Abstract
BACKGROUND: Steatotic liver disease (SLD) including metabolic dysfunction-associated SLD is the most prevalent chronic liver disease worldwide and is strongly associated with metabolic dysfunction as well as chronic hepatitis C (CHC). AIM: To compare the characteristics of patients with CHC virus infection and the treatment with direct-acting antivirals (DAAs), considering the presence of SLD comorbidity. METHODS: The study included all consecutive hepatitis C virus-infected patients treated with pangenotypic DAA regimens at a single tertiary hepatology center in 2018-2024. SLD was diagnosed via abdominal ultrasound. RESULTS: Among 688 patients included in the study, 290 (42.2%) had comorbid SLD. The highest prevalence (62.3%) was observed in patients infected with genotype 3. The SLD group was predominantly male (62.8%), in contrast to the non-SLD group, where women predominated. Patients with SLD were significantly older (P = 0.0007), had a higher body mass index (P < 0.0001), and more frequently presented with diabetes (P = 0.01), obesity (P < 0.0001), hyperlipidemia (P = 0.004), and a history of alcohol abuse (P < 0.0001). They also had more advanced liver disease as indicated by a higher rate of cirrhosis (35.5% vs 12% in the non-SLD group, P < 0.0001), elevated aminotransferase activity (P < 0.0001), bilirubin concentration (P < 0.0001), and international normalized ratio values (P = 0.0001), and lower albumin concentration (P = 0.0028). While most patients in both groups completed treatment as planned, adverse events, including severe events and deaths, were more frequent in the SLD group. A sustained virologic response was achieved in 97.6% of the overall population but was significantly lower among patients with SLD compared to the non-SLD group (95.6% vs 99.0%, P = 0.0081). However, logistic regression analysis did not identify SLD as an independent predictor of treatment failure. CONCLUSION: Comorbid SLD was common among CHC patients treated with DAAs and was associated with adverse baseline characteristics, including older age, higher body mass index, greater comorbidity burden, and more advanced liver disease. Although SLD patients achieved slightly lower rates of sustained virologic response, SLD itself was not an independent predictor of treatment failure. These findings suggest that poorer treatment outcomes in this subgroup are largely attributable to coexisting risk factors rather than SLD per se, highlighting the need for comprehensive management of metabolic and liver-related comorbidities to optimize antiviral therapy outcomes.