What is the workup for Non-Alcoholic Fatty Liver Disease (NAFLD)?

From the Guidelines

The workup for non-alcoholic fatty liver disease (NAFLD) should begin with a thorough history and physical examination, focusing on risk factors such as obesity, diabetes, and metabolic syndrome, as recommended by the most recent guidelines 1. The initial laboratory tests should include liver function tests (ALT, AST, alkaline phosphatase, bilirubin), complete blood count, lipid panel, fasting glucose, and hemoglobin A1c. Additional testing should rule out other causes of liver disease, including hepatitis B and C serologies, autoimmune markers (ANA, anti-smooth muscle antibody), iron studies (ferritin, transferrin saturation), and alpha-1 antitrypsin levels. Imaging typically starts with an abdominal ultrasound, which can detect steatosis when fat content exceeds 20-30%. In cases where more detailed assessment is needed, transient elastography (FibroScan) can evaluate both steatosis and fibrosis non-invasively. For risk stratification, non-invasive fibrosis scores such as NAFLD Fibrosis Score, FIB-4, or APRI can help identify patients at higher risk for advanced fibrosis, as suggested by 1 and 1. Liver biopsy remains the gold standard for diagnosis and staging but is typically reserved for cases with diagnostic uncertainty, suspected advanced disease, or before starting specific pharmacological treatments. The workup should also include cardiovascular risk assessment since NAFLD patients have increased cardiovascular morbidity and mortality, as highlighted by 1 and 1. Some key points to consider in the workup include:

• Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes or obesity with additional metabolic risk factor(s) 1.
• A stepwise approach using blood-based scores (such as the fibrosis-4 index [FIB-4]) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes 1.

From the Research

Diagnosis of NAFLD

• NAFLD is typically found incidentally on imaging such as abdominal ultrasound and CT 2
• Elevations in alanine aminotransferase (ALT) may prompt the clinician to evaluate for NAFLD, however ALT should not be used as a diagnostic tool 2
• The gold standard for diagnosis of NAFLD and NASH is a liver biopsy, which can distinguish simple steatosis from NASH 2, 3
• Risk scores or elastography tests can be used to identify patients who are likely to have fibrosis that will progress to cirrhosis 3

Risk Factors for NAFLD

• Obesity is a major risk factor for NAFLD, with individuals with obesity being at highest risk 3, 4
• Other established risk factors include metabolic syndrome and type 2 diabetes mellitus 3, 5
• NAFLD has been associated with several cardiovascular risk factors, including dyslipidemia, hyperglycemia, hypertension, and smoking 6

Treatment and Management of NAFLD

• Weight loss through diet and exercise is the primary treatment for NAFLD, with histological improvement seen in patients who lose 5-10% of their body weight 2, 3
• Certain dietary factors, such as excessive caloric intake and high fructose consumption, play a role in the development of NAFLD 2
• There are no approved FDA treatments for NAFLD, but several drugs are in advanced stages of development 5
• Bariatric surgery may be considered in selected morbidly obese individuals who have failed lifestyle modification and pharmacotherapy 4