Guideline sources The following summarized guidelines for the evaluation and management of alcoholic hepatitis (AH) are prepared by our editorial team based on guidelines from the American College of Gastroenterology (ACG 2018), the European Association for the Study of the Liver (EASL 2012), and the American College of Gastroenterology (ACG/AASLD 2010). 1 2 3 4 4 4 5 Definition AH is a life-threatening form of acute-on-chronic liver failure occurring in patients with sustained heavy alcohol use that is characterized by a rapid onset or worsening of jaundice, liver synthetic dysfunction, and features of hepatic decompensation. 4 Epidemiology AH is caused by intra- and extra-hepatic effects of alcohol. 4 Disease course https://web.pathway.md/diseases/recuYBTsmBvoQCsjt 1/5 6/23/23, 2:17 AM Alcoholic hepatitis Pathway The complex interplay between ethanol metabolism, inflammation, and innate immunity results in liver damage causing AH, which present with clinical manifestations of fever, jaundice, hepatomegaly, ascites, and hepatic encephalopathy. Disease progression leads to liver fibrosis, cirrhosis, and the need for liver transplantation. 5 Prognosis and risk of recurrence Severe AH is associated with 50% 90-day mortality. 4 Calculator Diagnostic criteria for alcoholic Guidelines 1. Screening and diagnosis Diagnostic criteria: Diagnose AH in a patient with: rapid development or worsening of jaundice and liver-related complications serum TBIL > 50 mol/L (> 3 mg/dL) ALT and AST elevated > 1.5 times the ULN but < 400 U/L with the AST/ALT ratio > 1.5 documentation of heavy alcohol use until 8 weeks prior to onset of symptoms exclusion of other liver diseases. E 2. Classification and risk stratification Severity grading: As per ACG 2018 guidelines, identify severe AH in patients with a Maddrey's discriminant function score > 32 or MELD score > 20. E As per EASL 2012 guidelines, stratify patients with severe alcoholic steatohepatitis using available scoring systems to identify patients who are at risk of death within 1-3 months. A As per AASLD 2010 guidelines: Stratify patients presenting with a high clinical suspicion of AH using Maddrey's discriminant function, as well as other available clinical data. B Consider serial calculation of the MELD score to evaluate a patient's condition over time. B 3. Diagnostic investigations https://web.pathway.md/diseases/recuYBTsmBvoQCsjt 2/5 6/23/23, 2:17 AM Alcoholic hepatitis Pathway Screening for infections: assess patients for acute infections as part of the routine workup of patients with AH. E 4. Diagnostic procedures Liver biopsy: As per ACG 2018 guidelines, perform a transjugular liver biopsy in patients with suspected AH when the clinical diagnosis is confounded by another etiology of liver disease, or there is uncertainty on alcohol consumption history. E As per EASL 2012 guidelines, perform liver biopsy if establishing a definite diagnosis of alcoholic steatohepatitis is desired, although the presence of AH can be suspected on clinical and biochemical grounds. A As per AASLD 2010 guidelines, consider performing liver biopsy, after a risk-benefit assessment, in patients with a clinical diagnosis of severe AH for whom medical treatment is contemplated, or for those in whom reasonable uncertainty exists regarding the underlying diagnosis. B 5. Medical management Supportive care: institute appropriate measures to prevent renal injury, such as avoidance of nephrotoxic drugs, judicious use of diuretics, and use a low threshold for expanding circulating blood volume with albumin or saline infusions. E Indications for corticosteroids: As per ACG 2018 guidelines: Treat patients with severe AH (Maddrey's discriminant function score > 32 or MELD score > 20) with corticosteroids (prednisolone 40 mg/day for 28 days, typically followed by discontinuation or a 2-week taper) if there are no contraindications for their use. B Discontinue corticosteroid therapy at 7 days in nonresponders, as defined by a Lille score > 0.45. E Landmark trials: STOPAH In patients with severe alcoholic hepatitis, treatment with pentoxifylline, as compared with placebo, did not reduce 28-day mortality. Treatment with prednisolone, as compared with placebo, was associated with a reduction in 28-day mortality that did not reach significance, with no improvement in outcomes at 90 days or 1 year. