Role of Cytokines in Pathogenesis and Progression of Nonalcoholic Steatohepatitisa

Abstract

Introduction: Non-alcoholic fatty liver disease (NAFLD) has been considered to be the hepatic manifestation of metabolic syndrome, and may progress to Non-alcoholic steatohepatitis NASH and / or hepatocellular carcinoma (HCC), thus being associated with a high cardiovascular and carcinogenic risk. Thus, it becomes necessary to understand the underlying mechanisms involved in the genesis of NAFLD and its progression to NASH and HCC, so that a better therapeutic approach can be defined in an attempt to cease and reverse this progression.

Objective: To review main mechanisms involved in NASH, from inflammatory pathways, microbiota, cytokines and some more current theories such as the role of the extracellular trap of degranulation and neutrophil production (NETs). Methods: An integrative review was conducted with active search of articles in English using Medline, Embase, Lilacs and Pubmed data, using descriptors related to “non-alcoholic fatty liver disease”, “non-alcoholic steatohepatitis”, “pathophysiology”, “cytokines” and “molecular mechanisms” without restriction of period.

Results: 182 articles were found, of which 40 were selected for this review, including original articles, clinical and experimental research, and systematic reviews.

Discussion: Non-alcoholic fatty liver disease may occur through increased absorption, fatty acid synthesis, lipogenesis, reduction of triglyceride hydrolysis and mitochondrial beta-oxidation of fatty acids, contributing to increased production of free radicals and reactive oxygen species, involving many inflammatory mediators. Cytokines may play an active role in the development and progression of NAFLD by stimulation hepatic inflammation, cell necrosis, apoptosis and induction of fibrosis. However, they are also essential for liver regeneration.

Conclusions: Metabolic dysfunction leads to lipotoxicity, innate immune responses and the resulting pattern of cellular inflammation in the liver are probably also relevant for liver fibrogenesis and hepatocarcinogenesis. The most studied and described cytokines were adiponectin, leptin, TNF-α, IL-6, visfatin, A-activator and chemerin.. This knowledge becomes fundamental for new diagnostic procedures and therapeutic strategies to avoid NASH progression.