Linking To And Excerpting From CoreIM’s “Alcohol-Associated Hepatitis: 5 Pearls Segment”

Today, I review, link to, and excerept from CoreIM‘s Alcohol-Associated Hepatitis: 5 Pearls Segment.

All that follows is from the above resource.

Posted: November 9, 2022
By: Dr. Sean Burke, Dr. Shreya P. Trivedi, Dr. Elliot Tapper, Dr. Kavish Patidar, Dr. Martin Fried and Dr. Indira Bhavsar-Burke
Graphic: Dr. Sam Woodworth
Audio: Daksh Bhatia
Peer Review: Dr. Alan Bonder, Dr. Nikhilesh Mazumder

Podcast: Play in new window | Download

Time Stamps CME-MOC Show Notes Transcript References

DILI – Drug Induced Liver Disease: Drug-Induced Hepatotoxicity from StatPearls. Last Update: September 10, 2024.

Autoimmune Hepatitis from StatPearls. Last Update: August 14, 2023.

Diagnosis of HELLP/AFLP – Google Search

MDF – Maddrey’s Discriminant Function for Alcoholic Hepatitis from MDCalc. “Predicts prognosis and steroid benefit in alcoholic hepatitis.”

MELD – Model for End-Stage Liver Disease (Combined MELD) from MDCalc. “Offers multiple versions of MELD for liver transplant planning.”

Sponsor: This episode is made possible with support from Panacea Financial. Panacea Financial is a national digital bank built for doctors by doctors. Visit panaceafinancial.com today to open your free account and join the growing community of physicians nationwide who expect more from their bank. Panacea Financial is a division of Primis, member FDIC.

Time Stamps

• 01:42 Intro
• 04:37 Pearl 1: Diagnosis
• 13:20 Pearl 2: Differential & Treatment
• 20:48 Pearl 3: Nutrition & Alcohol Cessation
• 27:45 Pearl 4: To steroids or to not steroids?!
• 35:34 Pearl 5: Throwback

CME-MOC

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Show Notes

There has been a significant uptick in alcohol use and alcohol-associated liver disease during the pandemic.

Pearl 1: How do you diagnose alcoholic hepatitis? Why is this important?

• Diagnosis is usually made by clinical history and laboratory values:
  • Typically with long history of drinking (e.g. 10+ years), with usually increase alcohol consumption over last 3-6 months
  • Symptoms often vague but may present with anorexia, malaise.
    • Patients usually jaundiced
      • Onset of jaundice within 60 days of heavy alcohol consumption for a minimum of 6 months
  • Patients with cirrhosis can present with acute on chronic liver failure (e.g. hepatic encephalopathy, variceal hemorrhage, increase in ascites, AKI)*
    • Acute on Chronic Liver Failure from StatPearls. Last update, June 2, 2025.
  • Moderately elevated AST, ALT
    • Typically less than 300 -400U/L
  • AST/ALT ratio > 1.5-2/1
  • Serum Bilirubin >3 mg/dL
• Alcohol-associated hepatitis is an immune-mediated reaction that is multifactorial.
  • There is an initial direct insult to the liver by alcohol which leads to the recruitment of inflammatory cells.
  • Alcohol also leads to disruption of the gut barrier which leads to bacterial translocation and inflammation.
  •  This is why symptoms can often be delayed by 2 months from heavy drinking until presentation.
• Patients with history of gastric bypass are at higher risk for developing alcohol-associated hepatitis.
• Other risk factors
  • Biologic females, because of lower amount of gastric alcohol dehydrogenase 
  • Smoking history
  • Genetic Component
  • Metabolic syndrome

Pearl 2: Differential Diagnosis and Workup

• What other things should you consider in your differential diagnosis?
  • When diagnosing, should exclude other causes:
    • Anti-hepatitis A IgM
    • Hepatitis B surface antigen, anti-hepatitis B core IgM
    • Anti-hepatitis C virus (HCV) antibodies
    • Drug screen including serum acetaminophen levels
    • Biliary obstruction or Budd-Chiari syndrome using transabdominal ultrasound
• True list of differential is much longer but should be considered based on patient demographics (e.g. HELLP, AFLP, DRESS, Autoimmune Hepatitis).
  • DILI is also considered but is a diagnosis of exclusion so labs should be ordered regardless.
    • DILI – Drug Induced Liver Disease: Drug-Induced Hepatotoxicity from StatPearls. Last Update: September 10, 2024.
• Workup should also include ruling out infection including blood cultures, urine cultures, CXR, peritoneal fluid studies and culture if appropriate since a large portion of patients with alcohol-associated hepatitis will die from infection.

