Decoding the Pathophysiology of Non-alcoholic Fatty Liver Disease Progressing to Non-alcoholic Steatohepatitis: A Systematic Review

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic manifestation of metabolic syndromes, and its roots are strongly associated with obesity and insulin resistance. The excess fat induces inflammatory pathways by tissue irritation and progresses to non-alcoholic steatohepatitis (NASH), fibrosis, and has emerged as the most frequent cause of hepatocellular cancer (HCC). This systematic review was structured per the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The evidence was obtained from 13 research articles published in PubMed, Google Scholar, and Science Direct databases, including cross-sectional, case-control, prospective cohort studies, meta-analysis, and systematic reviews. The inclusion/exclusion criteria of free articles, published in English involving humans of mid-age in the last five years were applied. This review highlights findings in 7781 individuals, including non-NAFLD, NAFLD, and NASH positive individuals based on anthropometric measurement, blood samples, FibroScan, flow cytometry, and liver biopsy. The results underscored that the onset of inflammation set on the background of NAFLD starts NASH; the understanding and control of inflammation will help us design definitive biomarkers and treatment modalities. The complex pathogenesis and comparatively slow advancement but high morbidity have led investigators to understand the nuts and bolts for early management and prevention. Lipotoxicity and dysbiosis stimulate the immune system to generate cytokines and chemokines and decline in adipokines. The role of proteinase3 (PR3) and antitrypsin (ATT) ratio and biliverdin reductase (BVR) compel the exploration for non-invasive tests for definitive therapy. Categories: Endocrinology/Diabetes/Metabolism, Internal Medicine, Pathology Keywords: nonalcoholic fatty liver disease, nafld and obesity, bariatric surgery and nafld, steatosis nash, pro-inflammatory cytokines, leptin adiponectin, intestinal dysbiosis, toll-like receptors, nafld and natural killer cells