(C-038) Association of Hepatitis B Surface Antigen Loss (HBsAg) with Clinical Outcomes Among Patients with Chronic Hepatitis B Virus (HBV) Infection: A Retrospective Cohort Study in the United States (US)

Background: Chronic HBV infection is a major public health concern in the US and globally, and liver-related complications are a leading cause of mortality in this population. The impact of HBsAg loss, a marker of functional cure for chronic HBV infection, on long-term clinical outcomes remains unclear in the US population.

Objectives: To assess the association between HBsAg loss and clinical outcomes (compensated cirrhosis [CC], decompensated liver disease [DLD], hepatocellular carcinoma [HCC], all-cause mortality) in an ethnically, racially, and economically diverse cohort of US adults with prevalent chronic HBV infection.

Methods: A retrospective cohort study was conducted using data from the Optum electronic health records database for patients with chronic HBV infection between 1 Jan 2012 and 31 Dec 2019 who had ≥1 positive HBsAg test. The exposure was HBsAg loss, identified by ≥1 negative HBsAg test. The first negative test was defined as the loss index date among the exposed; a comparator index date was imputed for the unexposed. Outcomes including CC, DLD, HCC, and all-cause mortality were assessed from the loss/comparator index date to the end of follow-up. Inverse probability of treatment weighting (IPTW) was used to balance the distribution of baseline characteristics between the two groups. Doubly robust IPTW-weighted Cox proportional hazard models were applied to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) between HBsAg loss and the clinical outcomes.

Results: A total of 15,760 patients with chronic HBV infection were included, among which 667 (4%) experienced HBsAg loss. Exposed patients were numerically older (median 49 vs 43 years of age) than unexposed patients, and had numerically higher proportions of patients who were Caucasian (44% vs 20%), obese (32% vs 21%), and hypertensive (32% vs 18%). Proportions of Asian (26% vs 45%) and Black/African American (19% vs 19%) patients were numerically lower and similar, respectively, in the exposed versus unexposed cohorts. Over a median follow-up of 25 months in both cohorts, HBsAg loss was significantly associated with a 89% reduced risk of HCC (adjusted HR [aHR]: 0.11, 95% CI: 0.01–0.76) and a 62% reduced risk of all-cause mortality (aHR: 0.38, 95% CI: 0.20–0.74). Those with HBsAg loss also had a lower (but non-significant) risk of CC (aHR: 0.84, 95% CI: 0.52–1.35) and DLD (aHR: 0.74, 95% CI: 0.37–1.48).

Conclusions: HBsAg loss was associated with a lower risk of HCC and all-cause mortality (likely due to liver-related complications) in a diverse population of patients with chronic HBV infection in the US. The risk of CC and DLD also appeared lower after HBsAg loss, but did not reach significance.