Clinical Significance of Occult Hepatitis B Infection in Progression of Liver Disease and Carcinogenesis

Abstract

Occult hepatitis B infection (OBI) is defined as long-lasting persistence of hepatitis B virus (HBV) DNA in the liver of patients with hepatitis B surface antigen (HBsAg)-negative status, with or without serological markers of previous exposure (antibodies to HBsAg and/or to hepatitis B core antigen). Over the past two decades, significant progress has been made in understanding OBI and its clinical implications. OBI as a cause of chronic liver disease in patients with HBsAg-negative status is becoming an important disease entity. In conditions of immunocompetence, OBI is inoffensive in itself and detection of HBV DNA in the liver does not always indicate active hepatitis. However, when other factors that cause liver damage, such as hepatitis C virus infection, obesity and alcohol abuse are present, the minimal lesions produced by the immunological response to OBI might worsen the clinical course of the underlying liver disease. Several lines of evidence suggest that OBI is associated with progression of liver fibrosis and the development of hepatocellular carcinoma in patients with chronic liver disease. The major interest in OBI is primarily associated with the growing, widely discussed evidence of its clinical impact. The aim of this review is to highlight recent data for OBI, with a major focus on disease progression or carcinogenesis in patients with chronic liver disease.

Characterization of hepatitis B virus (HBV) preS/S gene mutations in blood donors with occult HBV infection in the Baoji area of North China

“…3,4 The persistence of HBV DNA in the livers of individuals with OBI may provoke a mild but continuing necroinflammation, contributing to the progression of liver disease and increasing the risk of tumorigenesis. [5][6][7] The incidence of OBI was influenced by HBVendemic areas, the particular population studied, the public health status of the area, and screening methodology; and incidence differed extensively from previously reported values. For example, OBI detection rates have ranged from 0 to 54% in hemodialysis patients, 8 from 0.63 to 88.4% in HBV and human immunodeficiency virus co-infected patients, 9 and up to 73% (24 of 33 patients) in those with cryptogenic causes of hepatocellular carcinoma.…”

“…Immune system hypofunction and the use of immunosuppressive agents can lead to OBI reactivation and recurrence of typical serological evidence of infection . The persistence of HBV DNA in the livers of individuals with OBI may provoke a mild but continuing necroinflammation, contributing to the progression of liver disease and increasing the risk of tumorigenesis …”

Current Knowledge of Occult Hepatitis B Infection and Clinical Implications

“…In a similar manner, OBI has been shown to be associated with additional risk on progression of liver disease and development of HCC in patients with other chronic liver diseases, namely chronic hepatitis C and alcoholic cirrhosis. 17,71,72 The persistence of HBV DNA in hepatocytes continues to trigger immune response, inducing a mild but continuous hepatic inflammation, which can accelerate the liver injury and development of liver cirrhosis in other chronic liver diseases. 73 As a whole, OBI may contribute to HCC development under similar direct and indirect mechanisms as in chronic HBV infection.…”

Cytokine Profile During Occult Hepatitis B Virus Infection In Chronic Hepatitis C Patients

“…The persistence of HBV DNA in hepatocytes triggers a constant immune response, inducing mild but continuous liver in ammation, which can accelerate liver damage and favor the development of liver cirrhosis in other chronic liver diseases, such as in patients with chronic hepatitis C [22,[33][34][35]. OBI can contribute to the development of HCC under direct and indirect mechanisms similar to those of chronic HBV infection [36].…”