Reevaluation of the effect of lamivudine therapy preoperative to prevent HBV recurrence after liver transplantation

BACKGROUND: Hepatitis B virus (HBV) recurrence may result in hepatic, insufficiency or dysfunction of liver grafts. This study was to reevaluate the preventive effect of lamivudine therapy pretransplant on HBV recurrence after liver transplantation with combined lamivudine and hepatitis B immunoglobulin (HBIG) as a prophylactic regimen. METHODS: This is a single-center, retrospective study of 122 liver transplant recipients operated on from January 2002 to September 2006 at our hospital. All subjects showed positive hepatitis B surface antigen (HBsAg) and HBV DNA in blood, without HEX mutation in YMDD at the time of liver transplantation. The protocol with combined larnivudine and HBIG for preventing HBV recurrence was used on the day of operation. The initial immunosuppression therapy was identical. After one year follow-up, the recipients were divided into 2 groups: patients without HBV recurrence (group]) and patients with HBV recurrence (group 11). Preoperafive larnivudine therapy and postoperative mycophenolate mofetil (MMF) and glucocorticoid therapy were analyzed using the Wilcoxon's test and Stepwise logistic regression method. RESULTS: In the HBV recurrence group, the duration of pre-transplant lamivudine administration was significantly longer than that in the without HBV recurrence group (Z=-4.424, P=0.000). The HBV recurrence rate was significantly higher in patients with preoperative lamivudine therapy than in patients without lamivudine therapy (chi(2)= 13.11, P=0.000); the risk of HBV recurrence increased by a 10.909-fold in patients with pre-transplant lamivudine therapy compared with that in patients without larnivudine therapy (OR=10.909; 95% Cl for OR: 2.86-41.67). Seven (63.6%) of 11 HBV recurrence recipients had YMIDD mutants. The duration of MMF or glucocorticoid was not different between the 2 groups (Z(MMF)=-1.453, P-MMF=0.146; Z(Prc)=-0.795, P-Prc=0.427). No significant difference was noted in the HBV recurrent rate in patients with MMF duration <= 6 and > 6 months ( Z 2= 0.185, P=0.667), as it was in patients with prednisone therapy <= 3 and > 3 months (chi(2) = 0.067, P= 0.793). CONCLUSIONS: With the protocol of combined lamivudine and HBIG for preventing HBV recurrence in liver transplantation recipients, liver transplantation candidates with positive HBV DNA should not be subjected to preoperative administration of larnivudine. A high dose of HBIG during the ahepatic period and in the early stage of post-transplantation can fulfill the treatment target as a long-term lamivudine therapy before liver transplantation. Long-term preoperative lamivudine treatment may result in an earlier HBV mutation in YMDD and increase the HBV recurrence rate and risk in the first year after transplantation.

Prophylaxis of hepatitis B recurrence in post-liver transplantation patients with lamivudine-resistant YMDD mutant

Background The most frequently used therapy for post-transplantation recurrence of hepatitis B virus （HBV） infection is lamivudine, but this drug is associated with a high resistance rate due to YMDD mutant. In preliminary reports, adefovir dipivoxil （ADV） has been shown to have activity against lamivudine-resistant strains of HBV. However, clinical experience in treatment of HBV infection after liver transplantation （LT） is still not entirely clear. This study was aimed to evaluate the prophylactic efficacy of ADV plus hepatitis B immunoglobulin （HBIG） in patients with YMDD mutant before LT. Methods From March 2004 to March 2006, 16 patients with chronic hepatitis B had lamivudine-resistant YMDD mutants detected prior to liver transplantation and received treatment with ADV plus additional intramuscular HBIG after LT as prophylaxis against graft reinfection. Tests for liver function, serum HBsAg, anti-HBs （HBIG）, HBeAg, anti-HBc, anti-HBe, HBV-DNA, and creatinine were assessed pre- or post-liver transplantation. Results The median follow-up of these patients post-liver transplantation was 19.4 months. Fifteen patients survived and one patient died of recurrence of hepatocellular carcinoma （HCC）. There was significant difference （10.98% vs. 2.26%, P〈0.05） in YMDD mutant rate between the patients with HBV-DNA over 106 copies/ml and those with HBV-DNA less than 106 copies/mi. Fifteen patients （93.8%） had undetectable HBV-DNA at 4 weeks and 1 （6.3%） at 6 months after LT. No hepatitis B recurrence was detected by persistent testing of HBsAg, HBeAg, and HBV-DNA and no increase of serum creatinine level associated with ADV was observed in any of the patients. Conclusion ADV combined with intramuscular HBIG can effectively prevent patients with pre-transplantation YMDD mutant from HBV recurrence after LT.