Accuracy of the Enhanced Liver Fibrosis Test in Patients With Type 2 Diabetes Mellitus and Its Clinical Implications

Taeang Arai; Hirokazu Takahashi; Yuya Seko; Hidenori Toyoda; Hideki Hayashi; Kanji Yamaguchi; Michihiro Iwaki; Masato Yoneda; Toshihide Shima; Hideki Fujii; Asahiro Morishita; Kazuhito Kawata; Kengo Tomita; Miwa Kawanaka; Yuichi Yoshida; Tadashi Ikegami; Kazuo Notsumata; Satoshi Oeda; Masanori Atsukawa; Yoshihiro Kamada; Yoshio Sumida; Hideaki Fukushima; Eiji Miyoshi; Shinichi Aishima; Takeshi Okanoue; Yoshito Itoh; Atsushi Nakajima; Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)

doi:10.1016/j.cgh.2023.11.022

Accuracy of the Enhanced Liver Fibrosis Test in Patients With Type 2 Diabetes Mellitus and Its Clinical Implications

Clin Gastroenterol Hepatol. 2024 Apr;22(4):789-797.e8. doi: 10.1016/j.cgh.2023.11.022. Epub 2023 Dec 2.

Authors

Taeang Arai¹, Hirokazu Takahashi², Yuya Seko³, Hidenori Toyoda⁴, Hideki Hayashi⁵, Kanji Yamaguchi³, Michihiro Iwaki⁶, Masato Yoneda⁶, Toshihide Shima⁷, Hideki Fujii⁸, Asahiro Morishita⁹, Kazuhito Kawata¹⁰, Kengo Tomita¹¹, Miwa Kawanaka¹², Yuichi Yoshida¹³, Tadashi Ikegami¹⁴, Kazuo Notsumata¹⁵, Satoshi Oeda¹⁶, Masanori Atsukawa¹, Yoshihiro Kamada¹⁷, Yoshio Sumida¹⁸, Hideaki Fukushima¹⁹, Eiji Miyoshi²⁰, Shinichi Aishima²¹, Takeshi Okanoue⁷, Yoshito Itoh³, Atsushi Nakajima⁶; Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
² Liver Center, Saga University Hospital, Saga, Japan. Electronic address: takahas2@cc.saga-u.ac.jp.
³ Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁴ Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
⁵ Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan.
⁶ Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
⁷ Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan.
⁸ Department of Hepatology, Osaka Metropolitan University, Osaka, Japan.
⁹ Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan.
¹⁰ Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan.
¹¹ Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan.
¹² Department of General Internal Medicine 2, Kawasaki General Medical Center, Kawasaki Medical School, Okayama, Japan.
¹³ Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka, Japan.
¹⁴ Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan.
¹⁵ Department of General Internal Medicine, Fukui-ken Saiseikai Hospital, Fukui, Japan.
¹⁶ Liver Center, Saga University Hospital, Saga, Japan.
¹⁷ Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
¹⁸ Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Aichi, Japan.
¹⁹ Diagnostics Business Area, Siemens Healthcare Diagnostics K.K., Tokyo, Japan.
²⁰ Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan.
²¹ Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, Japan.

PMID: 38048934
DOI: 10.1016/j.cgh.2023.11.022

Abstract

Background and aims: The diagnostic performance of the Fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) is poor in patients with type 2 diabetes mellitus (T2DM). We determined the usefulness of the Enhanced Liver Fibrosis (ELF) test in patients with T2DM.

Methods: A total of 1228 patients with biopsy-proven NAFLD were enrolled. The diagnostic performance of the ELF test for predicting advanced fibrosis in participants with or without T2DM was evaluated in comparison with the FIB-4 index and NFS.

Results: Overall, the area under the curve of the ELF test for predicting advanced fibrosis was greater (0.828) than that of the FIB-4 index (0.727) and NFS (0.733). The diagnostic performance of the ELF test (area under the curve, 0.820) was also superior to that of the FIB-4 index (0.698) and NFS (0.700) in patients with T2DM. With the low cutoff values for each noninvasive test, the ELF test provided an acceptable false negative rate (cutoff value 9.8, 6.7%) in this population, unlike the FIB-4 index (1.30, 14.5%) and NFS (-1.455, 12.4%). After propensity score matching to avoid selection bias including age, sex, body mass index, and the prevalence of advanced fibrosis, the ELF test with a low cutoff value showed a high sensitivity (≥91.4%) and a high negative predictive value (≥96.8%), irrespective of the presence or absence of T2DM.

Conclusions: The high diagnostic performance of the ELF test for predicting advanced fibrosis in individuals with or without T2DM could address an unmet medical need for accurate assessment of liver fibrosis in patients with diabetes and NAFLD.

Keywords: Diabetes; ELF; Fibrosis; NAFLD; Noninvasive Tests.

MeSH terms

Alanine Transaminase
Aspartate Aminotransferases
Biopsy
Diabetes Mellitus, Type 2* / complications
Humans
Liver / pathology
Liver Cirrhosis / pathology
Non-alcoholic Fatty Liver Disease* / complications
Non-alcoholic Fatty Liver Disease* / diagnosis
Non-alcoholic Fatty Liver Disease* / epidemiology
Severity of Illness Index

Substances

Alanine Transaminase
Aspartate Aminotransferases