Unifying Concepts

Screening for Advanced Hepatic Fibrosis Related to NAFLD/NASH

Hepatic fibrosis is the most important determinant of liver and non-liver outcomes in patients with nonalcoholic fatty liver disease (NAFLD). Therefore, identifying patients with clinically significant hepatic fibrosis (fibrosis stage 2 or higher) is important for targeted efforts at preventing disease progression.
Nonalcoholic steatohepatitis (NASH), a subtype of NAFLD characterized by inflammation, ballooning, and Mallory’s hyaline on liver biopsy, can lead to hepatic fibrosis, cirrhosis, and hepatocellular cancer (HCC). Both NAFLD and NASH are also associated with an increased risk of cardiovascular disease, cardiovascular and liver-related mortality, and impaired health-related quality of life.

Screening for advanced fibrosis related to NAFLD/NASH

Primary care, endocrinologists, gastroenterologists, and obesity specialists should screen for NAFLD with advanced fibrosis

Step 1: Identify patients at risk

  • 2 or more metabolic risk factors1
  • Type 2 diabetes
  • Steatosis on any imaging modality or elevated aminotransferases

Step 2: History and laboratory tests

  • Excessive alcohol intake, CBC, liver function tests

Step 3: Non-invasive testing (NIT) for fibrosis (FIB-4 is a calculated value4 based on age, AST, ALT & platelet count) 2,3

  • Low risk: FIB-4 <1.3
  • Indeterminate risk: FIB-4 1.3 to 2.67
  • High risk: FIB-4 > 2.67

Step 4: Liver stiffness measurement (LSM) 5,6

  • Low risk: LSM < 8 kPa
  • Indeterminate risk: LSM 8 to 12 kPa
  • High risk: LSM > 12 kPa


  • Low Risk: Repeat NIT in 2-3 years unless clinical circumstances change
  • Indeterminate Risk: Refer to hepatologist for liver biopsy or MR elastography or monitoring with re-evaluation of risk in 2-3 years
  • High Risk: Refer to hepatologist


1. Metabolic risk factors: central obesity, high triglycerides, low HDL cholesterol, hypertension, prediabetes, or insulin resistance.
2. For patients 65+, use FIB-4 < 2.0 as the lower cutoff. Higher cutoff does not change.
3. Other NITs derived from routine laboratories can be used instead of FIB-4.
4. Many online FIB-4 calculators are available such as Fibrosis-4 (FIB4) Scoring System for Liver Fibrosis
5. Ultrasound acceptable if vibration-controlled transient elastography (VCTE, FibroScan®) is unavailable. Consider referral to hepatologist for patients with hepatic steatosis on ultrasound who are indeterminate or high risk based on FIB-4.
6. LSM values are for VCTE (FibroScan®). Other techniques such as bidimensional shear wave elastography or point shear wave elastography can also be used to measure LSM. Proprietary commercially available blood NITs may be considered for patients considered indeterminate or high risk based on FIB-4 or APRI, or where LSM unavailable.



  1. Kanwal F, Shubrook JH, Adams LA, Pfotenhauer K, Wai-Sun Wong V, Wright E, Abdelmalek MF, Harrison SA, Loomba R, Mantzoros CS, Bugianesi E, Eckel RH, Kaplan LM, El-Serag HB, Cusi K. Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2021 Nov;161(5):1657-1669. [Medline]
  2. Younossi ZM, Noureddin M, Bernstein D, Kwo P, Russo M, Shiffman ML, Younes Z, Abdelmalek M. Role of Noninvasive Tests in Clinical Gastroenterology Practices to Identify Patients With Nonalcoholic Steatohepatitis at High Risk of Adverse Outcomes: Expert Panel Recommendations. Am J Gastroenterol. 2021 Feb 1;116(2):254-262. [Medline]


Created Nov 15, 2021

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