Decoupled Glucose and Lipid Metabolic Recovery after Viral Clearance in Direct-Acting Antiviral-Treated HCV Patients: A 3-Year Prospective Cohort Study

Cells. 2021 Oct 28;10(11):2934. doi: 10.3390/cells10112934.

Abstract

Background/aim: The recovery pattern of hepatitis C virus (HCV)-associated metabolic alteration after sustained virological response (SVR) following direct-acting antivirals (DAAs) remains elusive.

Methods: A prospective cohort study of chronic HCV-infected (CHC) patients (n = 415) receiving DAAs (n = 365) was conducted. Metabolic profiles were examined in SVR patients (n = 360) every 3-6 months after therapy and compared with those of sex- and age-matched controls (n = 470).

Results: At baseline, of 415, 168 (40.5%) had insulin resistance (IR). The following were associated: levels of high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), HCV RNA, fibrosis-4 score, and interferon-λ3-rs12979860 genotype with total cholesterol (TC) levels; and TG levels and BMI with HOMA-IR. Over a 3-year follow-up, in SVR patients, BMI and TC levels and TG/HDL-C ratios increased from baseline, while HOMA-IR trended downward by 72 weeks after therapy and then increased. The increased HDL-C levels began to decrease after 72 weeks after therapy. TC and HOMA-IR were negatively associated with each other until 24 weeks after therapy. Earlier increases in BMI and decreases in HOMA-IR were noted in SVR patients with than in those without baseline IR. Compared with controls, in the subgroup without baseline IR, SVR patients had increased BMI and HOMA-IR levels. Metabolic profiles were similar between SVR patients and controls in the subgroup with baseline IR.

Conclusions: In SVR patients treated with DAAs, the recovery of altered lipid and glucose metabolism was not coupled until 72-week post-therapy, when HOMA-IR reached its nadir. SVR patients with baseline IR recovered from HCV-associated metabolic alterations earlier than those without baseline IR.

Keywords: DAA; HCV; HOMA-IR; lipid; metabolic alteration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Body Mass Index
  • Female
  • Fibrosis
  • Glucose / metabolism*
  • Hepacivirus / drug effects
  • Hepacivirus / physiology*
  • Hepatitis C / metabolism*
  • Hepatitis C / virology*
  • Homeostasis
  • Humans
  • Insulin Resistance
  • Interferons / metabolism
  • Lipid Metabolism* / drug effects
  • Lipids / blood
  • Male
  • Metabolomics
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Sustained Virologic Response

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Lipids
  • Interferons
  • Glucose