| 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 AND AIMS: The HFE p.C282Y+/+ (homozygous) genotype and central adiposity both increase liver disease and diabetes risks, but the 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 AND RESULTS: Baseline WHR data available in 1297 male and 1602 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 ( p = 7.7 × 10 -11 ), and type 2 diabetes ( p = 5.1 × 10 -16 ). The hazard ratio for high WHR in p.C282Y+/+ males (≥0.96; 33.9%) was 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 (hazard ratio = 9.17, 95% CI: 2.51-33.50, p = 3.8 × 10 -7 ) and Non-alcoholic fatty liver disease (hazard ratio = 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>
CONCLUSIONS: 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>
19 Keywords
- Adult
- Aged
- Aged, 80 and over
- Diabetes Mellitus, Type 2
- Female
- Hemochromatosis
- Hemochromatosis Protein
- Homozygote
- Humans
- Incidence
- Liver Cirrhosis
- Liver Neoplasms
- Male
- Middle Aged
- Non-alcoholic Fatty Liver Disease
- Obesity, Abdominal
- Risk Factors
- United Kingdom
- Waist-Hip Ratio
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