Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement.
Journal
Nature reviews. Gastroenterology & hepatology
ISSN: 1759-5053
Titre abrégé: Nat Rev Gastroenterol Hepatol
Pays: England
ID NLM: 101500079
Informations de publication
Date de publication:
07 Jun 2024
07 Jun 2024
Historique:
accepted:
22
04
2024
medline:
8
6
2024
pubmed:
8
6
2024
entrez:
7
6
2024
Statut:
aheadofprint
Résumé
Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions.
Identifiants
pubmed: 38849555
doi: 10.1038/s41575-024-00936-x
pii: 10.1038/s41575-024-00936-x
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. Springer Nature Limited.
Références
Rehm, J. & Shield, K. D. Global Burden of Alcohol Use Disorders and Alcohol Liver Disease. MDPI https://www.mdpi.com/2227-9059/7/4/99 (2019).
Chen, C. M. & Yoon, Y.-H. Surveillance Report #118 Liver Cirrhosis Mortality in the United States: National, State, and Regional Trends, 2000–2019. NIH https://www.niaaa.nih.gov/publications/surveillance-reports/surveillance118#:~:Text=Cirrhosis%20Mortality%20Trends,12.2%20deaths%20per%20100%2C000%20population (2022).
National Institute on Alcohol Abuse and Alcoholism. a. What is Heavy Drinking? NIH https://www.niaaa.nih.gov/health-professionals-communities/core-resource-on-alcohol/basics-defining-how-much-alcohol-too-much#pub-toc4 (2023).
World Health Organization. International Guide for Monitoring Alcohol Consumption and Related Harm (World Health Organization, 2000).
DiMartini, A., Weinrieb, R., Lane, T., Day, N. & Fung, J. Defining the alcoholic liver transplant population: implications for future research. Liver Transpl. 7, 428–431 (2001).
pubmed: 11349263
doi: 10.1053/jlts.2001.23915
Dawson, D. A., Li, T. K. & Grant, B. F. A prospective study of risk drinking: at risk for what? Drug Alcohol Depend. 95, 62–72 (2008).
pubmed: 18243584
pmcid: 2366117
doi: 10.1016/j.drugalcdep.2007.12.007
Singal, A. K., Leggio, L. & DiMartini, A. Alcohol use disorder in alcohol-associated liver disease: two sides of the same coin. Liver Transpl. 30, 200–212 (2023).
pubmed: 37934047
doi: 10.1097/LVT.0000000000000296
Louvet, A. et al. Low alcohol consumption influences outcomes in individuals with alcohol-related compensated cirrhosis in a French multicenter cohort. J. Hepatol. 78, 501–512 (2023).
pubmed: 36423805
doi: 10.1016/j.jhep.2022.11.013
Hofer, B. S. et al. Alcohol abstinence improves prognosis across all stages of portal hypertension in alcohol-related cirrhosis. Clin. Gastroenterol. Hepatol. 21, 2308–2317.e7 (2023).
pubmed: 36481475
doi: 10.1016/j.cgh.2022.11.033
Lackner, C. et al. Histological parameters and alcohol abstinence determine long-term prognosis in patients with alcoholic liver disease. J. Hepatol. 66, 610–618 (2017).
pubmed: 27894795
doi: 10.1016/j.jhep.2016.11.011
Mellinger, J., Winder, G. S. & Fernandez, A. C. Measuring the alcohol in alcohol-associated liver disease: choices and challenges for clinical research. Hepatology 73, 1207–1212 (2021).
pubmed: 32886409
doi: 10.1002/hep.31539
Singal, A. K. et al. Research methodologies to address clinical unmet needs and challenges in alcohol-associated liver disease. Hepatology 75, 1026–1037 (2022).
pubmed: 34496071
doi: 10.1002/hep.32143
Institute of Medicine (US) Committee to Improve the National Institutes of Health Consensus Development Program. Consensus Development at the NIH: Improving the Program 1st edn (National Academies Press, 1990).
Bellentani, S. et al. Drinking habits as cofactors of risk for alcohol induced liver damage. the Dionysos Study Group. Gut 41, 845–850 (1997).
pubmed: 9462221
pmcid: 1891602
doi: 10.1136/gut.41.6.845
Knox, J. et al. Reduction in nonabstinent WHO drinking risk levels and change in risk for liver disease and positive AUDIT-C scores: prospective 3-year follow-up results in the U.S. general population. Alcohol Clin. Exp. Res. 42, 2256–2265 (2018).
pubmed: 30204248
pmcid: 6263142
doi: 10.1111/acer.13884
Witkiewitz, K. et al. Drinking risk level reductions associated with improvements in physical health and quality of life among individuals with alcohol use disorder. Alcohol Clin. Exp. Res. 42, 2453–2465 (2018).
pubmed: 30395350
pmcid: 6286196
doi: 10.1111/acer.13897
American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders 5th edn (American Psychiatric Publishing, 2013).
World Health Organization. International Classification of Diseases 11th edn (World Health Organization, 2019).
