Current Knowledge of Occult Hepatitis B Infection and Clinical Implications

Occult hepatitis B infection (OBI) is a status of undetectable serum hepatitis B surface antigen (HBsAg) yet detectable serum and/or intrahepatic hepatitis B virus (HBV) DNA. Mutations in the preS1, preS2, and S regions of the HBsAg gene may result in undetectable HBsAg. OBI may either result from a self-limiting acute hepatitis, or in patients with chronic hepatitis B who achieved HBsAg seroclearance, which refers to the loss of detectability of serum HBsAg with or without antibody to HBsAg (anti-HBs) in chronic hepatitis B (CHB) patients. HBsAg seroclearance contributes to a significant proportion of population in seropositive OBI. Both spontaneous and antiviral treatment-induced HBsAg seroclearance rarely happens; yet both types of HBsAg seroclearance are durable. CHB patients who achieve HBsAg seroclearance generally have a favorable clinical course. There is still a low yet definite risk of HCC occurrence, particularly in male CHB patients who achieve HBsAg seroclearance after being 50 years old. Clinical implications of OBI include occurrence of cirrhosis and HCC, liver transplantation, blood products transfusion, hemodialysis, and so on. A potentially life-threatening condition would be OBI reactivation in patients during immunosuppression therapy, especially in the setting of intensified immunosuppression including in onco-hematological patients (those receiving hematopoietic stem cell transplantation and treated with the anti-CD20 monoclonal antibody [e.g., rituximab]). With more new insights into these two conditions, CHB patients who achieved HBsAg seroclearance generally have benign clinical course and good prognosis. Sensitive assay for serum HBV DNA should be considered to establish the presence of OBI in the clinical settings mentioned earlier, which will affect the management plan.