Guideline sources The following summarized guidelines for the evaluation and management of alcohol-related liver disease are prepared by our editorial team based on guidelines from the French Society of Alcohology (SFA/AFEF 2022), the American Association for the Study of Liver Diseases (AASLD 2020), the European Association for the Study of the Liver (EASL 2018), the U.S. Preventive Services Task Force (USPSTF 2018), and the American College of Gastroenterology (ACG 2018). 1 2 3 4 5 6 7 8 9 Definition Alcoholic liver disease encompasses a spectrum of disorders that may take an acute form (alcoholic hepatitis) or present as a chronic disease (steatosis, steatohepatitis, fibrosis, and cirrhosis). 6 Epidemiology Alcoholic liver disease is caused by heavy alcohol use. 7 https://web.pathway.md/diseases/recH96LhA8v1VcAWd 1/9 6/23/23, 2:17 AM Alcohol-related liver disease Pathway Disease course Alcohol abuse results in steatosis followed by steatohepatitis, alcoholic hepatitis, fibrosis, and liver cirrhosis due to inflammation, hepatocellular damage, and liver fibrosis. Disease progression may also cause liver decompensation and HCC. 8 Prognosis and risk of recurrence 1-year mortality of alcoholic liver disease as a single group is around 20%. 9 Calculator AUDIT C for alcohol use Guidelines 1. Screening and diagnosis Screening for alcohol abuse: As per AFEF 2022 guidelines, obtain systematic assessment of alcohol consumption in both general practice and specialist consultations. A Show 3 more As per AASLD 2020 guidelines, obtain routine screening for alcohol use using validated questionnaires in all patients receiving care in primary care and gastroenterology/hepatology outpatient clinics, emergency departments, and inpatient admissions. E As per ACG 2018 guidelines, use the AUDs Inventory Test as a validated tool to identify patients with alcohol use and dependence. E As per EASL 2018 guidelines, screen patients for harmful alcohol consumption by general practitioners and in emergency departments. B Show 2 more Screening for alcohol-related liver disease: As per AFEF 2022 guidelines, integrate screening for ALD in more general liver disease screening, including nonalcoholic fatty liver disease and hepatitis B and C viruses. E As per EASL 2018 guidelines, screen for ALD in high-risk populations, such as patients in alcohol rehabilitation clinics, or patients with harmful drinking identified by their general practitioner. B Show 2 more Diagnosis: As per AASLD 2020 guidelines: https://web.pathway.md/diseases/recH96LhA8v1VcAWd 2/9 6/23/23, 2:17 AM Alcohol-related liver disease Pathway Consider obtaining alcohol biomarkers to aid in diagnosis of AUD and support recovery. Prefer urine and hair ethyl glucuronide, urine ethyl sulfate, and phosphatidylethanol as they are not affected by liver disease. E Diagnose alcoholic hepatitis (definite, probable, possible) using the published consensus criteria. E As per EASL 2018 guidelines: Use the term AUD (defined by DSM-V criteria) in preference to alcoholic, alcohol abuse, alcohol dependence or risky drinker. A Suspect the diagnosis of alcoholic hepatitis in patients with excessive alcohol consumption and a recent onset of jaundice. A 2. Classification and risk stratification Prognostic scores: As per AFEF 2022 guidelines, use the NIAAA classification in the absence of liver biopsy to offer treatment only in patients with probable alcoholic hepatitis. E Show 7 more As per AASLD 2020 guidelines, use lab-based prognostic scores to determine prognosis in alcoholic hepatitis. E Show 3 more As per EASL 2018 guidelines, use available prognostic scores to identify patients with severe forms of alcoholic hepatitis at risk of early mortality. A 3. Diagnostic investigations Initial evaluation: obtain LFTs and an abdominal ultrasound in patients with harmful alcohol use and/or AUD. E Assessment of liver fibrosis: obtain noninvasive assessment (elastography or specialized blood tests) of liver fibrosis in all patients with