Hasin, D. S. et al. DSM-5 criteria for substance use disorders: recommendations and rationale. Am. J. Psychiatry 170, 834–851 (2013).
pubmed: 23903334
pmcid: 3767415
doi: 10.1176/appi.ajp.2013.12060782
Lundin, A. et al. Towards ICD-11 for alcohol dependence: diagnostic agreement with ICD-10, DSM-5, DSM-IV, DSM-III-R and DSM-III diagnoses in a Swedish general population of women. Drug Alcohol Depend. 227, 108925 (2021).
pubmed: 34358771
doi: 10.1016/j.drugalcdep.2021.108925
Slade, T. et al. DSM-5 and ICD-11 alcohol use disorder criteria in young adult regular drinkers: lifetime prevalence and age of onset. Drug Alcohol Depend. 229, 109184 (2021).
pubmed: 34813987
doi: 10.1016/j.drugalcdep.2021.109184
Scherrer, B. et al. Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: a meta-regression analysis to develop an enrichment strategy. Alcohol Clin. Exp. Res. 45, 1722–1734 (2021).
pubmed: 34418121
pmcid: 9291112
doi: 10.1111/acer.14670
Aberg, F. et al. Combined effects of alcohol and metabolic disorders in patients with chronic liver disease. Clin. Gastroenterol. Hepatol. 18, 995–997.e2 (2020).
pubmed: 31255807
doi: 10.1016/j.cgh.2019.06.036
Aberg, F., Byrne, C. D., Pirola, C. J., Mannisto, V. & Sookoian, S. Alcohol consumption and metabolic syndrome: clinical and epidemiological impact on liver disease. J. Hepatol. 78, 191–206 (2023).
pubmed: 36063967
doi: 10.1016/j.jhep.2022.08.030
Israelsen, M. et al. Metabolic and genetic risk factors are the strongest predictors of severity of alcohol-related liver fibrosis. Clin. Gastroenterol. Hepatol. 20, 1784–1794.e9 (2022).
pubmed: 33279778
doi: 10.1016/j.cgh.2020.11.038
Rinella, M. E. et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Hepatology 78, 1966–1986 (2023).
pubmed: 37363821
doi: 10.1097/HEP.0000000000000520
Chalasani, N. et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 55, 2005–2023 (2012).
pubmed: 22488764
doi: 10.1002/hep.25762
Chalasani, N. et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology 67, 328–357 (2018).
pubmed: 28714183
doi: 10.1002/hep.29367
Rehm, J. et al. Alcohol as a risk factor for liver cirrhosis: a systematic review and meta-analysis. Drug Alcohol Rev. 29, 437–445 (2010).
pubmed: 20636661
doi: 10.1111/j.1465-3362.2009.00153.x
Lee, B. P., Dodge, J. L. & Terrault, N. A. National prevalence estimates for steatotic liver disease and sub-classifications using consensus nomenclature. Hepatology 79, 666–673 (2023).
pubmed: 37732946
doi: 10.1097/HEP.0000000000000604
Crabb, D. W., Im, G. Y., Szabo, G., Mellinger, J. L. & Lucey, M. R. Diagnosis and treatment of alcohol-associated liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology 71, 306–333 (2020).
pubmed: 31314133
doi: 10.1002/hep.30866
Thiele, M. et al. Transient and 2-dimensional shear-wave elastography provide comparable assessment of alcoholic liver fibrosis and cirrhosis. Gastroenterology 150, 123–133 (2016).
pubmed: 26435270
doi: 10.1053/j.gastro.2015.09.040
Nguyen-Khac, E. et al. Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis. Lancet Gastroenterol. Hepatol. 3, 614–625 (2018).
pubmed: 29983372
doi: 10.1016/S2468-1253(18)30124-9
Pavlov, C. S. et al. Transient elastography for diagnosis of stages of hepatic fibrosis and cirrhosis in people with alcoholic liver disease. Cochrane Database Syst. Rev. 1, CD010542 (2015).
pubmed: 25612182
Trabut, J. B. et al. Rapid decline of liver stiffness following alcohol withdrawal in heavy drinkers. Alcohol Clin. Exp. Res. 36, 1407–1411 (2012).
pubmed: 22404692
doi: 10.1111/j.1530-0277.2012.01737.x
de Franchis, R. et al. Baveno VII — renewing consensus in portal hypertension. J. Hepatol. 76, 959–974 (2022).
pubmed: 35120736
doi: 10.1016/j.jhep.2021.12.022
de Franchis, R. & Baveno, V. I. F. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J. Hepatol. 63, 743–752 (2015).
pubmed: 26047908
doi: 10.1016/j.jhep.2015.05.022
Thiele, M. et al. Accuracy of the enhanced liver fibrosis test vs fibrotest, elastography, and indirect markers in detection of advanced fibrosis in patients with alcoholic liver disease. Gastroenterology 154, 1369–1379 (2018).
pubmed: 29317276
doi: 10.1053/j.gastro.2018.01.005
Papatheodoridi, M. et al. Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease. J. Hepatol. 74, 1109–1116 (2021).
pubmed: 33307138
doi: 10.1016/j.jhep.2020.11.050
Crabb, D. W. et al. Standard definitions and common data elements for clinical trials in patients with alcoholic hepatitis: recommendation from the NIAAA alcoholic hepatitis consortia. Gastroenterology 150, 785–790 (2016).
pubmed: 26921783
doi: 10.1053/j.gastro.2016.02.042
Kilian, C. et al. Stigmatization of people with alcohol use disorders: an updated systematic review of population studies. Alcohol Clin. Exp. Res. 45, 899–911 (2021).
pubmed: 33970504
doi: 10.1111/acer.14598
Schomerus, G. et al. The stigma of alcohol-related liver disease and its impact on healthcare. J. Hepatol. 77, 516–524 (2022).
pubmed: 35526787
doi: 10.1016/j.jhep.2022.04.026
Ashford, R. D., Brown, A. M. & Curtis, B. Substance use, recovery, and linguistics: the impact of word choice on explicit and implicit bias. Drug Alcohol Depend. 189, 131–138 (2018).
pubmed: 29913324
pmcid: 6330014
doi: 10.1016/j.drugalcdep.2018.05.005
Grant, B. F. et al. Epidemiology of DSM-5 alcohol use disorder: results from the National Epidemiologic Survey on alcohol and related conditions III. JAMA Psychiatry 72, 757–766 (2015).
