A pretransplant infection with precore mutants of hepatitis B virus does not influence the outcome of orthotopic liver transplantation in patients on high dose anti-hepatitis B virus surface antigen immunoprophylaxis

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Abstract

Hepatitis B virus (HBV) infection of the liver graft is a major complication after orthotopic liver transplantation (OLT) for HBV-related cirrhosis. A high viral load before OLT is a known risk factor, whereas the relevance of precore mutants of HBV is a subject of controversy. The aim of this study was to correlate the pretransplantation viral load and a pretransplantation infection with precore mutant HBV (pmHBV) or wildtype HBV (wtHBV) with allograft damage, graft failure, and survival after OLT. Sixty-nine patients with HBV cirrhosis underwent OLT under high dose immunoprophylaxis with anti-hepatitis B surface (HBs) hyperimmunoglobulins (HBIg). A pretransplantation infection with pmHBV and wtHBV was detected by polymerase chain reaction (PCR) and direct sequencing in 30 patients each (pmHBV and wtHBV group). Nine of 69 patients were PCR-negative (noHBV group). Median pretransplantation levels of HBV DNA assessed by hybridization assay were 42 pg/mL for pmHBV and 54 pg/mL for wtHBV patients. HBV recurred in 17 of 30 (57%) of pmHBV and in 14 of 30 (47%) of wtHBV patients and graft failure occurred in 6 of 30 (20%) of pmHBV and 7 of 30 (23%) of wtHBV patients. Neither HBV recurrence nor graft failure occurred in patients in whom no HBV DNA could be detected by PCR using primers flanking the HBV precore region (noHBV) patients. Allograft damage assessed by histology activity index (HAI) scoring was median 6 for pmHBV and 7 for wtHBV patients. Cumulative survival after 5 years was 72% for pmHBV, 74% for wtHBV, and 100% for noHBV patients. In this study, we provide evidence that pretransplantation viral load, but not infection with pmHBV, determines the outcome after OLT in patients on high dose HBIg prophylaxis.

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