Persistent Anti-Core Negative Serology during HBV Reactivation in a Recipient of Anti-Core+ Orthotopic Liver Transplantation

Letter to the Editor Dear Editor, The risk of HBV reactivation (HBVR) requires specific monitoring in occult HBV carriers receiving immunosuppressive treatment [1,2]. The presence of anti-HBcore antibodies (HBcAb) is considered as a reliable marker of the occult carrier status and the associated risk of HBVR [3,4]. Here, we report on a patient who underwent Orthotopic Liver Transplantation (OLT) following HCV-related cirrhosis and was the recipient of an anti-HBcore positive (HBcAb+) donor liver. Eight years post-transplantation he presented with HBVR. However, he remained persistently negative for the presence of HBcAbs in the serum throughout the long period of follow up. Transplantation was performed in 2014. As a recipient of a liver from an HBcAb+ donor, the patient was given preventive antiviral therapy with Lamivudine together with anti-HBV-Abs and standard immunosuppression with Tacrolimus+Everolimus. Signs of rejection presenting in 2019 required adding high doses of Methylprednisolone to the treatment above. In January 2022 a routine check-up displayed elevated ALT and AST (5 times above reference levels), elevated HBV-DNA, HBsAg and HBeAg positivity, indicating HBVR. Surprisingly, neither IgM nor total HBc-specific Abs was ever detected. Treatment switched from Lamivudine to Entecavir and quantitative assays for HBsAg (CMIA Architect Abbott) were introduced to better monitor therapeutic efficacy. The levels detected at initial check-up (8000 IU/ml) were comparable to those of acute hepatitis. After 32 weeks of therapy with Entecavir, the patient still showed elevated ALT and AST (about 4 times higher than normal), while HBV-DNA was greatly reduced and HBsAg was also decreased. However both IgM and total anti-HBc Abs remained undetectable; HbeAg was still present in the serum while anti-HBeAbs were absent (Table 1).