Abstract
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.
Keywords
antiviral therapy - cirrhosis - hepatocellular carcinoma - liver-related mortality
