From steatosis to alcohol-associated hepatitis to cirrhosis — how to diagnose, stratify severity, decide on steroids, assess response with the Lille model, and address alcohol use disorder with medication-assisted treatment.
Describe the spectrum of alcohol-associated liver disease from steatosis through cirrhosis and identify reversible stages
Apply the Maddrey Discriminant Function and Lille model to guide steroid use and assess response in severe alcoholic hepatitis
Counsel a patient on alcohol cessation and select appropriate medication-assisted treatment options given their degree of liver dysfunction
19 min · 8 sectionsCore Disease
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00Clinical Case
01Spectrum of Disease
02Diagnosing AAH vs. ASLD
03Severity — MDF Calculator
04Corticosteroid Therapy
05Lille Model — Response
06Medication-Assisted Treatment
07Nutrition in AAH
Progress0/8
Clinical Case
A 44-year-old man presents with 10 days of jaundice, abdominal distension, and low-grade fever. He reports drinking approximately 14 drinks per day for several years, with continued use until 5 days ago. Temp 38.0°C. Exam: icteric sclerae, tender hepatomegaly, 2+ ascites.
AST 215 · ALT 88 · AST:ALT 2.4 · Total bili 18.2 mg/dL · PT 22 s (control 12 s) · Albumin 2.6 · Creatinine 1.1 · WBC 14,200
Work through the management step by step before the answers are revealed.
Alcohol-Associated Steatotic Liver Disease (ASLD)
Reversible with abstinence
Macrovesicular fat accumulation in hepatocytes without significant inflammation or fibrosis. Occurs in up to 90% of people with heavy alcohol use. Typically asymptomatic — discovered incidentally on imaging or mildly elevated enzymes.
Laboratory: mild-to-moderate AST/ALT elevation, elevated GGT and MCV. Bilirubin and synthetic function (PT, albumin) are preserved. Distinguish from MASLD by alcohol intake history (>21 drinks/week in men, >14 in women).
Management: Alcohol cessation is the only treatment. Steatosis resolves within weeks of abstinence. No pharmacotherapy indicated for ASLD alone.
Quick recall
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A 44-year-old man with 15 years of heavy alcohol use presents with 3 weeks of jaundice, RUQ discomfort, and fever. Bilirubin 185 μmol/L, AST 280, ALT 110, WBC 18.2. What is the most likely diagnosis, and what is the key diagnostic ratio?
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AAH and ASLD share the same exposure but differ markedly in presentation, urgency, and management. The distinction is clinical — biopsy is not required when diagnostic criteria are met.
EASL Diagnostic Criteria for AAH (all must be met)
Criterion
Threshold
Recent heavy alcohol use
Active or within 8 weeks; >40 g/day women, >60 g/day men
Jaundice / hyperbilirubinaemia
Total bilirubin > 3 mg/dL
Aspartate aminotransferase
50–400 IU/L
AST:ALT ratio
> 1.5 (often ≥ 2:1 or 3:1)
Exclusion of other causes
Viral hepatitis, DILI, biliary obstruction ruled out
Why AST rarely exceeds 400 IU/L
Alcohol-mediated mitochondrial dysfunction and pyridoxal phosphate (B6) depletion selectively elevate AST without causing the profound necrosis seen in viral or ischemic hepatitis. AST > 400–500 should prompt evaluation for a superimposed etiology.
Side-by-side comparison — click to reveal detail
ASLD
Alcohol-Associated Steatotic Liver Disease
Click to expand
AAH
Alcohol-Associated Hepatitis
Click to expand
Quick recall
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What AST:ALT ratio is characteristic of AAH, and why does AST rarely exceed 400 IU/L?
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Two scores guide the steroid decision: Maddrey's Discriminant Function (MDF) and MELD. MDF ≥ 32 defines severe disease. MELD is increasingly used alongside MDF — the "MELD window" of approximately 25–40 represents the population most likely to benefit.
