Alcohol-associated liver disease (ALD) is the most common cause of advanced hepatic disease worldwide. Increasing alcohol use over the past decade has led to significant healthcare burden as rates of this preventable disease rise.
The American College of Gastroenterology convened a team of experts with the goal of helping clinicians recognize and treat ALD. This resulted in practice guidelines recently published in the American Journal of Gastroenterology.
To find out more about best practices surrounding ALD, Medscape contributor Nancy S. Reau, MD, chief of the hepatology section at Rush University Medical Center in Chicago, spoke with the guidelines' lead author, Ashwani Singal, MD, MS, professor of medicine at the University of Louisville School of Medicine, transplant hepatologist at the University of Louisville Health and Jewish Hospital, and director of clinical trials in liver diseases at the University of Louisville in Kentucky, as well as a health research scientist at VA Medical Center in Sioux Falls, South Dakota.
The Changing Face of ALD
How has the epidemiology of ALD changed significantly in the United States?
The availability of effective medications for hepatitis C virus infection in the past decade has shifted the burden away from it and toward other liver diseases. At the same time this shift was occurring, alcohol use was also increasing, especially during and after the COVID-19 pandemic. This has resulted in a higher rate of ALD-associated morbidity and mortality.
Specifically, the ALD-related burden has increased in young individuals in their third or fourth decade who are at the prime of their productive life, in females, and in racial/ethnic minorities.
In 2017, alcohol contributed to 47.9% of all cirrhosis-related hospitalizations, resulting in 27.3% of cirrhosis-related mortality.
From 2012 to 2016, alcohol-associated cirrhosis was estimated to have a $22.7 billion healthcare cost burden.
A 2019 analysis reported that ALD was the primary indication for liver transplantation in over 40% of cases in the United States.
Clinicians should screen patients at any healthcare encounter to identify at-risk populations, to identify those with ALD, and refer them to mental health specialists.
Treatment should then be designed to reduce alcohol use and the risk of developing advanced stages of ALD like cirrhosis and alcohol-associated hepatitis (AH).
What are common risk factors for ALD, and what tools can help clinicians screen for ALD?
The most important factor that puts individuals at risk for ALD is amount and duration of alcohol use.
Harmful alcohol use is defined as ≥ 2 drinks/day or ≥ 7/week in women and ≥ 3 drinks/day or ≥ 14/week in men. A standard drink, as defined by the National Institute on Alcohol Abuse and Alcoholism in the United States, is 12 oz of beer (5% weight/volume [w/v]), 5 oz of wine (12% w/v), or 1.5 oz of hard liquor (40-45% w/v).
Only 10%-20% of individuals using alcohol in an amount over the threshold for ALD risk go on to develop advanced-stage ALD.
Other disease modifiers, like gender (higher risk in females), obesity and metabolic syndrome with diabetes, and concomitant liver diseases like chronic viral hepatitis B or C infection, increase the ALD risk among at-risk populations.
Certain genetic polymorphisms of genes, like PNPLA3 (patatin-like phospholipase 3), MBOAT7 (membrane-bound O-acyltransferase 7), and TM6SF2 (transmembrane 6 superfamily member 2), also have synergistic interaction with alcohol to increase the risk for ALD.
Clinicians who identify at-risk individuals should screen for ALD with ultrasound examination and liver biochemical panel as the initial screening tests.
Is there a type of alcohol that is "safer" or, conversely, that is more harmful?
Any alcohol type, if taken in amounts higher than the threshold, increases the risk. However, data show that this risk may be higher with hard liquor than with wine.
In terms of pattern of drinking, ALD risk is higher with binging of alcohol (> 4 drinks in women and > 5 drinks in men over a period of 2 hours) and drinking on an empty stomach.
Are there individuals at higher risk for ALD who should avoid alcohol consumption?
Individuals who are overweight/obese, have metabolic syndrome and/or diabetes, have chronic viral hepatitis B or C or any other concomitant liver disease, or concomitant smokers or users of nicotine are at higher risk for ALD.
In the context of obesity, those who have had previous Roux-en-Y gastric bypass surgery are at higher risk for alcohol use and development of ALD.
Young individuals and Native Americans, due to higher use of alcohol, especially binging, and females are also at higher risk for ALD.
