Medicine Today Internal Medicine Webcast Series

Hepatitis C Management:

Management of Special Groups:
HCV Infection in Patients with
Cirrhosis

Print Monograph (pdf)

Key Points

  • Patients with chronic HCV infection and compensated cirrhosis can be successfully treated.

  • Patients with cirrhosis and HCV infection have a lower likelihood of response to therapy.

  • Patients with decompensated cirrhosis and HCV infection should be considered for referral to a liver transplant center.

  • Treatment of chronic HCV infection for patients awaiting liver transplantation is feasible, but it is associated with an increased risk of serious adverse events and is of uncertain value.

The treatment of patients with liver cirrhosis has been shown to be safe and effective, although the chance of achieving a sustained virologic response is measurably less than that in patients with chronic HCV infection and less advanced liver fibrosis.50 Treatment of patients with decompensated liver cirrhosis is controversial, since the likelihood of preventing complications in these patients is not clear. Treatment should be administered within the context of a carefully monitored clinical trial.

Back to Top

Compensated Cirrhosis

Patients with HCV infection and compensated liver cirrhosis were believed to have lower biochemical and virologic response rates than do patients without cirrhosis. However, in a randomized trial of PEG-IFN alfa-2a in patients with compensated liver cirrhosis, Heathcote et al50 found that the rate of sustained virologic clearance was comparable to rates reported for HCV-infected patients who did not have cirrhosis. The drug was well tolerated in this study. Long-term benefits of therapy are not proven in this population, although a few reports have suggested that therapy might reduce the risk of hepatocellular carcinoma and may be associated with regression of histologic cirrhosis.70

Shiffman et al described the largest experience to date with PEG-IFN and ribavirin in patients with advanced fibrosis and cirrhosis (Ishak fibrosis score of 3 to 6) after analyzing data from the first 604 patients enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial.58 All patients had chronic HCV infection, advanced liver fibrosis, and compensated liver function. All were prior nonresponders to IFN-based therapies and received a minimum of 24 weeks of therapy with PEG-IFN alfa-2a (180 µg/week) and ribavirin (1 to 1.2 g/d). Patients in whom HCV viremia did not clear by week 20 were randomized at week 24 to either maintenance PEG-IFN (90 µg/week) or no intervention for another 3.5 years. Patients with no detectable HCV RNA in serum at 20 weeks went on to complete 48 weeks of therapy and constitute the experience of the published report. As expected, patients in this trial were older (mean age, 49.9 years) and predominantly male and Caucasian; 89% were infected with HCV genotype 1, 75% had high viral loads (viremia > 1.5 million IU/mL), and 39% had cirrhosis. Of the 604 patients, 210 (35%) had an early virologic response. Thirty-two percent of the population went on to have an end-of-treatment response, and 18% achieved a sustained virologic response.

As in smaller trials, failure to respond to prior IFN-ribavirin therapy, African American race, age greater than 59 years, HCV genotype 1, high viral load, histologic cirrhosis, an inverted AST:ALT ratio, and lack of early virologic response were each associated with less than a 16% likelihood of sustained virologic response. Multivariate regression analysis showed that previous treatment with IFN monotherapy, genotype 2 or 3, low viral load at baseline, an ALT:AST ratio greater than 1, and absence of cirrhosis on liver biopsy were associated with an increased probability of sustained virologic response.

No mention of serious adverse events is made in the published study report.58 Reductions in the dose of either or both antivirals were made for the usual reasons, and when the ribavirin dose was reduced during the first 20 weeks of therapy (from >80% to <60% of target dose) the sustained virologic response rate fell significantly (from 21% to 11%).

Back to Top

Decompensated Cirrhosis

The goal of treatment of HCV in patients with end-stage liver disease due to HCV infection who are listed for liver transplantation is multifold. Theoretically, we would like to eradicate HCV and prevent recurrence after liver transplantation; other goals would be to decrease the risk of developing decompensated liver disease or hepatocellular carcinoma and to delay or even prevent the need for liver transplantation.

The results of preemptive therapy prior to liver transplantation have been mixed. Crippin et al treated 32 patients with Child-Pugh class B or C cirrhosis who were listed for liver transplantation.71 Despite using low-dose IFN therapy, with and without ribavirin, they encountered 22 serious adverse events, including 2 deaths. These findings led them to stop the trial.

Thomas et al presented data on patients who were treated with 5 million IU of IFN.72 Of the 12 HCV RNA-negative patients who went on to liver transplantation, 8 experienced a recurrence. Of note, no ribavirin was used in this study, and ribavirin has been shown to decrease the rate of HCV recurrence after discontinuation of IFN therapy.

Everson et al used an accelerated low-dose regimen of IFN alfa-2b and ribavirin in more than 100 patients who were listed for liver transplantation.73 Half of these patients had Child-Pugh class A cirrhosis and the rest had class B or C disease. Viral eradication was achieved in 40% of patients during treatment, and the response was sustained in 20%. The most important finding was that of 10 patients who underwent liver transplantation while HCV RNA-negative, none had experienced a recurrence at follow-up ranging from 6 months to 2 years, despite having received no anti-HCV treatment following transplantation.

The accelerated low-dose regimen involves starting with half the normal dose of IFN or PEG-IFN and increasing it to full dose at 2 weeks if there are no contraindications; ribavirin is started at 600 mg daily, and if no significant anemia is seen after week 4, it is increased by 200 mg daily every other week. Some patients on this regimen have developed typical complications of end-stage liver disease, but these rates are no higher than those seen in other liver transplant candidates on some waiting lists. Further follow-up of this population and more controlled data will be needed to determine if this approach will benefit these patients both before and after liver transplantation.

Patients with decompensated cirrhosis should be sent to a regional liver transplant center for evaluation for possible liver transplantation. Because sicker patients would probably be at increased risk if they were to be treated, we recommend considering therapy for patients with decompensated cirrhosis at liver transplant centers, preferably in the setting of clinical trials.

Back to Top

<< Previous | Next >>