Spotlight on MetALD

Hanna Blaney, MD, MPH, from Virginia Commonwealth University, set the stage by describing MetALD as a distinct disease entity from MASLD, where elevated alcohol use interacts with cardiometabolic risk factors (hypertension, hypertriglyceridemia, diabetes, obesity, and HDL elevation). MetALD has a global prevalence of 4% and US prevalence of 2.6%, which is higher than alcoholic liver disease (ALD). MetALD is the third leading reason for liver transplant, and these patients have worse pre- and posttransplant prognoses than those with ALD and a higher mortality rate than those with MASLD. Diagnosis of MetALD requires at least one cardiometabolic risk factor and current or historical high alcohol use, and noninvasive testing (NIT) us used to stage the disease (e.g., Fib-4, fibrosis score), confirmed with transient elastography. Binge drinking increases premature mortality risk.

Lamia Haque, Yale University School of Medicine, focused on how to approach diagnosis of alcohol use disorder (AUD) to distinguish between MASLD and MetALD. High-risk alcohol consumption that can lead to AUD and its complications is defined by the NIAAA as more than 15 drinks per week in men and more than 8 drinks per week in women, with a standard drink measured as 14 grams of alcohol (12 ounces of beer, 5 ounces of wine, and 1.5 ounces of liquor). Patients with health conditions that can be exacerbated by alcohol, such as SLD, should be counseled that there is no safe level of alcohol consumption, that “low risk” does not mean “no risk,” and that alcohol is directly connected to worsening liver disease. Alcohol cessation is a crucial part of treatment and patients should be screened for AUD. Screening tools such as the 3-question Alcohol Use Disorders Identification Test – Consumption (AUDIT-C) can be embedded in the EHR to assist in diagnosis. The Single Question Alcohol Use Test (SASQ) is even simpler, and can be used as a starting point to prompt more specific questions. Phosphatidylethanol (PEth) blood testing is increasingly being used as a complement to patient-reported alcohol use to diagnose MetALD. If PEth is not available, urine or serum ethyl glucuronide (EtG) could be measured. Quantifiable markers of alcohol consumption can sometimes become motivational tools for patients, and it is important to explain that it can be hard to keep track of the number of “standard” drinks and the test as a way to determine how much alcohol the body is being exposed to. Motivational interviewing and shared goal setting are helpful for engaging patients. Dr. Haque recommended the 2024 position statement on MetALD for further reading.

Cynthia L. Hsu, MD, PhD, from University of California San Diego, discussed treatment options for cardiometabolic risk factors in MetALD. Most evidence for treatment benefits come from MASLD trials. Managing metabolic dysfunction through lifestyle modifications and weight loss is important to reduce risk. A Mediterranean diet and exercise can improve outcomes of liver disease independent of weight loss. Bariatric surgery can improve outcomes of MASLD, but must be approached with caution in the setting of MetALD; alcohol reaches the liver faster and can cause more damage. For this reason, AUD treatment and alcohol cessation must occur before bariatric surgery.

Statin use is associated with lower all-cause mortality and liver-related events in MASLD. The GLP-1 receptor agonist semaglutide improved steatosis and fibrosis in MASLD (at lower doses), and a 2026 study showed a benefit in patients with obesity and AUD (at typical doses). PPAR agonists target hepatic carbohydrate and lipid metabolism and improve steatosis and fibrosis in MASLD, but these agents need to be used with caution in AUD because they can worsen cravings. Other adverse effects include weight gain, lower limb edema, and bone loss. A dual-PPAR agonist, lanafibranor, is in the pipeline. SGLT2 inhibitors are a mainstay of treatment for diabetes and can also be used in SLD, but are not recommended in those with active, heavy alcohol use because of the risk of ketosis. The thyroid hormone receptor-beta agonist resmetirom was first approved for metabolic dysfunction-associated steatohepatitis (MASH) and causes a significant reduction in steatohepatitis and fibrosis, but the interaction with alcohol use is unknown. A subset of patients in the MAESTRO-NASH study of resmetirom likely had MetALD, however. Many other medications are being tested in clinical trials, though most trials exclude individuals with severe alcohol consumption. FXR agonists (e.g., obeticholic acid) can reduce liver fat content in MASH, but studies have excluded those with AUD. FGF21 agonists (e.g., efruxifermin) are in the pipeline for treatment of AUD, and may also be beneficial for MetALD, but more studies are needed.

Margarita Nisman German, MD, from the University of Wisconsin, Madison, finished the session with a discussion of the need to provide multidisciplinary care to patients with MetALD. Multidisciplinary clinics are gaining momentum, particularly in oncology, and have been found to improve both outcomes and the patient care experience. Within hepatology, liver transplant and tumor clinics are already operational. Both MASLD and AUD are complex multisystem diseases, and their combination as MetALD requires care coordination to prevent progression. Existing multidisciplinary care programs for MASLD combine weight loss, cardiometabolic risk factor mitigation, dietician engagement, and regular fibrosis risk stratification and screening for variceal bleeding and fibrosis, with improvements in cardiometabolic risk factors, aminotransferases, steatosis, fibrosis progression, and risk reduction. ICHANGE at Weill Cornell Medicine proposed an algorithm to identify patients at risk of MetALD progression for referral, which is driven by hepatology with input from a dietician. For MetALD, hepatologists need to learn how to treat AUD and well as SLD, because many patients may not be willing to talk to an addiction specialist. Although existing models vary, many have hepatology at the center as the coordinator of care. There are greater challenges in the diagnosis, treatment, and referral of individuals with AUD to cognitive behavioral therapy and addiction specialists.

The ALD and AUD clinic at Wisconsin Madison integrates hepatology with psychiatry/addiction medicine and social work. Treatment focuses on weight loss or alcohol cessation first. The risk of treatment fatigue is lower when care is provided in a single clinic. Although this model is likely not going to work everywhere, parallel care risks loss to follow-up. Setting up a clinic starts with gathering the right people who are interested, finding a space, and then creating a business case to get university buy in. Once the clinic is established, it is important to collect data to demonstrate value.