Prophylactic and preemptive therapies for hepatitis C virus-infected patients undergoing liver transplantation

Abstract

Key Points 1. Preclinical data from chimpanzees and studies in hepatitis B virus/hepatitis C virus (HCV) coinfected transplant recipients suggest prophylactic HCV antibody therapy may have a role in the prevention of HCV recurrence. 2. There are insufficient data available to evaluate the efficacy of this therapeutic approach. A small study found no benefit. Other ongoing studies using alternative antibody preparations and more intensive dosing schedules are underway. 3. Preemptive antiviral therapy, started within the first 4 weeks posttransplantation and prior to the onset of clinical signs and symptoms, is effective in some patients (5-33%) and is not associated with an increased risk of acute rejection. Tolerability of antiviral agents in the early posttransplantation period may be a factor limiting treatment efficacy. 4. It is unclear whether the preemptive antiviral treatment is superior to delaying treatment until recurrent disease is present and controlled trials addressing this issue are needed. (Liver Transpl 2003;9:S95-S100.) R ecurrent disease is universal in patients who are viremic pretransplantation. 1 Progression of histological disease is variable, but more accelerated in liver transplant recipients compared with nontransplantation patients. The incidence of bridging fibrosis and cirrhosis is low during the first 1 to 2 years posttransplantation, but reaches 10% to 30% within 5 to 8 years posttransplantation. [2][3][4] After cirrhosis develops in the transplanted graft, complications are common, with a cumulative probability of decompensation of 42% within a year. 5 Retransplantation is a option for those with recurrent disease, but its application to those who have lost a graft because of recurrent disease, especially if within the first 5 years posttransplantation, is controversial because prognosis after retransplantation generally is poor.Thus, interventions to prevent or ameliorate recurrent hepatitis C virus (HCV) disease have been sought. Treatment strategies generally fall into four categories: (1) pretransplantation antiviral therapy, (2) prophylactic therapies started in the peritransplantation period and continued posttransplantation, (3) preemptive therapies started in the early posttransplantation period before the development of clinically apparent hepatitis, and (4) posttransplantation antiviral therapy for patients with established recurrent HCV disease. The rationale and efficacy of prophylactic and preemptive therapies are the focus of this review. Prophylactic TherapyProphylactic therapies typically are started during the anhepatic phase of the transplantation operation and continued for variable and often indefinite periods posttransplantation. The goal of therapy is to prevent reinfection of the graft by HCV. Rationale for Prophylactic TherapySeveral lines of evidence support the use of antibody to HCV (anti-HCV) therapy in the prevention or amelioration of HCV disease posttransplantation.In chimpanzees, administration of a hyperimmune rabbit serum raised against a synthetic...

Management of Recurrent HCV and HBV Infections after Liver Transplantation

“…Interestingly, those who cleared the virus, did not show recurrent hepatitis C. Less encouraging effects were shown by Terrault. Only 11% obtained SVR and there was no difference in the frequency of recurrent hepatitis between responders and non-responders (Terrault, 2003). In the latter trial therapy was initiated a bit later -within 6 weeks post LTand almost 50% of recipients did not meet inclusion criteria.…”

Liver Transplantation for Hepatitis C: Disease Management

“…Thus, attention has been focused on treating recurrent disease with the goal of preventing allograft failure. The disadvantage of waiting until progression occurs includes treating higher viral loads and more advanced fibrosis [111,112]. Most reports are not randomized, include small numbers of patients, and use widely variable treatment protocols.…”

Hepatitis C After Liver Transplantation: Treatment and Impact on Patient and Graft Survival

“…The safety and efficacy of antiviral therapy using IFN or pegylated IFN (Peg-INF) with or without ribavirin in both the nontransplant and the transplant population has been extensively explored (Table 1). However, only a few clinical trials have evaluated the preemptive approach, initiating therapy within 2 to 6 weeks after transplant, but all were limited by a high treatment discontinuation rate ranging from 25% to 41% as a result of poor tolerance and inability to reach the full dose of antiviral drugs [16][17][18][19]. The SVR after 48 weeks of treatment was low regardless of the type of treatment used, though a trend was observed toward better response rates with combination therapy.…”