Combined therapy with interferon and low-dose ribavirin in posttransplantation recurrent hepatitis C: A pragmatic study

Recurrent hepatitis C is a common problem after liver transplantation that can progress to liver cirrhosis of the graft. Preliminary reports of combin ation treatment with interferon (IFN) and ribavirin have been promising, bu t long-term follow-up data are not yet available. We report our experience with 1 year of combination therapy with IFN (3 million units thrice weekly) and low-dose ribavirin (600 mg/d), followed by long-term ribavirin monothe rapy in 18 patients with moderate to severe recurrent hepatitis C and a med ian follow-up of 32 months after the completion of combined therapy. All pa tients were followed up clinically and histologically at regular intervals. Overall, in an intention-to-treat analysis, 15 patients had normal alanine aminotransferase levels (biochemical end-treatment response [ETR], 83%), a nd 8 patients were also hepatitis C virus RNA negative in serum (virologica l ETR, 44%) at the end of combined treatment. At last follow-up after the c ompletion of combined therapy (median, 32 months; range, 18 to 73 months), 13 patients were biochemical responders (biochemical long term-sustained re sponse [LT-SR], 72%), and 5 patients also maintained viral clearance (virol ogical LT-SR, 27%). Comparison of liver biopsy specimens before and after 1 2 months of combined therapy showed improvement in grading scores of at lea st two points in the majority of the patients (73%). Notably, a trend towar d fibrotic progression was only noted in nonresponders. Regarding side effe cts, despite the low dose of ribavirn, almost half the patients developed h emolytic anemia requiring dose reductions. In addition, long-term ribavirin monotherapy was not associated with iron accumulation. We conclude that co mbined therapy with low-dose ribavirin followed by longterm ribavirin monot herapy can be recommended because it favorably modifies the natural history of recurrent hepatitis C in most patients and possibly halts histological disease progression without causing iron accumulation.