Persistence of Occult Hepatitis B after Removal of the Hepatitis B Virus—Infected Liver

Occult hepatitis B is defined as the persistence of hepatitis B virus (HBV) DNA in persons without HBV surface antigen (HBsAg). The primary site for HBV persistence in persons with occult hepatitis B is considered to be the liver.Weprovidevirologicalandimmunologicalevidenceforlong-termpersistenceofHBV,evenafterremovalof the infected liver, in 25 consecutive, randomly selected liver transplant recipients who tested positive for antiHBVcoreantigen(anti-HBcAg)andnegativeforHBsAgatthetimeoftransplantation.Furthermore,inacohort of 101 anti-HBcAg‐positive/HBsAg-negative patients, 2 showed clinical HBV reactivation after transplantation. Thus, these data indicate that a long-term extrahepatic HBV reservoir exists, which is relevant not only for liver transplantation but also for other types of transplantations, including bone marrow grafting. Hepatitis B virus (HBV) DNA can be detected in the serum, peripheral blood mononuclear cells (PBMCs), and liver of patients with serological recovery from hepatitis B (hereafter, “serologically recovered patients”) who tested positive for anti-HBV core antigen (antiHBcAg) and negative for HBV surface antigen (HBsAg) [1]. The risk for hepatitis B reactivation during receipt of immunosuppressive therapy is substantial and can be associated with significant morbidity and mortality [2]. Livers from anti-HBcAg–positive donors are considered to be HBV infected, and recipients of such organs should be treated with HBV-polymerase inhibitors in combination with anti-HBsAg immunoglobulins (HBIGs) [3]. We here aimed to investigate whether HBV DNA remains detectable in the peripheral blood after removal of the infected organ, whether HBV-specific T cell responses persist in serologically recovered patients after liver transplantation, and whether HBV reinfections occur after orthotopic liver transplantation (OLT) in antiHBcAg–positive and HBsAg–negative individuals who received an anti-HBcAg–negative organ.