ALD. A Show 3 more Evaluation for advanced disease: Define a target group meeting the following criteria in order to identify patients with advanced ALD in the general population: age 40-45 years, AUDIT score predictive of hazardous consumption, and/or consumption of 14 standard drinks/week. B Show 2 more Screening for infection: As per AFEF 2022 guidelines, obtain systematic evaluation for infection in patients with severe alcoholic hepatitis. A https://web.pathway.md/diseases/recH96LhA8v1VcAWd 3/9 6/23/23, 2:17 AM Alcohol-related liver disease Pathway As per EASL 2018 guidelines, obtain systematic screening for infection before initiating therapy, during corticosteroid treatment, and during the follow-up period in patients with alcoholic hepatitis. A Screening for cognitive impairment: screen for the presence of cognitive impairments because of their high prevalence. E 4. Diagnostic procedures Liver biopsy: As per AFEF 2022 guidelines: Perform liver biopsy to confirm the clinical suspicion of alcoholic hepatitis in patients being potential candidates for specific treatment. B Perform liver biopsy in patients with ALD in case of doubt concerning the presence of associated chronic liver disease, or in the case of a discordant noninvasive examination casting doubt on the presence of cirrhosis. E As per ACG 2018 guidelines: Avoid performing routine liver biopsy for the diagnosis of alcoholic fatty liver disease. D Consider performing liver biopsy and using noninvasive fibrosis assessment tools in patients with suspected steatohepatitis and/or liver fibrosis. E As per EASL 2018 guidelines, perform liver biopsy if there is diagnostic uncertainty, precise staging is required, or in clinical trials. A 5. Medical management General principles: As per AASLD 2020 guidelines, offer brief intervention, pharmacotherapy, and referral to treatment in patients engaged in hazardous drinking (AUDIT-C 4, AUDIT > 8, binge drinkers). E Show 2 more As per ACG 2018 guidelines, provide multidisciplinary care for ALD with the involvement of addiction specialists. E As per EASL 2018 guidelines, refer patients with ALD identified through screening to a multidisciplinary team. A Show 3 more Management of alcohol use disorder: As per AFEF 2022 guidelines, recognize that long-term outcomes in patients with ALD depend mainly on achieving abstinence. Offer addiction treatment systematically after an episode of alcoholic hepatitis. A Show 6 more https://web.pathway.md/diseases/recH96LhA8v1VcAWd 4/9 6/23/23, 2:17 AM Alcohol-related liver disease Pathway As per AASLD 2020 guidelines, consider offering acamprosate or baclofen for the treatment of AUD in patients with ALD. E As per ACG 2018 guidelines, consider offering baclofen for the prevention of alcohol relapse in patients with ALD. C Management of alcohol withdrawal: As per AFEF 2022 guidelines, offer benzodiazepines for the treatment of alcohol withdrawal syndrome until symptoms disappear. (G1+. As per ACG 2018 guidelines: Manage alcohol withdrawal syndrome according to the Clinical Institute Withdrawal Assessment for Alcohol protocol. E Offer benzodiazepines as the treatment of choice in patients with severe alcohol withdrawal syndrome and ALD. E Landmark trials: Symptom-triggered vs. fixed-dose benzodiazepines for alcohol withdrawal In patients with alcohol dependence entering an alcohol treatment program, symptom- triggered benzodiazepine administration was superior to fixed-schedule benzodiazepine administration with respect to total amount of oxazepam administered. Daeppen JB et al. Arch Intern Med. 2002 May 27. As per EASL 2018 guidelines, offer benzodiazepines for the treatment of alcohol withdrawal syndrome but not beyond 10-14 days because of the potential for abuse and/or encephalopathy. A Corticosteroids: As per AFEF 2022 guidelines, initiate corticosteroid therapy (prednisolone 40 mg/day or methylprednisolone 32 mg/day) to improve short-term survival in patients with severe alcoholic hepatitis. A As per AASLD 2020 