Association Between the Presence of Metabolic Comorbidities and Liver-Related Events in Patients With Chronic Hepatitis B

Abstract

Patients with chronic hepatitis B (CHB) are at increased risk of hepatocellular carcinoma (HCC) and (liver-related) mortality. In addition to hepatitis B related factors, metabolic comorbidities may contribute to the progression of fibrosis. Therefore, we studied the association between metabolic comorbidities and adverse clinical outcomes in patients with CHB. We conducted a retrospective cohort study of CHB patients attending the Erasmus MC, the Netherlands and CHB patients who underwent liver biopsy in the Toronto General Hospital, Canada. Presence of metabolic comorbidities (i.e. overweight, diabetes mellitus, hypertension and dyslipidemia) was assessed based on chart review. The primary endpoint was liver-related events, defined as the first composite of HCC, liver transplantation or liver-related mortality. We analyzed 1850 patients of which 926 (50.1%) patients were overweight, 161 (8.7%) had hypertension, 116 (6.3%) had dyslipidemia and 82 (4.4%) had diabetes. During a median follow-up of 7.3 years (IQR 2.9-11.5) a total of 111 first events were recorded. Hypertension (hazard ratio [HR] 8.3, 95%CI 5.5-12.7), diabetes (HR 5.4, 95%CI 3.2-9.1), dyslipidemia (HR 2.8, 95%CI 1.6-4.8) and overweight (HR 1.7, 95%CI 1.1-2.5) were associated with increased risk for liver-related events. Presence of multiple comorbidities further increased the risk. Findings were consistent for patients with and without cirrhosis, among non-cirrhotic HBeAg-negative patients with HBV DNA <2,000 IU/mL and in multivariable analysis adjusting for age, sex, ethnicity, HBeAg status, HBV DNA, use of antiviral therapy and presence of cirrhosis. Metabolic comorbidities in CHB patients are associated with increased risk for liver-related events, with the highest risk observed in patients with multiple comorbidities. Findings were consistent in various clinically relevant subgroups underscoring the need for thorough metabolic assessment in patients with CHB.