Occult hepatitis B virus reinfection in liver transplant recipient

Abstract

BACKGROUND AND AIM: Nucleoside analogue prophylaxis can prevent recurrent hepatitis B virus (HBV) infection with persistent clearance of serum hepatitis B surface antigen (HBsAg) after liver transplantation (OLT). Despite the absence of any serologic marker of HBV recurrence, however, it remains unknown whether there is occult reinfection in the liver graft. We aimed to detect and quantify the presence of intrahepatic HBV DNA in the liver grafts of patients who remain seronegative for HBsAg for more than 1 year after liver transplantation. MATERIALS AND METHODS: Liver biopsy and blood samples were obtained from 23 patients who had been receiving nucleoside analogue prophylaxis alone and remained persistently seronegative for HBsAg (medium, 40.6 months; range, 10.7 to 117.8 months) after OLT for chronic hepatitis B. Liver biopsies were stained for HBsAg and HBcAg by immunohistochemical staining. Quantitative polymerase chain reaction was performed to detect and quantify total and covalently closed circular (ccc) HBV DNA in the liver (lowest detection limit, 10 copies/mL ), serum and PBMC. Direct sequencing was used for HBV quasispecies screening. RESULTS: All serum samples were negative for HBV DNA but total &/or cccHBV DNA were detectable in the liver graft of 20 of 23 patients. It was positive in 17 of 20 liver grafts from donors seropositive for anti-HBc as compared to 1 of 3 from anti-HBc-negative donors (p=0.043). Pre-transplant liver biopsy specimen was available from 6 donors and intrahepatic HBV DNA was detectable in all 4 who were seropositive for anti-HBc. Comparison of the HBV DNA sequence from patients’ pre-transplant serum and posttransplant liver biopsy as well as the donor’s pre-transplant liver biopsy …