pubmed: 26039070
pmcid: 5240584
doi: 10.1001/jamapsychiatry.2015.0584
DiMartini, A. F., Leggio, L. & Singal, A. K. Barriers to the management of alcohol use disorder and alcohol-associated liver disease: strategies to implement integrated care models. Lancet Gastroenterol. Hepatol. 7, 186–195 (2022).
pubmed: 35026172
doi: 10.1016/S2468-1253(21)00191-6
Link, B. G. & Phelan, J. C. Conceptualizing stigma. Annu. Rev. Sociol. 27, 363–385 (2001).
doi: 10.1146/annurev.soc.27.1.363
Stangl, A. L. et al. The Health Stigma and Discrimination Framework: a global, crosscutting framework to inform research, intervention development, and policy on health-related stigmas. BMC Med. 17, 31 (2019).
pubmed: 30764826
pmcid: 6376797
doi: 10.1186/s12916-019-1271-3
Smith, L. R., Earnshaw, V. A., Copenhaver, M. M. & Cunningham, C. O. Substance use stigma: reliability and validity of a theory-based scale for substance-using populations. Drug Alcohol Depend. 162, 34–43 (2016).
pubmed: 26972790
pmcid: 5293183
doi: 10.1016/j.drugalcdep.2016.02.019
American Association for the Study of Liver Disease, European Association for the Study of the Liver, Latin American Association for the Study of the Liver & Asian Pacific Association for the Study of the Liver. Ending stigmatizing language in alcohol and liver disease: a liver societies’ statement†. Hepatology 78, 1682–1683 (2023).
National Institute on Alcohol Abuse and Alcoholism. Stigma: Overcoming a Pervasive Barrier to Optimum Care. NIH https://www.niaaa.nih.gov/health-professionals-communities/core-resource-on-alcohol/basics-defining-how-much-alcohol-too-much#pub-toc4 (2023).
Zhao, L., Tian, L., Cai, T., Claggett, B. & Wei, L. J. Effectively selecting a target population for a future comparative study. J. Am. Stat. Assoc. 108, 527–539 (2013).
pubmed: 24058223
pmcid: 3775385
doi: 10.1080/01621459.2013.770705
Karriker-Jaffe, K. J., Chartier, K. G., Bares, C. B., Kendler, K. S. & Greenfield, T. K. Intersection of familial risk and environmental social control on high-risk drinking and alcohol dependence in a US national sample of adults. Addict. Behav. 113, 106668 (2021).
pubmed: 33045642
doi: 10.1016/j.addbeh.2020.106668
Kezer, C. A., Simonetto, D. A. & Shah, V. H. Sex differences in alcohol consumption and alcohol-associated liver disease. Mayo Clin. Proc. 96, 1006–1016 (2021).
pubmed: 33714602
doi: 10.1016/j.mayocp.2020.08.020
Vaeth, P. A., Wang-Schweig, M. & Caetano, R. Drinking, alcohol use disorder, and treatment access and utilization among U.S. racial/ethnic groups. Alcohol Clin. Exp. Res. 41, 6–19 (2017).
pubmed: 28019654
doi: 10.1111/acer.13285
Moreno, C., Mueller, S. & Szabo, G. Non-invasive diagnosis and biomarkers in alcohol-related liver disease. J. Hepatol. 70, 273–283 (2019).
pubmed: 30658728
doi: 10.1016/j.jhep.2018.11.025
Witkiewitz, K., Finney, J. W., Harris, A. H., Kivlahan, D. R. & Kranzler, H. R. Recommendations for the design and analysis of treatment trials for alcohol use disorders. Alcohol Clin. Exp. Res. 39, 1557–1570 (2015).
pubmed: 26250333
pmcid: 4558228
doi: 10.1111/acer.12800
Koenig, L. B., Jacob, T. & Haber, J. R. Validity of the lifetime drinking history: a comparison of retrospective and prospective quantity–frequency measures. J. Stud. Alcohol Drugs 70, 296–303 (2009).
pubmed: 19261242
pmcid: 2653615
doi: 10.15288/jsad.2009.70.296
Longnecker, M. P. et al. The reliability of self-reported alcohol consumption in the remote past. Epidemiology 3, 535–539 (1992).
pubmed: 1420522
doi: 10.1097/00001648-199211000-00014
Jayasekara, H. et al. Alcohol consumption for different periods in life, intake pattern over time and all-cause mortality. J. Public Health 37, 625–633 (2015).
Litten, R. Z. & Fertig, J. Self-report and biochemical measures of alcohol consumption. Addiction 98, iii–iv (2003).
pubmed: 14984236
doi: 10.1046/j.1359-6357.2003.00580.x
Litten, R. Z., Bradley, A. M. & Moss, H. B. Alcohol biomarkers in applied settings: recent advances and future research opportunities. Alcohol Clin. Exp. Res. 34, 955–967 (2010).
pubmed: 20374219
doi: 10.1111/j.1530-0277.2010.01170.x
Dettling, A. et al. Ethanol elimination rates in men and women in consideration of the calculated liver weight. Alcohol 41, 415–420 (2007).
pubmed: 17936510
doi: 10.1016/j.alcohol.2007.05.003
Ulwelling, W. & Smith, K. The PEth blood test in the security environment: what it is; why it is important; and interpretative guidelines. J. Forensic Sci. 63, 1634–1640 (2018).
pubmed: 30005144
doi: 10.1111/1556-4029.13874
Helander, A. & Hansson, T. The alcohol biomarker phosphatidylethanol (PEth) — test performance and experiences from routine analysis and external quality assessment. Scand. J. Clin. Lab. Invest. 83, 424–431 (2023).
