Serum levels of miRNA in patients with hepatitis B virus-associated acute-on-chronic liver failure

Hepatobiliary Pancreat Dis Int. 2018 Apr;17(2):126-132. doi: 10.1016/j.hbpd.2018.03.004. Epub 2018 Mar 13.

Abstract

Background: Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum miRNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ACLF.

Methods: Serum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to 30 chronic asymptomatic HBV carriers as controls. The miRNAs expressions were measured by real-time quantitative PCR (q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed miRNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model.

Results: Real-time q-PCR indicated that serum miR-146a-5p, miR-122-3p and miR-328-3p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and miR-122-3p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+ - 1.72 × INR - 4.963 × gastrointestinal bleeding (Yes = 0; No = 1)-0.278 × (miR-122-3p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve (AUROC) was 0.847.

Conclusions: Expression levels of these miRNAs (miR-146a-5p, miR-122-3p and miR-328-3p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.

Keywords: Acute-on-chronic liver failure; Hepatitis B virus; MicroRNA; Prognosis.

MeSH terms

  • Acute-On-Chronic Liver Failure / blood*
  • Acute-On-Chronic Liver Failure / diagnosis
  • Acute-On-Chronic Liver Failure / genetics
  • Acute-On-Chronic Liver Failure / virology
  • Adult
  • Area Under Curve
  • Case-Control Studies
  • Circulating MicroRNA / blood*
  • Circulating MicroRNA / genetics
  • Female
  • Gastrointestinal Hemorrhage / blood
  • Gastrointestinal Hemorrhage / genetics
  • Gastrointestinal Hemorrhage / virology
  • Genetic Markers
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / virology
  • Humans
  • International Normalized Ratio
  • Logistic Models
  • Male
  • MicroRNAs
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prognosis
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Severity of Illness Index
  • Sodium / blood
  • Up-Regulation
  • Young Adult

Substances

  • Circulating MicroRNA
  • Genetic Markers
  • MIRN122 microRNA, human
  • MIRN146 microRNA, human
  • MIRN328 microRNA, human
  • MicroRNAs
  • Sodium