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Hepatitis
Interferon or Peginterferon with Ribavirin for Treatment of Hepatitis C
Prior to and After Liver Transplantation
a report by
Gregory T Everson, MD
Professor of Medicine, and Director of Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Colorado
Chronic hepatitis C (CHC) has emerged as the most frequent indication for fibrosis.
8
Unfortunately, all of these factors associated with diminished
liver transplantation. Recurrent viral infection is universal and the majority of response are amplified in patients with decompensated cirrhosis awaiting
recipients experience recurrent hepatitis C virus (HCV) in the allograft within liver transplantation. There are four published and one unpublished
one year.
1
In many cases, recurrent HCV is rapidly progressive. The mean (Forns et al.) series encompassing a total of 134 patients who were
time to recurrence is six to 12 months, and progression to cirrhosis occurs treated prior to transplantation (see Table 1).
9–12
Thirty-eight percent were
in approximately one-quarter of patients within five years. Risk factors HCV RNA-negative on the day of transplantation and post-transplant
associated with disease progression are donor age, cytomegalovirus recurrent HCV was prevented in 24%. The patients in these reports,
infection, pre-transplant viral load, and treatment of acute rejection with although decompensated, were relatively stable, and were typically
steroids or antilymphocyte therapies.
2–5
Modifications to immuno- transplanted at MELD scores <18. In the US, the average MELD score at
suppression, including steroid withdrawal, are frequent strategies for the time of performance of liver transplantation is currently 25. Since
managing recurrent HCV, but no specific regimen or strategy has been current antiviral therapy may be restricted to patients with MELD score
proved to be superior.
6
≤18, the applicability of pre-transplant treatment to the overall population
of HCV patients undergoing liver transplantation is limited. However, two
Studies of the treatment of hepatitis C in either the pre- or post-transplant groups of patients may be ideally suited to this strategy: patients with
setting are hampered by a lack of large multicenter randomized controlled cirrhosis from CHC undergoing living-donor liver transplantation (LDLT), or
trials. Most of the reports emanate from single centers and are patients with otherwise stable CHC but who have received MELD
uncontrolled, and the published controlled trials have typically involved exceptions for intercurrent development of hepatoma.
13,14
small numbers of patients. For these reasons, recommendations regarding
pre- and post-transplant antiviral therapy based on current studies should Another goal of pre-transplant therapy is SVR with intent to stabilize liver
be interpreted with caution. The American Association for the Study of disease. A recent randomized controlled trial by Lacobellis et al. has
Liver Disease (AASLD)
7
and the International Liver Transplantation Society addressed this point.
15
Patients were enrolled on this trial after hospital
(ILTS)
4
have recommended that treatment of HCV in the setting of admission for ascites, variceal bleeding, or encephalopathy; there were 63
decompensated cirrhosis be restricted to patients with a Model for controls and 66 treated with peginterferon/RBV. The average MELD score
End-stage Liver Disease (MELD) score of ≤18. The same Societies suggest for all patients was 14. SVR was 44% in patients with genotypes 2 or 3, but
that treatment of patients with decompensated cirrhosis or patients after only 7% in patients with genotype 1 HCV. The clinical outcomes of
liver transplantation should be performed only under the supervision of complications of liver disease, need for transplantation, and death occurred
a physician experienced in the treatment of CHC and in the management less frequently in patients with SVR (p=0.07). Although analyses have been
of patients with cirrhosis or patients who have undergone liver limited, at least two factors are associated with SVR in those patients
transplantation.
7
It should be noted that optimal timing, regimen, dose, with decompensated cirrhosis: HCV genotype and maximum tolerable
and duration of antiviral therapy or use of growth factors in the pre- and doses of antiviral therapy. In the study, using a low accelerating dose
post-transplant settings have not been defined. regimen (LADR) of standard IFN and RBV, 13% of patients with genotype
1 infection and 50% of patients infected with non-1 genotypes achieved
Pre-transplant Antiviral Therapy of Chronic Hepatitis C SVR.
10
The results from Lacobellis et al. are remarkably similar.
15
The
The two primary goals of pre-transplant antiviral therapy are first, treatment course has been a major determinant of SVR, especially in
prevention of post-transplant recurrence of HCV, and second, sustained
virological response (SVR) and stabilization of liver disease.
Gregory T Everson, MD, is a Professor of Medicine and the
Director of Hepatology in the Division of Gastroenterology and
Patients with cirrhosis are less likely to experience SVR to combination
Hepatology, Department of Internal Medicine, at the University of
treatment with interferon (IFN) or peginterferon plus ribavirin (RBV). In an Colorado. He is a distinguished Fellow of the American College of
analysis of 1,145 patients enrolled in the Hepatitis C Antiviral Long-term
Physicians (ACP) and the American Gastroenterologic Association
(AGA), and a member of the American Association for the Study
Treatment against Cirrhosis (HALT-C) Trial, important factors associated
of Liver Disease (AASLD), the International Liver Transplant Society
with diminished antiviral response included genotype 1 HCV, (ILTS), and the American Society of Transplantation (AST).
non-response to prior treatment with combination therapy, dose
E: greg.everson@uchsc.edu
reductions in antiviral therapy, thrombocytopenia, and severe hepatic
© TOUCH BRIEFINGS 2008
33
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