Cardiometabolic Comorbidities in Patients With Chronic Hepatitis B and Impact on Incidence of Liver Complications. A Danish Nationwide Cohort Study

Sofie Jespersen,1,2,* Signe Bollerup,1,* Sten Madsbad,3,4 Rikke Krogh-Madsen,1,2,4 Stine Byberg,5 Nina Weis1,4 On behalf of The DANHEP group1Department of Infectious Diseases, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark; 2Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 3Department of Endocrinology, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark; 4Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 5Steno Diabetes Center Copenhagen, Herlev, Denmark*These authors contributed equally to this workCorrespondence: Nina Weis, Department of Infectious Diseases, Copenhagen University Hospital - Hvidovre, Kettegaard Alle 30, Hvidovre, 2650, Denmark, Tel +45 3862 3514, Email [email protected]: To evaluate liver complications in patients with chronic hepatitis B, both with and without cardiometabolic comorbidities, and to compare the incidence of cardiometabolic comorbidities in these patients with that of the general population.Study Population and Methods: This nationwide registry-based cohort study included data from 2002– 2020. In the primary analysis, we used multivariate Poisson regression to estimate the incidence rate and incidence rate ratio of liver complications in patients with chronic hepatitis B, stratified by the presence of cardiometabolic comorbidities. In the secondary analysis, we compared the incidence rate of developing cardiometabolic comorbidities in patients with chronic hepatitis B to those of the general population. Both analyses were adjusted for sex, age, and country of origin, while the primary analysis was additionally adjusted for time since cardiometabolic comorbidity diagnosis and calendar year.Results: The primary analysis included 4731 patients with chronic hepatitis B, of whom 532 (11%) had at least one cardiometabolic comorbidity. The unadjusted overall incidence rate of liver complications in patients with cardiometabolic comorbidities was 1.0 per 100 person-years (95% confidence intervals: 0.84– 1.30) compared to 0.4 per 100 person-years (95% confidence intervals: 0.30– 0.42) in those without. The incidence rate ratio for liver complications was highest in the first year following the diagnosis of cardiometabolic comorbidity. The incidence rate ratio for developing cardiometabolic comorbidities in the chronic hepatitis B cohort compared to the general population, was 1.10 (95% confidence intervals: 1.02– 1.19). Sensitivity analyses revealed a higher incidence rate ratio for type 2 diabetes and hypertension but a lower incidence rate ratio for hypercholesterolemia.Conclusion: Patients with chronic hepatitis B and cardiometabolic comorbidities exhibit a higher incidence of liver complications, particularly in the first year following comorbidity diagnosis compared to those without comorbidities. Furthermore, patients with chronic hepatitis B have a higher incidence of cardiometabolic comorbidities than the general population.Keywords: chronic hepatitis B, DANHEP, comorbidity, type 2 diabetes, hypertension, hypercholesterolemia, liver disease