Metabolomic Changes Associated With the Change in HVPG After DAAs Therapy in HCV Cirrhotic Patients

Liver Int. 2025 Jan;45(1):e16204. doi: 10.1111/liv.16204.

Abstract

Background and aims: In response to direct-acting antivirals (DAAs) therapy, patients who experience a decrease in hepatic venous pressure gradient (HVPG) considerably reduce liver complications and have increased survival. This study aimed to assess the metabolomic changes associated with the changes in HVPG from the start of DAA therapy until 48 weeks after effective DAA therapy in patients with advanced HCV-related cirrhosis.

Methods: We carried out a multicenter longitudinal study in 31 patients with advanced hepatitis C virus (HCV)-related cirrhosis. We performed a non-targeted metabolomic analysis using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, as well as analysis of inflammation-related biomarkers using Luminex technology. The statistical analysis was performed by Generalised Linear Mixed-effects Models (GLMM), correcting for multiple testing.

Results: We found that increases of 2,3-butanediol (AMR = 1.15; q-value = 0.023) and taurocholic acid (AMR = 1.06; q-value < 0.001) were significantly associated with increases in HVPG and inflammatory biomarker levels from before DAA therapy to one year after completion of successful HCV treatment.

Conclusions: These metabolites have a potential role as indicators of portal hypertension evolution.

Keywords: HCV; HIV; HVPG; cirrhosis; metabolomics.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Antiviral Agents* / therapeutic use
  • Biomarkers* / blood
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Hypertension, Portal* / etiology
  • Hypertension, Portal* / physiopathology
  • Liver Cirrhosis* / drug therapy
  • Longitudinal Studies
  • Male
  • Metabolomics*
  • Middle Aged

Substances

  • Antiviral Agents
  • Biomarkers