pubmed: 37697976
doi: 10.1080/00365513.2023.2253734
DiMartini, A. et al. Carbohydrate deficient transferrin in abstaining patients with end-stage liver disease. Alcohol Clin. Exp. Res. 25, 1729–1733 (2001).
pubmed: 11781505
pmcid: 4700931
Morgan, M., Sharma, M. & Atkinson, S. Genetic and environmental susceptibility to alcoholic hepatitis. Clin. Liver Dis. 25, 517–535 (2021).
pubmed: 34229837
doi: 10.1016/j.cld.2021.04.001
Liangpunsakul, S., Haber, P. & McCaughan, G. W. Alcoholic liver disease in Asia, Europe, and North America. Gastroenterology 150, 1786–1797 (2016).
pubmed: 26924091
doi: 10.1053/j.gastro.2016.02.043
Schnabl, B. et al. Liver specific, systemic and genetic contributors to alcohol-related liver disease progression. J. Gastroenterol. 60, 36–44 (2022).
Liangpunsakul, S. et al. Interaction between the patatin-like phospholipase domain-containing protein 3 genotype and coffee drinking and the risk for acute alcoholic hepatitis. Hepatol. Commun. 2, 29–34 (2017).
pubmed: 29404510
pmcid: 5776869
doi: 10.1002/hep4.1123
Ajoolabady, A., Aslkhodapasandhokmabad, H., Zhou, Y. & Ren, J. Epigenetic modification in alcohol-related liver diseases. Med. Res. Rev. 42, 1463–1491 (2022).
pubmed: 35187693
doi: 10.1002/med.21881
Degre, D. et al. Long-term outcomes in patients with decompensated alcohol-related liver disease, steatohepatitis and Maddrey’s discriminant function < 32. J. Hepatol. 72, 636–642 (2020).
pubmed: 31954208
doi: 10.1016/j.jhep.2019.12.023
Moon, A. M., Yang, J. Y., Barritt, A. S. T., Bataller, R. & Peery, A. F. Rising mortality from alcohol-associated liver disease in the United States in the 21st century. Am. J. Gastroenterol. 115, 79–87 (2020).
pubmed: 31688021
doi: 10.14309/ajg.0000000000000442
Israelsen, M. et al. Validation of the new nomenclature of steatotic liver disease in patients with a history of excessive alcohol intake: an analysis of data from a prospective cohort study. Lancet Gastroenterol. Hepatol. 9, 218–228 (2024).
pubmed: 38218202
doi: 10.1016/S2468-1253(23)00443-0
Dam-Larsen, S. et al. Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut 53, 750–755 (2004).
pubmed: 15082596
pmcid: 1774026
doi: 10.1136/gut.2003.019984
Moreau, R. et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 144, 1426–1437.e1–9 (2013).
pubmed: 23474284
doi: 10.1053/j.gastro.2013.02.042
Bajaj, J. S. et al. Second infections independently increase mortality in hospitalized patients with cirrhosis: the North American Consortium for the Study of End-Stage Liver Disease (NACSELD) experience. Hepatology 56, 2328–2335 (2012).
pubmed: 22806618
doi: 10.1002/hep.25947
Vergis, N. et al. In patients with severe alcoholic hepatitis, prednisolone increases susceptibility to infection and infection-related mortality, and is associated with high circulating levels of bacterial DNA. Gastroenterology 152, 1068–1077.e4 (2017).
pubmed: 28043903
doi: 10.1053/j.gastro.2016.12.019
Louvet, A. et al. Infection in patients with severe alcoholic hepatitis treated with steroids: early response to therapy is the key factor. Gastroenterology 137, 541–548 (2009).
pubmed: 19445945
doi: 10.1053/j.gastro.2009.04.062
Szabo, G. et al. IL-1 receptor antagonist plus pentoxifylline and zinc for severe alcohol-associated hepatitis. Hepatology 76, 1058–1068 (2022).
pubmed: 35340032
doi: 10.1002/hep.32478
Gawrieh, S. et al. Randomized-controlled trial of anakinra plus zinc vs. prednisone for severe alcohol-associated hepatitis. J. Hepatol. 80, 684–693 (2024).
pubmed: 38342441
doi: 10.1016/j.jhep.2024.01.031
Carlson, R. W. et al. Alcohol withdrawal syndrome. Crit. Care Clin. 28, 549–585 (2012).
pubmed: 22998991
doi: 10.1016/j.ccc.2012.07.004
Rasmussen, D. N. et al. Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease. J. Hepatol. 75, 1017–1025 (2021).
pubmed: 34118335
pmcid: 8522804
doi: 10.1016/j.jhep.2021.05.037
Labenz, C. et al. Health-related quality of life in patients with compensated and decompensated liver cirrhosis. Eur. J. Intern. Med. 70, 54–59 (2019).
pubmed: 31530418
doi: 10.1016/j.ejim.2019.09.004
Mellinger, J. L. et al. The high burden of alcoholic cirrhosis in privately insured persons in the United States. Hepatology 68, 872–882 (2018).
pubmed: 29579356
doi: 10.1002/hep.29887
Pocock, S., Ariti, C., Collier, T. & Wang, D. The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities. Eur. Heart J. 33, 176–182 (2012).
pubmed: 21900289
doi: 10.1093/eurheartj/ehr352
Perez, F. et al. Desirability of outcome ranking for the management of antimicrobial therapy (DOOR MAT) reveals improvements in the treatment of bloodstream infections caused by Escherichia coli and Klebsiella pneumoniae in patients from the Veterans Health Administration. Clin. Infect. Dis. 73, 1231–1238 (2021).
