| Title: | Incidence of liver complications with hemochromatosis associated HFE p.C282Y homozygosity: The role of central adiposity. |
| Journal: | Hepatology |
| Published: | 23 Aug 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39178373/ |
| DOI: | https://doi.org/10.1097/hep.0000000000001056 |
| URL: | https://journals.lww.com/hep/abstract/9900/incidence_of_liver_complications_with.1000.aspx |
Publication 13145
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Abstract
BACKGROUND AIMS: The HFE p.C282Y+/+ (homozygous) genotype and central adiposity both increase liver disease and diabetes risks, but combined effects are unclear. We estimated waist-to-hip ratio (WHR) associations with incident clinical outcomes in routine care in p.C282Y+/+ participants in the UK Biobank community cohort.</p>
APPROACH RESULTS: Baseline WHR in 1,297 male and 1,602 female p.C282Y+/+ with 13.3-year mean follow-up for diagnoses. Spline regressions and Cox proportional hazard models were adjusted for age and genetic principal components. Cumulative incidence was from age 40 to 80 years. In p.C282Y+/+ males, there were positive linear WHR relationships for hospital inpatient diagnosed liver fibrosis/cirrhosis (p=2.4*10-5), liver cancer (p=0.007), non-alcoholic fatty liver disease (NAFLD) (p=7.7*10-11), and type 2 diabetes (T2D) (p=5.1*10-16). The Hazard Ratio (HR) for high WHR in p.C282Y+/+ males (≥0.96; 33.9%) was HR=4.13 for liver fibrosis/cirrhosis (95%CI: 2.04-8.39, p=8.4*10-5 vs. normal WHR); cumulative age 80 incidence 15.0% (95%CI: 9.8%-22.6%) versus 3.9% (95%CI: 1.9%-7.6%); for liver cancer, cumulative incidence was 9.2% (95%CI: 5.7%-14.6%) versus 3.6% (95%CI: 1.9%-6.6%). Hemochromatosis was diagnosed in 23 (96%) of the 24 high WHR p.C282Y+/+ males with incident fibrosis/cirrhosis. High WHR (≥0.85; 30.0%) p.C282Y+/+ females had raised hazards for liver fibrosis/cirrhosis (HR=9.17, 95%CI: 2.51-33.50, p=3.8*10-7) and NAFLD (HR=5.17, 95%CI: 2.48-10.78, p=1.2*10-5). Fibrosis/cirrhosis associations were similar in the subset with additional primary care diagnoses.</p>
CONCLUSION: In p.C282Y+/+ males and females, increasing WHR is associated with substantially higher risks of liver complications. Interventions to reduce central adiposity to improve these outcomes should be tested.</p>
4 Authors
- Mitchell R Lucas
- Luke C Pilling
- Janice L Atkins
- David Melzer
1 Application
| Application ID | Title |
|---|---|
| 14631 | Genetic and environmental influences on ageing well |
Enabling scientific discoveries that improve human health