The Study Of Low-dose Intramuscular Hepatitis B Immunoglobulin Combined With Lamivudine For Long-term Prophylaxis Of Hepatitis B Recurrence After Liver Transplantation

Background The hepatitis B immunoglobulins (HBIg) combined with lamivudine to prevent recurrence of hepatitis B virus(HBV) has significantly improved the survival of transplant grafts and patients transplanted for HBV-related end-stage liver disease. Generally, HBIg are administered intravenously. The high-cost, inconvenience to administer and bad tolerance of high-dose HBIg were its defects. To explore the availability of low-dose intra-muscular HBIg and to lower the expenditure of prophylaxis are needed.Objective We evaluated the efficacy of long-term, low-dose intra-muscular HBIg combined with LAM in 173 patients who received liver transplants (LT) and have been followed up for acute or chronic HBV-related end-stage liver disease.Methods The liver transplantation recipients who have been followed up and received antiviral prophylaxis post-LT were dividedinto 3 sub-groups according to their post-LT antiviral therapy, which were Group 1(LAM monotherapy n=2), Group 2(HBIg and LAM therapy n=168) and Group 3(HBIg and ADF therapy n=3). All started LAM 1 or 2 weeks ahead of LT. Either LAM(100mg) or ADF(adefovir dipivoxil 10mg) was administered by means of the oral every day. HBIg were administered intravenously during the first post-operative week (5000 or 10,000 IU according to HBV copies/ml pre-operative) and intramuscularly thereafter (400 IU per time, the interval can be adjusted according to HBsAb titer in the blood ) to maintain an HBsAb titer >300 IU/L within 1 month, >200 IU/L within 3 months and >100IU/L beyond 3 months. Mean follow-up was 20. 8 ±14 months. The periodical investigation of the liver function, the serological HBV and the analyses of liver tissue by immunohistochemical assay were performed in our institute. The recurrent HBV and the death suffered from it were recorded and analyzed in this research. The recurrence rates of HBV between some foreign institutes and our institute were statistic. Results Four patients experienced HBV recurrence overall. One patient in Group 1 experienced HBV recurrence (1 week after LT) and positive HBV-DNA (2 months after LT) associated with an increase in serum alanine aminotransferase . The treatment resistance of LAM was defined and the recipient died of the multiple organ failure8 months after LT. Three patients whose HBV-DNA in the pre-LT blood was more than 10°copies/ml in Group 2 appeared recurrent HBV (I2days, 1.5 months and 12 months after LT respectively). The pre- and post-operative HBeAg and HBV-DNA were always positive in the first case whose blood concentration of HBsAb titer were far lower than programming effective titer. The treatment resistance of HBIg was defined and the case died of fulminant hepatitis 11 months after LT. The second has been fine with the treatment of HBIg combined with ADF and has had negative HBsAg after 5. 5 months. The third became a HBsAg-taker after HBV recurrence and was dead due to tumor recurrence 15 months after LT. The HBV mutant may exist in both of the second and third case. None of Group 3 appeared HBV recurrence. The recurrence rates for HBV under the prophylaxis of HBIg combined with LAM were 1. 8%(3/168). Intra-muscular HBIg was tolerated well in all cases. There is no difference between UCLA and our institute(p=NS).Conclusion The low-dose intra-muscular HBIg combined with LAM are efficacious for long-term prophylaxis of hepatitis B recurrence after LT. The total expenditure of prophylaxis is lower. ADF has showed efficacy against the YMDD lamivudine-resistant mutant and may be a more efficacious agent for prophylaxis of HBV recurrence after LT.