Defining success in functional cure for chronic hepatitis B: a nationwide survey of physician benchmarks to guide clinical practice and trial design

Background: While functional cure (FC) is the elusive endpoint of chronic hepatitis B (CHB) therapy, a clear consensus on its practical expectations is lacking. To inform the development of new treatments and clinical guidelines, we conducted a nationwide survey to quantify Chinese physicians' perceptions of FC and their benchmarks for successful novel therapies. Methods: In this cross-sectional study, we administered a detailed online questionnaire to 151 attending physicians and above with extensive experience treating CHB. A quota sampling method was employed to ensure a geographically balanced cohort representative of practice patterns across China. Results: A total of 151 physicians were surveyed, with the vast majority (70.8%) endorsing functional cure (FC) as the ultimate treatment goal. The most valued clinical benefit of FC was the reduction in liver cirrhosis and hepatocellular carcinoma (mean score 9.6/10). Combination therapy containing Peg-IFNα was favored by 76.1% of respondents as the preferred strategy to achieve FC. Post-treatment, physicians strongly recommended a minimum of one year of follow-up and adjunct consolidation therapy to mitigate relapse risk. Critically, a consensus emerged on key benchmarks for novel therapies: a minimal acceptable FC rate of 30% and a strong preference for regimens based on Nucleos(t)ide Analogs (NAs) and/or Peg-IFNα. Conclusions: Our findings translate the collective expertise of Chinese physicians into actionable benchmarks for HBV functional cure. The consensus on a minimal 30% cure rate and a preference for combination therapy provide crucial guidance for clinical trial design and the development of novel antiviral strategies.