Development and validation of a novel non-invasive test for diagnosing fibrotic non-alcoholic steatohepatitis in patients with biopsy-proven non-alcoholic fatty liver disease

J Gastroenterol Hepatol. 2020 Oct;35(10):1804-1812. doi: 10.1111/jgh.15055. Epub 2020 Apr 28.

Abstract

Background and aim: There is an immediate need for non-invasive accurate tests for diagnosing liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). Previously, it has been suggested that MACK-3 (a formula that combines homeostasis model assessment-insulin resistance with serum serum aspartate aminotransferase and cytokeratin [CK]18-M30 levels) accurately identifies patients with fibrotic NASH. Our aim was to assess the performance of MACK-3 and develop a novel, non-invasive algorithm for diagnosing fibrotic NASH.

Methods: Six hundred and thirty-six adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from two independent Asian cohorts were enrolled in our study. Liver stiffness measurement (LSM) was assessed by vibration-controlled transient elastography (Fibroscan). Fibrotic NASH was defined as NASH with a NAFLD activity score (NAS) ≥ 4 and F ≥ 2 fibrosis.

Results: Metabolic syndrome (MetS), platelet count and MACK-3 were independent predictors of fibrotic NASH. On the basis of their regression coefficients, we developed a novel nomogram showing a good discriminatory ability (area under receiver operating characteristic curve [AUROC]: 0.79, 95% confidence interval [CI 0.75-0.83]) and a high negative predictive value (NPV: 94.7%) to rule out fibrotic NASH. In the validation set, this nomogram had a higher AUROC (0.81, 95%CI 0.74-0.87) than that of MACK-3 (AUROC: 0.75, 95%CI 0.68-0.82; P < 0.05) with a NPV of 93.2%. The sequential combination of this nomogram with LSM data avoided the need for liver biopsy in 56.9% of patients.

Conclusions: Our novel nomogram (combining MACK-3, platelet count and MetS) shows promising utility for diagnosing fibrotic NASH. The sequential combination of this nomogram and vibration-controlled transient elastography limits indeterminate results and reduces the number of unnecessary liver biopsies.

Keywords: NAFLD, clinical; NASH; diagnostic tests; liver biopsy; liver fibrosis.

MeSH terms

  • Adult
  • Algorithms
  • Asian People
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Biopsy
  • Cohort Studies
  • Elasticity Imaging Techniques
  • Female
  • Fibrosis
  • Humans
  • Insulin Resistance
  • Keratin-18 / blood
  • Liver / pathology*
  • Male
  • Metabolic Syndrome
  • Middle Aged
  • Nomograms
  • Non-alcoholic Fatty Liver Disease / diagnosis*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Platelet Count
  • ROC Curve

Substances

  • Biomarkers
  • Keratin-18
  • Aspartate Aminotransferases