Increased Risk for Liver Disease in Patients With Chronic Hepatitis B Virus Infection and Low‐Level Viraemia

BACKGROUND: The relationship between hepatitis B virus low-level viraemia (HBV-LLV; HBV DNA ≤ 2000 IU/mL) and the risk of liver-related events is unclear. AIM: To evaluate the relationship between HBV-LLV and subsequent liver-related outcomes in patients with chronic HBV. METHODS: Using Optum's deidentified Clinformatics Data Mart Database, propensity score-matched cohorts of adults (aged ≥ 18 years) with chronic HBV-LLV vs. controls without evidence of chronic HBV were identified. Cox proportional-hazards models were used to estimate the risk of compensated cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), liver transplant, and a composite outcome of these four liver-related events among people with HBV-LLV vs. those without HBV. Incidence rates per 100 person-years and corresponding Poisson 95% CIs were calculated for each cohort. RESULTS: Demographic and clinical characteristics were similar between cohorts. The risk of cirrhosis, decompensation, HCC, and the composite outcome was significantly higher for patients with HBV-LLV than for individuals without HBV. Elevated liver disease risk remained in a sensitivity analysis of a subgroup with no nucleos(t)ide analogue treatment or HBV DNA > 2000 IU/mL during follow-up. Elevated risk of cirrhosis and composite outcomes in patients with HBV-LLV was confirmed in a second US dataset (HealthVerity Marketplace). CONCLUSIONS: In this analysis of US administrative claims data, individuals with HBV-LLV had a significantly increased risk of liver-related events compared with those without evidence of HBV. Additional research is needed to identify risk stratification and mitigation strategies, including earlier antiviral treatment.