Role of serum toll-like receptors 2 and 4 in non-alcoholic steatohepatitis and liver fibrosis

Abstract

Background and aim: Non-alcoholic fatty liver disease is a common cause of chronic liver disease, including non-alcoholic steatohepatitis (NASH). Our aim was to investigate whether serum toll-like receptors 2 and 4 (TLR2 and TLR4) levels are correlated with NASH and able to predict liver fibrosis, as well as to compare these markers with other non-invasive fibrosis scores (aspartate aminotransferase [AST] to alanine aminotransferase ratio, AST to platelet ratio index, fibrosis index, fibrosis 4, and fibrosis cirrhosis index).

Methods: Serum samples were obtained from consecutive biopsy proven NASH patients and healthy controls. Serum TLR2 and TLR4 were measured using ELISA. Stage of fibrosis was evaluated using the Brunt Criteria. The different non-invasive fibrosis scores were compared using areas under the curve.

Results: Fifty-seven patients with NASH and 57 healthy individuals were enrolled in the study. Serum TLR2 levels were not significantly different between the healthy controls and NASH patients. The medians were 3.88 ng/mL ± 0.29 versus 3.81 ng/mL ± 0.32, respectively (P = 0.587). In comparing the levels of TLR4 between groups, the medians were 1.05 ng/mL ± 0.13 versus 1.46 ng/mL ± 0.27, respectively (P < 0.001). In NASH patients, the levels of serum TLR4 increased with the stage of fibrosis: TLR4 medians were F0:1.01, F1:1.46, F2:2.14, F3:3.74, F4:5.83 (P < 0.001). TLR4 produced AUCs for ≥ F1, ≥ F2, and ≥ F3 of 0.862, 0.810, and 0.905, respectively (P < 0.001). TLR4 levels were more predictive than other non-invasive fibrosis scores in liver fibrosis.

Conclusion: Serum TLR4 levels but not TLR2 were elevated in NASH patients in comparison with healthy controls. And in NASH patients, serum TLR4 levels both correlated with and were able to predict liver fibrosis.

Keywords: NASH; non-invasive marker; toll-like receptors.