Usually, NAFLD is diagnosed incidentally when ALT/AST elevations or steatosis on liver ultrasound are noted in obese patients and other competing diagnoses are ruled out. See the diagnosis algorithm below. It is important to note that normal ALT/AST is not sensitive enough to exclude the possibility of NAFLD, so patients could still have NAFLD despite normal AST/ALT. The other challenge with NAFLD diagnosis is differentiating the benign form, NAFL, from the more severe form, NASH. Liver biopsy was traditionally the only way to differentiate between NAFL and NASH and determine severity of fibrosis. However, biopsy is costly and has risks. So, newer approaches like the NAFLD-FS and transient elastography (Liver Stiffness Measurement) have been developed. Their use is described below. These methods cannot differentiate the diagnosis between NAFL and NASH, but can differentiate between advanced fibrosis and less severe fibrosis. Specialists consider this acceptable and believe that even if patients have NASH, they do not need to be seen by specialists prior to advanced fibrosis. This page includes tools designed to help you in the diagnosis of NAFLD and determining which patients may have advanced fibrosis and see a specialist. It is also important to rule out concern for Hepatitis C or alcohol as the cause of ALT/AST elevations. If these conditions are suspected, a referral to hepatology is warranted (see algorithm). United States guidelines do not recommend screening for NAFLD at this time.
Diagnosis Algorithm
The Diagnosis Algorithm figure is the recommended pathway for determining if patients need referral.
NAFLD Fibrosis Score
The NAFLD Fibrosis Score (NAFLD-FS) is the preferred non-invasive diagnostic option for detecting advanced fibrosis in NASH and is recommended by experts. NAFLD-FS is calculated using age, AST, ALT, platelet level, albumin level, presence of hyperglycemia, and Body Mass Index (BMI): all factors inversely related to severity of liver fibrosis in NASH (Chalasani et al., 2017). Scores below -1.455 are used to rule out severe liver fibrosis (these patients would be safe to monitor in primary care). There is no research to guide how often to recheck the score for change but most experts recommend yearly. Scores >0.676 presented concern for severe fibrosis and scores of -1.455 to 0.676 are considered indeterminate. Both should be referred to speciality care. The link to the left takes you to a calculator that will calculate your patients NAFLD Fibrosis score. Note: NAFLD guidelines also support use of the Fibrosis-4 (Fib-4) score to determine severity of NASH.
**There are several other diagnostic scores that can be used to diagnose NAFLD, however, these are less accurate than the NAFLD-FS. The other diagnostic scores are the Enhanced Liver Fibrosis (ELF) blood test score, BARD score (BMI, AST/ALT Ratio, presence of Diabetes), and APRI (AST to Platelet Ratio Index).
- NAFLD-FS Documentation Forms – Forms to use when documenting your use of NAFLD-FS with patients.
Identify Hepatitis
Hepatitis C and B viral infection should be ruled out with antibody testing before solidifying a diagnosis of NAFLD. Remember many patients already meet the criteria of being born between 1945 and 1965 which meets Center for Disease Control recommendations for HCV screening. In acute hepatitis C, Hepatitis C Virus (HCV) antibody may be negative and Polymerase Chain Reaction (PCR) should be obtained if suspicion for HCV infection is high.
Audit C
The Audit C is a tool used to screen for problematic use of alcohol. It can be used in the differential diagnosis process of alcoholic versus non-alcoholic steatohepatitis.
Fibroscan is a brand of transient elastography Liver Stiffness Measurement (LSM) that is measured using ultrasound. LSM is used to estimate the presence of advanced fibrosis. It is used to clarify the picture when the NAFLD-FS is in the indeterminate range and determine which patients need biopsy. United States guidelines do not provide recommendations on how often to recheck Fibroscan readings on patients to monitor for progression. European guidelines recommend every 3 years.
Fibroscan is currently only available at specialist offices (Gastroenterology or Hepatology). Find a Fibroscan location near you.
Case Study on Diagnosis
Marsha is a 53 year old female whom you know well and is your patient for the last 10 years. You are following up with her after receiving lab results showing an AST of 39 IU/L and ALT 45 IU/L respectively. Bilirubin and alkaline phosphatase were normal. You had checked these labs as part of your yearly evaluation for use of statin. The patient is a type 2 diabetic but is controlled on metformin with last HgB A1c of 6.8. Her BMI is 33 kg/m2, platelets are 200 x10⁹/µL, and albumin is 4.0 g/dL. You were out on vacation last week and your partner ordered a RUQ ultrasound on Marsha which showed steatosis. You recall that Marsha told you at the last visit that she drinks 1 glass of wine about every 2 weeks and never binge drinks. She does not have a history of alcohol overuse. Calculate Marsha’s NAFLD-FS and decide would you proceed to evaluate Marsha’s elevated AST/ALT?