Circulating miRNA-122 Levels Are Associated With Hepatic Necroinflammation and Portal Hypertension in HIV/HCV Coinfection

PLoS One. 2015 Feb 3;10(2):e0116768. doi: 10.1371/journal.pone.0116768. eCollection 2015.

Abstract

Background: Introduction of combined antiretroviral therapy (cART) has improved survival of HIV infected individuals, while the relative contribution of liver-related mortality increased. Especially in HIV/HCV-coinfected patients hepatic fibrosis and portal hypertension represent the main causes of liver-related morbidity and mortality. Circulating miRNA-122 levels are elevated in HIV patients and have been shown to correlate with severity of liver injury. However, the association of miRNA-122 levels and hepatic fibrosis and portal hypertension remains to be explored in HIV/HCV coinfection.

Methods: From a total of 74 (31% female) patients with HIV/HCV coinfection were included. Serum levels of miRNA-122 were analyzed by quantitative polymerase chain reaction (PCR) and normalized to SV-40 spike-in RNA. Hepatic venous pressure gradient (HVPG) was measured in 52 (70%) patients and the fibrosis stage was determined in 63 (85%) patients using transient elastography.

Results: The levels of circulating miRNA-122 were increased in HIV/HCV coinfected patients and significantly correlated with the alanine aminotransferase (ALT) (rs = 0.438; p<0.001) and aspartate transaminase AST values (rs = 0.336; p = 0.003), but not with fibrosis stage (p = n.s.). Interestingly, miRNA-122 levels showed an inverse correlation with hepatic venous pressure gradient (HVPG) (rs = -0.302; p = 0.03).

Conclusion: Elevated miRNA-122 levels are associated with liver injury, and with low HVPG. Though, miRNA-122 levels are not suitable to predict the degree of fibrosis, they might function as indicators for portal hypertension in HIV/HCV coinfected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Coinfection / complications*
  • Female
  • HIV Infections / complications*
  • Hepatitis C / complications*
  • Humans
  • Hypertension, Portal / blood*
  • Hypertension, Portal / complications
  • Hypertension, Portal / physiopathology
  • Liver / injuries
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / physiopathology
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Portal Pressure
  • Retrospective Studies
  • Young Adult

Substances

  • MIRN122 microRNA, human
  • MicroRNAs

Grant support

This work was supported by the Deutsche Forschungsgemeinschaft (SFB TRR57 P18 to J.T.), J. & W. Hector-Foundation (M60.2 to J.T.), unrestricted research grants from Roche Austria (to M.P.R.), MSD Austria (to M.P.R.), DZIF TTU HIV Project 05.803, and the German Center for Infection Research (DZIF), Research and Education program of the Medical Faculty of the University of Cologne, German Competence Network for Viral Hepatitis (Hepnet), German Ministry of Education and Research (BMBF), Grant No 01KI0601 (to M.O.), and German Liver Foundation (to M.O.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.