Fibrosis-4 (FIB-4) Index for Liver Fibrosis

According to McPherson (2017), in many developed countries, non-alcoholic fatty liver disease (NAFLD) is the most common liver disease impacting 20-30% of the population. Of those patients, approximately 40% will develop progressive liver fibrosis that may progress to cirrhosis, putting patients at risk for cancer, liver failure and portal hypertension-related complications. Early identification, lifestyle interventions, treatment and monitoring is key to mitigate the more than threefold increased risk of mortality (all cause and liver related) in patients with NAFLD. 

Non-invasive tests for liver fibrosis, such as the Fibrosis-4 (FIB-4) Index, are considered first line assessing fibrosis in patients with abnormal liver enzymes and suspected NAFLD. While liver biopsy is the gold standard for the diagnosis of liver fibrosis, it is subject to sampling errors and also comes with substantial morbidity. Additionally, there is a need to frequently re-assess and track fibrosis trends over time as liver fibrosis often progresses in a non-linear fashion. FIB-4 provides a non-invasive liver fibrosis assessment to minimize invasive assessments, such as biopsy, which carries significant patient risk. The FIB-4 Index was shown to outperform 7 other noninvasive markers of fibrosis in patients with NAFLD (Shah, 2009).

FIB-4 was developed in patients with HIV and HCV co-infections, but it can be used in patients with any known risk factors for liver disease, chronic hepatitis, alcoholic liver disease, NAFLD and the cholestatic and metabolic liver diseases. The FIB-4 has been shown to be less reliable in patients <35 or > 65 years old.

The Fibrosis-4 (FIB-4) Index is a non-invasive liver fibrosis assessment based on age, liver enzymes (AST & ALT) and platelet count. Caution: Historically, the score is less reliable in patients < 35 or > 65 years old.* However, improvements have recently been made for those > 64 years.

FIB-4 Score = (Age * AST) / (Platelets * √(ALT))

*New Updates (McPherson, 2017)

• The FIB-4 score continues to perform poorly in patients aged < 35 years
• The FIB-4 score has low specificity for advanced fibrosis in patients aged > 65 years leading to a high false positive rate.
• New cutoffs for excluding advanced fibrosis for patients aged > 65 years have been derived (and validated) for FIB-4 score, which reduced the false positive rate without adversely affecting sensitivity.

*FIB-4 was developed to correlate with Ishak levels of fibrosis (by biopsy) staging (Sterling, 2006).

• 0-2 (mild fibrosis)
• 3-4 (moderate fibrosis)
• 5-6 (severe fibrosis/cirrhosis)

Interpretation

1. Use alternative fibrosis assessment (Age ≤ 35).
2. Advanced fibrosis* excluded (FIB-4 Score < 2 & age > 64 years).
3. Advanced fibrosis* excluded (FIB-4 Score < 1.3 & age 36-64 years).
4. Further investigation needed (FIB-4 Score 2.0 - 2.67 & age > 64 years).
5. Further investigation needed (FIB-4 Score 1.3 - 2.67 & age 36-64 years).
6. Advanced fibrosis* likely (FIB-4 Score > 2.67 & age >35 years).

*Advanced fibrosis was defined as METAVIR stage F3-F4 (McPherson, 2017).

Management

• Frequently re-assess and track fibrosis trends over time as liver fibrosis often progresses in a non-linear fashion. FIB-4 provides a non-invasive liver fibrosis assessment to minimize invasive assessments, such as biopsy, which carries significant patient risk.
• Severe fibrosis/cirrhosis scores may need liver biopsy for confirmation of cirrhosis unless there are other clinical or imaging signs of progression to end-stage liver disease.
• Low fibrosis scores may be appropriate candidates for medical management and may not require liver biopsy if FIB-4 scores continue to stay low.