pubmed: 33978146
pmcid: 8492112
doi: 10.1093/cid/ciab384
Louvet, A. et al. Main drivers of outcome differ between short term and long term in severe alcoholic hepatitis: a prospective study. Hepatology 66, 1464–1473 (2017).
pubmed: 28459138
doi: 10.1002/hep.29240
Lee, B. P., Vittinghoff, E., Dodge, J. L., Cullaro, G. & Terrault, N. A. National trends and long-term outcomes of liver transplant for alcohol-associated liver disease in the United States. JAMA Intern. Med. 179, 340–348 (2019).
pubmed: 30667468
pmcid: 6439700
doi: 10.1001/jamainternmed.2018.6536
Asrani, S. K. et al. Meeting report: the Dallas Consensus Conference on liver transplantation for alcohol associated hepatitis. Liver Transpl. 26, 127–140 (2020).
pubmed: 31743578
pmcid: 8151800
doi: 10.1002/lt.25681
European Association for the Study of the Liver. EASL clinical practice guidelines: management of alcohol-related liver disease. J. Hepatol. 69, 154–181 (2018).
Arab, J. P. et al. Alcohol-related liver disease: clinical practice guidelines by the Latin American Association for the Study of the Liver (ALEH). Ann. Hepatol. 18, 518–535 (2019).
pubmed: 31053546
doi: 10.1016/j.aohep.2019.04.005
Sobell, L. C. & Sobell, M. B. Measuring Alcohol Consumption: Psychosocial and Biochemical Methods 41–72 (Humana Press/Springer Nature, 1992).
Collins, R. L., Parks, G. A. & Marlatt, G. A. Social determinants of alcohol consumption: the effects of social interaction and model status on the self-administration of alcohol. J. Consult. Clin. Psychol. 53, 189–200 (1985).
pubmed: 3998247
doi: 10.1037/0022-006X.53.2.189
Saunders, J. B., Aasland, O. G., Babor, T. F., de la Fuente, J. R. & Grant, M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption — II. Addiction https://doi.org/10.1111/j.1360-0443.1993.tb02093.x (1993).
Wu, T. et al. Smartphone sensor data estimate alcohol craving in a cohort of patients with alcohol-associated liver disease and alcohol use disorder. Hepatol. Commun. 7, e0329 (2023).
pubmed: 38055637
pmcid: 10984664
doi: 10.1097/HC9.0000000000000329
Pelkonen, O. & Sotaniemi, E. Drug metabolism in alcoholics. Pharmacol. Ther. 16, 261–268 (1982).
pubmed: 6752978
doi: 10.1016/0163-7258(82)90057-2
Moore, A., Whiteman, E. & Ward, K. Risks of combined alcohol/medication use in older adults. Am. J. Geriatr. Pharmacother. 5, 64–74 (2007).
pubmed: 17608249
pmcid: 4063202
doi: 10.1016/j.amjopharm.2007.03.006
Pena, M., Horga, J. & Zapater, P. Variations of pharmacokinetics of drugs in patients with cirrhosis. Expert Rev. Clin. Pharmacol. 9, 441–458 (2016).
pubmed: 26696448
doi: 10.1586/17512433.2016.1135733
Ting, P. S., Wheatley, J. & Chen, P. H. Behavioral treatment for patients with alcohol-related liver disease: a primer for hepatologists. Clin. Liver Dis. 15, 31–35 (2020).
doi: 10.1002/cld.854
Hemrage, S., Brobbin, E., Deluca, P. & Drummond, C. Efficacy of psychosocial interventions to reduce alcohol use in comorbid alcohol use disorder and alcohol-related liver disease: a systematic review of randomized controlled trials. Alcohol Alcohol. 58, 478–484 (2023).
pubmed: 37530582
pmcid: 10493519
doi: 10.1093/alcalc/agad051
DeMartini, K. S. et al. Text messaging to reduce alcohol relapse in prelisting liver transplant candidates: a pilot feasibility study. Alcohol Clin. Exp. Res. 42, 761–769 (2018).
pubmed: 29498753
pmcid: 6438371
doi: 10.1111/acer.13603
Suffoletto, B. & Scaglione, S. Using digital interventions to support individuals with alcohol use disorder and advanced liver disease: a bridge over troubled waters. Alcohol Clin. Exp. Res. 42, 1160–1165 (2018).
pubmed: 29750368
pmcid: 6028285
doi: 10.1111/acer.13771
Magill, M. et al. A meta-analysis of motivational interviewing process: technical, relational, and conditional process models of change. J. Consult. Clin. Psychol. 86, 140–157 (2018).
pubmed: 29265832
doi: 10.1037/ccp0000250
Magill, M. et al. Do what you say and say what you are going to do: a preliminary meta-analysis of client change and sustain talk subtypes in motivational interviewing. Psychother. Res. 29, 860–869 (2018).
pubmed: 29954290
pmcid: 6310665
doi: 10.1080/10503307.2018.1490973
McCrady, B. S., Owens, M. D., Borders, A. Z. & Brovko, J. M. Psychosocial approaches to alcohol use disorders since 1940: a review. J. Stud. Alcohol Drugs Suppl. 75, 68–78 (2014).
pubmed: 24565313
doi: 10.15288/jsads.2014.75.68
Miller, W. R. & Rose, G. S. Toward a theory of motivational interviewing. Am. Psychol. 64, 527–537 (2009).
pubmed: 19739882
pmcid: 2759607
doi: 10.1037/a0016830
Dieperink, E. et al. Efficacy of motivational enhancement therapy on alcohol use disorders in patients with chronic hepatitis C: a randomized controlled trial. Addiction 109, 1869–1877 (2014).
