Oral nucleoside/nucleotide analogs without hepatitis B immune globulin after liver transplantation for hepatitis B - long term outcome

Abstract

BACKGROUND: The long term outcomes of oral antiviral therapy without hepatitis B immune globulin (HBIG) are not known. This study reports the results from a large population of chronic hepatitis B (CHB) liver transplant recipients treated with a HBIG-free regimen by using oral antiviral therapy alone METHODS: 363 consecutive CHB patients transplanted from Jan 2003 to May 2011 were included. None of the patients received HBIG. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up. Mutational analyses were performed for those with virological rebound. RESULTS: Of the 363 patients, 174 (48%), 142 (39%) and 47 (13%) were on lamivudine (LAM), entecavir (ETV), and combination therapy (predominantly LAM + adefovir) respectively at the time of liver transplant. The indications for transplant were chronic decompensation (35%), acute flare of CHB (32.5%), and hepatocellular carcinoma (32.5%), with 221 (61%) from living donors. The median follow-up length was 53 months. The cumulative rate of HBV DNA suppression to undetectable levels was 91.2% at 6 months and 95.6% at 12 months, with no significant difference between the three treatment groups (p=0.541). The virological relapse rates (defined as >1 log increase IU/mL) at 1, 3, 5, and 8 years were 5%, 11%, 14%, and 18% respectively, with significant differences between the treatment groups. The rebound rate at 5 years for LAM, ETV, and combination group was 20.2%, 5%, and 11% respectively (p=0.001). Thirty six patients had virological relapse in LAM group, of which 25 had YMDD mutation, and were treated with additional therapy. Five patients in the combination group had virological relapse, of which 4 had evidence of YMDD mutation. In the ETV group, one patient developed virological relapse of 282 IU/mL, which subsequently returned to undetectable levels, without evidence of mutation. Overall 8 year survival was 83%, with no difference between the 3 treatment groups (p=0.98). There were 44 deaths during the follow-up period, of which none were due to hepatitis B recurrence. One patient required re-transplantation due to fibrosing cholestatic hepatitis from hepatitis B recurrence in the LAM group due to resistance. At the time last follow-up, 317 were alive with 307 having undetectable HBV DNA (97%). The remaining 10 patients had a low median HBV DNA of 53 IU/mL with normal ALT levels. CONCLUSION: Oral nucleoside/nucleotide analogs without HBIG are effective as in preventing graft loss secondary to hepatitis B recurrence after liver transplantation. However, newer agents should be used to minimize drug resistance and to prevent virological rebound.