Diabetes Standards of Care and Resources for Clinicians and Educators

Recommendations for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH)

• Screening and Monitoring

  Most individuals with MASLD/MASH are asymptomatic. The goal of routine screening is to identify those with fibrosis and associated cardiometabolic risk. A liver biopsy is the gold standard for diagnosing and categorizing the stage and severity of hepatic fibrosis. However, there are several non-invasive tests that can be used alone, or in combination, to identify and categorize risk for fibrosis. They can also be utilized to monitor and track progression or improvements over time.

  The Fibrosis-4 Index (FIB-4) is currently recommended as an initial screening test for risk of hepatic fibrosis in adults with type 2 diabetes or prediabetes. It utilizes age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. Online calculators, such as the Fibrosis-4 (FIB-4) Index for Liver Fibrosis, are available. If the value is within a low-risk range it should be repeated every 1-2 years. Despite a low FIB-4 many of these individuals have MASLD and may have significant risk of progression to fibrosis. Lifestyle interventions are recommended to reduce this risk.

  Additional testing, such as a liver stiffness measurement (LSM) or enhanced liver fibrosis (ELF) score, to define a risk category is recommended if the FIB-4 value exceeds the low-risk range. Referral to hepatology is recommended when the FIB-4 value falls in a high-risk range but obtaining an LSM or ELF prior to consultation will facilitate evaluation. (See Screening and Management Algorithm for Hepatic Fibrosis) [PDF – 141 KB]

  • Obtain a FIB-4 in adults with type 2 diabetes or prediabetes. The table below provides guidance for screening, interpretation of test results, follow-up testing, and referral.
    

    Test Results	Fibrosis Risk Category	Follow Up/Next Step
    FIB-4 <1.3	Low	Rescreen with FIB-4 every 1-2 years.
    FIB-4 1.3 – 2.67	Indeterminate	Obtain liver stiffness measurement (LSM) using vibration controlled transient elastography (VCTE) (e.g., FibroScan). * Alternately, order an enhanced liver fibrosis (ELF) score to stratify risk if LSM is not available.
    LSM (VCTE) <8.0 kPa or ELF <9.8	Indeterminate	Repeat LSM or ELF every 2-3 years.
    FIB-4 >2.67 LSM (VCTE) ≥8.0 kPa or ELF ≥9.8	High	Refer to hepatologist. Perform LSM or ELF, if not completed prior to consultation.

    * Shear wave elastography (SWE) may be used as alternative LSM, however fibrosis risk thresholds differ from VCTE, and clinical consensus on standardized cut-off values is still being established.
  • Check AST and ALT annually in people with diabetes. The American Diabetes Association recommends the following upper limits of normal for ALT level: 29-33 units/L for men, 19-25 units/L for women. Note that lab normal ranges may vary.
• Evaluate for Additional Disorders

  People with diabetes may have liver disease due to other etiologies in addition to MASLD and MASH. These conditions may present with abnormal liver tests or as hepatic steatosis (“fatty liver”) detected incidentally on imaging. AST and ALT elevation may indicate an alternative or concomitant etiology for liver disease, such as autoimmune hepatitis, hemochromatosis, viral hepatitis, or alcohol-associated liver disease.

  • Review use of medications and supplements that may contribute to liver toxicity.
  • Use of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) and other over the counter and prescription drugs including methotrexate and some antibiotics should be assessed. More detailed information is available at LiverTox Exit Disclaimer: You Are Leaving www.ihs.gov  home page.
  • Frequently reported hepatotoxic botanicals include vitamin A, kava, comfrey, high dose turmeric, curcumin, green tea extract, garcinia cambogia, black cohosh, red yeast rice, and ashwagandha. Specific information on herbs and supplements is available at LiverTox Herbs and Supplements. Exit Disclaimer: You Are Leaving www.ihs.gov 
  • Consider referral for medication and supplement review by pharmacist.
  • Review alcohol and substance use history.
    • Metabolic dysfunction and alcohol-associated liver disease (MetALD) may be diagnosed in individuals with steatotic liver disease who consume moderate amounts of alcohol: 10-25 standard drinks*/week (140-350 g/week) for women or 15-30 standard drinks/week (210-420 g/week) for men.
    • Alcohol-associated liver disease (ALD) is associated with the consumption of ≥ 25 standard drinks*/week (350 g/week) for women, or ≥ 30 standard drinks/week (420 g/week) for men.
    * Note: In the U.S., a standard drink contains 14 grams of alcohol. Examples include: 12 ounces of beer with 5% alcohol, 8 ounces of malt liquor with 7% alcohol, 5 ounces of wine with 12% alcohol, or a shot of 1.5 ounces of liquor or distilled spirits (80-proof liquor/40% alcohol).
  • Consider additional evaluation if AST and ALT elevation persist for six months or longer, including:
  • Liver ultrasound evaluation.
  • Serologic testing for hepatitis B, hepatitis C, autoimmune disorders, iron overload, and celiac disease, as indicated.
  • A phosphatidylethanol (PEth) test, a whole blood alcohol biomarker, if more clarity is needed regarding the impact of alcohol consumption on liver function.
  • Refer to hepatology for further evaluation if diagnosis is unclear.
• Management

