22 March 2022 In Liver Disease
No abstract available

Erratum for

  • A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers.
    Whitfield JB, Schwantes-An TH, Darlay R, Aithal GP, Atkinson SR, Bataller R, Botwin G, Chalasani NP, Cordell HJ, Daly AK, Day CP, Eyer F, Foroud T, Gleeson D, Goldman D, Haber PS, Jacquet JM, Liang T, Liangpunsakul S, Masson S, Mathurin P, Moirand R, McQuillin A, Moreno C, Morgan MY, Mueller S, Müllhaupt B, Nagy LE, Nahon P, Nalpas B, Naveau S, Perney P, Pirmohamed M, Seitz HK, Soyka M, Stickel F, Thompson A, Thursz MR, Trépo E, Morgan TR, Seth D; GenomALC Consortium.J Hepatol. 2022 Feb;76(2):275-282. doi: 10.1016/j.jhep.2021.10.005. Epub 2021 Oct 14.PMID: 34656649
22 March 2022 In Liver Disease

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 chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

26 January 2022 In Liver Disease

The diagnosis of metabolic-associated fatty liver disease is based on the detection of liver steatosis together with the presence of metabolic dysfunction. According to this new definition, the diagnosis of metabolic-associated fatty liver disease is independent of the amount of alcohol consumed.

Actually, alcohol and its metabolites have various effects on metabolic-associated abnormalities during the process of alcohol metabolism. Studies have shown improved metabolic function in light to moderate alcohol drinkers. There are several studies focusing on the role of light to moderate alcohol intake on metabolic dysfunction.

However, the results from studies are diverse, and the conclusions are often controversial. This review systematically discusses the effects of alcohol consumption, focusing on light to moderate alcohol consumption, obesity, lipid and glucose metabolism, and blood pressure.

26 January 2022 In Liver Disease

OBJECTIVES: Liver disease is a leading cause of premature death, partly driven by the increasing incidence of non-alcohol-related fatty liver disease (NAFLD). Many people with a diagnosis of NAFLD drink moderate amounts of alcohol. There is limited guidance for clinicians looking to advise these patients on the effect this will have on their liver disease progression. This review synthesises the evidence on moderate alcohol consumption and its potential to predict liver disease progression in people with diagnosed NAFLD.

METHODS: A systematic review of longitudinal observational cohort studies was conducted. Databases (Medline, Embase, The Cochrane Library and ClinicalTrials.gov) were searched up to September 2020. Studies were included that reported progression of liver disease in adults with NAFLD, looking at moderate levels of alcohol consumption as the exposure of interest. Risk of bias was assessed using the Quality in Prognostic factor Studies tool.

RESULTS: Of 4578 unique citations, 6 met the inclusion criteria. Pooling of data was not possible due to heterogeneity and studies were analysed using narrative synthesis. Evidence suggested that any level of alcohol consumption is associated with worsening of liver outcomes in NAFLD, even for drinking within recommended limits. Well conducted population based studies estimated up to a doubling of incident liver disease outcomes in patients with NAFLD drinking at moderate levels.

CONCLUSIONS: This review found that any level of alcohol intake in NAFLD may be harmful to liver health.Study heterogeneity in definitions of alcohol exposure as well as in outcomes limited quantitative pooling of results. Use of standardised definitions for exposure and outcomes would support future meta-analysis.Based on this synthesis of the most up to date longitudinal evidence, clinicians seeing patients with NAFLD should currently advise abstinence from alcohol.

PROSPERO REGISTRATION NUMBER: The protocol was registered with PROSPERO (#CRD42020168022).

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