pubmed: 25040898
doi: 10.1111/add.12679
Magill, M. & Ray, L. A. Cognitive-behavioral treatment with adult alcohol and illicit drug users: a meta-analysis of randomized controlled trials. J. Stud. Alcohol Drugs 70, 516–527 (2009).
pubmed: 19515291
pmcid: 2696292
doi: 10.15288/jsad.2009.70.516
Ray, L. A. et al. Combined pharmacotherapy and cognitive behavioral therapy for adults with alcohol or substance use disorders: a systematic review and meta-analysis. JAMA Netw. Open 3, e208279 (2020).
pubmed: 32558914
pmcid: 7305524
doi: 10.1001/jamanetworkopen.2020.8279
Witkiewitz, K., Pfund, R. A. & Tucker, J. A. Mechanisms of behavior change in substance use disorder with and without formal treatment. Annu. Rev. Clin. Psychol. 18, 497–525 (2022).
pubmed: 35138868
doi: 10.1146/annurev-clinpsy-072720-014802
Witkiewitz, K., Litten, R. Z. & Leggio, L. Advances in the science and treatment of alcohol use disorder. Sci. Adv. 5, eaax4043 (2019).
pubmed: 31579824
pmcid: 6760932
doi: 10.1126/sciadv.aax4043
Mann, K., Aubin, H.-J. H.-J. & Witkiewitz, K. Reduced drinking in alcohol dependence treatment, what is the evidence? Eur. Addict. Res. 23, 219–230 (2017).
pubmed: 28934736
doi: 10.1159/000481348
Marlatt, G. A. & Witkiewitz, K. Harm reduction approaches to alcohol use: health promotion, prevention, and treatment. Addict. Behav. 27, 867–886 (2002).
pubmed: 12369473
doi: 10.1016/S0306-4603(02)00294-0
Hallgren, K. A. & Witkiewitz, K. Missing data in alcohol clinical trials: a comparison of methods. Alcohol Clin. Exp. Res. 37, 2152–2160 (2013).
pubmed: 23889334
pmcid: 4113114
doi: 10.1111/acer.12205
Bhatt, D. L. & Mehta, C. Adaptive designs for clinical trials. N. Engl. J. Med. 375, 65–74 (2016).
pubmed: 27406349
doi: 10.1056/NEJMra1510061
Chow, S. C. Adaptive clinical trial design. Annu. Rev. Med. 65, 405–415 (2014).
pubmed: 24422576
doi: 10.1146/annurev-med-092012-112310
Thorlund, K., Haggstrom, J., Park, J. J. & Mills, E. J. Key design considerations for adaptive clinical trials: a primer for clinicians. Br. Med. J. 360, k698 (2018).
doi: 10.1136/bmj.k698
Murphy, S. A. An experimental design for the development of adaptive treatment strategies. Stat. Med. 24, 1455–1481 (2005).
pubmed: 15586395
doi: 10.1002/sim.2022
Sola, E. et al. Endpoints and design of clinical trials in patients with decompensated cirrhosis: position paper of the LiverHope Consortium. J. Hepatol. 74, 200–219 (2021).
pubmed: 32896580
doi: 10.1016/j.jhep.2020.08.009
FDA. Guidance for Industry Pharmacokinetics in Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling. FDA https://www.fda.gov/media/71311/download (2003).
Sarin, S. K. et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol. Int. 13, 353–390 (2019).
pubmed: 31172417
doi: 10.1007/s12072-019-09946-3
O’Leary, J. G. et al. NACSELD Acute-on-Chronic Liver Failure (NACSELD-ACLF) score predicts 30-day survival in hospitalized patients with cirrhosis. Hepatology 67, 2367–2374 (2018).
pubmed: 29315693
doi: 10.1002/hep.29773
Singal, A. K. & Mathurin, P. Diagnosis and treatment of alcohol-associated liver disease: a review. JAMA 326, 165–176 (2021).
pubmed: 34255003
doi: 10.1001/jama.2021.7683
Szabo, G., Romics, L. Jr & Frendl, G. Liver in sepsis and systemic inflammatory response syndrome. Clin. Liver Dis. 6, 1045–1066 (2002).
pubmed: 12516206
doi: 10.1016/S1089-3261(02)00058-2
Mookerjee, R. P. et al. The role of liver biopsy in the diagnosis and prognosis of patients with acute deterioration of alcoholic cirrhosis. J. Hepatol. 55, 1103–1111 (2011).
pubmed: 21376092
doi: 10.1016/j.jhep.2011.02.021
Adebayo, D. & Wong, F. Pathophysiology of hepatorenal syndrome — acute kidney injury. Clin. Gastroenterol. Hepatol. 21, S1–S10 (2023).
pubmed: 37625861
doi: 10.1016/j.cgh.2023.04.034
Thursz, M., Kamath, P. S., Mathurin, P., Szabo, G. & Shah, V. H. Alcohol-related liver disease: areas of consensus, unmet needs and opportunities for further study. J. Hepatol. 70, 521–530 (2019).
pubmed: 30658117
doi: 10.1016/j.jhep.2018.10.041
Bataller, R., Arab, J. P. & Shah, V. H. Alcohol-associated hepatitis. N. Engl. J. Med. 387, 2436–2448 (2022).
pubmed: 36577100
doi: 10.1056/NEJMra2207599
Sarin, S. K. et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL). Hepatol. Int. 3, 269–282 (2009).
pubmed: 19669378
doi: 10.1007/s12072-008-9106-x
Welch, N. et al. Continued muscle loss increases mortality in cirrhosis: impact of aetiology of liver disease. Liver Int. 40, 1178–1188 (2020).
