Alcohol-associated hepatitis

To see contributor disclosures related to this article, hover over this reference: ^[1]

Physicians may earn CME/MOC credit by reading information in this article to address a clinical question, and then completing a brief evaluation, in which they will identify their question and report the impact of any information learned on their clinical practice.

AMBOSS designates this Internet point-of-care activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should claim only credit commensurate with the extent of their participation in the activity.

For answers to questions about AMBOSS CME, including how to redeem CME/MOC credit, see "Tips and Links" at the bottom of this article.

Alcohol-associated hepatitis is a clinical syndrome with a broad range of manifestations, from vague malaise to fulminant liver failure. The diagnosis should be considered in patients with a history of heavy alcohol use who develop jaundice, fever, leukocytosis, and tender hepatomegaly. Typical liver chemistry findings include elevated transaminases and hyperbilirubinemia. Diagnosis is often clinical, with liver biopsy reserved for uncertain cases after excluding other differential diagnoses. The MELD score helps assess disease severity and prognosis and guide therapy. Complete alcohol abstinence is the key intervention. Supportive care includes nutritional support, monitoring for alcohol withdrawal, and treatment for alcohol use disorder. Patients with severe alcohol-associated hepatitis may benefit from glucocorticoids (with or without N-acetyl cysteine) or early liver transplantation. Those unresponsive to glucocorticoids and ineligible for transplant should be referred for palliative care.

• Incidence: ∼ 0.8% of all hospitalizations in the US per year ^[2][3]
• Survival ^[4]
  • 4-year survival: ∼ 58%
  • 1-year survival in patients with concomitant cirrhosis: ∼ 35%
  • 6-month survival for severe alcohol-associated hepatitis that does not respond to medical therapy: ∼ 30%

Epidemiological data refers to the US, unless otherwise specified.

• Risk factors include: ^[2][3][4][5]
  • History of chronic heavy alcohol use
  • Cigarette smoking
  • Genetic predisposition
  • Female sex ^[5]
  • Nutritional factors: obesity, malnutrition
  • Viral hepatitis: e.g., hepatitis C

• Acute hepatitis: : tender hepatomegaly, acute jaundice, malaise, nausea, anorexia, fatigue, fever, weight loss, tachypnea
• Acute alcohol withdrawal: tremor, agitation, tachycardia, alcohol withdrawal seizures, alcohol withdrawal delirium
• Long-term alcohol use: rhinophyma, Dupuytren contracture, sarcopenia, temporal muscle wasting
• Cirrhosis: : clinical features of liver cirrhosis (e.g., jaundice, ascites, palmar erythema, spider angiomata)

Acute alcohol-associated hepatitis may be reversible in mild cases. ^[2][3]

Symptoms of alcohol-associated hepatitis are nonspecific. The presence of acute-onset jaundice can help differentiate acute alcohol-associated hepatitis from decompensated cirrhosis. ^[6]

Approach ^[3][7]

Suspect alcohol-associated hepatitis in patients with suggestive clinical features and a history of chronic heavy alcohol use.

• Use the consensus definitions for alcohol-associated hepatitis to establish a definite, probable, or possible diagnosis.
• Obtain laboratory and imaging studies to support the diagnosis and rule out differential diagnoses.
• Perform a thorough infectious disease workup guided by clinical suspicion.
• Consider referral for transjugular liver biopsy if the diagnosis remains uncertain.
• Assess severity using the MELD score.
• Identify patients with alcohol use disorder (e.g., using the AUDIT-C score).

The presence of systemic inflammatory response syndrome (SIRS) criteria at admission is a predictor of multiorgan failure (especially AKI) and early death. ^[7]

Infections are common in patients with alcohol-associated hepatitis and are associated with a poorer prognosis. An infectious disease workup is recommended in all patients. ^[7]

Consensus definitions for alcohol-associated hepatitis ^[3][4][7]

• Clinical diagnosis of alcohol-associated hepatitis
  • Onset of jaundice within the past 8 weeks
  • ≥ 6 months of ongoing alcohol consumption above the threshold and < 60 continuous days of abstinence from alcohol before jaundice onset
    • > 40 g alcohol per day for female patients
    • > 60 g alcohol per day for male patients
  • Characteristic liver chemistries in alcohol-associated hepatitis
• Confounding factors
  • Atypical laboratory results
  • Uncertain alcohol use
  • Presence of other potential causes of liver disease; see “Differential diagnoses of alcohol-associated hepatitis.”
• Classification
  • Definite alcohol-associated hepatitis: clinical diagnosis PLUS histological confirmation
  • Probable alcohol-associated hepatitis: clinical diagnosis
  • Possible alcohol-associated hepatitis: uncertain clinical diagnosis because of the presence of confounding factors