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (p=0.002). Thursz MR et al. N Engl J Med. 2015 Apr 23. https://web.pathway.md/diseases/recuYBTsmBvoQCsjt 3/5 6/23/23, 2:17 AM Alcoholic hepatitis Pathway As per EASL 2012 guidelines, administer corticosteroids as first-line therapy in patients with severe alcoholic steatohepatitis who do not have ongoing sepsis. B As per AASLD 2010 guidelines, consider a four week course of prednisolone (40 mg/day for 28 days, typically followed by discontinuation or a 2-week taper) in patients with severe disease (Maddrey's discriminant function 32, with or without hepatic encephalopathy) who lack contraindications to steroid use. B Indications for pentoxifylline: As per ACG 2018 guidelines, avoid the use of pentoxifylline for patients with severe AH. D As per EASL 2012 guidelines, consider administering pentoxifylline as first-line therapy in patients with severe AH in whom ongoing sepsis is present. B As per AASLD 2010 guidelines, consider pentoxifylline therapy in patients with severe AH (Maddrey's discriminant function > 32), especially if there are contraindications to steroid therapy. B N-acetylcysteine therapy: consider initiating N-acetylcysteine therapy in patients with severe alcoholic steatohepatitis receiving corticosteroids. C 6. Inpatient care Monitoring for infections and renal injury: monitor patients with severe alcoholic steatohepatitis for deterioration of renal function and incidence of new infection. A 7. Nonpharmacologic interventions Nutritional support: as per ACG 2018 guidelines, consider nutritional supplementation in patients with AH to maintain adequate caloric intake and correct specific deficits. C Alcohol use cessation: As per EASL 2012 guidelines, advise total alcohol abstinence in patients with ALD, as persistent alcohol intake is associated with disease progression. A As per AASLD 2010 guidelines, advise strict abstinence in patients with evidence of alcohol- induced liver disease, because continued alcohol use is associated with disease progression. B 8. Surgical interventions Liver transplantation: as per ACG 2018 guidelines, consider liver transplantation for highly selected patients with severe AH. B Landmark trials: Early liver transplantation for severe alcoholic hepatitis https://web.pathway.md/diseases/recuYBTsmBvoQCsjt 4/5 6/23/23, 2:17 AM Alcoholic hepatitis Pathway In patients with no prior episodes of alcoholic hepatitis and had scores of 0.45 according to the Lille model, undergoing early liver transplantation was superior to not undergoing liver transplantation with respect to cumulative survival at 6 months. Mathurin P et al. N Engl J Med. 2011 Nov 10. 9. Follow-up and surveillance Palliative care: consider palliative care for patients with multi-organ failure who are non- responsive to corticosteroids and ineligible for early liver transplantation. E References 1. Singal AK, Bataller R, Ahn J et al. ACG Clinical Guideline: Alcoholic Liver Disease. Am J Gastroenterol. 2018 Feb;113 2 175 194. Open 2. European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol. 2012 Aug;57 2 399 420. Open 3. O'Shea RS, Dasarathy S, McCullough AJ et al. Alcoholic liver disease. Hepatology. 2010 Jan;51 1 307 28. Open 4. Vikrant Rachakonda, Ramon Bataller, Andres Duarte-Rojo. Recent advances in alcoholic hepatitis. 2020 Feb 10;9 F1000 Faculty Rev-97.2020 Feb 10;9 F1000 Faculty Rev-97. Open 5. Maneerat Chayanupatkul, Suthat Liangpunsakul. Alcoholic hepatitis: a comprehensive review of pathogenesis and treatment. 2014 May 28;20 20 6279 86.2014 May 28;20 20 6279 86. Open 6. O'Shea RS, McCullough AJ. Treatment of alcoholic hepatitis. Clin Liver Dis. 2005 Feb;9 1 103 34. Open 7. 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 https://web.pathway.md/diseases/recuYBTsmBvoQCsjt 5/5