pubmed: 31889396
pmcid: 7195232
doi: 10.1111/liv.14358
Shi, X., DeLucia, A. L., Bao, J. & Zhang, P. Alcohol abuse and disorder of granulopoiesis. Pharmacol. Ther. 198, 206–219 (2019).
pubmed: 30831129
pmcid: 6536325
doi: 10.1016/j.pharmthera.2019.03.001
Silczuk, A. & Habrat, B. Alcohol-induced thrombocytopenia: current review. Alcohol 86, 9–16 (2020).
pubmed: 32330589
doi: 10.1016/j.alcohol.2020.02.166
Simou, E., Britton, J. & Leonardi-Bee, J. Alcohol and the risk of pneumonia: a systematic review and meta-analysis. BMJ Open. 8, e022344 (2018).
pubmed: 30135186
pmcid: 6112384
doi: 10.1136/bmjopen-2018-022344
Sanvisens, A. et al. Folate deficiency in patients seeking treatment of alcohol use disorder. Drug Alcohol Depend. 180, 417–422 (2017).
pubmed: 28988003
doi: 10.1016/j.drugalcdep.2017.08.039
McClain, C. J., Rios, C. D., Condon, S. & Marsano, L. S. Malnutrition and alcohol-associated hepatitis. Clin. Liver Dis. 25, 557–570 (2021).
pubmed: 34229839
pmcid: 8672300
doi: 10.1016/j.cld.2021.03.002
Larsson, S. C., Drca, N. & Wolk, A. Alcohol consumption and risk of atrial fibrillation: a prospective study and dose–response meta-analysis. J. Am. Coll. Cardiol. 64, 281–289 (2014).
pubmed: 25034065
doi: 10.1016/j.jacc.2014.03.048
Taylor, B. et al. Alcohol and hypertension: gender differences in dose–response relationships determined through systematic review and meta-analysis. Addiction 104, 1981–1990 (2009).
pubmed: 19804464
doi: 10.1111/j.1360-0443.2009.02694.x
Manthey, J., Probst, C., Rylett, M. & Rehm, J. National, regional and global mortality due to alcoholic cardiomyopathy in 2015. Heart 104, 1663–1669 (2018).
pubmed: 29535230
doi: 10.1136/heartjnl-2017-312384
Andersson, C., Schou, M., Gustafsson, F. & Torp-Pedersen, C. Alcohol intake in patients with cardiomyopathy and heart failure: consensus and controversy. Circ. Heart Fail. 15, e009459 (2022).
pubmed: 35593142
doi: 10.1161/CIRCHEARTFAILURE.121.009459
Kaul, R. et al. Alcohol and atrial fibrillation: a pathophysiologic perspective. Cardiol. Rev. 31, 177–184 (2023).
pubmed: 36398336
doi: 10.1097/CRD.0000000000000479
Puddey, I. B., Mori, T. A., Barden, A. E. & Beilin, L. J. Alcohol and hypertension — new insights and lingering controversies. Curr. Hypertens. Rep. 21, 79 (2019).
pubmed: 31494743
doi: 10.1007/s11906-019-0984-1
Lankisch, P. G., Apte, M. & Banks, P. A. Acute pancreatitis. Lancet 386, 85–96 (2015).
pubmed: 25616312
doi: 10.1016/S0140-6736(14)60649-8
Vanella, G., Archibugi, L., Stigliano, S. & Capurso, G. Alcohol and gastrointestinal cancers. Curr. Opin. Gastroenterol. 35, 107–113 (2019).
pubmed: 30550381
doi: 10.1097/MOG.0000000000000502
Hammoud, N. & Jimenez-Shahed, J. Chronic neurologic effects of alcohol. Clin. Liver Dis. 23, 141–155 (2019).
pubmed: 30454828
doi: 10.1016/j.cld.2018.09.010
Chalasani, N. et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 135, 1924–1934 (2008).
pubmed: 18955056
doi: 10.1053/j.gastro.2008.09.011
European Association for the Study of the Liver. EASL clinical practice guidelines: drug-induced liver injury. J. Hepatol. 70, 1222–1261 (2019).
doi: 10.1016/j.jhep.2019.02.014
Kamath, P. S. et al. A model to predict survival in patients with end-stage liver disease. Hepatology 33, 464–470 (2001).
pubmed: 11172350
doi: 10.1053/jhep.2001.22172
Jeong, R. et al. Model for end-stage liver disease score as a predictor of short-term outcome in patients with drug-induced liver injury. Scand. J. Gastroenterol. 50, 439–446 (2015).
pubmed: 25639449
doi: 10.3109/00365521.2014.958094
Schmidt, L. E. & Larsen, F. MELD score as a predictor of liver failure and death in patients with acetaminophen-induced liver injury. Hepatology 45, 789–796 (2007).
pubmed: 17326205
doi: 10.1002/hep.21503
Reuben, A., Koch, D. G., Lee, W. & the Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 52, 2065–2076 (2010).
pubmed: 20949552
doi: 10.1002/hep.23937
FDA. Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation. FDA https://www.fda.gov/media/116737/download (2009).
Nadim, M. K. & Garcia-Tsao, G. Acute kidney injury in patients with cirrhosis. N. Engl. J. Med. 388, 733–745 (2023).
pubmed: 36812435
doi: 10.1056/NEJMra2215289
Treem, W. R. et al. Consensus guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury during clinical trials in adults with chronic viral hepatitis and adults with cirrhosis secondary to hepatitis B, C and nonalcoholic steatohepatitis. Drug Saf. 44, 133–165 (2021).
pubmed: 33141341
doi: 10.1007/s40264-020-01014-2
Coates, S., Taubel, J. & Lorch, U. Practical risk management in early phase clinical trials. Eur. J. Clin. Pharmacol. 75, 483–496 (2019).
pubmed: 30569285
doi: 10.1007/s00228-018-02607-8
Food and Drug Administration. Guidance for industry and investigators safety reporting requirements for INDs and BA/BE studies. FDA https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safety-reporting-requirements-inds-and-babe-studies (2012).