  Management of People at Risk for Liver Fibrosis in Primary Care

  There is evidence that weight loss of 5-10% can result in significant improvement or reversal of MASLD and MASH and weight loss of greater than 10% can reverse fibrosis. Calorie reduction, physical activity, and diet modifications to reduce saturated fats and sugars can reduce steatosis and inflammation and improve outcomes. Primary care management of cardiometabolic risk factors such as glucose, weight, blood pressure, and lipids is critical. Primary care teams should also play a central and ongoing role in the multidisciplinary management of liver disease, particularly if access to specialty consultation is delayed or limited.

  • Counsel individuals that weight loss of 5-10% can result in significant improvement or reversal of MASLD and MASH.
  • Provide guidance on diet and lifestyle.
    • Recommend a diet that is rich in fiber, fruits, vegetables, lean protein, whole grains, and unsaturated fat, and that limits saturated fat, refined carbohydrate, added sugars, high fructose corn syrup, especially sugar sweetened beverages, and red and processed meats. Black coffee may provide additional benefits.
    • Advise to avoid alcohol intake.
    • Advise that reducing sedentary time and increasing aerobic and resistance exercise is beneficial in reducing liver fat.
    • Refer to a registered dietitian, if available, who can provide more specific guidance regarding weight loss, diet composition, and physical activity as well as caloric requirements and macronutrients. This is especially important if the person has cirrhosis.
    • Recommend smoking cessation.
  • Consider glucagon-like peptide-1 (GLP-1) or dual glucose dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists in people with prediabetes or diabetes to facilitate weight loss.
  • Consider referral for metabolic (bariatric) surgery for people who are candidates for the procedure.
  • Review medication and pharmacologic therapy considerations.
    • Reevaluate use of medications that may be contributing to weight gain.
    • Consider use of medications for glycemic management that also have evidence for improvement in liver histology and/or outcomes.
      • GLP-1 or dual GIP/GLP-1 receptor agonists can reduce liver fat content, inflammation, and/or fibrosis.
      • Low-dose pioglitazone therapy, with or without GLP-1 or dual GIP/GLP-1 receptor agonists, can also reduce liver fat content, inflammation, and/or fibrosis in persons who are at high risk for liver fibrosis (or biopsy proven MASH).
      • Semaglutide (2.4 mg/week) is FDA approved for the treatment of MASH with clinically significant liver fibrosis.
    • Address cardiovascular disease (CVD) risk reduction due to increased risk of CVD.
      • Continue or recommend statin therapy as first-line dyslipidemia therapy in persons with MASLD.
      • Consider use of diabetes medications with proven CVD risk reduction, i.e. GLP-1 receptor agonists or sodium-glucose cotransporter 2 (SGLT-2) inhibitors. Low-dose pioglitazone (15-30 mg) may provide additional benefit.
    • Recommend vaccination for Hepatitis A and B. See DDTP Immunization Standard of Care for additional recommendations for individuals with diabetes.
    • Consider follow-up liver stiffness measurement (LSM) (e.g., Fibroscan) or enhanced liver fibrosis (ELF) to assess therapeutic response every 2-3 years.

  Management of Complications

  The care of individuals with severe/advanced fibrosis (stage F3) and cirrhosis (stage F4 fibrosis) is best coordinated by a hepatologist. Primary care providers have an important role to play in managing diabetes, CVD risk, and other comorbidities. Medication adjustments are often necessary.

  • Refer individuals to hepatology for evaluation and treatment of clinically significant fibrosis, signs of cirrhosis, unclear diagnosis, and consideration of treatment with resmetirom. This agent is a once daily thyroid hormone receptor-? agonist which is FDA approved for the treatment of MASH with clinically significant liver fibrosis.
  • Recommend insulin therapy for treatment of hyperglycemia if decompensated cirrhosis.
  • Continue statin use with significant fibrosis but use with caution in people with decompensated cirrhosis, ascites, or encephalopathy.
  • Obtain ultrasound and alpha-fetoprotein (AFP) testing every 6 months in patients with cirrhosis to screen for hepatocellular carcinoma.

Featured Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH) Resources

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH) Resources