The risk factors and prognosis of hepatitis B virus re-infection after liver transplantation with prophylaxis of combined low-dose hepatitis B immunoglobulin and nucleoside analogues

Abstract

Objective To investigate the risk factors and prognosis of hepatitis B virus (HBV) re-infection after liver transplantation with prophylaxis of combined low-dose hepatitis B immunoglobulin (HBIG) and nucleoside analogues. Methods The clinical data of 340 patients who have underwent liver transplantation for HBV related end-stage liver disease and have received long-term follow-up were retrospectively analyzed. All patients received nucleoside analogues therapy formally before entering into the waiting list And nucleoside analogues combined with low-dose HBIG therapy was prescribed during and after transplantation. Patients were regularly followed up at the outpatient clinic by monitoring the HBV re-infection, survival and prognosis. Univariable analysis was performed to determine whether gender, age, concomitance with HCC, serum positive HBeAg, HBV DNA >5 log10 copies/ml, YMDD mutants or type of nucleoside analogues predicted HBV recurrence. Parameters with P<0. 1 in the univariable analysis were entered into multivariate Cox regression analysis. Results Thirty-three patients suffered from HBV re-infection post transplantation, with the overall re-infection rate being 9. 7 % (33/340). The mean HBV recurrence time was 8. 4 ± 13. 2 months (2～49 months). 1-, 3-, 5-year recurrence rate was 7. 0 %, 10 %, 13 % respectively. HBIG was terminated and the dose of nucleoside analogues was modulated in 33 patients who developed HBV re-infection. Except 3 patients whose HBV DNA was between 3 log10-5 log10 copies/ml, the other patients' HBV DNA was controlled less than 3 log10 copies/ml. The 1 -, 3-, 5- year survival rate of 340 patients was 94 %,87 %,and 81 % respectively. There was no significant difference in the survival rate between re-infection group and control group (94 %,87 %,81 % vs 89 %,82 %,82 %). COX regression analysis revealed that risk factors for HBV re-infection were hepatocellula carcinoma (P = 0.035) and HBV-DNA load over 5 log10 copies/ml (P<0.001). Further stratified analysis showed that patients who suffered from carcinoma recurrence had a higher incidence of HBV recurrence than those who did not, which was 27. 9 % and 8. 7 % respectively (P = 0. 001). Conclusion The risk factors for HBV recurrence are HCC and HBV-DNA load with this combined therapy. HBV recurrence is not the main cause of graft loss and death under the prophylaxis of nucleoside analogues and low-dose HBIG. Key words: Liver transplantation ; Hepatitis B virus; Risk factors