Initial studies ^[3][7]

Laboratory studies

• Liver chemistries in alcohol-associated hepatitis
  • AST: > 50 IU/L
  • Both AST and ALT: < 400 IU/L
  • AST:ALT ratio: > 1.5
  • Total bilirubin: > 3 mg/dL
• Additional liver studies ^[4]
  • GGT: > 100 IU/L
  • ALP: ↑
  • INR: > 1.5
  • Albumin: < 3 g/dL
• CBC
  • WBC: > 12,000/mm³
  • Platelets: ↓ or ↑
  • Macrocytic anemia; (↓ hemoglobin with ↑ MCV)
• BMP: to assess for AKI and calculate severity scores

AST > ALT in alcohol-associated hepatitis: Remember “make a toAST with alcohol!”

Imaging studies ^[7]

Obtain imaging studies in all patients to rule out differential diagnoses (e.g., portal vein thrombosis, Budd-Chiari syndrome, HCC, biliary obstruction with cholangitis). ^[7]

• RUQ ultrasound with Doppler: (preferred): may show findings of fatty liver disease; (e.g., steatosis, hepatomegaly, and periportal edema) and/or cirrhosis ^[5]
• CT or MRI abdomen: : may show findings of fatty liver disease ; (e.g., decreased liver attenuation, heterogeneous steatosis) and/or cirrhosis ^[5][8]

Additional diagnostic workup ^[7][9]

Obtain additional studies to exclude differential diagnoses and identify comorbidities; workup should be guided by clinical suspicion and may include the following:

• Infection
  • Workup for sepsis
  • Viral hepatitis panel
• Autoimmune hepatitis: e.g., ANAs, anti-smooth muscle antibodies, IgG levels
• Metabolic liver disease: e.g., serum ceruloplasmin, alpha-1 antitrypsin levels
• Drug-induced liver injury: e.g., medication review, urine toxicology, serum acetaminophen levels
• Metabolic dysfunction-associated steatotic liver disease (MASLD): e.g., alcohol-associated liver disease/nonalcoholic fatty liver disease index (ANI) to help differentiate alcohol-associated liver disease from MASLD ^[10]

Sepsis should always be ruled out in patients with alcohol-associated hepatitis and SIRS.

Liver biopsy ^[3][7]

• Indications: (not routinely recommended)
  • Unclear diagnosis because of the presence of confounding factors (e.g., chronic jaundice)
  • Uncertain alcohol consumption
  • Recruitment to a clinical trial
• Technique: Transjugular liver biopsy is preferred. ^[7]
• Findings: signs of alcoholic steatohepatitis and/or cirrhosis (see “Pathology” in “Alcoholic liver disease” for details).

Histopathological findings of alcohol-associated steatohepatitis may be indistinguishable from findings of metabolic dysfunction-associated steatohepatitis; the ANI can help differentiate between the two.

• Prognostic scoring systems are used to guide management and determine disease severity.
• Severe alcohol-associated hepatitis is defined as MELD score > 20. ^[7]

• Other alcohol-associated liver diseases (e.g., decompensated cirrhosis)
• MASLD
• Infection (e.g., acute cholangitis)
• Biliary obstruction (e.g., stones, tumors, strictures)
• Drug-induced liver injury (e.g., due to the use of acetaminophen, cocaine, prescription pharmaceuticals)
• Acute viral hepatitis (e.g., hepatitis A, hepatitis B, hepatitis C)
• Autoimmune hepatitis
• Metabolic liver disease, e.g., Wilson disease, α1-antitrypsin deficiency
• Ischemic hepatitis (e.g., due to hypotension, shock, massive blood loss, or cocaine or other vasoconstrictor use)

AST > 400 IU/L should raise concern for drug-induced liver injury or ischemic hepatitis. ^[4]

The differential diagnoses listed here are not exhaustive.

