The significance of genetic risk factors in non-alcoholic fatty liver disease (NAFLD)
Date
2011
Authors
Kruger F.C.
Kotze M.J.
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in Western countries, extending from steatosis (FLD) to steatohepatitis (NASH). Differentiation between NASH and nonprogressive NAFLD is difficult on clinical grounds, therefore a need exists to identify reliable biomarkers of disease progression. NAFLD is considered the hepatic manifestation of the metabolic syndrome and discrimination of patients at increased risk of cardiovascular disease (CVD) as apposed to the development of advanced liver disease poses an important clinical question. In this context, an overview of biochemical abnormalities and genetic risk factors implicated in NAFLD and the metabolic syndrome is provided. In addition to standard metabolic indicators, we studied low-density lipoprotein (LDL) particle size and APRI as biomarkers to distinguish between South African NAFLD patients at increased risk of CVD or advanced liver disease, respectively. In relation to gene expression patterns, TNF-α and IKKβ implicated in insulin resistance and inflammation showed the most significant association with NASH in the South African study cohort. There was virtually no knowledge of the existence or clinical consequences of NAFLD in the local population at initiation of this study in 2004. Today, South African patients can reap clinical benefits through increased awareness of NAFLD among South African medical practitioners and the public. A sound basis has also been provided for the application of cardio-vascular testing not only in patients with high cholesterol levels, but also in patients with features of the metabolic syndrome, to facilitate 1) diagnosis of treatable disease subtypes, 2) prevention of cumulative risk, and 3) formulation of individualised treatment plans guided partly by the genetic background.
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South African Gastroenterology Review
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