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 HBV mutation in YMDD at the time of liver transplantation. The protocol with combined lamivudine 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 I) and patients with HBV recurrence (group II). Preoperative lamivudine 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 (X2=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 lamivudine therapy (OR=10.909; 95% CI for OR: 2.86-41.67). Seven (63.6%) of 11 HBV recurrence recipients had YMDD mutants. The duration of MMF or glucocorticoid was not different between the 2 groups (Z(MMF)=-1.453, P(MMF)=0.146; Z(Pre)=-0.795, P(Pre)=0.427). No significant difference was noted in the HBV recurrent rate in patients with MMF duration < or =6 and >6 months (X2=0.185, P=0.667), as it was in patients with prednisone therapy < or =3 and >3 months (X2=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 lamivudine. 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.
Lu
An-Wei
AW
Hepatobiliary Pancreatic Surgery Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Zheng
Shu-Sen
SS
Wu
Mei-Ping
MP
Shen
Yi
Y
Yang
Rong-Wei
RW
D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000627:therapeutic use; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D006510:Hepatitis B Antibodies / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D019259:Lamivudine / Q000008:administration & dosage*; D016031:Liver Transplantation; D009154:Mutation; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016017:Odds Ratio; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D018570:Risk Assessment; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome
D004279:DNA, Viral; D005938:Glucocorticoids; D006510:Hepatitis B Antibodies; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D009173:Mycophenolic Acid; C045213:hepatitis B hyperimmune globulin