What are the new phases of Hepatitis B (Hepatitis B virus) infection?

From the Guidelines

Hepatitis B infection progresses through several distinct phases, each requiring different management approaches, with the most recent guidelines emphasizing the importance of early treatment initiation and long-term monitoring to prevent disease progression and improve quality of life. The five recognized phases include the immune-tolerant phase, immune-active phase, inactive carrier phase, HBeAg-negative chronic hepatitis B phase, and the HBsAg-negative phase.

Key Phases of Hepatitis B

• In the immune-tolerant phase, patients have high viral loads but normal liver enzymes and minimal inflammation.
• The immune-active phase features elevated liver enzymes, active inflammation, and potential liver damage, with treatment with antivirals like entecavir (0.5mg daily) or tenofovir (300mg daily) typically initiated when ALT is elevated and HBV DNA exceeds 2,000 IU/mL, as recommended by the EASL guidelines 1.
• The inactive carrier phase shows low viral replication and minimal liver damage, requiring monitoring but not typically treatment.
• HBeAg-negative chronic hepatitis B involves viral mutations that allow continued replication despite HBeAg negativity, often requiring long-term antiviral therapy.
• Finally, the HBsAg-negative phase (occult hepatitis B) occurs after HBsAg clearance but with detectable HBV DNA in liver tissue.

Treatment and Monitoring

Regular monitoring with liver function tests and HBV DNA levels every 3-6 months is essential across all phases to determine disease activity and treatment needs, with the goal of improving survival and quality of life by preventing disease progression and HCC development, as outlined in the EASL 2017 clinical practice guidelines 1.

Important Considerations

The main goal of therapy is to improve survival and quality of life by preventing disease progression, and consequently HCC development, with the induction of long-term suppression of HBV replication representing the main endpoint of current treatment strategies, while HBsAg loss is an optimal endpoint, as noted in the study by 1. Treatment with antivirals like entecavir or tenofovir is typically initiated during the immune-active phase when ALT is elevated and HBV DNA exceeds 2,000 IU/mL, with long-term administration of a potent nucleos(t)ide analogue with high barrier to resistance representing the treatment of choice. All patients should be monitored for risk of disease progression and HCC, with treated patients monitored for therapy response and adherence, as recommended by the EASL guidelines 1.

From the Research

New Phases of Hepatitis B

• Hepatitis B virus (HBV) is a partly double-stranded DNA virus that causes acute and chronic liver infection 2.
• The initial evaluation of a patient with hepatitis B virus infection should attempt to assess the disease activity and stage in the context of the known natural history of this infection and to properly assess the needs for treatment and surveillance 3.
• Chronic hepatitis B is defined as the persistence of hepatitis B surface antigen for more than six months, and individuals with chronic hepatitis B are at risk of hepatocellular carcinoma and cirrhosis 2.
• Determining the stage of liver disease is important to guide therapeutic decisions and the need for surveillance for hepatocellular carcinoma 2.
• Quantitative markers of hepatitis B core-related antigen (HBcrAg) and anti-hepatitis B core antigen antibodies HbcAb can be used to predict liver fibrosis levels in chronic hepatitis B patients, especially in HBeAg-negative patients 4.
• Serum hepatitis B surface antigen (HBsAg) level has been developed as an important marker to predict treatment outcome, and there is a positive correlation between quantitative HBsAg and HBV DNA level in HBeAg positive patients 5.

Diagnosis and Treatment

• Screening for hepatitis B is recommended in pregnant women at their first prenatal visit and in adolescents and adults at high risk of chronic infection 2.
• Hepatitis B vaccination is recommended for medically stable infants weighing 2,000 g or more within 24 hours of birth, unvaccinated infants and children, and unvaccinated adults requesting protection from hepatitis B or who are at increased risk of infection 2.
• Treatment should be individualized based on clinical and laboratory characteristics and the risks of developing cirrhosis and hepatocellular carcinoma 2.
• Pegylated interferon alfa-2a, entecavir, and tenofovir are recommended as first-line treatment options for chronic hepatitis B 2.

Monitoring and Surveillance

• Follow-up monitoring is aimed at determining disease progression, development of complications, and reassessing the need for treatment 3.
• Monitoring frequency should be determined based on the activity and stage of disease 3.
• Initiation of screening for HCC should be based on age, race, sex, family history, and stage and duration of disease 3.
• The current recommended method of screening and surveillance for HCC is by ultrasonography and alpha-fetoprotein measurements every 6-12 months 3.