By Liz Highleyman

Numerous studies have assessed the efficacy of treatment for chronic hepatitis C virus (HCV) infection using pegylated interferon plus ribavirin in patients receiving liver transplants. Different trials, however, have looked at varying patient populations and regimens, so outcomes have not always been consistent.

As reported in the August 2008 Journal of Hepatology, Marina Berenguer of Hospital La Fe in Valencia, Spain, and colleagues conducted a systematic review of studies evaluating antiviral therapy with pegylated interferon alfa in combination with ribavirin for the management of recurrent hepatitis C after liver transplantation.

LIVER TRANSPLANTATION

HCV almost always recurs in the new liver after transplantation. As background, the authors noted that HCV-related cirrhosis occurs in the new liver in 20% to 30% of transplant recipients within 5 years after surgery, frequently causing allograft failure and need for re-transplantation

Data sources for the analysis included electronic databases (MEDLINE) and a manual literature search. Studies evaluating the efficacy and tolerability of pegylated interferon alfa plus ribavirin in transplant patients with recurrent hepatitis C were selected for inclusion. Studies of transplant recipients treated pre-emptively (that is, before histologic evidence of recurrent HCV), patients treated with conventional interferon or not receiving ribavirin, and HIV-HCV coinfected patients were not included.

The authors extracted information from each of the selected publications including study design details, patient characteristics (including HCV genotype, HCV viral load, ALT level, fibrosis stage, body mass index, and type of prior therapy, if any), treatment regimens, efficacy, and tolerability.

Results

• 19 studies including a total of 611 patients were identified.

• Studies were conducted primarily in Europe (12) and the United States (6), with 1 from Canada.

• All studies were published between 2004 and 2007.

• Most patients were men (71%), the median age was 54 years, 86% had HCV genotype 1, and 74% had not previously been treated with pegylated interferon plus ribavirin.

• Antiviral therapy was generally started 1-3 years after transplantation (mean 24 months from transplantation to therapy).

• Most patients had mild-to-moderate liver disease when they started treatment for recurrent HCV, but a few had cirrhosis or fibrosing cholestatic hepatitis.

• Pegylated interferon alfa-2b (PegIntron) was used in 16 studies and pegylated interferon alfa-2a (Pegasys) was used in 6 (3 studies used both).

• Most studies initiated ribavirin at a dose of 600-800 mg/day, although 5 started at low doses of 400 mg/day or less; the maximum dose was 1200 mg/day.

• The mean rate of sustained virological response (SVR), or continued undetectable HCV RNA 24 weeks after completion of therapy, was 30% (range 0%-50%).

• SVR rates for patients with HCV genotypes other than 1 ranged from 60% to 75%

• 55% of patients achieved biochemical response (ALT normalization).

• Dose reduction and treatment discontinuation were common in these studies, occurring in 73% and 28% of patients, respectively.

• Causes of treatment discontinuation included cytopenias (particularly anemia), neuropsychiatric conditions, thyroid abnormalities, poor tolerability, and allograft rejection.

• Lack of early virological response (EVR) at 3 months of therapy was the most frequently noted predictive factor for lack of sustained response.

• Other predictors of SVR were HCV genotype 2, good adherence to therapy, and low baseline HCV viral load.

"Treatment discontinuation and dose reductions due to adverse events were frequent and possibly represent important obstacles to attainment of SVR," the investigators concluded. "EVR at 3 months of treatment should be considered an important predictor of treatment outcome."