摘要
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.
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.
基金
a grant from Science and Technology Commission of Zhejiang Province(No.2008C23055).
