Functional Cure for Chronic Hepatitis B: A Clinical Perspective

Chronic hepatitis B (CHB) remains a significant global health challenge, but recent advances in treatment have brought the concept of a clinical or functional cure within reach. A functional cure refers to the sustained clearance of hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA (HBV DNA) from the serum following a finite course of treatment. This outcome is often accompanied by seroconversion of HBeAg, reduction in liver inflammation, and improvement in liver histology, ultimately leading to a marked decrease in the risk of cirrhosis and hepatocellular carcinoma (HCC). Achieving this goal is a major milestone in the management of chronic hepatitis B.

Who is eligible for a functional cure?

Patients with chronic hepatitis B who are undergoing antiviral therapy may be candidates for a functional cure. Those with HBsAg levels below 3000 IU/ml and undetectable HBV DNA are particularly suitable for combination therapy involving interferon and antiviral drugs. This approach has shown promising results in increasing the likelihood of functional clearance of the virus.

What is the typical treatment duration for a functional cure?

The timeline for achieving a functional cure can vary. Key evaluation points occur at 12, 24, 48, and 96 weeks of treatment. Patients with lower baseline HBsAg levels have a higher probability of achieving clinical remission. For example, individuals with HBeAg-negative status and HBsAg levels below 1500 IU/ml have a HBsAg loss rate of 22.2% to 26.5% after 48 weeks of treatment. In contrast, those with HBsAg levels of 1500 IU/ml or higher have a much lower clearance rate (1.6%-3.8%). Notably, patients who achieve HBsAg levels below 200 IU/ml by week 12 or 24 show the highest likelihood of HBsAg loss, ranging from 48.9% to 77.8%. Even in cases where a full functional cure is not achieved, interferon-based therapies have been shown to significantly reduce the risk of liver cancer over the long term.

Monitoring after functional cure

Despite successful HBsAg clearance, long-term monitoring remains essential. Patients should be regularly evaluated for potential reactivation of hepatitis B, development of hepatocellular carcinoma, and other liver-related complications. In the first year after treatment, follow-up visits every three months are recommended. During the second year, visits can be spaced to every six months. If HBsAg remains undetectable beyond that period, annual check-ups may be sufficient. In the event of disease recurrence, re-initiating therapy may be considered based on a comprehensive clinical assessment.

In conclusion, while a complete cure for chronic hepatitis B remains elusive, the concept of a functional cure offers a realistic and impactful treatment goal. With appropriate patient selection, timely intervention, and diligent follow-up, significant improvements in long-term outcomes can be achieved.