Ratios of regulatory T cells/T-helper 17 cells and transforming growth factor-β1/interleukin-17 to be associated with the development of hepatitis B virus-associated liver cirrhosis

J Gastroenterol Hepatol. 2014 May;29(5):1065-72. doi: 10.1111/jgh.12459.

Abstract

Background and aim: The aim of this study is to evaluate the association of the regulatory T cells (Treg)/T-helper (Th) 17 cells and transforming growth factor-β1 (TGF-β1)/interleukin-17 (IL-17) ratios with the survival and disease progression in patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC).

Methods: The frequencies of Treg and Th17 cells were analyzed in 28 patients with HBV-LC, 70 patients with chronic hepatitis B (CHB) and 20 normal controls (NC) by flow cytometry. The levels of cytokines related to Treg/Th17 differentiation, including IL-10, TGF-β1, IL-17, and IL-23, were measured by ELISA.

Results: Compared with NC, Treg cells were significantly increased in CHB patients and slightly increased in HBV-LC patients, whereas Th17 cells were markedly increased both in patients with CHB and HBV-LC. HBV-LC patients, especially the nonsurvival ones, manifested a profound decrease in the Treg/Th17 ratio, which was negatively correlated with Child-Pugh and model of end-stage liver disease scores. Serum IL-10, TGF-β1, IL-17, and IL-23 levels were all significantly higher in HBV-LC patients than in NC. In addition, the TGF-β1/IL-17 ratio was also markedly increased in patients with HBV-LC, especially in nonsurvival and decompensated liver cirrhosis patients, and positively correlated with total bilirubin, Child-Pugh, and model of end-stage liver disease scores.

Conclusions: The decreased Treg/Th17 ratio and increased TGF-β1/IL-17 ratio may be associated with the survival and disease progression in HBV-LC patients, and both of the two ratios can be used independently to predict the prognosis and disease progression of HBV-LC patients.

Keywords: TGF-β1; Th17 cells; Treg cells; hepatitis B virus; interleukin-17; liver cirrhosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Disease Progression
  • Female
  • Hepatitis B virus*
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Interleukin-17 / immunology*
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / immunology*
  • Liver Cirrhosis / virology*
  • Male
  • Middle Aged
  • Prognosis
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*
  • Transforming Growth Factor beta1 / immunology*
  • Young Adult

Substances

  • Interleukin-17
  • Transforming Growth Factor beta1