Serum hepatitis B virus DNA before liver transplantation correlates with HBV reinfection rate even under successful low-dose hepatitis B immunoglobulin prophylaxis

PURPOSE: The combination of hepatitis B immunoglobulin (HBIg) and nucleos(t)ide analogues has been accepted as the best treatment to control hepatitis B recurrence after orthotopic liver transplantation (OLT). However, the optimal dose of HBIg remains unclear. We have previously reported that high-dose HBIg in the early period followed by low-dose HBIg with nucleos(t)ide analogues offers reliable and cost-effective control of hepatitis B recurrence. The aim of this study was to investigate intrahepatic hepatitis B virus (HBV) reinfection status with our clinically successful protocol. METHODS: We quantified levels of intrahepatic HBV covalently closed circular (ccc) deoxyribonucleic acid (DNA) and serum hepatitis B core-related antigen (HBcrAg), a new serological marker that can estimate intrahepatic cccDNA levels. Nucleos(t)ide analogues were administered in all cases. RESULTS: No patients showed recurrence of hepatitis B surface antigen (HBsAg) or HBV-DNA. However, HBV, cccDNA, and HBcrAg were positive in 57% and 48% of patients after OLT, respectively. Pre-OLT serum HBV-DNA and HBcrAg levels correlated linearly with post-OLT cccDNA levels (r = 0.534, P < 0.05, and r = 0.634, P < 0.05, respectively). High serum HBV-DNA and HBcrAg levels, particularly with >3 log(10) copies/mL and >4 log(10) IU/mL, respectively, at the time of OLT, were associated with high levels of post-OLT cccDNA. Even with our successful protocol, nearly half of patients showed HBV reinfection. CONCLUSIONS: Patients with high serum HBV-DNA and HBcrAg levels before OLT (particularly >3 log(10) copies/mL and >4 log(10) IU/mL, respectively) should be followed with care for HBV recurrence.