Does moderate alcohol consumption accelerate the progression of liver disease in NAFLD? A systematic review and narrative synthesis

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).

[1]  A. Kulkarni,et al.  Non-alcoholic Fatty Liver Disease and Alcohol-Related Liver Disease: Two Intertwined Entities , 2020, Frontiers in Medicine.

[2]  T. Kanai,et al.  Moderate alcohol consumption is not associated with subclinical cardiovascular damage but with hepatic fibrosis in non-alcoholic fatty liver disease. , 2020, Alcohol.

[3]  Youming Li,et al.  Light-to-Moderate Alcohol Consumption Is Associated With Increased Risk of Type 2 Diabetes in Individuals With Nonalcoholic Fatty Liver Disease: A Nine-Year Cohort Study. , 2020, The American journal of gastroenterology.

[4]  Patricia N Soliz,et al.  Trends in premature avertable mortality from non-communicable diseases for 195 countries and territories, 1990-2017: a population-based study. , 2020, The Lancet. Global health.

[5]  V. Salomaa,et al.  Combined Effects of Alcohol and Metabolic Disorders in Patients With Chronic Liver Disease. , 2020, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[6]  V. Salomaa,et al.  Risks of Light and Moderate Alcohol Use in Fatty Liver Disease: Follow‐Up of Population Cohorts , 2020, Hepatology.

[7]  M. Färkkilä,et al.  Drinking and Obesity: Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Interactions , 2020, Seminars in Liver Disease.

[8]  F. Negro Natural history of NASH and HCC , 2020, Liver international : official journal of the International Association for the Study of the Liver.

[9]  L. Bolondi,et al.  Moderate alcohol consumption is associated with risk of fibrosis in patients with non-alcoholic fatty liver disease , 2020 .

[10]  T. H. Nguyen,et al.  The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017 , 2020, The lancet. Gastroenterology & hepatology.

[11]  G. Tarantino,et al.  Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy , 2019, Journal of clinical medicine.

[12]  M. Färkkilä,et al.  Interaction between alcohol use and metabolic risk factors for liver disease: a critical review of epidemiological studies. , 2019, Alcoholism, clinical and experimental research.

[13]  M. Petroni,et al.  Moderate Alcohol Intake in Non-Alcoholic Fatty Liver Disease: To Drink or Not to Drink? , 2019, Nutrients.

[14]  S. Wild,et al.  Low Levels of Alcohol Consumption, Obesity, and Development of Fatty Liver With and Without Evidence of Advanced Fibrosis , 2019, Hepatology.

[15]  K. Kagawa,et al.  Comparison of the effect of light alcohol consumption on Japanese men with and without fatty liver , 2019, Biomedical reports.

[16]  W. Dunn,et al.  Effect of alcohol consumption on nonalcoholic fatty liver disease. , 2019, Translational gastroenterology and hepatology.

[17]  V. Wong,et al.  Effects of Alcohol Consumption and Metabolic Syndrome on Mortality in Patients With Nonalcoholic and Alcohol-Related Fatty Liver Disease. , 2019, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[18]  Katherine Fennedy,et al.  Moderate , 2019, Definitions.

[19]  V. Salomaa,et al.  LBP-01-In NAFLD, alcohol drinking habits and genetics predict progression to advanced liver disease: follow-up of population surveys , 2019, Journal of Hepatology.

[20]  Yoosoo Chang,et al.  Nonheavy Drinking and Worsening of Noninvasive Fibrosis Markers in Nonalcoholic Fatty Liver Disease: A Cohort Study , 2018, Hepatology.

[21]  A. McCullough,et al.  Effect of Alcohol Consumption on Survival in Nonalcoholic Fatty Liver Disease: A National Prospective Cohort Study , 2018, Hepatology.

[22]  Dan J Stein,et al.  Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 , 2018, Lancet.

[23]  B. Neuschwander‐Tetri,et al.  Among Patients With Nonalcoholic Fatty Liver Disease, Modest Alcohol Use Is Associated With Less Improvement in Histologic Steatosis and Steatohepatitis , 2018, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[24]  P. Trivedi,et al.  Alcohol Consumption in Patients with Non-alcoholic Fatty Liver Disease: Convenient vs. Inconvenient Truths. , 2018, The American journal of gastroenterology.

[25]  J. Hamdorf,et al.  Type and Pattern of Alcohol Consumption is Associated With Liver Fibrosis in Patients With Non‐alcoholic Fatty Liver Disease , 2018, The American Journal of Gastroenterology.

[26]  N. Tanaka,et al.  Mild drinking habit is a risk factor for hepatocarcinogenesis in non-alcoholic fatty liver disease with advanced fibrosis , 2018, World journal of gastroenterology.

[27]  H. Yoshiji,et al.  Moderate alcohol consumption protects against fatty liver in males , 2018 .

[28]  Q. Anstee,et al.  The bidirectional impacts of alcohol consumption and the metabolic syndrome: Cofactors for progressive fatty liver disease. , 2018, Journal of hepatology.

[29]  M. Honda,et al.  Light alcohol consumption has the potential to suppress hepatocellular injury and liver fibrosis in non-alcoholic fatty liver disease , 2018, PloS one.

