Expanding treatment guidelines for chronic hepatitis B: A narrative review

A significant proportion of chronic hepatitis B (CHB) patients who do not meet the conventional treatment criteria are designated "grey zone" or "indeterminate phase" patients. Although the grey zone patients have a higher HCC risk than inactive hepatitis B virus (HBV) carriers, the clinical significance of treating these patients remains controversial. Current international guidelines recommend antiviral therapy for chronic HBV infection, because antiviral therapy can reduce hepatocellular carcinoma (HCC) incidence in patients with sustained response. Several recent cohort studies showed that antiviral therapy for CHB patients in the "grey zone" could lower the risk of cirrhosis, HCC, and liver-related events, especially in high-risk subgroups such as older patients, those with low platelets, and HBeAg-positive individuals. Lines of evidence from retrospective studies, meta-analysis, and randomized trials also support initiating treatment before biochemical or histological deterioration occurs. However, expanding treatment indications for CHB may increase pill burden, reduce adherence, and raise the concerns of relapse or resistance. In addition, affordability and patient compliance should also be addressed. Taken together, clinical evidence and public health rationale lend support to expand treatment eligibility for a broader population of CHB patients, which is an essential step to achieve the WHO's 2030 elimination targets of HBV.