Why are patients who have had obesity surgery at higher risk for ALD?
After gastric bypass surgery, about 10%-20% of individuals develop alcohol use disorder (AUD). Surgery-induced anatomical and physiologic changes also change alcohol metabolism.
The risk is higher in young people, in males, and in those with a previous history of alcohol or other substance use disorder.
Taking Advantage of Biomarkers and Diagnostic Tests
Several biomarkers can help with ALD management. Can you discuss how to use them?
There are biomarkers to determine fibrosis risk and stage the disease.
The Fibrosis-4 score (FIB-4) is an algorithm using aspartate aminotransferase, alanine transaminase, platelets, and age.
There's also FibroScan, which is used with cut-offs of 3.25 and 12 kPa liver stiffness measurement to rule out advanced fibrosis or cirrhosis. It should be noted that FibroScan can be confounded by active alcohol use and inflammation with overestimation of liver stiffness and fibrosis risk. Hence, it should ideally be repeated after 1-2 weeks of alcohol abstinence for accurate estimation of fibrosis risk.
Enhanced liver fibrosis score and magnetic resonance elastography are more specific tests for diagnosis of advanced fibrosis, but they are limited by cost and widespread availability.
Self-reported alcohol use can be unreliable; in a systematic review of seven studies, 6%-56% of patients underreported alcohol use. Biomarkers of alcohol metabolism can help substantiate this information.
Of all the metabolites, whole blood phosphatidylethanol level measurement is a specific biomarker for identifying ongoing alcohol use within a time window of up to 3-4 weeks prior to its measurement.
What can gastroenterologists and primary care physicians do for patients who are identified with ALD and AUD?
At any healthcare encounter, it is important to screen for AUD while obtaining a social history.
Alcohol Use Disorders Identification Test-Consumption is a simple three-item questionnaire to accurately identify those with AUD, and it can be completed in less than a minute.
If AUD is identified, use simple markers, such as FIB-4 and FibroScan, to identify those with advanced fibrosis/cirrhosis or with AH, and refer these to hepatology.
For those with established cirrhosis, referral to transplant center is recommended if decompensated (hepatic encephalopathy, ascites, variceal bleed, hepatocellular carcinoma) and/or with a Model for End-Stage Liver Disease (MELD) score of > 17, even after 2-3 months of abstinence.
Clinicians should also provide a brief intervention through counseling on the harmful effects of alcohol to help reduce ongoing alcohol use.
How is AH different from ALD? What patient with AH is at risk for liver failure?
AH is a unique clinical phenotype of ALD presenting with jaundice in patients with ongoing alcohol use (last drink within previous 8 weeks). Frequently they have features of systemic inflammatory response syndrome, even in the absence of infection (sterile systemic inflammatory response syndrome).
It is important to recognize AH, as it is amenable to treatment with corticosteroids. If left untreated, there is a risk for up to 90% mortality at 3 months in the most severe forms with acute-on-chronic multiorgan failure.
Patients with severe AH, ongoing alcohol use, and superimposed bacterial or fungal infections are at high risk for liver failure. Hence, these patients should be hospitalized for comprehensive management to improve outcomes.
Even patients with a moderate episode of AH (ie, a MELD score ≤ 20) have a potential risk of dying: 6%-12% at 90 days and 13%-20% at 1 year from presentation.
Are there tools that can help a clinician identify those who are at high risk for complications or those responding to treatment?
When it comes to determining the severity of AH, patients having a MELD score of > 20 and/or presence of hepatic encephalopathy, and who meet the clinical and/or histologic criteria of AH, determines a severe episode of AH.
These patients are also potential candidates for corticosteroid therapy.
For measuring the response to medical therapy, including corticosteroids, the Lille score can be used.
A Lille score of > 0.45 on days 4-7 of starting medical therapy defines a response to treatment. An online tool is available for the Lille score in AH. The major factor in its calculation is a change in bilirubin by days 4-7 of treatment.
There is a clear unmet need for biomarkers to identify patients likely to further progress to severe disease. Biomarkers should be incorporated into clinical trials for drug development.
Nancy S. Reau, MD, is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to Medscape. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels.
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Cite this: Nancy S. Reau. Alcohol-Associated Liver Disease Is On the Rise: What to Know - Medscape - Mar 11, 2024.
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