BACKGROUND: Liver allograft hepatitis B virus (HBV) reinfection and hepatitis B (HB) recurrence jeopardize the long-term survival of recipient and liver allograft. Lamivudine has been referred as a novel antiviral agent against HBV in HBV cirrhotic patients even in liver transplantation setting. We assessed the prophylatic effect of lamivudine on liver allograft HBV reinfection and clarified the dynamic changes of HBV markers in HBV related decompensated liver cirrhosis after liver transplantation. METHODS: Twenty-five recipients were divided into three groups: HBV active replication group (15 recipients), HBV inactive replication group (7), and control group (3). 100 mg/d lamivudine was administered preoperatively except in the control group. The HBV markers of serial sera and liver biopsy samples of the 25 recipients were evaluated regularly with enzyme-linked radioimmunoassay, HBV DNA fluorescent quantitative assay, immunohistochemical staining, labelled streptavidin biotin (LSAB) and digoxin labelled HBV DNA hybridization in situ. The dynamic alternation of HBV markers under lamivudine prophylaxis was observed. RESULTS: In the HBV active replication group who had received lamivudine 2 weeks before liver transplantation, serum HBV DNA positive converted to negative by 80%. HBsAg of all recipients disappeared after liver transplantation, but corresponding antibodies of HBV appeared within one week after the operation. HBsAb 9/15, HBcAb 13/15 and HBeAb 11/15 appeared and subsided gradually within 24 weeks. HBV DNA in sera was kept negative; HBsAg, HBcAg and HBV DNA hybridization in situ of liver biopsy samples remained negative after use of lamivudine. Ten of the 15 recipients showed clearance of HBV, and per se HBV markers were undetectable both in serum and liver biopsy samples between 12 to 44 weeks (24 weeks on average). The 1-, 2-year survival rates were 83% in this group. Two of the 15 recipients developed HBV allograft reinfection or recurrence of hepatitis 2 years after lamivudine monoprophylaxis (2/15, 13.3%). In the HBV inactive replication group, the outcome was similar to that of the HBV active group. The HBV antibody frequency was HBsAb 4/7, HBcAb 6/7, and HBeAb 2/7. Three of 7 recipients showed HBV clearance both in sera and liver biopsy samples, whereas in the control group all 3 recipients developed HBV allograft reinfection and recurrent hepatitis 8, 10, 12 months postoperatively; one of them died of fibrosing cholestatic hepatitis, and the remaining 2 recovered after additional lamivudine therapy. The overall allograft reinfection rate was 9.1% (2/22) and the overall 1-, 2-year survival rates were 87% in the lamivudine prophylaxis group. CONCLUSIONS: Lamivudine prophylaxis can prevent effectively liver allograft from HBV reinfection in patients with HBV-related decompensated liver cirrhosis even in HBV active replication recipient after liver transplantation. Its long-term outcome remains to be studied.
BACKGROUND: Liver allograft hepatitis B virus (HBV) reinfection and hepatitis B (HB) recurrence jeopardize the long-term survival of recipient and liver allograft. Lamivudine has been referred as a novel antiviral agent against HBV in HBV cirrhoticpatients even in liver transplantation setting. We assessed the prophylatic effect of lamivudine on liver allograft HBV reinfection and clarified the dynamic changes of HBV markers in HBV related decompensated liver cirrhosis after liver transplantation. METHODS: Twenty-five recipients were divided into three groups: HBV active replication group (15 recipients), HBV inactive replication group (7), and control group (3). 100 mg/d lamivudine was administered preoperatively except in the control group. The HBV markers of serial sera and liver biopsy samples of the 25 recipients were evaluated regularly with enzyme-linked radioimmunoassay, HBV DNA fluorescent quantitative assay, immunohistochemical staining, labelled streptavidin biotin (LSAB) and digoxin labelled HBV DNA hybridization in situ. The dynamic alternation of HBV markers under lamivudine prophylaxis was observed. RESULTS: In the HBV active replication group who had received lamivudine 2 weeks before liver transplantation, serum HBV DNA positive converted to negative by 80%. HBsAg of all recipients disappeared after liver transplantation, but corresponding antibodies of HBV appeared within one week after the operation. HBsAb 9/15, HBcAb 13/15 and HBeAb 11/15 appeared and subsided gradually within 24 weeks. HBV DNA in sera was kept negative; HBsAg, HBcAg and HBV DNA hybridization in situ of liver biopsy samples remained negative after use of lamivudine. Ten of the 15 recipients showed clearance of HBV, and per se HBV markers were undetectable both in serum and liver biopsy samples between 12 to 44 weeks (24 weeks on average). The 1-, 2-year survival rates were 83% in this group. Two of the 15 recipients developed HBV allograft reinfection or recurrence of hepatitis 2 years after lamivudine monoprophylaxis (2/15, 13.3%). In the HBV inactive replication group, the outcome was similar to that of the HBV active group. The HBV antibody frequency was HBsAb 4/7, HBcAb 6/7, and HBeAb 2/7. Three of 7 recipients showed HBV clearance both in sera and liver biopsy samples, whereas in the control group all 3 recipients developed HBV allograft reinfection and recurrent hepatitis 8, 10, 12 months postoperatively; one of them died of fibrosing cholestatic hepatitis, and the remaining 2 recovered after additional lamivudine therapy. The overall allograft reinfection rate was 9.1% (2/22) and the overall 1-, 2-year survival rates were 87% in the lamivudine prophylaxis group. CONCLUSIONS:Lamivudine prophylaxis can prevent effectively liver allograft from HBV reinfection in patients with HBV-related decompensated liver cirrhosis even in HBV active replication recipient after liver transplantation. Its long-term outcome remains to be studied.