John B Whitfield1, Steven Masson2, Suthat Liangpunsakul3, Sebastian Mueller4, Guruprasad P Aithal5, Florian Eyer6, Dermot Gleeson7, Andrew Thompson8, Felix Stickel9, Michael Soyka10,11, Beat Muellhaupt9, Ann K Daly2, Heather J Cordell12, Tatiana Foroud13, Lawrence Lumeng3,14, Munir Pirmohamed8, Bertrand Nalpas15,16, Jean-Marc Jacquet15, Romain Moirand17, Pierre Nahon18,19,20, Sylvie Naveau21, Pascal Perney22, Paul S Haber23,24, Helmut K Seitz4, Christopher P Day25, Philippe Mathurin26, Timothy R Morgan27,28, Devanshi Seth23,24,29. 1. Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia. 2. Faculty of Medical Sciences, Newcastle University Medical School, Newcastle upon Tyne, United Kingdom. 3. Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA. 4. Department of Internal Medicine, Salem Medical Center and Center for Alcohol Research, University of Heidelberg, Heidelberg, Germany. 5. NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals and the University of Nottingham, Nottingham, United Kingdom. 6. Division of Clinical Toxicology, Department of Internal Medicine 2, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany. 7. The Clinical Research Facility, Royal Hallamshire Hospital, Sheffield, United Kingdom. 8. MRC Centre for Drug Safety Science, University of Liverpool, Liverpool; and Liverpool Centre for Alcohol Research, University of Liverpool, Liverpool, United Kingdom. 9. Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland. 10. Psychiatric Hospital University of Munich, Munich, Germany. 11. Privatklinik Meiringen, Meiringen, Switzerland. 12. Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom. 13. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA. 14. Deceased: Dr. Lumeng died on June 21, 2017. 15. Service Addictologie, CHRU Caremeau, Nîmes, France. 16. DISC, INSERM, Paris, France. 17. Univ Rennes, INRA, INSERM, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), Rennes, France. 18. APHP, Liver Unit, Hospital Jean Verdier, Bondy, France. 19. University Paris 13, Bobigny, France. 20. INSERM U1162 "Functional Genomics of Solid Tumors," Paris, France. 21. Hôpital Antoine-Béclère, Clamart, France. 22. Hôpital Universitaire Carémeau, Nîmes, France. 23. Drug Health Services, Royal Prince Alfred Hospital, Camperdown, Australia. 24. Faculty of Medicine and Health, The University of Sydney, Sydney, Australia. 25. Newcastle University, Newcastle upon Tyne, United Kingdom. 26. CHRU de Lille, Hôpital Claude Huriez, Lille Cedex, France. 27. Department of Veterans Affairs, VA Long Beach Healthcare System, Long Beach, California, USA. 28. Department of Medicine, University of California, Irvine, USA. 29. Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, Sydney, Australia.
Abstract
INTRODUCTION: Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. METHODS: We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. RESULTS: The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10-18) and higher premorbid body mass index (26.37 ± 0.16 kg/m2) than controls (24.44 ± 0.18 kg/m2, P = 5.77 × 10-15). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. DISCUSSION: If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.
INTRODUCTION: Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. METHODS: We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. RESULTS: The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10-18) and higher premorbid body mass index (26.37 ± 0.16 kg/m2) than controls (24.44 ± 0.18 kg/m2, P = 5.77 × 10-15). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. DISCUSSION: If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.
Authors: Augustin G L Vannier; Vladislav Fomin; Raymond T Chung; Suraj J Patel; Esperance Schaefer; Russell P Goodman; Jay Luther Journal: Gastro Hep Adv Date: 2022-03-30
Authors: John B Whitfield; Tae-Hwi Schwantes-An; Rebecca Darlay; Guruprasad P Aithal; Stephen R Atkinson; Ramon Bataller; Greg Botwin; Naga P Chalasani; Heather J Cordell; Ann K Daly; Christopher P Day; Florian Eyer; Tatiana Foroud; Dermot Gleeson; David Goldman; Paul S Haber; Jean-Marc Jacquet; Tiebing Liang; Suthat Liangpunsakul; Steven Masson; Philippe Mathurin; Romain Moirand; Andrew McQuillin; Christophe Moreno; Marsha Y Morgan; Sebastian Mueller; Beat Müllhaupt; Laura E Nagy; Pierre Nahon; Bertrand Nalpas; Sylvie Naveau; Pascal Perney; Munir Pirmohamed; Helmut K Seitz; Michael Soyka; Felix Stickel; Andrew Thompson; Mark R Thursz; Eric Trépo; Timothy R Morgan; Devanshi Seth Journal: J Hepatol Date: 2021-10-14 Impact factor: 30.083
Authors: Mario R Álvares-da-Silva; Claudia P Oliveira; Andrew Fagan; Larisse Longo; Rutiane U Thoen; Patricia M Yoshimura Zitelli; Renee M Tanaka Ferreira; Sara Mcgeorge; Amirhossein Shamsaddini; Alberto Q Farias; Masoumeh Sikaroodi; Patrick M Gillevet; Jasmohan S Bajaj Journal: Clin Gastroenterol Hepatol Date: 2021-04-02 Impact factor: 11.382