Metabolic factors drive early increase in hepatic steatosis despite improvement in non-invasive fibrosis markers after hepatitis C eradication with direct-acting antivirals

Abstract

Background: While direct-acting antivirals (DAAs) achieve high sustained virologic response (SVR) rates in people with hepatitis C virus (HCV), their impact on hepatic steatosis (HS) remains unclear. Methods: We conducted a retrospective cohort study of 108 HCV patients from McGill University and the University of Milan who achieved SVR following DAAs. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were used to assess HS and liver fibrosis at baseline and 24 weeks post-SVR. HS was defined as CAP ≥248 dB/m, significant liver fibrosis as LSM ≥8 kPa, and metabolic dysfunction-associated steatotic liver disease (MASLD) as HS plus ≥1 cardiometabolic risk factors. Changes were evaluated using Wilcoxon signed-rank test and standardized mean difference (SMD). Multivariable logistic regression identified predictors of post-SVR HS. Results: HS prevalence increased from 47 % to 61 % post-SVR (p = 0.0007, SMD = 0.30). Among patients with baseline HS, 88 % had persistent steatosis. New-onset steatosis developed in 37 % of patients without baseline HS, with a significant CAP increase (p < 0.0004, SMD=0.48). In patients without baseline HS, total cholesterol and triglycerides increased (p = 0.0084, SDM = 0.43 and p < 0.0001, SDM = 0.71, respectively), whereas in those with baseline HS, only total cholesterol rose (p = 0.0296, SDM = 0.50). MASLD remained the leading etiology at both time points (94 % at baseline, 92 % post-SVR). Significant fibrosis declined markedly from 49 % to 17 % (p < 0.0001, SMD = –0.80). Higher BMI at 24 weeks was independently associated with HS (adjusted odds ratio 1.92, 95 %CI 1.22–3.03). Conclusions: Despite improvement in liver fibrosis markers, HS often persists or emerges following DAAs therapy, particularly alongside metabolic dysfunctions marked by elevated cholesterol and triglycerides.