If your patient has cardiometabolic risk factors, ACT AGAINST THE UNDERLYING THREAT OF MASH

The AGA assembled a multidisciplinary panel of experts to develop a Clinical Care Pathway, providing guidance on the screening, diagnosis, and management of MASLD.²⁹

Identify those with 2 or more metabolic risk factors,* type 2 diabetes, steatosis, or elevated aminotransferases.

Take medical history to evaluate excessive alcohol intake, and request laboratory testing for CBC and liver function.

Carry out noninvasive FIB-4 assessment for fibrosis (FIB-4 is a calculated value based on age, AST, ALT, and platelet count)^†‡§:

• If FIB-4 <1.3: low risk. Repeat test in 2 to 3 years unless there is a change in clinical circumstance.
• If FIB-4 1.3 to 2.67: indeterminate risk. Order liver stiffness measurement (LSM) to estimate risk^¶||#:
  • LSM <8 kPa: low risk. Repeat test in 2 to 3 years unless there is a change in clinical circumstance.
  • LSM >12 kPa: high risk. Refer to a hepatologist.
  • LSM 8 kPa to 12 kPa: indeterminate risk. Refer to hepatologist for liver biopsy, MR elastography, or monitoring with re-evaluation of risk in 2-3 years.
• If FIB-4 >2.67: high risk. Refer to a hepatologist.

To identify clinically significant fibrosis (stage ≥2), the AASLD recommends targeted screening of populations at increased risk of advanced liver disease¹⁰:

• Type 2 diabetes
• Medically complicated obesity
• MASLD in context of moderate alcohol use
• First-degree relative of a patient with cirrhosis due to MASLD/MASH

The AASLD recommends that patients with metabolic risk factors undergo regular risk assessments depending on their likelihood of having advanced fibrosis.¹⁰

Adapted from Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835.

Algorithm for the evaluation of patients at risk for or with established MASLD across practice settings. Patients with steatosis noted on imaging or for whom there is a clinical suspicion of MASLD, such as those with metabolic risk factors or unexplained elevation in liver chemistries, should undergo further evaluation. In settings with a low prevalence of advanced fibrosis, such as in the primary care setting, the emphasis is on excluding advanced fibrosis using a test with a high negative predictive value. When the fibrosis-4 index (FIB-4) is <1.3, patients can be followed in the primary care setting and reassessed periodically. Patients without prediabetes/type 2 diabetes (T2D) and 1–2 metabolic risk factors can be reassessed every 2–3 years. Patients with prediabetes/T2D or 2 or more metabolic risk factors are at higher risk for disease progression, and more frequent FIB-4 monitoring (eg, every 1–2 years) should be considered. In patients older than age 65, a FIB-4 cutoff of >2.0 should be used. FIB-4 has low accuracy in those under age 35; thus, secondary assessment should be considered in those <35 with increased metabolic risk or elevated liver chemistries. FIB-4 should not be used in acutely ill patients. In patients with FIB-4≥1.3, a secondary assessment should be done (preferentially vibration-controlled elastography [VCTE] or Enhanced Liver Fibrosis™ [ELF™] initially) or the patient referred for further risk stratification (if being seen in a nongastroenterology/hepatology setting). Direct referral to gastroenterology/hepatology should be considered in those with aminotransferases persistently (>6 months) above normal to exclude other causes of liver disease or when FIB-4>2.67 due to the increased risk of clinically significant fibrosis. In higher prevalence settings, such as gastroenterology/hepatology clinics, additional risk assessment with magnetic resonance elastography (MRE) may be appropriate when noninvasive tests (NITs) are indeterminate or there is clinical suspicion of more advanced disease. Identification of cirrhosis should prompt screening for HCC and esophageal varices. In addition, MRE or corrected T1 (cT1) may help identify patients with “at-risk” MASH (MASH with MASLD activity score ≥4 and fibrosis stage ≥2) who may benefit from a therapeutic intervention as they become available. If cirrhosis is suspected based on NITs, clinical data, or imaging findings, then cirrhosis-based management may be initiated without a liver biopsy. Liver biopsy should be considered when NITs suggest significant fibrosis (≥F2), especially if additional evaluation suggests the presence of “at-risk” MASH (eg, using FAST, MEFIB, MAST, or cT1), NIT assessment is indeterminate, aminotransferases are persistently elevated (>6 months), or additional/alternate diagnoses are suspected. Note that in patients with confirmed or suspected advanced fibrosis, an ELF™≥11.3 is a predictor of future liver-related events and is approved for this purpose; use of other ELF™ cutoffs in secondary risk assessment is based on expert option. Patients at all stages of disease should be counseled on lifestyle modifications, and those with ≥F2 fibrosis targeted for pharmacological interventions as they become available. Specific threshold values of NITs are approximations supported by current evidence and are meant to guide clinical management through primary care to gastroenterology/hepatology practices rather than be interpreted in isolation.¹⁰