Pearl 3: Nutrition and Alcohol Cessation

Alcohol cessation and nutrition are interventions most linked to improved mortality

• Abstinence of alcohol after episode of alcohol associated hepatitis positively impacts long term survival.
  • It reduces risk of mortality by close to 50%. 
• Patients with cirrhosis have a reduction in decompensation and mortality with abstinence.
• Hospitalization is a good opportunity to discuss abstinence
  • A recent study of over 35,000 patients with ALD found less than 2% were started on medical therapy for AUD.
• Correction of nutritional deficiencies:
  • Some studies have shown 100% of patients with alcohol associated liver disease have some form of malnutrition. 
• Pathophysiology: Alcohols metabolized first and impairs absorption and digestion of macro- and micro-nutrients.
  • Mechanisms including exocrine pancreas insufficiency, increased gut wall permeability, portosystemic shunting, and an early shift to gluconeogenesis in patients with portal HTN while fasting.
    • Directly leads to decreased absorption of proteins, carbs, and fats as well as impaired absorption of micronutrients
  • AH induces a profound catabolic state and patients are at risk for malnutrition given their drinking habits.
• General guidelines include:
  • Nutrition should be provided orally if able but enteral access should be obtained if patients do not meet calorie goals.
  • Supplement nutrition with thiamine, folate, multivitamin.
  • Avoid maintenance fluid to avoid fluid retention.
  • Monitor for refeeding and consider vitamin K supplementation if needed.
  • Target approximately 30calories/kg per day, with 1-1.5 g/kg protein

Pearl 4: Prognostication and steroids

• MELD score is the best indicator at this point and has been used more commonly to risk stratify patients with Alcohol associated hepatitis.
• Maddrey Discriminate Function is used to decide use of steroids.
  • Can only deem high risk vs low risk
  • Score >32 indicates poor prognosis
• Steroids or nah?
  • Of note, mortality from AAH has not improved over the past decades. About one in 5 patients will die in 6 months.
  • Steroids:
    • STOPAH trial is probably the most cited trial.
      • RCT Evaluated both prednisilone and PTX [Pentoxifylline]. Prednisolone was associated with nonsignificant mortality benefit at 28 days but no benefit at 90 days or 1 year.
    • Mild forms can be treated conservatively
      • (MDF < 32 or MELD < 20).
    • More severe forms consider treatment
      • (MDF > 32 or MELD > 20).
    • Usual course of treatment is ~28 days followed by taper.
    • Can use Lille score to see if steroids are improving and can help guide early termination of steroids.
      • Initial model used 7 days but 4 day score can also be used.
    • If steroids will be used, infection must first be ruled out.
    • Diagnosis of an infection at the time of presentation does not mean that steroids can never be used – the infection just needs to be under control prior to starting them.
    • There is no data to support immediate use of steroids.
      • Delaying steroids for a few days won’t harm the patient but starting them hastily may cause problems. Steroids are often not started in the presence of AKI either.
    • Cochrane review of 721 patients concluded that glucocorticosteroids did not statistically reduce mortality but there was a trend toward benefit.
• Pentoxyfyline
  • Older studies showed possible benefit but STOPAH trial showed no mortality benefit.
• NAC:
  • Some consideration for use of NAC [N-Acetylcysteine]; can be used in some patients as studies showed a trend toward significance but overall mainstay of treatment is nutrition +/- steroids.
• Liver transplant is an option but an ethical dilemma because alcohol associated hepatitis implies recent drinking which usually precludes transplant.
  • Some centers will perform transplant in highly selective patients with AAH.

Pearl 5: Throwback

• Throwback pearl? How do you treat EtOH use disorder?
  • Supportive care should be offered to everyone including peer support groups, 12-step groups, and psychiatric support and counseling.
  • Medications
    • First line
      • Naltrexone – One of the most effective meds for AUD. NNT is 12. Traditionally taught to avoid in cirrhosis due to hepatotoxicity though data is emerging that it can be safely given in patients with alcohol liver disease. Many argue that the risk of ongoing drinking outweighs the theoretical risk of liver injury and one study found decrease in liver enzymes with naltrexone (through abstinence)
      • Acamprosate – has not been studied in patients with lvier disease but is thought to be safe because does not undergo hepatic metabolism.
    • Second line
      • Topamax and gabapentin – Their well-known side effect profiles (including memory impairment and somnolence, respectively) at the doses required to achieve efficacy may hinder their broader use in the outpatient setting.
      • Baclofen – individual studies have shown effectiveness compared with placebo in reducing alcohol intake and increasing abstinence rate among patients with alcohol use disorder and chronic liver disease. However, Cochrane review of all RCTs has not shown overall effectiveness in patients with alcohol use disorder when compared to placebo.
    • Emerging therapy
      • New study showing patients receiving psilocybin plus psychotherapy reduced their heavy drinking days.