[30]  N. Bhala,et al.  Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK , 2017, The Lancet.

[31]  K. Irvine,et al.  Alcohol Consumption in Diabetic Patients with Nonalcoholic Fatty Liver Disease , 2017, Canadian journal of gastroenterology & hepatology.

[32]  C. Lewis,et al.  Alcohol Use and Cardiovascular Disease Risk in Patients With Nonalcoholic Fatty Liver Disease. , 2017, Gastroenterology.

[33]  N. Terrault,et al.  Is moderate alcohol use in nonalcoholic fatty liver disease good or bad? A critical review , 2017, Hepatology.

[34]  J. Lake,et al.  Long-Term Outcomes of Patients with Non-Obese Fatty Liver Disease (NOFLD): A Study from the National Health and Nutrition Examination Survey , 2017 .

[35]  R. Hultcrantz,et al.  Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease , 2017, Scandinavian journal of gastroenterology.

[36]  Hossam M. Hammady,et al.  Rayyan—a web and mobile app for systematic reviews , 2016, Systematic Reviews.

[37]  S. Sookoian,et al.  Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease , 2016, Alimentary pharmacology & therapeutics.

[38]  H. Tilg,et al.  EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease , 2016, Obesity Facts.

[39]  Yoshiyuki Suzuki,et al.  Effects of Alcohol Consumption on Hepatocarcinogenesis in Japanese Patients With Fatty Liver Disease. , 2016, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[40]  M. Bellis,et al.  Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis , 2014, The Lancet.

[41]  G. Collins,et al.  Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies: The CHARMS Checklist , 2014, PLoS medicine.

[42]  D. Sinn,et al.  Modest alcohol consumption and carotid plaques or carotid artery stenosis in men with non-alcoholic fatty liver disease. , 2014, Atherosclerosis.

[43]  H. Conjeevaram,et al.  Effect of lifetime alcohol consumption on the histological severity of non‐alcoholic fatty liver disease , 2014, Liver international : official journal of the International Association for the Study of the Liver.

[44]  S. Sookoian,et al.  Modest alcohol consumption decreases the risk of non-alcoholic fatty liver disease: a meta-analysis of 43 175 individuals , 2013, Gut.

[45]  C. Bombardier,et al.  Assessing Bias in Studies of Prognostic Factors , 2013, Annals of Internal Medicine.

[46]  A. Sanyal,et al.  Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD). , 2012, Journal of hepatology.

[47]  Michael Charlton,et al.  The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. , 2012, Gastroenterology.

[48]  M. Hauser,et al.  Modest Alcohol Consumption Attenuates Expression of Fibrosis-Associated Genes in Patients With Non-Alcoholic Fatty Liver Disease (NAFLD) , 2011 .

[49]  Rocio Lopez,et al.  The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis , 2010, Hepatology.

[50]  V. Beral,et al.  Body mass index and risk of liver cirrhosis in middle aged UK women: prospective study , 2010, BMJ : British Medical Journal.

[51]  D. May,et al.  Effects of light-to-moderate alcohol consumption on steatosis and steatohepatitis in severely obese patients , 2009, European journal of gastroenterology & hepatology.

[52]  D. Moher,et al.  Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement , 2009, BMJ : British Medical Journal.

[53]  M. Holmqvist,et al.  Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease , 2009, Scandinavian journal of gastroenterology.

[54]  Anna Castiglione,et al.  The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population , 2006, BMC gastroenterology.

[55]  M. Russell,et al.  Cognitive Lifetime Drinking History in Nonalcoholic Fatty Liver Disease: Some Cases May Be Alcohol Related , 2004, American Journal of Gastroenterology.

[56]  A. Klatsky Alcohol and Cardiovascular Diseases , 2002, Annals of the New York Academy of Sciences.

[57]  S. Naumovski-Mihalić,et al.  Prognosis for the patients with alcoholic and nonalcoholic liver disease. , 2000, Collegium antropologicum.

[58]  Alan D. Lopez,et al.  Alcohol consumption and mortality among middle-aged and elderly U.S. adults. , 1997, The New England journal of medicine.

[59]  G. Práctica,et al.  European Association for the Study of the Liver , 1971 .

[60]  K. Irvine,et al.  Can modest alcohol intake be dismissed as a co-factor in diabetic patients with non-alcoholic fatty liver disease? , 2017 .

[61]  European Association for the Study of the Liver,et al.  EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease , 2016, Obesity Facts.

[62]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.

[63]  George Davey Smith,et al.  Supplementary Table S1 , 2008 .

[64]  Jennie Popay,et al.  Guidance on the conduct of narrative synthesis in systematic Reviews. A Product from the ESRC Methods Programme. Version 1 , 2006 .

[65]  U. John,et al.  Riskanter Alkoholkonsum und alkoholbezogene Störungen in Vorpommern: Die Studie Leben und Gesundheit in Vorpommern (SHIP) und der Bundesgesundheitssurvey 1998 im Vergleich , 2005 .

[66]  U. John,et al.  [Health Risk drinking and problematic consumption of alcohol in Pomerania: comparative analysis of the Study of Health in Pomerania (SHIP) compared with the Federal German Health and Examination Survey in 1998]. , 2005, Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany)).