Association between Leptin and Complement in Hepatitis C Patients with Viral Clearance: Homeostasis of Metabolism and Immunity

PLoS One. 2016 Nov 21;11(11):e0166712. doi: 10.1371/journal.pone.0166712. eCollection 2016.

Abstract

Background: The association between leptin and complement in hepatitis C virus (HCV) infection remains unknown.

Methods: A prospective study was conducted including 474 (250 genotype 1, 224 genotype 2) consecutive chronic hepatitis C (CHC) patients who had completed an anti-HCV therapy course and undergone pre-therapy and 24-week post-therapy assessments of interferon λ3-rs12979860 and HCV RNA/genotypes, anthropometric measurements, metabolic and liver profiles, and complement component 3 (C3), C4, and leptin levels.

Results: Of the 474 patients, 395 had a sustained virological response (SVR). Pre-therapy leptin levels did not differ between patients with and without an SVR. Univariate and multivariate analyses showed that sex (pre- and post-therapy, p<0.001), body mass index (BMI) (pre- and post-therapy, p<0.001), and C3 levels (pre-therapy, p = 0.027; post-therapy, p = 0.02) were independently associated with leptin levels with or without HCV infection. Pre-therapy BMI, total cholesterol (TC), C4 levels, and the rs12979860 genotype were independently associated with pre-therapy C3 levels in all patients. Post-therapy BMI, alanine aminotransferase, TC, C4 levels, white blood cell counts, and hepatic steatosis were independently associated with the post-therapy C3 levels of SVR patients. Compared with pre-therapy levels, SVR patients showed higher 24-week post-therapy C4 (20.32+/-7.30 vs. 21.55+/-7.07 mg/dL, p<0.001) and TC (171.68+/-32.67 vs. 186.97+/-36.09 mg/dL, p<0.001) levels; however, leptin and C3 levels remained unchanged after therapy in patients with and without an SVR.

Conclusions: Leptin and C3 may maintain immune and metabolic homeostasis through association with C4 and TC. Positive alterations in C4 and TC levels reflect viral clearance after therapy in CHC patients.

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / metabolism
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Body Mass Index
  • Complement C3 / metabolism
  • Complement C4 / metabolism
  • Complement System Proteins / metabolism*
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / metabolism
  • Homeostasis
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Leptin / metabolism*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • RNA, Viral / genetics
  • Sustained Virologic Response

Substances

  • Antiviral Agents
  • Complement C3
  • Complement C4
  • interferon-lambda, human
  • Interleukins
  • Leptin
  • RNA, Viral
  • Complement System Proteins
  • Interferons
  • Alanine Transaminase

Grants and funding

This study was supported by grants from the Chang Gung Medical Research Program (CMRPG3F0471, CRRPG3F0011, XMRPG3A0521 and CIRPG3D0121) and the National Science Council, Taiwan (102-2628-B-182-021-MY3, MOST 105-2314-B-182-023, and MOST 105-2629-B-182-001-) to Ming-Ling Chang. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.