?

Abstract

After liver transplantation (LT), hepatitis C virus (HCV) recurrence is almost universal particularly if HCV RNA is detectable at the time of transplant and can lead in a great number of patients to recurrent cirrhosis and graft failure [1,2]. This recurrence is often rapid [1]. Several studies have shown that the treatment by combination therapy using interferon alfa and ribavirin is possible after liver transplantation but the virological response rate is low and the treatment is usually associated with major side effects, requiring dose reduction or stopping treatment [3]. Another strategy is the eradication of HCV RNA before LT in order to prevent HCV recurrence after LT and reduction in the level of HCV RNA to reduce the severity of post-transplantation liver disease. Forns et al. [4] evaluated the efficacy and safety of antiviral therapy in 30 patients with post-hepatitis C cirrhosis awaiting liver transplantation. Only patients having an expected time on the waiting list shorter than four months were included. Patients with hepatic encephalopathy, renal failure or co-infection by hepatitis B virus or human immunodeficiency virus were excluded. Patients were treated with interferon alfa 2b 3 MUI/day and ribavirin 800 mg/day. The reduction dose was realized according to the laboratory recommendations. Fifty patients were screened during a 15 month period, but 19 (38%) were excluded due to contra-indication or refusal. The median duration of treatment was 12 weeks (2–33). Virological response was observed in nine patients (30%). Variables associated with a good response to treatment were age, ALT level, genotype non 1 and low viral load. A decrease of viral load $2 log had a positive predictive value of 100% at week 4. After liver transplantation, among the nine patients with virological response, HCV infection recurred in only three patients at week 2, 4, 5, respectively after liver transplantation. All these patients were infected with genotype 1b. Six patients became HCV RNA negative after a mean follow-up of 46 weeks (24–80). Indeed, 4/5 patients also tested in the liver were HCV RNA negative. Side effects were frequent. Two patients developed sepsis; in both cases, neutrophil counts were above 1.2 £ 10/l at the time of hospital admission. Interferon dose reduction was necessary in 60% of cases and ribavirin dose reduction in 24% of cases. Eleven patients required filgrastim due to neutropenia and eight erythropoietin due to anemia. No patients died during therapy. Assessment of interferon in patients with decompensated chronic hepatitis C was until now based on limited small case series. A gradually increasing dose regimen of combination therapy with interferon and ribavirin has been used in patients with both compensated and decompensated cirrhosis due to hepatitis C by Everson et al. [5]. Patients were started on low dose of interferon (1.5 MUI, tiw) and ribavirin (600 mg/day) with slowly increasing dose of both drugs every 2 weeks as tolerated. Preliminary results of treating 91 patients, the majority infected with genotype 1, were recently reported. On-treatment virological responses occurred in 38% and a sustained virological response in 22% of patients. Sustained responses were more common in patients treated for more than 6 months. Eight patients who were treated and were HCV RNA negative at the time of transplantation remained virus free post-transplantation. On the other hand, recurrent and persistent HCV infection of the allograft was observed in all patients with detectable HCV RNA at the time of transplantation. No significant change was observed regarding the hepatic synthetic function and/or Child Pugh score. Indeed, 27 of non-responders were reported to develop adverse events. Less favorable