Optimizing Use of Nonalcoholic Fatty Liver Disease Fibrosis Score, Fibrosis-4 Score, and Liver Stiffness Measurement to Identify Patients With Advanced Fibrosis

Abstract

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e147. Learning Objective-Upon completion of this activity, successful learners will be able to apply the use of noninvasive fibrosis score and liver stiffness measurement for evaluation of advanced fibrosis in patients with nonalcoholic fatty liver disease. BACKGROUND & AIMS: Measuring liver stiffness only in patients with indeterminate or high nonalcoholic fatty liver disease (NAFLD) fibrosis scores (called a 2-step approach) was reported to reduce indeterminate or discordant results while maintaining the accuracy to identify patients with advanced fibrosis. We aimed to validate this approach using data collected from the Gut and Obesity in Asia Workgroup. METHODS: We performed a retrospective analysis of data from 759 patients with biopsy-proven NAFLD (24% with advanced fibrosis), seen at 10 centers in 9 countries in Asia, from 2006 through 2018. By using liver biopsies as the reference standard, we calculated percentages of misclassifications and indeterminate or discordant results from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis-4 score) and liver stiffness measurements (LSMs), alone or in combination. The analysis was repeated using randomly selected subgroups with a different prevalence of advanced fibrosis (histologic fibrosis stage ‡F3). RESULTS: In groups in which 3.7% and 10% of patients had advanced fibrosis, a 2-step approach (using the NFS followed by LSM only for patients with indeterminate or high NFS) and using a gray zone of 10 to 15 kPa for LSM, produced indeterminate or discordant results for 6.9% of patients and misclassified 2.7% of patients; only 25.6% of patients required LSM. In the group in which 10% of patients had advanced fibrosis, the same approach produced indeterminate or discordant results for 7.9% of patients and misclassified 6.6% of patients; only 27.4% of patients required LSM. In groups in which 24% and 50% of patients had advanced fibrosis, using LSM ‡10 kPa alone for the diagnosis of advanced fibrosis had the highest accuracy and misclassified 18.1% and 18.3% of patients, respectively. These results were similar when the Fibrosis-4 score was used in place of NFS.

Serial Transient Elastography Examinations to Monitor Patients With Type 2 Diabetes: A Prospective Cohort Study

“…Alternatively, one may perform another noninvasive test to gain more information. (26,27) With regard to CAP changes, 52.0% of patients showed an increased CAP suggestive of new NAFLD development and 12.2% had a CAP that decreased to <248 dB/m at the 3-year follow-up. Previous studies using oral glucose tolerance tests showed that insulin resistance was almost universal in patients with NAFLD, highlighting the close relationship between NAFLD and prediabetes and diabetes.…”

Advances in non-invasive assessment of hepatic fibrosis

“…+++++AUC ≥0.90, ++++AUC 0.85–0.89, +++AUC 0.80–0.84, ++AUC 0.75–0.79, +AUC <0.75 (Harrell’s c index substituted for AUC for prognostic category).*Accuracy for determining advanced (bridging) fibrosis abstracted from meta-analyses where available7 9 12 118 or from large cohorts of chronic liver disease patients 26 59 74 119–123†Proportion of cases falling within an indeterminate range for the prediction of advanced fibrosis 6 38 72 119 120 124–127‡AUC for significant (F2-4) fibrosis.ALD, alcoholic liver disease; ALT, alanine aminotransferase; Apo-A1, apolipoprotein-A1; APRI, AST-Platelet Ratio Index; AST, aspartate aminotransferase; AUC, area under the curve; BMI, body mass index; CHB, Chronic hepatitis B; CHC, chronic hepatitis C; HA, hyaluranic acid; IFG, impaired fasting glucose; α2-M, α2-macroglobulin; NA, not applicable; NAFLD, non-alcoholic fatty liver disease; PNPIII, procollagen N-terminal peptide III; PSC, primary sclerosing cholangitis; PTI, prothrombin index; TIMP-1, tissue inhibitor of matrix metalloproteinase-1.…”

“…†Proportion of cases falling within an indeterminate range for the prediction of advanced fibrosis 6 38 72 119 120 124–127…”

Non‐invasive tests for liver fibrosis in NAFLD: Creating pathways between primary healthcare and liver clinics

“…It should be kept in mind that FIB‐4 and NFS do not adequately rule‐in advanced fibrosis (with a high rate of false‐positive results), thus further assessment with a more specific test is required in case of positive results. Several tests have been proposed for these cases, including ELF TM , Fibrometer® and TE . For instance, in a large, prospective study of a UK primary care referral pathway in 1,452 patients with NAFLD, Srivastava et al recently showed that a two‐step pathway (FIB‐4 followed by ELF TM performed in those with an indeterminate (score 1.3‐3.25) FIB‐4) reduced unnecessary referrals to liver specialists by 81%, and also markedly increased (five‐fold) the accurate referral of cases with advanced fibrosis.…”

“…Several tests have been proposed for these cases, including ELF TM , 24,25 Fibrometer® 26 and TE. 23,[25][26][27] For instance, in a large, prospective study of a UK primary care referral pathway in 1,452 patients with NAFLD, Srivastava et al 24 recently showed that a two-step pathway (FIB-4 followed by ELF TM performed in those with an indeterminate (score 1.3-3.25) FIB-4) reduced unnecessary referrals to liver specialists by 81%, and also markedly increased (five-fold) the accurate referral of cases with advanced fibrosis. Importantly, because of the dual FIB-4 or NFS cut-offs, a significant proportion of patients (around 30%) fall in the intermediate risk category and cannot be correctly classified (indeterminate results).…”