Alcohol-associated Hepatitis

Natalie Vellutini

Background

  • Acute presentation of symptomatic hepatitis with the following criteria: 1) onset of rapidly progressive jaundice within previous 8 weeks 2) ongoing or recent heavy alcohol use (EtOH/day >40g in females or >60g in males for >6 mos with <60 days of abstinence) 3) moderately elevated liver biochemistries and total bilirubin and 4) exclusion of other liver pathology 
    • May present even if not actively drinking due to immunosuppressive effects of alcohol (<60 days of abstinence)
    • Risk Factors: Female sex, Hispanic ethnicity, binge drinking, cigarette use, obesity 
    • Signs/Symptoms: jaundice, anorexia, muscle wasting, fever, malaise, RUQ tenderness, and, if underlying cirrhosis, HE, GI bleeding, Ascites

Evaluation

  • Labs: CBC w/ Diff, BMP, HFP, INR, EtOH/PEth, UDS, Folate, B12 - AST >60, AST/ALT >= 1.5, both values <400 units/L; TBili >3.0 mg/dL 
  • Full infectious workup (CXR, UA/UCx, BCx, diagnostic paracentesis) regardless of symptoms 
  • Screen for other causes of acute hepatitis (viral hepatitis, ischemic hepatitis, DILI, biliary obstruction, autoimmune hepatitis, Budd-Chiari) 
    • Imaging: RUQ US with Doppler to r/u obstructive cause 
    • Biopsy is gold-standard for diagnosis but is not typically required, except in instances of uncertain diagnosis

Considerations

  • Phosphatidylethanol (PEth) level is a biomarker of ethanol consumption over ~ 4wks. A single consumption can result in detectable PEth for up to 12 days (note PETH may negative in patients with acute alcohol associated hepatitis). PEth >20 ng/mL can indicate chronic moderate/heavy alcohol intake. A negative test result can help confirm abstinence 
    • EtOH levels will be negative unless acutely intoxicated

Prognostication

  • Original MELD score > 20 (“severe”) indicates estimated 90-day mortality of 20 percent -- may benefit from pharmacologic treatment (steroids +/- NAC) 
  • Maddrey’s Discriminant Function score > 32 (also indicates “severe”) indicates poor 28d prognosis -- may benefit from pharmacologic treatment (steroids +/- NAC) 
  • Further criteria for steroid treatment seen further below. 
  • The Lille score assesses response to steroids after 7 d of therapy 
  • Lille score> 0.45 indicates no response to steroids and predicts 75% mortality at 6 months, supports cessation of steroids

Management

  • IV fluids and electrolyte replacement PRN, monitor for refeeding syndrome 
  • Consult nutrition, start high protein/high calorie diet 
  • Supportive Care and abstinence from alcohol 
  • Supplement with high dose thiamine x 3d, Folate, Pyridoxine, MVI 
  • Monitor on CIWA vs phenobarbital 
  • Psychiatry consultation for consideration of medical therapy for alcohol cessation 
  • For those with MELD > 20 or DF ≥ 32 (severe alcohol-associated hepatitis), can consider glucocorticoid therapy +/- NAC. Discuss with hepatology service as >20 clinical trials conducted with inconsistent results. Largest trial was the STOP-AH Trial which showed improved mortality at 28 days but not at 90 days in patients with MDF > 32. VA trial (patients with MDF >54) showed increased mortality, indicating a possible ceiling at which point steroids may be harmful 
  • Steroid treatment dose is PO prednisolone 40mg daily/IV methylprednisolone 32 mg daily (preferred over prednisone as it requires hepatic metabolism). 5 day IV NAC dosing protocol available on UptoDate 
  • Contraindications to steroids: active infection, GI bleeding, AKI w/ Cr >2.5 mg/dL 
  • Additional criteria is Neutrophil to Lymphocyte ratio on admission, if N:L ratio <5 unlikely to benefit. If N:L >8, high risk of infection. Therefore consider in patients with initial/admission N:L ratio of 5-8. 
  • Use Lille score (see above) on day 7 of steroid therapy to assess response 
  • Patients who do not respond to therapy may be evaluated for liver transplant 
  • Studies suggest most patients with alcohol-associated hepatitis have underlying cirrhosis – OP follow-up for diagnosis/management
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