Hemochromatosis gene and nonalcoholic fatty liver disease: A systematic review and meta-analysis

Abstract

Background and aims Previous studies examining the relationship between the C282Y and H63D HFE mutations and presence of nonalcoholic fatty liver disease (NAFLD) have yielded conflicting results. The goal of this study was to systematically evaluate and summarize data on the association between these two variants and the presence of NAFLD. Methods The authors searched EMBASE and PUBMED from August 1, 1996 to August 12, 2010. Two investigators independently conducted data abstraction. Ethnic specific weighted prevalence was calculated, and pooled odds ratios were estimated using random effects model. Results From 2,542 references, the authors included 16 case-control studies and 14 case-only studies, or 2,610 cases and 7,298 controls. The majority of the studies came from Caucasian populations (2,287 cases and 4,275 controls). The weighted prevalence of HFE mutations in cases was comparable to controls. The meta-analysis was restricted to Caucasians only because the small sample size of non Caucasian participants. The pooled odds ratio for the presence of any HFE genetic variant in cases was 1.03 (95% CI: 0.90, 1.17; I2: 65.8%, 95% CI: 38.5, 81.0). The presence of other genotypes, and secondary analyses yielded similar non significant findings. Conclusion Our systematic review does not support an association between the HFE genetic variants and the presence of NAFLD.

Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries

“…The C282Y mutation has been associated with NASH [169] as well as hepatocellular iron accumulation which could promote the progression of hepatic fibrogenesis, thereby conferring risk for increased histological severity secondary to ironmediated oxidative stress and lipotoxicity [170][171][172] . Findings from conflicting studies [173,174] as well as a systematic review and meta-analysis [175] however fail to support the notion that HFE genotype is a significant genetic determinant of risk for the onset or progression of NAFLD and/or DIOS. In patients with a known diagnosis of NAFLD, confirmation that HFE genotype allows for the non-invasive prediction of parenchymal as opposed to sinusoidal iron overload could also provide evidence supporting the relevance of personalized genomic testing in the non-invasive differentiation between hepatosteatosis/DIOS and type Ⅰ HH.…”

Iron homeostasis in the Metabolic Syndrome

“…Clinically important serum ferritin has been associated with increased mortality of patients on the waiting list as well as after transplantation [40,41]. Mutations in the most frequent iron overload-related HFE mutation are likely not related to iron excess in NAFLD [43]. Mutations in the most frequent iron overload-related HFE mutation are likely not related to iron excess in NAFLD [43].…”

Cryptogenic Chronic Hepatitis and Its Changing Guise in Adults

“…Mutations of the transferrin receptor 2, hemojuvelin, ferroportin and hepcidin genes can result in toxic accumulations of iron in liver, heart and endocrine glands, and they may have clinical manifestations that vary from those associated with the classical HFE mutations, C282Y and H63D [26,142,143]. Furthermore, abnormal serum and hepatic iron studies may occur in 30-50% of patients with chronic hepatitis C [144][145][146][147][148][149][150], alcoholic liver disease [151,152] and NAFLD [73,114], and they are not ascribable to the HFE variants [153].…”