A longitudinal assessment of non-invasive biomarkers to diagnose and predict cystic fibrosis-associated liver disease

J Cyst Fibros. 2020 Jul;19(4):546-552. doi: 10.1016/j.jcf.2020.05.002. Epub 2020 May 30.

Abstract

Background & aims: A practical, inexpensive, and non-invasive biomarker of liver fibrosis is needed as a reliable screening test for cystic fibrosis-associated liver disease (CFLD). Studies have shown the utility of AST to Platelet Ratio Index (APRI), fibrosis index based on 4 factors (FIB-4), and gamma-glutamyl transferase (GGT) as good biomarkers for identifying CFLD. The goal of the study was to evaluate the effectiveness of APRI, FIB-4, AST/ALT ratio, platelet count, GGT, and GGT platelet ratio (GPR) in predicting CFLD development.

Methods: Data was collected from CF Foundation Patient Registry for patients aged 3-21 years at Johns Hopkins from January 1, 2002 to December 31, 2014. Collected data included demographic characteristics, presence of splenomegaly, hepatomegaly, ascites, and variceal bleeding, AST, ALT, GGT, platelet count, and FEV1. The sensitivity and specificity of each biomarker were analyzed and reported by the area under receiver operating characteristic (AUROC) curve.

Results: By the end of the study, 144 "healthy" CF, 12 CFLD, 19 CF-associated pulmonary disease (CFPD), and 4 CFLD with CFPD cases were identified. APRI scores were higher in CFLD, 0.85 versus 0.28 in "healthy" CF and 0.23 in CFPD groups (p<0.001). GPR had the highest AUROC curve at 0.91.

Conclusions: GPR, GGT, APRI score, and platelet count were potentially useful biomarkers while FIB-4 did not predict CFLD development. Cost-effectiveness studies are needed to analyze the utility of these biomarkers in clinical practice.

Keywords: Blood chemical analysis; Blood platelets; Liver cirrhosis; Respiratory tract infections; Transferases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alanine Transaminase / blood*
  • Aspartate Aminotransferases / blood*
  • Biomarkers / blood
  • Child, Preschool
  • Cystic Fibrosis* / blood
  • Cystic Fibrosis* / complications
  • Cystic Fibrosis* / physiopathology
  • Female
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / etiology
  • Liver Function Tests / methods
  • Male
  • Mass Screening / methods
  • Mass Screening / standards
  • Platelet Count / methods*
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Severity of Illness Index
  • United States / epidemiology
  • Young Adult
  • gamma-Glutamyltransferase / blood*

Substances

  • Biomarkers
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase