Combined and sequential non-invasive approach to diagnosing non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease and persistently normal alanine aminotransferase levels

BMJ Open Diabetes Res Care. 2020 Mar;8(1):e001174. doi: 10.1136/bmjdrc-2020-001174.

Abstract

Background and aim: Imaging-confirmed non-alcoholic fatty liver disease (NAFLD) with normal alanine aminotransferase (nALT) levels is infrequently the subject for further evaluation. Early diagnosis of non-alcoholic steatohepatitis (NASH) is needed to prevent disease progression. Thus, we tested the clinical utility of serum Golgi protein 73 (GP73) levels and developed a new non-invasive score to diagnose NASH in patients with biopsy-confirmed NAFLD and persistent nALT levels.

Methods: Serum GP73 and cytokeratin-18 M30 fragments (CK18-M30) levels were measured in 345 patients with biopsy-proven NAFLD. We developed a new score, named G-NASH model (by incorporating serum GP73), and combined it with serum CK18-M30 measurement in a sequential non-invasive approach to accurately identify NASH among patients with NAFLD and persistent nALT levels.

Results: 105 (30.4%) patients had persistent nALT, 53 of whom had histologically confirmed NASH. Both serum GP73 and CK18-M30 levels alone had poor diagnostic accuracy in identifying NASH (55.2% and 51.6%, respectively) in these patients. Conversely, G-NASH model performed better than other established non-invasive scoring systems, and by using our proposed sequential non-invasive approach 82.9% of patients with NASH were correctly identified.

Conclusions: NASH is highly prevalent in patients with NAFLD with persistent nALT levels. The G-NASH model accurately identifies NASH in this patient group.

Keywords: NAFLD; diagnosis; liver disease; nonalcoholic steatohepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood*
  • Biomarkers / blood
  • Female
  • Humans
  • Keratin-18 / blood
  • Male
  • Membrane Proteins / blood
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood*
  • Non-alcoholic Fatty Liver Disease / diagnosis*
  • Sensitivity and Specificity

Substances

  • Biomarkers
  • GOLM1 protein, human
  • Keratin-18
  • Membrane Proteins
  • Alanine Transaminase