Linking To And Excerpting From Addiction Medicine’s “#28 Alcohol-Associated Liver Disease with Dr. Lamia Haque” With Links To Additional Resources

Posted on January 7, 2025 by Tom Wade MD

In addition to today’s resource, please review:

Today, I review, link to, and excerpt from Addiction Medicine‘s #28 Alcohol-Associated Liver Disease with Dr. Lamia Haque.*

*Morford KL, Leyde S, Stahl N, Haque L, Chan, CA. “Alcohol-Associated Liver Disease”. The Curbsiders Addiction Medicine Podcast.https://thecurbsiders.com/addiction. August 8th, 2024.

All that follows is from the above resource.

 

Helping Patients Liver Longer

Maximize your treatment of alcohol-associated liver disease. Learn how to evaluate liver disease in patients with alcohol use disorder (AUD), choose AUD medications that are safe and effective, and identify patients who may be eligible for early liver transplantation. We’re joined by Dr. Lamia Haque, @lykhaque (Yale School of Medicine).

Claim CME for this episode at curbsiders.vcuhealth.org!

By listening to this episode and completing CME, this can be used to count towards the new DEA 8-hr requirement on substance use disorders education.

Learning objectives

After listening to this episode listeners will…

  1. Recognize the spectrum of liver disease associated with alcohol use disorder (AUD)
  2. Describe how to evaluate for liver disease in patients with AUD
  3. Identify safe and effective medications for AUD in patients with cirrhosis
  4. Recognize common requirements for liver transplant in patients with AUD

Production Partner: ACAAM

Show Segments

  • Intro, disclaimer, guest bio 0:00
  • Guest one-liner 3:10
  • Case from Kashlak 6:30
  • Epidemiology of alcohol-associated liver disease (ALD) 7:40
  • How does alcohol affect the liver? 11:11
  • Spectrum of ALD 13:10
  • Risk factors for ALD 16:13
  • Evaluating for ALD 19:35
  • When to refer to hepatology 33:08
  • Medications for AUD in patients with ALD 37:00
  • Monitoring liver tests for naltrexone 44:27
  • Optimizing treatment for patients who continue drinking 47:18
  • ALD and liver transplantation 50:45
  • Post-transplant care 1:00:15
  • Take-home points 1:02:30
  • Outro 1:04:56

Alcohol-Associated Liver Disease Pearls

ALD is the leading indication for liver transplants in the U.S., with a shift towards early transplantation for severe cases of alcohol-associated hepatitis guided by the Dallas Consensus Conference. This is an evolving area and practice variation between transplant centers exists..

The primary mechanisms of alcohol-induced liver injury involve direct toxicity mediated by metabolites such as acetaldehyde and reactive oxygen species, lipid metabolism, and immune-mediated processes leading to inflammation, fat accumulation, fibrosis, and necrosis.

Alcohol-associated liver disease (ALD) includes a spectrum of conditions, including steatosis, steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and acute alcohol-associated hepatitis.

Patients with alcohol use disorder (AUD) who have persistent liver test (LT) abnormalities or clinical signs of liver disease should be evaluated for fibrosis with transient elastography. Serum fibrosis marker panels are effective alternatives when transient elastography is unavailable.

Abstinence from alcohol is recommended for patients with ALD. When a patient is unable to stop drinking alcohol, a goal of moderation and safer alcohol use should be considered as a harm reduction strategy. Treatment involves both medications and psychosocial interventions to treat AUD and mitigate liver disease progression.

Most medications for AUD are safe in patients with ALD, although disulfiram is typically avoided in patients with cirrhosis or severe acute alcohol-associated hepatitis. Naltrexone is generally considered safe in patients with Child-Pugh Class A and B cirrhosis; it may be considered in those with Child-Pugh Class C cirrhosis balancing risks and benefits.

*Use Of The Child Pugh Score In Liver Disease from StatPearls. Andrea Tsoris; Clinton A. Marlar. Last Update: March 13, 2023.

