VIRAL HEPATITIS WITH CONCURRENT METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE IS A SUBGROUP AT HIGH RISK FOR ADVANCED FIBROSIS

Background: Although metabolic dysfunction-associated steatotic liver disease (MASLD) and viral hepatitis are both important etiologies of liver fibrosis, the interaction between the pathologies remains unclear. The aim of our study was to identify the association between MASLD and viral hepatitis regarding advanced fibrosis.
Methods: Participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were utilized. MASLD was defined using the US-fatty liver index ≥30 with metabolic dysfunction. Viral hepatitis was defined as positive serology tests for hepatitis B surface antigen or hepatitis C RNA. Advanced fibrosis was defined as NAFLD fibrosis score (NFS) ≥0.675. Exclusion criteria included alcohol use greater than 1 drink/day in women or 2 drinks/day in men and participants with missing data. Odds ratios were calculated using logistic regression. Statistical analysis was conducted using R (V.4.0.1, http://cran.r-project.org). We used the published weights of each participant to account for the survey study design.
Results: Of the total cohort (n=3,305), 30.6% had MASLD, 3.3% had viral hepatitis, and 5.1% had advanced fibrosis. 69.8% of participants had neither MASLD nor viral hepatitis, 26.8% had MASLD without viral hepatitis, 1.4% had viral hepatitis without MASLD, and 1.9% had concurrent MASLD and viral hepatitis. When compared to participants without MASLD or viral hepatitis, participants with viral hepatitis only (odds ratio [OR]=2.7; 95% confidence interval [CI], 1.1–6.8; P=0.036), participants with MASLD only (OR=7.3; 95% CI, 5.2-10.4; P<0.001), and participants with concurrent MASLD and viral hepatitis (OR=16.9; 95% CI, 7.1–40.5; P<0.001) were associated with risk of advanced fibrosis, after adjusting for age, and gender (Table 1, Model 1). Presence of MASLD in addition to viral hepatitis was a significant risk factor for advanced fibrosis (likelihood ratio test chi-squared=115.15, P<0.001). Further adjustment for metabolic risk factors associated with MASLD including BMI ≥ 25, hypertension, type 2 diabetes mellitus, serum low-density lipoprotein, and triglyceride levels significantly attenuated the difference in risk of advanced fibrosis between patients with viral hepatitis and those with combined viral hepatitis and MASLD (Table 1, Model 2).
Conclusion: In the NHANES population, participants with concurrent MASLD and viral hepatitis had 7 times higher odds of advanced fibrosis compared to those with viral hepatitis but without MASLD. Significant attenuation of this risk difference after adjusting for metabolic risk factors supported a causal association between metabolic dysfunction and increased risk of fibrosis in patients with viral hepatitis. Given advances in antiviral therapy, identifying MASLD and its management are important targets to minimize liver disease progression in patients with viral hepatitis.