Liver Fibrosis Stage Based on the Fibrosis-4 Score or Forns Index in Adults With Chronic Hepatitis C Virus Infection

Can the Fibrosis-4 (FIB-4) score and/or Forns index accurately predict significant or severe liver fibrosis in adults with chronic hepatitis C virus (HCV) infection?

Using low cutoffs with the FIB-4 score (ie, 1.45 or greater for detecting at least severe fibrosis [F3 or higher]) or Forns index (ie, 4.2 or greater for detecting at least significant fibrosis [F2 or higher]) yields relatively accurate results for predicting fibrosis with a sensitivity of 81.1% and 84.7%, respectively, in patients with HCV infection. Both measures may be used for initial fibrosis staging in adults with chronic HCV infection.¹ (Strength of Recommendation: C, disease-oriented evidence.)

In the United States, more than 2 million people are living with HCV infection, which causes more than 12,000 deaths each year.^2,3 The availability of direct-acting antiviral drugs has simplified treatment; primary care clinicians can manage much of the treatment of HCV infection.^4,5

Before prescribing direct-acting antiviral drugs, clinicians must determine liver fibrosis stage because stage affects drug choice and risk of hepatocellular carcinoma. Noninvasive methods for determining fibrosis have simplified this process, making assessment efficient and accessible.⁶

Of note, the liver fibrosis stages by the Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) scoring system are categorized as: F0 = absence of fibrosis; F1 = mild fibrosis; F2 = significant fibrosis; F3 = severe/advanced fibrosis; and F4 = cirrhosis.^6,7

The FIB-4 score is used to predict the likelihood of severe fibrosis (ie, F3 or higher) based on patient age and on alanine transaminase, aspartate transaminase, and platelet levels.¹ The Forns index is used to predict the likelihood of significant fibrosis (F2 or higher) based on patient age and gamma glutamyltransferase, platelet, and total cholesterol levels. The authors of this Cochrane review sought to assess the diagnostic accuracy of the FIB-4 score and Forns index for staging liver fibrosis in adults with chronic HCV infection.

This Cochrane review included 84 cross-sectional or case-control studies from 28 countries (nine in the United States) with a total of 107,583 participants.¹ Adult participants who had an FIB-4 score or Forns index score and a liver biopsy result regardless of fibrosis staging were included. The primary outcome was the diagnostic accuracy of the FIB-4 score and Forns index compared with the liver biopsy result. For both staging tools, this review used a low cutoff for ruling out fibrosis and a high cutoff for ruling it in.

This analysis showed that FIB-4 scores had a high sensitivity and low specificity for detecting fibrosis when the cutoffs were low, defined here as 1.45 or more (sensitivity = 81.1%; 95% CI, 75.6%–85.6%; specificity = 62.3%; 95% CI, 57.4%–66.9%). The FIB-4 score had a low sensitivity and high specificity for detecting fibrosis when the cutoffs were high, defined as 3.25 or more (sensitivity = 41.4%; 95% CI, 33.0%–50.4%; specificity= 92.6%; 95% CI, 89.5%–94.4%).

The pattern was similar for the Forns index. When the cutoff was low, defined here as 4.2 or more, the sensitivity was high but specificity was low (sensitivity = 84.7%; 95% CI, 77.9%–89.7%; specificity = 47.9%; 95% CI, 38.6%–57.3%). When the cutoff was high, defined here as 6.9 or more, sensitivity was low and specificity was high (sensitivity = 34.1%; 95% CI, 26.4%–42.8%; specificity = 97.3%; 95% CI, 92.9%–99.0%; see accompanying table).