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Tacrolimus triple therapy reduced fibrosis among cirrhotic HCV patients after liver transplantation

Hepatitis C virus-infected patients with cirrhosis treated with tacrolimus triple therapy after liver transplantation experienced a slower progression to fibrosis, compared with those who received tacrolimus monotherapy, according to recent study data.

Researchers conducted a study of 97 hepatitis C virus (HCV) cirrhotic-infected patients who received a liver transplant between January 2000 and June 2007. Patients were randomly assigned 0.1 mg/kg/day in two divided doses of tacrolimus monotherapy (MT; n=49), or tacrolimus, azathioprine and prednisolone triple therapy (TT; n=48). The TT group received the same tacrolimus dosing as MT patients with 16 mg/day of methylprednisolone that escalated to 20 mg/day after oral intake was established, and 1 mg/kg/day of azathioprine.

Tacrolimus doses changed according to the maintenance of whole blood levels between 5 and 14 ng/mL. Azathioprine remained constant unless neutropenia developed. Median follow-up was 96 months, and 80% of all patients had a follow-up greater than 3 years. Fifteen patients died within 3 years from randomization.

Nineteen MT and 11 TT patients reached stage four fibrosis or greater at 96 months median follow-up, although the TT group progessed more slowly (P=.009). Through univariate and multivariate analyses, researchers determined that randomization of patients to allocated MT treatment, discontinuation of azathioprine and histological de novo hepatitis were factors that led to stage four or greater fibrosis. Among 37 MT patients, 54% reached a collagen proportionate area (CPA) at least 6% (median, 41 months), compared with 30% of 44 TT patients (median, 49 months). Fourteen MT patients and three TT patients reached a hepatic venous pressure gradient of at least 10 mm/Hg (P=.002). Ten MT patients and three TT reached decompensation. MT was associated with decompensation (OR=3.23; 95% CI, 1.01-10.3).

“Given that our TT arm has the lowest fibrosis progression rate published so far — lower than sirolimus — and that there is some evidence that azathioprine is better than mycophenalate, our TT regimen could be considered as a first choice for patients transplanted for HCV cirrhosis, until other evidence proves otherwise,” the researchers wrote.

Disclosure: Researchers Andrew K. Burroughs and Amar P. Dhillon report an unrestricted educational grant from Pfizer.