Liver transplantation for chronic hepatitis B with lamivudine-resistant YMDD mutant using add-on adefovir dipivoxil plus lamivudine.
Lamivudine treatment in patients with chronic hepatitis B virus (HBV) infection may improve clinical state and suppress viral replication before liver transplantation. Emergence of lamivudine-resistant YMDD mutant is common. We report the results of liver transplantation in 16 patients with pretransplantation YMDD mutants after receiving lamivudine treatment for a median of 738 days (range, 400-1799 days). Adefovir dipivoxil (10 mg daily) was added on to lamivudine for a median of 20 days (range, 8-271 days) before (n = 11) or at (n = 5) liver transplantation, 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 HBV DNA levels had a median titer of 14,200 x 10(3) copies/mL (2 x 10(3) to 4,690,000 x 10(3) copies/mL), and 14 had HBV DNA >10(5) copies/mL. All but 1 patient remained positive for HBV DNA (by quantitative polymerase chain reaction [qPCR]) at the time of liver transplantation, and the titer was greater than10(5) copies/mL in 8 patients. The median follow-up after liver transplantation was 21.1 (range, 4.4-68.9) months. One patient (6%) died of an unrelated cause 12.2 months after transplantation, and 15 patients (94%) were alive with the original graft. All patients cleared HBV DNA and had no detectable HBV DNA by qPCR at the latest follow-up. Fourteen patients had cleared hepatitis B surface antigen (HBsAg), but 2 patients who received only adefovir dipivoxil and lamivudine without HBIG remained HBsAg positive after 7.7 and 9.5 months. Serum HBV DNA, however, was negative, and there was no biochemical or histological evidence of recurrence. Adefovir dipivoxil was well tolerated with no significant renal toxicity. In conclusion, a combination of add-on adefovir dipivoxil plus lamivudine therapy provides effective prophylaxis in patients with pretransplantation YMDD mutant that may be actively replicating. The cost effectiveness of additional passive immunoprophylaxis remains to be defined.
Lo
Chung Mau
CM
Center for the Study of Liver Disease and the Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China.
Liu
Chi Leung
CL
Center for the Study of Liver Disease and the Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China.
Lau
George K
GK
Center for the Study of Liver Disease and the Departments of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Chan
See Ching
SC
Center for the Study of Liver Disease and the Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China.
Ng
Irene O
IO
Center for the Study of Liver Disease and the Departments of Pathology, The University of Hong Kong, Pokfulam, Hong Kong, China.
Fan
Sheung Tat
ST
Center for the Study of Liver Disease and the Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China.
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000601:surgery* / Q000821:virology; D006801:Humans; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use*; D017093:Liver Failure / Q000601:surgery / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D007136:Immunoglobulins; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D004259:DNA-Directed DNA Polymerase; D000225:Adenine; C106812:adefovir dipivoxil; C045213:hepatitis B hyperimmune globulin