Hepatitis B Surface Antigen Loss and Improved Clinical Outcomes in US Individuals With Chronic Hepatitis B Virus Infection

Hepatitis B surface antigen (HBsAg) loss is associated with improved clinical outcomes in patients with chronic hepatitis B virus (HBV) infection based on studies predominantly in Asian populations. We assessed real-world associations between HBsAg loss and long-term clinical outcomes in a diverse US population with chronic HBV infection. This retrospective cohort study (January 2012-December 2019) used Optum electronic health records data from patients with chronic HBV infection, identified via diagnosis codes or laboratory assessments. Patients with advanced liver disease and hepatitis C, hepatitis D or HIV co-infection at baseline were excluded. Associations between HBsAg loss, as a proxy of functional cure, and clinical outcomes were assessed using doubly robust inverse probability of treatment-weighted Cox proportional hazards models. In total, 15,760 patients with chronic HBV infection were included; 5.6% were receiving stable antiviral treatment. Overall, 4.2% (n = 667) experienced HBsAg loss across the study period. HBsAg loss was associated with an 89% and 62% reduced risk of hepatocellular carcinoma (HCC; adjusted hazard ratio [aHR]: 0.11, 95% CI: 0.01-0.76) and all-cause mortality (ACM; aHR: 0.38, 95% CI: 0.20-0.74), respectively. Risks of compensated cirrhosis (aHR: 0.84, 95% CI: 0.52-1.35) and decompensated liver disease (aHR: 0.74, 95% CI: 0.37-1.48) were lower after HBsAg loss, but did not reach significance. In this large, diverse population of patients with chronic HBV infection without advanced liver disease, HBsAg loss was associated with reduced risks of HCC and ACM compared with those without HBsAg loss.