Hepatitis. Liver Toxic Damage. Liver Steatosis

Typically, the immune-active phase ends with loss of HBeAg and the development of antibodies to HBeAg.

Individuals who seroconvert from an HBeAg-positive state to an HBeAg-negative state may enter the so-called inactive carrier state (previously known as the healthy carrier state). Such individuals are asymptomatic, have normal liver chemistry test results, and have normal or minimally abnormal liver biopsy results. Blood test evidence of HBV replication should be nonexistent or minimal, with a serum HBV DNA level in the range of 0-2000 IU/mL.

Inactive carriers remain infectious to others through parenteral or sexual transmission. Inactive carriers may ultimately develop anti-HBs and clear the virus. However, some inactive carriers develop chronic hepatitis, as determined by liver chemistry results, liver biopsy findings, and HBV DNA levels. 

Other patients who seroconvert may enter the so-called reactivation phase of disease. These individuals remain HBeAg-negative but have serum HBV DNA levels higher than 2000 IU/mL and show evidence of active liver inflammation. These patients are said to have HBeAg-negative chronic hepatitis.

 

The 10-30% of HBsAg carriers who develop chronic hepatitis are often symptomatic. Chronic hepatitis B patients have abnormal liver chemistry results, blood test evidence of active HBV replication, and inflammatory or fibrotic activity on liver biopsy.

Liver biopsy with trichrome stain showing stage 3 fibrosis in patient with hepatitis B.Liver biopsy with hematoxylin stain showing stage 4 fibrosis (ie, cirrhosis) in patient with hepatitis B.

Patients with chronic hepatitis may be considered either HBeAg-positive or HBeAg-negative. In North America and Northern Europe, about 80% of chronic hepatitis B cases are HBeAg positive and 20% HBeAg negative. In Mediterranean countries and in some parts of Asia, 30-50% of cases are HBeAg positive and 50-80% HBeAg negative.

Patients with HBeAg-positive chronic hepatitis have signs of active viral replication, with an HBV DNA level greater than 2 × 104 IU/mL.[3, 5] HBV DNA levels may be as high as 1011 IU/mL.

Patients with HBeAg-negative chronic hepatitis were presumably infected with wild-type virus at some point. Over time, they acquired a mutation in either the precore or the core promoter region of the viral genome. In such patients with a precore mutant state, HBV continues to replicate, but HBeAg is not produced. Patients with a core mutant state appear to have downregulated HBeAg production.

The vast majority of patients with HBeAg-negative chronic hepatitis B have a serum HBV DNA level greater than 2000 IU/mL. Typically, HBeAg-negative patients have lower HBV DNA levels than HBeAg-positive patients do. Commonly, the HBV DNA level is no higher than 2 × 104 IU/mL.

 

Ultimately, approximately 20% of HBsAg carriers (approximately 1% of all adult patients with acute HBV infection) go on to develop cirrhosis or HCC. The incidence of HCC parallels the incidence of HBV infection in various countries around the world. Worldwide, up to 1 million cases of HCC are diagnosed each year. Most appear to be related to HBV infection.

 

In HBV-induced cirrhosis, as in cirrhosis due to other causes, hepatic inflammation and regeneration appear to stimulate mutational events and carcinogenesis. 

The American Association for the Study of Liver Diseases recommends screening for HBV-infected individuals who are at high risk for HCC, including men older than 45 years, persons with HBV-induced cirrhosis, and persons with a family history of HCC.

For these patients, ultrasonography of the liver and alpha-fetoprotein (AFP) testing every 6 months are recommended. No specific recommendations have been made for patients at low risk for HCC. Some recommend that low-risk patients (including inactive carriers) undergo only AFP and liver chemistry testing every 6 months.