Time-dependent events in natural history of occult hepatitis B virus infection: the importance of population-based long-term follow-up study with repeated measurements

Abstract

More than 350 million persons in the world are affected with chronic infection of hepatitis B virus (HBV) [1]. It is particularly prevalent in the Asian-Pacific region, where patients usually acquire the infection perinatally or in early childhood through iatrogenic transmission [2]. Chronic HBV infection is associated with an increased risk of liver cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC) [3], and 15–40% patients chronically infected with HBV will develop these serious sequelae during their lifetime [4]. Chronic HBV infection has been documented as the single most common cause of liver cirrhosis and HCC worldwide [5]. It is well known that HBV is not directly cytopathic, and the development of liver cirrhosis and HCC in patients with chronic HBV infection is a multistage process with involvement of multifactorial etiology including interactions between host and environmental factors [6,7]. Other risk factors for chronic hepatitis B-related liver cirrhosis and HCC include gender, age, habits of cigarette smoking and alcohol consumption, exposures to chemical carcinogens, hormonal factors, as well as genetic susceptibility [6–9]. Chronic HBV infection is usually defined as the persistence of hepatitis B surface antigen (HBsAg) in serum for more than 6 months. HBsAg-seropositivity has been well documented as a major HCC risk factor in ecological correlation, case-control and cohort studies. The relative HCC risk for seropositivity of HBsAg ranges from 5 to 98-fold, with population attributable risk percentage ranging from 8 to 94% [8]. In addition to HBsAg, seropositivity of (HBeAg) hepatitis B e antigen, as a marker of active replication of HBV has been found to increase the risk of HCC in several case-control studies with a wide