| Description: |
Background & Aims: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. Methods: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). Results: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18–8.60) (GenomALC-1), 2.81 (2.03–3.89) (GenomALC-2), and 3.10 (2.32–4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69–28.1) (GenomALC-1) and 17.1 (11.3–25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 0.61 ± 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. Conclusions: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions. Lay summary: Excessive ... |
| Relation: |
https://livrepository.liverpool.ac.uk/3152778/1/Submitted%20manuscript.pdf; Collapse authors list. Whitfield, JB orcid:0000-0002-1103-0876 , Schwantes-An, TH orcid:0000-0001-6387-0095 , Darlay, R orcid:0000-0002-7526-5527 , Aithal, GP, Atkinson, SR, Bataller, R orcid:0000-0002-1119-7799 , Botwin, G, Chalasani, NP, Cordell, HJ orcid:0000-0002-1879-5572 , Daly, AK orcid:0000-0002-7321-0629 et al (show 31 more authors) , Day, CP, Eyer, F orcid:0000-0002-4753-2747 , Foroud, T orcid:0000-0002-5549-2212 , Gleeson, D orcid:0000-0001-8714-2367 , Goldman, D orcid:0000-0002-1724-5405 , Haber, PS, Jacquet, JM, Liang, T, Liangpunsakul, S, Masson, S orcid:0000-0003-1041-9844 , Mathurin, P, Moirand, R orcid:0000-0002-5346-5755 , McQuillin, A, Moreno, C, Morgan, MY, Mueller, S, Müllhaupt, B orcid:0000-0002-9020-8192 , Nagy, LE orcid:0000-0002-0580-2809 , Nahon, P orcid:0000-0003-2489-0768 , Nalpas, B, Naveau, S, Perney, P, Pirmohamed, M orcid:0000-0002-7534-7266 , Seitz, HK, Soyka, M, Stickel, F, Thompson, A orcid:0000-0002-7087-9415 , Thursz, MR orcid:0000-0002-8218-192X , Trépo, E, Morgan, TR and Seth, D (2022) A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers Journal of Hepatology, 76 (2). pp. 275-282. ISSN 0168-8278, 1600-0641 |