# Influence of antiviral treatment in hepatitis C patients on metabolism and fibrosis process

## TL;DR

This study shows how antiviral treatments for hepatitis C can improve liver health and metabolism, with different treatments working better at different stages of liver damage.

## Contribution

The study identifies specific metabolic and inflammatory biomarker changes in HCV patients treated with different DAAs, revealing treatment-specific and fibrosis-stage-dependent effects.

## Key findings

- Antiviral treatments significantly alter metabolic and inflammatory biomarkers in HCV patients.
- Sofosbuvir/Velpatasvir provides broader metabolic benefits in advanced fibrosis, while Glecaprevir/Pibrentasvir shows stronger anti-inflammatory effects in early fibrosis.
- Changes in biomarkers like ANGPTL6, FGF-19, and ghrelin suggest improved liver health post-treatment.

## Abstract

Chronic Hepatitis C Virus (HCV) infection is associated with systemic metabolic disturbances, including glucose intolerance, lipid dysregulation, and inflammation, accelerating liver fibrosis and increasing hepatocellular carcinoma risk. Biomarkers such as Glucagon-Like Peptide-1 (GLP-1), Fatty Acid-Binding Protein 1 (FABP-1), Monocyte Chemoattractant Protein-1 (MCP-1), Angiopoietin-Like Protein 6 (ANGPTL6), ibroblast Growth Factor 19 (FGF-19), and ghrelin offer insights into these mechanisms and may reflect the impact of antiviral treatments.

This study evaluated the effects of two direct-acting antiviral (DAA) regimens—Glecaprevir/Pibrentasvir (G/P) and Sofosbuvir/Velpatasvir (S/V)—on metabolic and inflammatory biomarkers in 70 HCV-infected patients with comorbidities including obesity, type 2 diabetes, and hypertension.

Serum biomarker levels were assessed pre- and post-treatment using the Luminex FlexMAP 3D system. Patients were stratified by treatment type, fibrosis stage (F0–F4), and baseline cholesterol. Liver stiffness was evaluated via FibroScan.

Both regimens induced significant biomarker changes. ANGPTL6, FGF-19, ghrelin, total cholesterol, HDL, and non-HDL increased, while FABP-1 and MCP-1 decreased, indicating reduced inflammation and lipid stress. Stronger effects were seen in patients with lower baseline cholesterol and with S/V in advanced fibrosis. G/P showed marked anti-inflammatory effects in early fibrosis.

DAA therapy significantly alters metabolic and inflammatory biomarkers in HCV patients, with regimen- and fibrosis stage-specific effects. S/V may provide broader metabolic benefits in advanced disease, while G/P offers stronger anti-inflammatory responses earlier, supporting personalized treatment approaches.

(a) The figure shows the effect of HCV on disrupting mTORC2 and AMPK-dependent cellular mechanisms, resulting in deregulated carbohydrate, protein and lipid metabolism and liver fibrosis. (b) The figure shows the effect of antiviral treatment on improving carbohydrate, protein, and lipid metabolism, and consequently to improving liver health. Created with BioRender.com.Conceptual diagram showing how HCV impairs mTORC2 and AMPK pathways, leading to dysregulation of metabolic biomarkers and liver fibrosis (top), while treatments restore these pathways, normalize biomarkers, and improve liver condition (bottom).

(a) The figure shows the effect of HCV on disrupting mTORC2 and AMPK-dependent cellular mechanisms, resulting in deregulated carbohydrate, protein and lipid metabolism and liver fibrosis. (b) The figure shows the effect of antiviral treatment on improving carbohydrate, protein, and lipid metabolism, and consequently to improving liver health. Created with BioRender.com.