The imbalance of peripheral interleukin-18 and transforming growth factor-β1 levels in patients with cirrhosis and esophageal varices

Cytokine. 2019 Jan:113:440-445. doi: 10.1016/j.cyto.2018.10.024. Epub 2018 Nov 2.

Abstract

Introduction: The presence of esophageal varices in liver cirrhosis indicates clinically significant portal hypertension (PH), that results from structural and dynamic changes in the liver and systemic circulation including the activation of several fibrotic and inflammatory pathways. We assessed if interleukin-18 (IL-18) and transforming growth factor-β1 (TGF-β1) serum levels can be used as PH markers and reflect its severity.

Material and methods: IL-18 and TGF-β1 peripheral blood levels were analyzed in 83 cirrhotic patients with esophageal varices compared to healthy individuals, in relation to MELD and Child-Pugh scores, laboratory and Doppler ultrasound parameters, and non-selective beta-blocker therapy (NSBB).

Results: IL-18 concentration was significantly higher in cirrhotic patients, while TGF-β1 concentration was lower than in controls. MELD score correlated positively with IL-18 levels and negatively with TGF-β1 levels. IL-18 levels correlated positively with bilirubin, INR, ALT and AST levels, and negatively with albumin levels and erythrocyte count. TGF-β1 levels correlated positively with platelet count, leukocyte, and erythrocyte count, and negatively with bilirubin levels and prothrombin time. Moreover, significant correlations were found: between IL and 18 levels and portal, mesenteric superior, and splenic vein velocity, and between TGF-β1 levels and splenic vein diameter and spleen size. In a subgroup of patients, IL-18 levels significantly decreased after NSBB.

Conclusion: The observed imbalance of peripheral IL-18 and TGF-β1 levels indicates clinically significant PH associated with the presence of esophageal varices in cirrhosis. The correlation of IL-18 levels with liver failure indicators and decrease with NSBB suggest an important role of IL-18 in disease progression and its potential use as noninvasive test for PH assessment.

Keywords: Cirrhosis; Esophageal varices; Interleukin-18; Transforming growth factor beta1.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adult
  • Biomarkers / blood
  • Esophageal and Gastric Varices / blood*
  • Esophageal and Gastric Varices / diagnostic imaging
  • Esophageal and Gastric Varices / drug therapy
  • Female
  • Humans
  • Hypertension, Portal / blood*
  • Hypertension, Portal / diagnostic imaging
  • Hypertension, Portal / drug therapy
  • Interleukin-18 / blood*
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / diagnostic imaging
  • Liver Cirrhosis / drug therapy
  • Male
  • Middle Aged
  • Transforming Growth Factor beta1 / blood*

Substances

  • Adrenergic beta-Antagonists
  • Biomarkers
  • Interleukin-18
  • TGFB1 protein, human
  • Transforming Growth Factor beta1