guidelines, consider initiating oral prednisolone 40 mg/day, if not contraindicated, to improve 28-day mortality in patients with severe alcoholic hepatitis (MDF 32). E As per EASL 2018 guidelines: Consider initiating corticosteroids (prednisolone 40 mg/day or methylprednisolone 32 mg/day) to reduce short-term mortality in patients with severe alcoholic hepatitis, in the absence of active infection. B Identify patients with early nonresponse (at day 7) to corticosteroids and apply strict rules of cessation therapy. A N-acetylcysteine: https://web.pathway.md/diseases/recH96LhA8v1VcAWd 5/9 6/23/23, 2:17 AM Alcohol-related liver disease Pathway As per AFEF 2022 guidelines, offer adding N-acetylcysteine to corticosteroids in patients with severe alcoholic hepatitis. B As per AASLD 2020 guidelines, consider administering IV N-acetylcysteine in addition to prednisolone (40 mg/day) to improve 30-day survival in patients with severe alcoholic hepatitis. E As per EASL 2018 guidelines, consider administering IV N-acetylcysteine for 5 days combined with corticosteroids in patients with severe alcoholic hepatitis. C Pentoxifylline: As per AFEF 2022 guidelines, do not use pentoxifylline in patients with severe alcoholic hepatitis because of its ineffectiveness. D As per AASLD 2020 guidelines, do not use pentoxifylline for the treatment of alcoholic hepatitis. D 6. Nonpharmacologic interventions Alcohol abstinence: As per AFEF 2022 guidelines, advise patients with cirrhosis and/or HCC to completely and permanently stop all alcohol consumption in order to limit the risk of excess mortality. B As per AASLD 2020 guidelines, advise patients with ALD or other liver diseases, in particular nonalcoholic fatty liver disease, NASH, viral hepatitis, and hemochromatosis to abstain from drinking. E As per ACG 2018 guidelines, advise complete abstinence from alcohol consumption in patients with ALD. E As per EASL 2018 guidelines, advise and encourage patients with ALD cirrhosis to achieve complete abstinence from alcohol to reduce the risk of liver-related complications and mortality. A Brief behavioral intervention: As per AFEF 2022 guidelines, offer brief behavioral intervention in patients identified as alcohol misusers. Ensure that all practitioners are able to carry out this brief intervention. A As per AASLD 2020 guidelines, offer brief intervention in patients engaged in hazardous drinking (AUDIT-C 4, AUDIT > 8, binge drinkers). E As per ACG 2018 guidelines, consider offering brief motivational interventions to reduce alcohol relapse in patients with ALD. C As per EASL 2018 guidelines, offer a brief intervention in patients with ALD identified through screening. A As per USPSTF 2018 guidelines, provide brief behavioral counseling interventions to reduce unhealthy alcohol use in persons engaged in risky or hazardous drinking. B Smoking cessation: https://web.pathway.md/diseases/recH96LhA8v1VcAWd 6/9 6/23/23, 2:17 AM Alcohol-related liver disease Pathway As per AFEF 2022 guidelines, advise smoking cessation in patients with ALD as it increases the risk of fibrosis and HCC in the course of ALD. A As per ACG 2018 guidelines, advise abstaining from cigarette smoking in patients with ALD. B Weight loss: consider offering specific management for obesity/overweight as it accelerates the progression of ALD. E Nutritional support: As per AASLD 2020 guidelines, address and treat malnutrition, preferably with enteral nutrition, in patients with alcoholic hepatitis. E As per EASL 2018 guidelines, obtain careful evaluation of nutritional status and advise patients to achieve a daily energy intake 35-40 kcal/kg body weight and 1.2-1.5 g/kg protein, and to adopt the oral route as first-line intervention. B 7. Perioperative care Pretransplantation care: decide on the duration of abstinence before listing depending on the degree of liver insufficiency in selected patients with a favorable addiction and psychological profile and supportive relatives. A Show 5 more 8. Surgical interventions