Clinically Significant Fibrosis Is Associated With Longitudinal Increases in Fibrosis-4 and Nonalcoholic Fatty Liver Disease Fibrosis Scores

Preya Janubhai Patel; Johnson Chieh-Yu Cheng; Xuan Banh; Lucy Gracen; Daniel Radford-Smith; Fabrina Hossain; Leigh Ula Horsfall; Kelly Lee Hayward; Suzanne Williams; Tracey Johnson; Nigel Neil Brown; Nivene Saad; Katherine Anne Stuart; Anthony William Russell; Patricia Casarolli Valery; Andrew Donald Clouston; Katharine Margaret Irvine; Anne Bernard; Elizabeth Ellen Powell

doi:10.1016/j.cgh.2019.07.036

Clinically Significant Fibrosis Is Associated With Longitudinal Increases in Fibrosis-4 and Nonalcoholic Fatty Liver Disease Fibrosis Scores

Clin Gastroenterol Hepatol. 2020 Mar;18(3):710-718.e4. doi: 10.1016/j.cgh.2019.07.036. Epub 2019 Jul 25.

Authors

Preya Janubhai Patel¹, Johnson Chieh-Yu Cheng², Xuan Banh², Lucy Gracen², Daniel Radford-Smith³, Fabrina Hossain⁴, Leigh Ula Horsfall¹, Kelly Lee Hayward², Suzanne Williams⁴, Tracey Johnson⁴, Nigel Neil Brown⁵, Nivene Saad⁶, Katherine Anne Stuart⁷, Anthony William Russell⁸, Patricia Casarolli Valery⁹, Andrew Donald Clouston², Katharine Margaret Irvine¹⁰, Anne Bernard¹¹, Elizabeth Ellen Powell¹²

Affiliations

¹ Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia; Centre for Liver Disease Research, University of Queensland, Brisbane, Australia.
² Centre for Liver Disease Research, University of Queensland, Brisbane, Australia.
³ Faculty of Medicine, University of Queensland, Brisbane, Australia.
⁴ Inala Primary Care, Brisbane, Australia.
⁵ Pathology Queensland, Brisbane, Australia.
⁶ Faculty of Medicine, University of Queensland, Brisbane, Australia; Department of Radiology, Princess Alexandra Hospital, Brisbane, Australia.
⁷ Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.
⁸ Faculty of Medicine, University of Queensland, Brisbane, Australia; Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Australia.
⁹ QIMR Berghofer Medical Research Institute, Brisbane, Australia.
¹⁰ Centre for Liver Disease Research, University of Queensland, Brisbane, Australia; Mater Research, Translational Research Institute, University of Queensland, Brisbane, Australia.
¹¹ QFAB Bioinformatics, Institute for Molecular Bioscience, Queensland Bioscience Precinct, University of Queensland, Brisbane, Australia.
¹² Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia; Centre for Liver Disease Research, University of Queensland, Brisbane, Australia. Electronic address: e.powell@uq.edu.au.

PMID: 31352092
DOI: 10.1016/j.cgh.2019.07.036

Abstract

Background & aims: There is limited knowledge regarding the longitudinal utility of biomarkers of fibrosis, such as the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) or the fibrosis-4 score (FIB-4) score. We examined longitudinal changes in the NFS and the FIB-4 score in patients with NAFLD, with and without clinically significant fibrosis (CSF).

Methods: We performed a retrospective study of 230 patients with NAFLD, collecting clinical and laboratory records to calculate NFS and FIB-4 scores at 6 monthly intervals for 5 years before hepatology assessment of fibrosis. Linear mixed models with random intercept and slope and adjusted for age at baseline were used to assess the progression of NFS and log-transformed FIB-4 scores over time in subjects with and without CSF, determined by liver stiffness measurements of 8.2 kPa or greater.

Results: Patients had a median of 11 (minimum, 10; maximum, 11) retrospective observations over a median time period of 5 years (minimum, 4.5 y; maximum, 5 y). Of patients with low baseline NFS and FIB-4 scores, 31.11% and 37.76%, respectively, had CSF at the time of hepatology assessment. There was a correlation between NFS and log₁₀ FIB-4 over time (repeated measure r = 0.55; 95% CI, 0.52-0.59). The rate of increase in NFS and log₁₀ FIB-4 was significantly higher in patients with than without CSF (both P < .001). Predicted NFS increased by 0.17 and 0.06 units per year in subjects with and without CSF, respectively. Predicted log₁₀ FIB-4 score increased by 0.032 and 0.0003 units per year in subjects with and without CSF, respectively.

Conclusions: Noninvasively measured fibrosis scores increase progressively in patients with NAFLD and CSF. Further studies are needed to determine whether repeated measurements can identify patients at risk for CSF.

Keywords: Fibrosis; Nonalcoholic Fatty Liver Disease; Noninvasive Biomarkers; Repeated Measurements.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aspartate Aminotransferases
Humans
Liver Cirrhosis
Non-alcoholic Fatty Liver Disease* / complications
Retrospective Studies
Severity of Illness Index

Substances

Aspartate Aminotransferases