MDF Calculator
Patient PT
seconds
Control PT
seconds · lab reference
Total Bilirubin
mg/dL
Enter all three values to calculate MDF
MDF = 4.6 × (PTpatient − PTcontrol) + total bilirubin (mg/dL) · Threshold ≥ 32 = severe AAH
The MELD Window
Patients with MELD approximately 25–40 appear to derive the greatest benefit. Below MELD ~20–25, spontaneous recovery is more likely; above MELD ~40, the severity and competing infection risk may outweigh steroid benefit.
Prednisolone 40 mg/day for 28 days is the standard treatment for severe AAH. Before starting, work through the pre-treatment checklist below — each box corresponds to a contraindication or required pre-treatment step.
Pre-Treatment Checklist
MDF ≥ 32 (or MELD 20–40) confirmed
Steroids are indicated for severe AAH. Use the calculator in Section 03 to confirm.
Not confirmed
Active uncontrolled infection ruled out or treated
Blood and ascitic fluid cultures done. If SBP present, treat with ceftriaxone first — reassess for steroids once controlled.
Hold steroids
No uncontrolled GI bleeding
Active variceal or ulcer bleeding precludes starting prednisolone safely.
Hold steroids
HBsAg and HBcAb checked; antiviral prophylaxis started if positive
Steroids reactivate HBV — this is potentially fatal. Start entecavir or tenofovir before steroids if any HBV marker is positive.
Patients with creatinine > 2.5 mg/dL were excluded from pivotal trials. Benefit is uncertain; individualize with hepatology.
Discuss risk
0 of 5 complete
Steroid Equivalency
Agent
Dose
Route
Note
Prednisolone ★
40 mg/day
Oral
Preferred — biologically active. Used in all landmark trials (STOPAH, STEROH).
Prednisone
40 mg/day
Oral
Prodrug — requires hepatic conversion. No demonstrated inferiority in trials; widely used in North America.
Methylprednisolone
32 mg/day
IV
Equipotent to prednisolone 40 mg (5:4 ratio). Use when oral route is not feasible.
Pentoxifylline — No Longer Recommended
STOPAH trial (Thursz et al., NEJM 2015, n = 1,053): no 28-day or 90-day survival benefit of pentoxifylline vs. placebo, and no additive benefit with prednisolone. Not recommended by AASLD or ACG.
N-Acetylcysteine — ACG vs. AASLD Discordance
ACG includes it; AASLD does not recommend it as standard of care. Nguyen-Khac et al. (NEJM 2011): reduced 1-month infection + HRS in prednisolone + NAC arm vs. prednisolone alone. However 6-month survival benefit was not sustained. An active area of societal disagreement.
Quick recall
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Why is prednisolone preferred over prednisone in severe AAH?
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The Lille score is calculated at Day 4 or Day 7 of corticosteroid therapy. Score ≥ 0.45 indicates non-response — stop prednisolone immediately. The same formula and threshold apply at both timepoints.
Day Selection
Age
years
Albumin (Day 0)
g/dL
Bilirubin (Day 0)
mg/dL
Creatinine (Day 0)
mg/dL
PT Prolongation (Day 0)
seconds above control
Bilirubin (Day 7)
mg/dL
Enter all six values to calculate Lille score
Cutoff ≥ 0.45 = non-response. Day 4 assessment uses the same formula — substitute Day 4 bilirubin.
MAT for alcohol use disorder (AUD) is systematically underutilised in patients with ALD despite being standard of care. Abstinence is the most effective intervention at every stage. Agent selection depends on liver and renal function.
Acamprosate
FDA ApprovedPreferred in ALD
GABA/glutamate modulation — reduces protracted withdrawal and relapse urge
In liver disease: Preferred in advanced liver disease. Renally cleared — no hepatic metabolism. Dose-reduce for CrCl < 30 mL/min. Not effective during active drinking.
FDA-approved 2004
Naltrexone (oral)
FDA Approved
Opioid receptor antagonist — reduces alcohol reward and craving
In liver disease: Use with caution in Child-Pugh B/C or active hepatitis. Hepatotoxicity at supratherapeutic doses. Safe in compensated cirrhosis with LFT monitoring (ALT < 3–5× ULN).
