Towards precision medicine in non-alcoholic fatty liver disease

AbstractNon-Alcoholic Fatty Liver Disease (NAFLD) refers to the accumulation of lipid laden vacuoles in hepatocytes, occurring in the context of visceral adiposity, insulin resistance and other features of the metabolic syndrome. Its more severe form (NASH, Non-Alcoholic Steatohepatitis) is becoming the leading aetiology of end-stage liver disease and hepatocellular carcinoma, and also contributes to cardiovascular disease, diabetes and extrahepatic malignancy. Management is currently limited to lifestyle modification and optimisation of the metabolic co-morbidities, with some of the drugs used for the latter also having shown some benefit for the liver. Licensed treatment modalities are currently lacking. A particular difficulty is the notorious heterogeneity of the patient population, which is poorly understood. A spectrum of disease severity associates in a non-linear way with a spectrum of severity of underlying metabolic factors. Heterogeneity of the liver in terms of mechanisms to cope with the metabolic and inflammatory stress and in terms of repair mechanisms, and a lack of knowledge hereof, further complicate the understanding of inter-individual variability. Genetic factors act as disease modifiers and potentially allow for some risk stratification, but also only explain a minor fraction of disease heterogeneity. Response to treatment shows a large variation in treatment response, again with little understanding of what is driving the absence of response in individu...
Source: Reviews in Endocrine and Metabolic Disorders - Category: Endocrinology Source Type: research