Clinical implication of occult hepatitis B infection

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Occult hepatitis B infection (OBI) can be found in three different clinical groups of patients according to the documentation of the history of hepatitis B virus (HBV) exposure. They are patients with definite history of apparently self-limiting acute hepatitis B infection, patients with known chronic hepatitis B (CHB) infection with loss of hepatitis B surface antigen (HBsAg) (HBsAg seroclearance) and patients without prior history of hepatitis B infection. The second group likely contributes the largest group of patient population in OBI. These patients have same rate of development of end-staged liver disease including cirrhosis-related complications and hepatocellular carcinoma (HCC) if HBsAg seroclearance occurs when there is pre-existing cirrhosis or at the age older than 50 years. Nevertheless, majority of the patients with OBI usually have normal liver biochemistry and histology. The intrahepatic HBV DNA is detectable in almost all the patients whereas the covalently closed circular (ccc)DNA and pre-genomic RNA levels are usually very low. With regard to the clinical implications, HBV transmission from the blood products of occult hepatitis B donors is possible as demonstrated in animal and human experiments, although the actual HBV transmission rate in human is quite low especially in anti-HBs positive recipients. HBV can also be transmitted to the recipients through organ transplantation especially liver transplantation from occult hepatitis B donors. OBI may be an accelerating risk factor for development of HCC in patients with chronic hepatitis C infection and patients with alcoholic liver disease. Importantly, OBI may also contribute to a great extent in patients with cryptogenic cause of HCC. In another scenario, patients with OBI may have severe hepatitis B reactivation with a surge of viral replication and hence clinical hepatitis and mortality. This phenomenon is more commonly seen in patients receiving immunosuppressive therapy especially anti-CD monoclonal antibody. Patients receiving haematopoetic stem cell transplantation also carry a high risk of hepatitis B reactivation. Prompt antiviral therapy at the time of detectable HBV DNA upon interval monitoring is very effective in controlling hepatitis B viral replication and therefore is associated with a hepatitis-free recovery.