FDA-approved 1994
Naltrexone (injectable)
FDA Approved
Same mechanism as oral; monthly injection improves adherence
In liver disease: Same hepatic cautions as oral. Preferred when adherence is a significant concern.
FDA-approved 2006 (Vivitrol)
Baclofen
Off-label
GABA-B agonist — reduces craving and alcohol-related anxiety
In liver disease: Supported in ALD including cirrhosis. Addolorato et al. (Lancet 2007): 10 mg TID. Renally cleared — dose-reduce in renal impairment. Risk of CNS depression at high doses.
Off-label; Lancet 2007
Gabapentin
Off-label
α2δ calcium channel modulator — reduces withdrawal symptoms and craving
In liver disease: Mason et al. (JAMA IM 2014): 1,800 mg/day increased abstinence. Renally cleared. Caution in cirrhosis: CNS depression and encephalopathy risk at higher doses.
Off-label; JAMA IM 2014
GLP-1 agonists
Off-label
GLP-1R expressed in reward circuitry — attenuates dopamine-mediated alcohol reward
In liver disease: Observational data suggest reduced consumption. Multiple RCTs ongoing. Not yet an approved indication — but compelling in ALD + MASLD overlap.
Emerging — investigational
Disulfiram
FDA ApprovedContraindicated in ALD
Aldehyde dehydrogenase inhibitor — aversive reaction to alcohol ingestion
In liver disease: Contraindicated in significant liver disease. Hepatotoxicity risk.
Contraindicated in ALD
Emerging — GLP-1 Receptor Agonists
GLP-1 receptors are expressed in the brain's reward circuitry. Observational data suggest reduced alcohol consumption in patients receiving semaglutide or liraglutide. Multiple prospective RCTs are ongoing. Particularly relevant in ALD + MASLD overlap.
Quick recall
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Which MAT agent is preferred in Child-Pugh C cirrhosis and why?
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Severe protein-calorie malnutrition is nearly universal in patients with severe AAH and is an independent predictor of 30-day and 90-day mortality. Nutrition is not an adjunct in AAH — it is a primary therapeutic intervention.
First Priority
Nutrition Consultation
Every patient with severe AAH should be seen by a registered dietitian (RD). Assessment of baseline nutritional status guides the care plan and informs goals.
Targets
Protein and Energy Goals
Protein: 1.2–1.5 g/kg/day (actual or adjusted body weight). Do NOT restrict protein to manage encephalopathy risk — protein restriction worsens sarcopenia and outcomes. Energy: 35–40 kcal/kg/day.
Route
Enteral Nutrition
Enteral nutrition (EN) is preferred over parenteral. Initiate within 24–48 hours of admission. NG tube feeding if patient cannot meet ≥60% of targets orally.
Sarcopenia
Muscle Wasting
Sarcopenia predicts mortality in AAH independently of MELD and MDF. It is a key driver of infection susceptibility, HE risk, and poor wound healing.
Micronutrient Repletion
Thiamine 100–200 mg IV before any dextrose — prevents Wernicke encephalopathy. Never give glucose first.
Magnesium and phosphate — monitor and replete, especially during refeeding
Vitamin D — deficiency prevalent in ALD; associated with worse fibrosis and immune function
Historical context: Cabre et al. (1990) demonstrated enteral nutrition was as effective as corticosteroids for 1-month survival in severe AAH — with better long-term outcomes due to lower infection rates. Nutrition provides survival benefit through mechanisms distinct from and complementary to anti-inflammatory therapy.
References
Crabb DW, Im GY, Szabo G, 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;71(1):306-333. PubMed 31314133
Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med. 2015;372(17):1619-1628. PubMed 25901427
Louvet A, Naveau S, Abdelnour M, et al. The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology. 2007;45(6):1348-1354. PubMed 17518367
Ghany MG, Pan CQ, Lok AS, et al. AASLD-IDSA Practice Guideline on treatment of chronic hepatitis B. Hepatology. 2025;83(4):974-997. PubMed 41186418