Development of a pathology supported genetic testing strategy for improved clinical management of patients with non-alcoholic fatty liver disease (NAFLD)

Abstract

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent chronic liver disease in Western countries and is considered the hepatic manifestation of the Metabolic Syndrome (MetS). This study was modelled on a Pathology Supported Genetic Testing (PSGT) approach whereby genetic and pathology tests are combined to overcome the limitations of single disciplines. An important aim of this study was to determine the appropriateness of adding HFE genotyping to Cardiovascular Disease (CVD) risk assessment for improved risk management in patients with NAFLD. Materials and Methods: A total of 178 patients diagnosed with NAFLD and 75 controls were studied using a CVD multi-gene test including eight deleterious low-penetrance mutations in five genes: APOE (rs7412, rs429358), F2 (rs1799963), FV (rs6025), HFE (rs1799945, rs1800562) and MTHFR (rs1801131, rs1801133). Relevant biochemical determinations including the ALT level was determined on all the subjects and compared using appropriate statistical analysis. Results: There was no statistically significant difference in genotype distribution for individual mutations between the NAFLD vs. control subjects. However, in a sub-analysis a significant increase (P = 0.04) in ALT levels was detected in Non-Alcoholic Steatohepatitis (NASH) patients found to be heterozygous or homozygous for the C282Y and H63D mutations in the HFE gene (n = 10), compared to mutation-negative patients (n = 34). Conclusion: These findings emphasize the importance of the HFE mutation detection component of the CVD multi-gene test as it may facilitate an effective treatment strategy in patients with a medical history of CVD and/or high iron stores.

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