Non-alcoholic fatty liver disease: The mist gradually clears☆

Non-alcoholic fatty liver disease (NAFLD) is now the commonest liver disorder in the developed world affecting up to a third of individuals. It is closely associated with features of the metabolic syndrome, particularly obesity and diabetes. It can progress to cirrhosis, hepatocellular carcinoma and liver failure and is an increasing indication for transplantation. Dietary and genetic factors determine susceptibility to NAFLD and its progression. NAFLD may also be involved in the pathogenesis of cardiovascular disease. Most patients present with incidentally found abnormal liver blood tests. Diagnosis is usually one of exclusion. Liver biopsy is required for disease staging, but new imaging modalities and biomarkers are emerging which may eventually fulfil this role. There is, as yet no firm evidence-based treatment for NAFLD. Therapy is currently directed at treating components of the metabolic syndrome which may also be beneficial for the liver. The recent elucidation of the mechanisms leading to progressive disease suggests a variety of novel targets worthy of testing in animal models of NAFLD and subsequently in pilot studies in humans.

Abbreviations: AIH, autoimmune hepatitis, ALT, alanine transaminase, ANA, anti-nuclear antibody, Apo-B, apolipoprotein B, AST, aspartate transaminase, BMI, body mass index, CB₁, cannabinoid-1, FFA, free fatty acids, GGT, gamma glutaryl transpeptidase, HCC, hepatocellular carcinoma, HMGCoA, 3-hydroxy 2-methyl glutaryl-coenzyme A, MRI, magnetic resonance imaging, MRS, magnetic resonance spectroscopy, NAFLD, non-alcoholic fatty liver disease, NASH, non-alcoholic steatohepatitis, OSA, obstructive sleep apnoea, PCOS, polycystic ovarian syndrome, PPARα, peroxisome proliferator-activated receptor alpha, PPARγ, peroxisome proliferator-activated receptor gamma, RCT, randomised control trial, SMA, smooth muscle antibody, T2DM, type 2 diabetes mellitus, TNFα, tumour necrosis factor alpha, TGFβ, triglyceride transfer factor beta, TZD, thiozolidinediones, UDCA, ursodeoxycholic acid

Keywords: NAFLD, NASH, Steatosis