Alcohol-Associated Liver Disease – Notes

Epidemiology of Alcohol-Associated Liver Disease (ALD)

In 2022, 46% of nearly 99,000 liver disease deaths in the U.S. involved alcohol (NIAAA, 2024). Rates of unhealthy alcohol use, alcohol use disorder (AUD), and ALD were all increasing prior to the COVID-19 pandemic and further increased during the pandemic (Deutsch-Link, 2022). The highest relative increases in ALD-related mortality from 2017 to 2020 were among women, younger adults (ages 25-34), and Native American and Alaska Native populations (Deutsch-Link, 2022).

How does alcohol affect the liver? 

Alcohol is primarily metabolized in the liver by the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (AHDH). ADH metabolizes ethanol to acetaldehyde, a highly toxic substance and carcinogen. AHDH then metabolizes acetaldehyde to acetate, which is broken down into water and carbon dioxide for elimination from the body (NIAAA, 2022).

Alcohol causes liver injury both from direct toxicity of acetaldehyde as well as immune-mediated processes that lead to inflammation (Li, 2019, Rusyn & Bataller, 2013). The impairment of immune function increases the risk of infections, which are a main cause of morbidity and mortality among patients with ALD.

Spectrum of ALD

ALD represents a spectrum of conditions ranging from steatosis to more advanced forms including acute alcohol-associated hepatitis, cirrhosis, and hepatocellular carcinoma (Crabb, 2019). The progression of ALD does not follow a predictable timeline and can vary significantly between individuals. Factors influencing progression include the amount and duration of alcohol consumption, female sex, genetic predisposition, coexisting liver conditions, and overall health (Ramkissoon & Shah, 2022).

Steatosis is the initial and most common response of the liver to heavy alcohol consumption. It involves the accumulation of fat within liver cells. Alcohol metabolism in the liver increases the synthesis and deposition of fatty acids, leading to fat accumulation. Steatosis affects about 90% of individuals who engage in heavy drinking for approximately two weeks. Steatosis is reversible if the individual stops drinking alcohol. Abstinence for several weeks can lead to the liver returning to its normal state.

Steatohepatitis is a more severe form of liver disease where inflammation accompanies fat accumulation. It develops in up to 35% of individuals with steatosis (Gao, 2018). Persistent inflammation can further damage liver tissue and lead to more severe conditions such as fibrosis and cirrhosis.

Fibrosis refers to the formation of a fibrous scar from the accumulation of extracellular matrix proteins that replace damaged normal tissue in the liver (Kisseleva & Brenner, 2020). Chronic liver damage from alcohol stimulates the production of collagen and other extracellular matrix components, leading to scar tissue formation. While fibrosis itself may not cause symptoms, it can progress to cirrhosis, where the liver’s structure and function are significantly impaired.

Cirrhosis is the advanced stage of liver fibrosis that results from the accumulation of fibrotic tissue over time. It is characterized by severe scarring and significant alteration of liver architecture.

Decompensated cirrhosis occurs when the liver can no longer perform its vital functions resulting in a range of severe complications, including:

  • Ascites: Accumulation of fluid in the abdominal cavity, the most common complication.
  • Variceal Hemorrhage: Bleeding from varices, which are enlarged veins primarily in the esophagus or stomach.
  • Hepatic Encephalopathy (HE): Cognitive dysfunction due to the liver’s inability to detoxify substances in the blood.
  • Hepatorenal Syndrome (HRS): Kidney failure associated with severe liver disease.
  • Hepatopulmonary Syndrome (HPS): Impaired pulmonary function due to severe liver disease.

Hepatocellular Carcinoma (HCC): A primary liver cancer that can develop as a consequence of chronic liver inflammation and cirrhosis.

Acute Alcohol-Associated Hepatitis: A severe form of liver inflammation that can occur suddenly in people with heavy alcohol use. It can be mild, moderate, or severe and often requires urgent medical attention if severe.

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