Genotype-dependent Changes in Hepatic Steatosis and Fibrosis Following Sustained Virologic Response in Chronic Hepatitis C: A Prospective Cohort Study
DOI:
https://doi.org/10.52340/GBMN.2026.01.01.188Keywords:
Direct-acting antivirals, Fibrosis, Genotype 3, Hepatic steatosis, Hepatitis C virus, Sustained virologic responseAbstract
BACKGROUND. Chronic hepatitis C virus (HCV) infection remains a major global cause of hepatic steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma. Mechanisms of steatosis vary by viral genotype, with genotypes 1 and 2 primarily associated with metabolic steatosis and genotype 3 with virus-induced steatogenesis. Although direct-acting antivirals (DAAs) achieve high sustained virologic response (SVR) rates, post-SVR changes in steatosis and fibrosis remain poorly characterized, particularly in populations with high metabolic burden, such as in Georgia. OBJECTIVES. To evaluate genotype-specific changes in hepatic steatosis and fibrosis after SVR and assess the relative contributions of metabolic and viral factors. METHODS. A prospective cohort of 200 patients with chronic HCV infection was followed from baseline through SVR24 in Tbilisi, Georgia, at the Infectious Diseases, AIDS and Clinical Immunology Research Center and the Hepatology Clinic “Hepa”. Liver steatosis and fibrosis were assessed using transient elastography with controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). RESULTS. SVR was achieved in 100% of patients with genotypes 1/2 and 93.3% of patients with genotype 3. Liver enzymes normalized across groups. In genotypes 1/2, steatosis remained strongly associated with metabolic factors and persisted after SVR, with minimal fibrosis regression. In genotype 3, steatosis was more prevalent at baseline but significantly improved after SVR (mean CAP reduction −38 dB/m; p<0.001). BMI remained stable in genotypes 1/2 and showed a small but statistically significant decrease in genotype 3, although the magnitude of change was modest. Genotype 3 and baseline CAP independently predicted improvement in steatosis. CONCLUSIONS. Hepatic recovery after HCV eradication is genotype-dependent. Steatosis persists in genotypes 1/2 due to metabolic drivers, whereas genotype 3 shows improvement following viral clearance. These findings support genotype-specific post-SVR management strategies.References
Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of hepatitis C virus infection. Hepatology. 2015;62(1):123–130.
Estes C, Razavi H, Loomba R, et al. Modeling the global burden of HCV infection. J Hepatol. 2017;66(1):48–57.
European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C. J Hepatol. 2020;73(5):1170– 1218.
American Association for the Study of Liver Diseases. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Hepatology. 2018;67(4):1473–1517.
Bachofner JA, Valli PV, Kröger A, et al. Fibrosis regression after HCV cure. J Hepatol. 2017;67(5):912–918.
Petta S, Wong VW, Cammà C, et al. Persistent steatosis after SVR. Hepatology. 2017;66(5):1444–1453.
Dyson JK, Anstee QM, McPherson S. NAFLD and fibrosis progression. Hepatology. 2014;60(4):1392–1400.
Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated steatotic liver disease. Hepatology. 2020;72(1):219–230.
Chekuri S, Nickerson J, Bichoupan K, et al. Liver stiffness decreases after SVR. Hepatol Commun. 2018;2(5):654–662.
Lonardo A, Ballestri S, Guaraldi G, et al. Fatty liver in hepatitis C virus infection: metabolic vs viral steatosis. Hepatology. 2006;43(4):1000–1009.
Chalasani N, Younossi Z, Lavine JE, et al. NAFLD diagnosis and management. Hepatology. 2018;67(1):328–357.
Singh S, Facciorusso A, Loomba R. Impact of SVR on fibrosis outcomes. Gastroenterology. 2017;152(6):1364–1379.
Sanyal AJ, Friedman SL, McCullough AJ, et al. Mechanisms of fibrosis progression. Gastroenterology. 2015;149(2):389–402.
Clouston AD, Jonsson JR, Purdie DM, et al. Steatosis and fibrosis progression in chronic hepatitis C. Hepatology. 2001;34(2):366–372.
Gvinjilia L, Nasrullah M, Sergeenko D, et al. HCV elimination program in Georgia. MMWR. 2016;65(41):1132–1135.
Stvilia K, Sharvadze L, Chkhartishvili N, et al. HCV epidemiology in Georgia. J Viral Hepat. 2020;27(4):350–358.
Razavi H, Sanchez Gonzalez Y, Yuen C, et al. HCV elimination efforts in Georgia. Lancet Gastroenterol Hepatol. 2021;6(5):356– 3.
Wong VW, Adams LA, de Lédinghen V, et al. Noninvasive biomarkers in liver disease. J Hepatol. 2018;68(2):296–304.
Younossi ZM, Stepanova M, Negro F, et al. Viral genotype and hepatic steatosis in chronic hepatitis C. Hepatology. 2019;70(4):1234– 1245.
Mamatsashvili I, Chelidze K, Jgharkava M, et al. NAFLD in the Georgian population. Georgian Biomed News. 2025;1(1):117.
Negro F. Mechanisms and significance of steatosis in hepatitis C virus infection. J Hepatol. 2014;61(1):188–196.
