Long-term therapy with lamivudine in renal transplant recipients with chronic hepatitis B

Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. As other available HBV therapies, its efficacy is hampered by relapse after discontinuation and by the risk of viral breakthrough. A recent study suggests that pre-emptive lamivudine therapy improves survival in HBV renal transplants, but few data are available regarding its long-term use in this population. The clinical features, course and viral mutations associated with the emergence of viral resistance in this population have not been well studied.

We followed 14 consecutive renal transplant patients treated with lamivudine for chronic hepatitis B. Breakthrough was defined as the reappearance of HBV DNA by hybridization. In patients with breakthrough, lamivudine was always continued and patients were followed up monthly. Mutations associated with viral resistance were determined by sequencing the polymerase encoding gene at the beginning of treatment and at the time of breakthrough.

The median duration of treatment was 64.5 months. Resistance to lamivudine appeared in eight patients (57%) after a median duration of treatment of 15 (9-24) months. During a 51 month follow-up after breakthrough, only three of eight patients had a flare-up with alanine aminotransferase levels more than 5 ULN, and no hepatic decompensation was observed. Analysis of HBV sequencing after breakthrough revealed specific resistance mutations in both the B and C domains of the polymerase (rtL180M/M204V, n = 5; rtM204I, n = 2).

Lamivudine is a safe and effective treatment of active hepatitis B in renal transplant patients. Resistance to treatment is frequent but seems to have little clinical impact over the considered period. In our experience, the YMDD mutation accounts for most cases of virological escape in patients with good compliance.