Does inactive Hepatitis B (HBV) require treatment?

From the Guidelines

Hepatitis B in the inactive carrier state does not typically require treatment, but rather regular monitoring every 6-12 months to check liver enzymes and viral load, as indicated by the 2012 EASL clinical practice guidelines 1.

Key Considerations

• Inactive HBV carriers are characterized by very low or undetectable serum HBV DNA levels and normal serum aminotransferases, with a minimum follow-up of 1 year with ALT levels at least every 3-4 months and serum HBV DNA levels required for diagnosis 1.
• Patients with HBV DNA <2000 IU/ml and elevated ALT values should undergo liver biopsy for evaluation of the cause of liver injury, as recommended by the guidelines 1.
• The inactive HBV carrier state confers a favorable long-term outcome with a very low risk of cirrhosis or HCC in the majority of patients, but progression to CHB, usually HBeAg-negative, may also occur 1.
• Regular monitoring is essential to detect potential reactivation, which may require treatment with antivirals like entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide 1.

Monitoring and Follow-up

• Inactive HBV carriers should be followed up for life with ALT determinations at least every 6 months after the first year and periodical measurement of HBV DNA levels 1.
• The follow-up should be closer in cases with baseline serum HBV DNA levels above 2000 IU/ml, in whom non-invasive evaluation of liver fibrosis may be useful and even liver biopsy might be considered 1.
• It is crucial to distinguish true inactive HBV carriers from patients with active HBeAg negative CHB, as the latter have a high risk of progression to advanced hepatic fibrosis, cirrhosis, and subsequent complications 1.

From the Research

Inactive Hepatitis B (HBV) Treatment

• Inactive HBV, also known as inactive carrier, is a phase where the virus is not actively replicating, but the patient is still at risk of reactivation and disease progression 2.
• The decision to treat inactive HBV is based on individual patient factors, such as age, sex, family history of liver cancer, and liver fibrosis status 3.
• Treatment is generally reserved for patients with active inflammation and/or at risk of disease progression and hepatocellular carcinoma (HCC) development 2.
• However, some studies suggest that antiviral therapy can be effective in achieving HBsAg clearance and conversion in inactive HBsAg carriers (IHCs) 4.
• A meta-analysis of 11 studies found that Pegylated interferon (Peg-IFN) treatment resulted in an overall HBsAg clearance rate of 47% and a conversion rate of 26% in IHCs 4.

Treatment Guidelines

• The European Association for the Study of the Liver (EASL) and the Asian Pacific Association for the Study of the Liver (APASL) have introduced new terms to replace the historical term "inactive carrier" disease phase 2.
• The EASL uses the term "HBeAg-negative chronic infection", while the APASL uses the term "Incidentally Detected Asymptomatic Hepatitis B surface antigen (HBsAg)-positive Subject (IDAHS)" 2.
• Treatment guidelines recommend antiviral therapy for patients with chronic hepatitis B who have HBV DNA >2000 IU/mL, elevated ALT, and/or at least moderate histological lesions 5.
• Patients with cirrhosis and detectable HBV DNA should also be treated, as well as those with HBV DNA >20,000 IU/mL and ALT >2xULN 5.

Considerations for Treatment

• The goal of treatment is to achieve persistent inhibition of viral replication and ALT normalization, rather than eradication of the virus 5.
• Treatment should be individualized based on patient factors, such as age, sex, family history of liver cancer, and liver fibrosis status 3.
• Regular blood tests are recommended to monitor patients with inactive HBV and to accurately diagnose the immune-inactive or -tolerant phases 3.
• A "Treat All" approach may be considered in the future, especially with the emergence of novel HBV therapies 2.