The AACE has published guidelines to provide endocrinologists and PCPs with practical, evidence-based recommendations for the diagnosis of MASLD in adults. Below is a summary of recommendations.³⁰

Q2.1 Which adults with MASLD should be considered at “high risk” of clinically significant fibrosis (stages F2-F4) and at risk of cirrhosis?
R2.1.1 Clinicians should consider persons with obesity and/or features of metabolic syndrome, those with prediabetes or T2D, and those with hepatic steatosis on any imaging study and/or persistently elevated plasma aminotransferase levels (over 6 months) to be “high risk” and screen for MASLD and advanced fibrosis.
Grade B; Intermediate/High Strength of Evidence; BEL 2
R2.1.2 Persons undergoing bariatric surgery should be evaluated for the presence and severity of MASH, and a liver biopsy should be considered at the time of bariatric surgery. Liver biopsy should be recommended if presurgical stratification suggests indeterminate or high risk of liver fibrosis.
Grade B; Intermediate Strength of Evidence; BEL 2


Q2.2 What blood tests (eg, diagnostic panels and specific biomarkers) can be used to diagnose MASLD with clinically significant fibrosis (stages F2-F4) in adults?
R2.2.1 Clinicians should use liver fibrosis prediction calculations to assess the risk of MASLD with liver fibrosis. The preferred noninvasive initial test is the FIB-4.
Grade B; Intermediate Strength of Evidence; BEL 2
R2.2.2 Clinicians should consider persons belonging to the “high-risk” groups (as defined under R2.1.1) who have an indeterminate or high FIB-4 score for further workup with an LSM (transient elastography) or ELF™ test, as available.
Grade B; Intermediate Strength of Evidence; BEL 2


Q2.3 What imaging studies can be used to diagnose MASLD with clinically significant fibrosis (stages F2-F4) in adults?
R2.3 To stage the risk of fibrosis in persons with MASLD, clinicians should prefer the use of VCTE as best validated to identify advanced disease and predict liver-related outcomes. Alternative imaging approaches may be considered, including shear wave elastography (less well validated) and/or magnetic resonance elastography (most accurate but with a high cost and limited availability; best if ordered by liver specialist for selected cases).
Grade B; Intermediate Strength of Evidence; BEL 2


Q2.4 Should all persons with diabetes be screened for clinically significant fibrosis (stages F2-F4) associated with MASLD?
R2.4.1 In persons with T2D, clinicians should consider screening for clinically significant fibrosis (stages F2-F4) using the FIB-4, even if they have normal liver enzyme levels.
Grade B; High/Intermediate Strength of Evidence; BEL 2
R2.4.2 In persons with T1D, clinicians may consider screening for MASLD with clinically significant fibrosis (stages F2-F4) using the FIB-4, only if there are risk factors such as obesity, features of metabolic syndrome, elevated plasma aminotransferase levels (>30 U/L), or hepatic steatosis on imaging.
Grade C; Intermediate/Weak Strength of Evidence; BEL 2; downgraded based on the heterogeneity of studies and moderate-to-high probability of bias
R2.4.3 Clinicians should further risk stratify persons with T2D, or T1D with cardiometabolic risk factors and/or elevated plasma aminotransferase levels (>30 U/L) using the FIB-4, elastography, and/or ELF™ test.
Grade B; High/Intermediate Strength of Evidence; BEL 2

Q2.5 When should an adult be referred to a gastroenterologist/hepatologist for management?
R2.5.1 Persons with persistently elevated ALT or AST levels and/or with hepatic steatosis on imaging and indeterminate risk (FIB-4, 1.3-2.67; LSM, 8-12 kPa; or ELF™ test, 7.7-9.8) or high risk (FIB-4, >2.67; LSM, >12 kPa; or ELF™ test, >9.8) based on blood tests and/or imaging (as described in R2.2.1, R2.2.2, and R2.3) should be referred to a gastroenterologist or hepatologist for further assessment, which may include a liver biopsy.
Grade B; Intermediate Strength of Evidence; BEL 2
R2.5.2 Clinicians should refer persons with clinical evidence of advanced liver disease (ascites, hepatic encephalopathy, esophageal varices, or evidence of hepatic synthetic dysfunction) to a gastroenterologist/hepatologist for further care.
Grade B; Intermediate/High Strength of Evidence; BEL 2

The AACE offers detailed recommendations for the diagnosis of MASLD in both adults and children. To see a full list of recommendations, visit the AACE website.