Liver transplantation: As per AFEF 2022 guidelines, consider offering fast-track liver transplantation in patients at the end of their therapeutic options. Select candidates rigorously and in a multidisciplinary setting in the reference transplant center. B As per AASLD 2020 guidelines, refer patients with decompensated alcohol-associated cirrhosis, CPT class C or MELD-Na 21 for liver transplantation. E Show 2 more As per ACG 2018 guidelines, consider performing liver transplantation while formulating a management plan for patients with end-stage ALD. E As per EASL 2018 guidelines, consider performing liver transplantation in patients with ALD (classified as Child-Pugh C and/or MELD 15) as it confers a survival benefit. B Show 3 more 9. Preventative measures Alcohol restriction: As per AFEF 2022 guidelines, consider advising alcohol consumption of 10 standard drinks per week in the general population to avoid overall health risks. C https://web.pathway.md/diseases/recH96LhA8v1VcAWd 7/9 6/23/23, 2:17 AM Alcohol-related liver disease Pathway Show 2 more As per AASLD 2020 guidelines, counsel patients without liver disease about safe levels of alcohol use for males ( 2 standard drinks per 24 hours) and females ( 1 standard drink per 24 hours). E 10. Follow-up and surveillance Monitoring of abstinence: consider obtaining hair or urine ethyl glucuronide for accurate monitoring of abstinence in patients with ALD. B Monitoring of transplant recipients: As per ACG 2018 guidelines, screen transplant recipients at each visit for use of alcohol and other substances especially tobacco and cannabis. E As per EASL 2018 guidelines, obtain a multidisciplinary evaluation for medical and psychological suitability for transplantation after liver transplantation. A Show 2 more 11. Quality improvement Public health measures: As per AFEF 2022 guidelines, disseminate information to the general population on the risks associated with binge drinking, particularly in terms of cardiovascular morbidity and mortality and physical and psychological injuries. A As per EASL 2018 guidelines, address excess alcohol consumption using pricing-based policies and regulation of availability. A Show 3 more References 1. European Association for the Study of the Liver. EASL clinical practice guidelines: management of alcohol-related liver disease. J Hepatol. 2018 Jul;69 1 154 181. Open 2. David W Crabb, Gene Y Im, Gyongyi Szabo et al. Diagnosis and Treatment of Alcohol-Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases. Hepatology. 2020 Jan;71 1 306 333. Open 3. US Preventive Services Task Force, Curry SJ, Krist AH et al. Screening and Behavioral Counseling Interventions to Reduce Unhealthy Alcohol Use in Adolescents and Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2018 Nov 13;320 18 1899 1909. Open 4. Alexandre Louvet, Jean-Baptiste Trabut, Christophe Moreno et al. Management of alcohol-related liver disease: the French Association for the Study of the Liver and the French Alcohol Society clinical guidelines. Liver Int. 2022 Apr 29. Online ahead of print. Open https://web.pathway.md/diseases/recH96LhA8v1VcAWd 8/9 6/23/23, 2:17 AM Alcohol-related liver disease Pathway 5. Singal AK, Bataller R, Ahn J et al. ACG Clinical Guideline: Alcoholic Liver Disease. Am J Gastroenterol. 2018 Feb;113 2 175 194. Open 6. Radan Bruha, Karel Dvorak, Jaromir Petrtyl. Alcoholic liver disease. 2012 Mar 27;4 3 81 90.2012 Mar 27;4 3 81 90. Open 7. Koichiro Ohashi, Michael Pimienta, Ekihiro Seki. 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Alexandre Louvet, Julien Labreuche, Thong Dao et al. Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial. JAMA. 2023 May 9;329 18 1558 1566. Open 20. Mads Israelsen, Bj rn St hr Madsen, Nikolaj Torp et al. Rifaximin- for liver fibrosis in patients with alcohol-related liver disease GALA RIF a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Gastroenterol Hepatol. 2023 Jun;8 6 523 532. Open https://web.pathway.md/diseases/recH96LhA8v1VcAWd 9/9