Functional Cure for Chronic Hepatitis B: A Clinical Perspective

The ultimate goal in treating chronic hepatitis B (CHB) is achieving a clinical or functional cure. This means that after a finite course of treatment, serum HBsAg and HBV DNA become undetectable, HBeAg turns negative, and there may or may not be the presence of anti-HBs antibodies. Significant improvements in liver inflammation and histopathology are observed, and the risks of cirrhosis and hepatocellular carcinoma are markedly reduced.

Who is a suitable candidate for functional cure?

Patients undergoing antiviral therapy with HBsAg levels below 3000 IU/ml are considered ideal candidates for combination therapy with interferon and antiviral drugs. This approach has shown the strongest potential for achieving functional cure in clinical studies.

How long does the treatment last?

The duration of therapy for clinical functional cure is typically evaluated at 12, 24, 48, and 96 weeks. Patients with lower baseline HBsAg titers have a higher probability of achieving a cure. For example, patients who are HBeAg-negative and have HBsAg levels below 1500 IU/ml achieve HBsAg loss in 22.2% to 26.5% of cases after 48 weeks of treatment, while those with HBsAg levels above 1500 IU/ml experience much lower clearance rates (1.6% to 3.8%). Moreover, patients whose HBsAg levels drop below 200 IU/ml by week 12 or 24 have the highest chance of HBsAg loss (48.9% to 77.8%).

Reduced risk of liver cancer even without full functional cure

Even if a full functional cure isn't achieved, studies have shown that interferon-based treatment significantly reduces the risk of hepatocellular carcinoma throughout the disease course, offering long-term protective benefits.

Monitoring after functional cure

Despite successful HBsAg clearance, long-term monitoring remains essential. Patients should be followed up every 3 months during the first year post-treatment, every 6 months in the second year, and annually thereafter if HBsAg remains undetectable. Reactivation of hepatitis B or the development of liver-related complications, including hepatocellular carcinoma, should be closely monitored. If relapse occurs, retreatment may be considered following a comprehensive evaluation.