Liver transplantation for chronic hepatitis B with lamivudine-resistant YMDD mutant using add-on adefovir dipivoxil to lamivudine

Abstract

Lamivudine treatment for patients with chronic hepatitis B virus (HBV) infection may improve clinical state and suppress viral replication before liver transplantation (LTx). Emergence of lamivudine-resistant YMDD mutant is common and may be regarded as a contraindication for transplantation. We report the results of LTx in 16 patients with pre-transplant YMDD mutants after receiving lamivudine for a median of 738 days (400 to 1799 days). Adefovir dipivoxil (10 mg daily) was added-on to lamivudine for a median duration of 20 (8 to 271) days before (n=11) or at (n=5) LTx and the combination was continued indefinitely thereafter. Eight patients received additional intravenous hepatitis B immune globulin (HBIG) for a median of 24 months. Fifteen patients with known pre-adefovir serum HBVDNA level had a median titer of 14,200 x 103 (2.2 x 103 to 4,690,000 x 103) copies/ml and 14 had HBVDNA >105 copies/ml. All except one patient remained positive for HBVDNA (by qPCR) at the time of LTx and the titer was >105 copies/ml in 8 patients. The median follow-up after LTx was 21.1 (4.4 to 68.9) months. One patient died of an unrelated cause at 12.2 months post-transplant and 15 (94%) patients were alive with the original graft. All patients cleared HBVDNA and had no detectable HBVDNA by qPCR at the latest follow-up. Fourteen patients had HBsAg seroconversion but 2 patients who received only adefovir dipivoxil and lamivudine without HBIG had not cleared HBsAg after 7.7 and 9.5 months. Serum HBVDNA, however was negative and there was no biochemical or histologic evidence of recurrence. Adefovir dipivoxil was well-tolerated with no significant renal toxicity. In conclusion, combination of add-on adefovir dipivoxil to lamivudine therapy provides effective prophylaxis in patients with pre-transplant YMDD mutant that may be actively replicating. The cost effectiveness of additional passive immunoprophylaxis remains to be defined.