Walters, S. J. et al. Recruitment and retention of participants in randomised controlled trials: a review of trials funded and published by the United Kingdom health technology assessment programme. BMJ Open 7, e015276 (2017).
pubmed: 28320800
pmcid: 5372123
doi: 10.1136/bmjopen-2016-015276
Fogel, D. B. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: a review. Contemp. Clin. Trials Commun. 11, 156–164 (2018).
pubmed: 30112460
pmcid: 6092479
doi: 10.1016/j.conctc.2018.08.001
Wong, C. H., Siah, K. W. & Lo, A. W. Estimation of clinical trial success rates and related parameters. Biostatistics 20, 273–286 (2019).
pubmed: 29394327
doi: 10.1093/biostatistics/kxx069
Briel, M. et al. Exploring reasons for recruitment failure in clinical trials: a qualitative study with clinical trial stakeholders in Switzerland, Germany, and Canada. Trials 22, 844 (2021).
pubmed: 34823582
pmcid: 8613940
doi: 10.1186/s13063-021-05818-0
Kasenda, B. et al. Prediction of RECRUITment in randomized clinical trials (RECRUIT-IT) — rationale and design for an international collaborative study. Trials 21, 731 (2020).
pubmed: 32825846
pmcid: 7441612
doi: 10.1186/s13063-020-04666-8
Jacques, R. M. et al. Recruitment, consent and retention of participants in randomised controlled trials: a review of trials published in the National Institute for Health Research (NIHR) Journals Library (1997–2020). BMJ Open 12, e059230 (2022).
pubmed: 35165116
pmcid: 8845327
doi: 10.1136/bmjopen-2021-059230
Natale, P. et al. Transparency, trust and minimizing burden to increase recruitment and retention in trials: a systematic review. J. Clin. Epidemiol. 134, 35–51 (2021).
pubmed: 33515656
doi: 10.1016/j.jclinepi.2021.01.014
Bentley, C. et al. Conducting clinical trials — costs, impacts, and the value of clinical trials networks: a scoping review. Clin. Trials 16, 183–193 (2019).
pubmed: 30628466
doi: 10.1177/1740774518820060
Gul, R. B. & Ali, P. A. Clinical trials: the challenge of recruitment and retention of participants. J. Clin. Nurs. 19, 227–233 (2010).
pubmed: 20500260
doi: 10.1111/j.1365-2702.2009.03041.x
Comerford, M. et al. Challenges in patient enrollment and retention in clinical studies for alcoholic hepatitis: experience of the TREAT consortium. Alcohol Clin. Exp. Res. 41, 2000–2006 (2017).
pubmed: 28981151
pmcid: 5711577
doi: 10.1111/acer.13515
Dasarathy, S. et al. Development and evaluation of objective trial performance metrics for multisite clinical studies: experience from the AlcHep Network. Contemp. Clin. Trials 138, 107437 (2024).
pubmed: 38215876
doi: 10.1016/j.cct.2024.107437
Mellinger, J. L. & Winder, G. S. Alcohol use disorders in alcoholic liver disease. Clin. Liver Dis. 23, 55–69 (2019).
pubmed: 30454833
doi: 10.1016/j.cld.2018.09.004
Winder, G. S., Clifton, E. G., Perumalswami, P. & Mellinger, J. L. The art of interprofessional psychosocial communication: optimizing patient interfaces with psychiatric specialists in liver transplantation. Transpl. Rev. 36, 100728 (2022).
doi: 10.1016/j.trre.2022.100728
Winder, G. S., Fernandez, A. C. & Mellinger, J. L. Integrated care of alcohol-related liver disease. J. Clin. Exp. Hepatol. 12, 1069–1082 (2022).
pubmed: 35814517
pmcid: 9257883
doi: 10.1016/j.jceh.2022.01.010
Kintz, P. Consensus of the society of hair testing on hair testing for chronic excessive alcohol consumption 2011. Forensic Sci. Int. 218, 2 (2012).
pubmed: 22024658
doi: 10.1016/j.forsciint.2011.10.025
Berger, L. et al. Ethyl glucuronide in hair and fingernails as a long-term alcohol biomarker. Addiction 109, 425–431 (2014).
pubmed: 24524319
doi: 10.1111/add.12402
Lees, R. et al. Comparison of ethyl glucuronide in hair with self-reported alcohol consumption. Alcohol Alcohol. 47, 267–272 (2012).
pubmed: 22336766
doi: 10.1093/alcalc/ags010
Vaa, B., Asrani, S., Dunn, W., Kamath, P. & Shah, V. Influence of serum sodium on MELD-based survival prediction in alcoholic hepatitis. Mayo Clin. Proc. 86, 37–42 (2011).
pubmed: 21193654
pmcid: 3012632
doi: 10.4065/mcp.2010.0281
Dunn, W. et al. MELD accurately predicts mortality in patients with alcoholic hepatitis. Hepatology 41, 353–358 (2005).
pubmed: 15660383
doi: 10.1002/hep.20503
Sullivan, J. T., Sykora, K., Schneiderman, J., Naranjo, C. A. & Sellers, E. M. Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar). Br. J. Addict. 84, 1353–1357 (1989).
pubmed: 2597811
doi: 10.1111/j.1360-0443.1989.tb00737.x