Pathophysiological, Molecular and Therapeutic Issues of Nonalcoholic Fatty Liver Disease: An Overview

Abstract

Nonalcoholic Fatty Liver Disease (NAFLD) represents the leading cause of liver disease in developed countries but its diffusion is currently also emerging in Asian countries, in South America and in other developing countries. It is progressively becoming one of the main diseases responsible for hepatic insufficiency, hepatocarcinoma and the need for orthotopic liver transplantation. NAFLD is linked with metabolic syndrome in a close and bidirectional relationship. To date, NAFLD is a diagnosis of exclusion, and liver biopsy is the gold standard for diagnosis. NAFLD pathogenesis is complex and multifactorial, mainly involving genetic, metabolic and environmental factors. New concepts are constantly arising in the literature promising new diagnostic and therapeutic tools. One of the challenges will be to better characterize not only NAFLD development but overall NAFLD progression, in order to better identify NAFLD patients at higher risk of metabolic, cardiovascular and neoplastic complications. This review analyses NAFLD epidemiology and the different prevalence of the disease in distinct groups, particularly according to sex, age, body mass index, type 2 diabetes and dyslipidemia. Furthermore, the work expands on the pathophysiology of NAFLD, examining multiple-hit pathogenesis and the role of different factors in hepatic steatosis development and progression: genetics, metabolic factors and insulin resistance, diet, adipose tissue, gut microbiota, iron deposits, bile acids and circadian clock. In conclusion, the current available therapies for NAFLD will be discussed.

Human Liver Spheroids as a Model to Study Aetiology and Treatment of Hepatic Fibrosis

“…Co-cultures of donor 1, which progressively and reproducibly developed a pro-fibrogenic phenotype, were used to screen anti-fibrotic compounds currently in Phases II and III of clinical development [34][35][36]. Spheroids were repeatedly exposed to cenicriviroc (HY-14882; MedChem Express, NJ, USA), elafibranor (HY-16737; MedChem Express, NJ, USA), or lanifibranor (HY-104049; MedChem Express, NJ, USA) from day 7 to 14.…”

PNPLA2 influences secretion of triglyceride-rich lipoproteins by human hepatoma cells

“…Accumulation of excessive amounts of triglycerides results in hepatic steatosis, ultimately leading to NAFLD 104,105 . The main metabolic aspects associated with hepatic steatosis are cellular dysfunction and apoptosis 106,107 . Oleic acid is the most abundant non-saturated fatty acid present in circulation and has been used in numerous studies as an in vitro model of hepatic steatosis.…”

Obesidad y enfermedad hepática grasa no alcohólica en Pediatría.

“…Al resumir los resultados de 6 ensayos clínicos en meta-análisis, los agonistas GLP-1 mejoraron todos los parámetros histológicos en relación al comparador. También el uso de estos fármacos redujo el nivel sérico de gamma-glutamil transferasa (2,21,22).…”