Nonalcoholic Steatohepatitis: Involvement of the Telomerase and Proinflammatory Mediators.

Rim Serhal,George Hilal,Joseph Sidaoui,Salah Ezzeddine,George Boutros,Nada Alaaeddine,Layal Wardi

doi:10.1155/2015/850246

Abstract

Nonalcoholic steatohepatitis or NASH is an excessive accumulation of fat in hepatocytes accompanied by inflammation and hepatic injury. Proinflammatory molecules such as IL-17, CCL20, S100A8, S100A9, and S100A8/A9 have been shown to be implicated in many types of cancer. Telomerase activity has been found to be associated with chronic inflammation and cancer. NASH can progress to fibrosis then cirrhosis and finally to hepatocellular carcinoma (HCC). Our objective is to try to find a relation between inflammation and the progression of NASH into HCC. We found that there was a significant elevation in the telomerase activity, detected by real-time PCR, between NASH and fibrotic NASH in the liver biopsies of patients. The expression of S100A8, S100A9, S100A8/A9, CCL20, and IL-17, detected by ELISA, is significantly increased in NASH patients with fibrosis in comparison with controls. But, in NASH patients, S100A9, S100A8/A9, and IL-17 only are significantly elevated in comparison with controls. The same, on the mRNA level, expression of IL-17, detected by RT-PCR, is significantly elevated in NASH patients in comparison with controls. Therefore, there is a direct link between the expression of IL-17, CCL20, telomerase, S100A8, and S100A9 in the fibrotic condition and the progression towards cancer.

Highlights

Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, hepatocellular injury, and parenchymal and portal inflammation [1]
The diagnosis of NASH was based on the following criteria: (1) intake of less than 20 g of ethanol per day, (2) a positive ultrasonography for steatosis, (3) biopsy proven steatohepatitis, steatosis, inflammatory infiltrates, and ballooning degeneration with or without Mallory bodies or pericellular/perivenular fibrosis, and (4) appropriate exclusion of other liver diseases patients had to have an increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of 1 to 4 times the upper limit of normal, with an AST/ALT ratio of
We were trying to elucidate the factors involved in the progression of NASH to cirrhosis hepatocellular carcinoma (HCC)

Summary

Introduction

Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, hepatocellular injury, and parenchymal and portal inflammation [1]. Inflammation is thought to be the main factor in the development of NASH Proinflammatory mediators such as IL-6 and TNF-α have been shown to be associated with increased severity of hepatic inflammation [2, 3]. IL-17 is another proinflammatory cytokine associated with hepatic steatosis and proinflammatory response in nonalcoholic fatty liver disease (NAFLD) and has been suggested to facilitate the transition from simple steatosis to steatohepatitis [5]. Those inflammatory cytokines perpetuate inflammation and may contribute to the differentiation of NASH to fibrosis. The most worrying scenario is the potential for the progression of NASH to cirrhosis hepatocellular carcinoma (HCC) [6]

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Conclusion