Clinical, Metabolic, and Virological Insights into Hepatitis C Virus-Infected Patients through the Combinatorial Metabolic Dysfunction-associated Steatotic Liver Disease Framework: Evidence from an Italian Cohort

Giuseppe Guido Maria Scarlata; Maria Luisa Gambardella; Arcangelo Loberto; Francesco Di Giovanni; Elisabetta Falbo; Valentina La Gamba; Lorenzo Antonio Surace; Francesca Serapide; Massimo Borelli; Alessandro Russo; Ludovico Abenavoli

doi:10.15403/jgld-6739

Authors

Giuseppe Guido Maria Scarlata Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro; Center for Chronic Liver Diseases, Renato Dulbecco University Hospital, Catanzaro, Italy https://orcid.org/0000-0002-7084-8264
Maria Luisa Gambardella Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro; Center for Chronic Liver Diseases, Renato Dulbecco University Hospital, Catanzaro, Italy
Arcangelo Loberto Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro; Center for Chronic Liver Diseases, Renato Dulbecco University Hospital, Catanzaro, Italy
Francesco Di Giovanni School of Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy
Elisabetta Falbo Center for Travel and Migration Medicine, Provincial Health Authority of Catanzaro, Lamezia Terme, Italy
Valentina La Gamba Center for Travel and Migration Medicine, Provincial Health Authority of Catanzaro, Lamezia Terme, Italy
Lorenzo Antonio Surace Center for Travel and Migration Medicine, Provincial Health Authority of Catanzaro, Lamezia Terme, Italy
Francesca Serapide Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
Massimo Borelli UMG School of PhD Programmes "Life Sciences and Technologies", Magna Graecia University of Catanzaro, Catanzaro, Italy
Alessandro Russo Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
Ludovico Abenavoli Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro; Center for Chronic Liver Diseases, Renato Dulbecco University Hospital, Catanzaro, Italy

DOI:

https://doi.org/10.15403/jgld-6739

Keywords:

steatotic liver disease, viral hepatitis, diagnosis, management, nomenclature

Abstract

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) frequently overlaps with hepatitis C virus (HCV) infection, yet the recently proposed combinatorial MASLD (cMASLD) classification remains poorly characterized in this setting. This study aimed to evaluate the prevalence, metabolic profile, and virological determinants of cMASLD in an Italian cohort of HCV-infected patients.

Methods: We conducted a cross-sectional study on 169 HCV-infected patients evaluated at two referral Centers in Southern Italy (between 2020 and 2024). All subjects underwent transient elastography, and cMASLD was diagnosed according to international guidelines. Group comparisons were performed using ANOVA or Kruskal-Wallis tests with appropriate post-hoc analyses, categorical variables by Chi-square or Fisher’s exact test, and multivariate logistic regression to identify factors independently associated with cMASLD (p<0.05).

Results: Among 169 patients, n=52 (31%) fulfilled cMASLD criteria, n=14 (8%) had HCV with liver steatosis, and n=103 (61%) had HCV infection alone. Compared with other groups, cMASLD patients showed higher body mass index (28±8 kg/m²; p<0.001), larger waist circumference (p<0.001), increased controlled attenuation parameter (298±41 dB/m; p<0.001), and higher fasting insulin (p=0.029). HCV RNA levels were significantly elevated in the cMASLD group (p=0.014). Multivariate logistic regression identified HCV RNA as independently associated with cMASLD (OR=1.48; 95%CI: 1.01-2.17; p=0.045).

Conclusions: Applying the cMASLD nomenclature emphasizes the need for a multidisciplinary management approach integrating antiviral and metabolic care. This classification provides a more comprehensive understanding of liver injury mechanisms in patients with overlapping metabolic and viral etiologies.