However, studies have indicated that T-cells often display inefficient T-cell response and could be a factor in IT phase ( 10, 11). Generally, HBV specific T lymphocytes have shown to be key players in inducing liver injury during CHB infection ( 9). When the immune response against viral antigens is more intensive, histological damage and progressive fibrosis are greater ( 8). The role of immune responses in the discrimination between different clinical states of CHB infection has remained to be unclear ( 6, 7). Natural History of Perinatally Acquired Chronic HBV Infection In addition, HBV basal core promoter (BCP) and precore/core mutation strains may increase more significantly in IA phase than IT phase ( 5). Based on viral factors, different HBV genotypes have been indicated to be a key factor in the clinical history of CHB infection. However, some of the IC patients continue to show active liver disease and detectable serum HBV DNA, defined as HBeAg negative reactivation phase that can progress to liver cirrhosis ( 4).

Low HBV DNA, repetitive normal ALT values, and slight hepatic necroinflammation are associated with the IC phase. The majority of patients subsequently enter the inactive HBsAg carrier state after HBeAg seroconversion. A consequence of this phase is HBeAg seroconversion and appearance of anti-HBe ( 4).

The IA phase is characterized by HBeAg positivity, elevated HBV DNA levels (above at least 2000 IU/mL), elevated ALT levels, active liver necroinflammation, and varying degrees of fibrosis. The immune tolerant phase can last from a few years to more than 30 years ( 2, 3). The IT phase occurs most frequently after perinatal transmission from HBsAg/HBeAg-positive mother. High HBV DNA levels (> 20,000 IU/mL), presence of hepatitis B e antigen (HBeAg), continual normal alanine aminotransferase (ALT) levels in the absence of active liver disease, and inflammation or fibrosis are indicators of IT phase of CHB infection. The natural history of CHB infection can be widely sub-divided into four phases including, immune tolerance (IT), immune clearance (or immune active ), inactive HBsAg carrier (IC), and reactivation phase ( Figure 1). Persistence of hepatitis B surface antigen (HBsAg) for more than six months is an indicator of the development of chronic hepatitis B (CHB) ( 1). This virus plays a significant role in liver cirrhosis and hepatocellular carcinoma (HCC). It has been estimated that about 350 million people in the world are chronically infected with hepatitis B virus (HBV). The LCK hub gene might help the pathogenesis of different phases of CHB and serve as a therapeutic target for the treatment of hepatitis B virus.Ĭhronic Hepatitis B Immune Tolerant Immune Clearance Inactive Carrier Gene Ontology 1. The immune response-related pathways were found to be up and downregulated in the immune clearance phase and inactive carrier phase of CHB, respectively.

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