Approach ^[3][7]

• Advise immediate alcohol cessation; no amount of alcohol consumption is considered safe. ^[6]
• Assess for alcohol withdrawal syndrome: Calculate the patient's CIWA-Ar score. ^[6][7]
• Provide management for alcohol withdrawal (e.g., benzodiazepines), and management of alcohol use disorder.
• Ensure adequate calorie and micronutrient intake.
• In patients with severe disease (i.e., MELD > 20), consider glucocorticoid therapy, IV n-acetylcysteine (NAC), and referral for early liver transplantation.
• Prevent and manage comorbidities and complications.
• Consult palliative care for patients who do not improve with glucocorticoid therapy and are not eligible for early liver transplant.

Alcohol cessation is the only management strategy with proven long-term benefits in alcohol-associated hepatitis. ^[3][5][7]

Alcohol cessation may lead to alcohol withdrawal syndrome. ^[2]

Disposition ^[2]

Consider ICU admission in any of the following situations:

• Extrahepatic organ failure
• Stage III or IV hepatic encephalopathy
• Respiratory failure or the need for ventilatory support
• Hemodynamic instability or septic shock

Nutritional support ^{[3][6][7][15]}

Patients with alcohol-associated hepatitis may be very malnourished. Consider specialist consultation for specialized nutritional support.

• Enteral route is preferred.
• Ensure a caloric intake of 35–40 kcal/kg/day.
• Daily protein requirement: 1.2–1.5 g/kg
• Replete zinc and other trace elements.
• Replete thiamine and other B-complex vitamins.
• IV albumin is preferred over IV crystalloids for volume replacement.

Pharmacological therapy ^[3][7]

Glucocorticoids ^[7]

• Indication: : Severe alcohol-associated hepatitis (i.e., MELD score > 20) and no contraindications ^[3][7]
• Preferred agents
  • Prednisolone (off label) ^[7]
  • Methylprednisolone (off label) ^[7]
• Monitoring: Calculate the Lille score to assess response after 4 or 7 days of treatment with glucocorticoids. ^[7][12]
  • Lille score > 0.45: Patient is not responding; stop glucocorticoids and consider further treatment options (e.g., supportive care, palliative care, early liver transplantation).
  • Lille score ≤ 0.45: Patient is responding; continue glucocorticoids to complete 28 days of treatment, followed by 2–4 weeks of taper.

Patients who do not respond within the first week of glucocorticoid treatment are unlikely to derive benefit from continued treatment. ^[7]

Other medications ^[7][16]

• N-Acetylcysteine ^[7][17]
  • May reduce complications and mortality when given as a 5-day infusion in combination with glucocorticoids
  • Evidence that N-acetylcysteine improves outcomes is limited, but the risks of treatment are low.
• Pentoxifylline: no longer recommended

Early liver transplantation ^[3][7][18]

• Definition: liver transplantation without 6 months of abstinence from alcohol
• Consider in patients with the following:
  • No response to medical management
  • Favorable psychosocial profiles

Liver transplantation should be considered in selected patients with acute alcohol-associated hepatitis, even if they have not abstained from alcohol for the required 6 months.

Management of complications and comorbidities

Monitor for and manage the following:

• Infection and sepsis (routine use of prophylactic antibiotics is not recommended)
• Complications of cirrhosis (e.g., ascites, hepatic encephalopathy, esophageal variceal hemorrhage)
• Prevention of AKI and hepatorenal syndrome (e.g., avoidance of nephrotoxins and cautious use of diuretics)
• Mental health disorders and psychosocial factors (e.g., major depressive disorder, generalized anxiety disorder)

• Check indications for ICU level of care.
• Obtain initial studies (e.g., CBC, liver chemistries, BMP, INR, RUQ ultrasound).
• Obtain an infectious disease workup (e.g., blood cultures).
• Consider referral for liver biopsy if confounding factors (e.g., differential diagnoses of alcohol-associated hepatitis, uncertain alcohol use) are present.
• Assess disease severity using the MELD score.
• Start glucocorticoid therapy in patients with severe disease and no contraindications.
• Monitor response to glucocorticoids using the Lille score.
• Monitor and manage patients for alcohol withdrawal syndrome (e.g., using the CIWA-Ar score).
• Encourage abstinence from alcohol and provide treatment for alcohol use disorder.
• Consider referral for liver transplant in patients with severe disease who are unresponsive to supportive management and pharmacological treatment.