A blood-based biomarker panel for non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis

Xiang Zhang; Ming-Hua Zheng; Dehua Liu; Yufeng Lin; Sherlot Juan Song; Eagle Siu-Hong Chu; Dabin Liu; Seema Singh; Michael Berman; Harry Cheuk-Hay Lau; Hongyan Gou; Grace Lai-Hung Wong; Ni Zhang; Hai-Yang Yuan; Rohit Loomba; Vincent Wai-Sun Wong; Jun Yu

doi:10.1016/j.cmet.2024.10.008

A blood-based biomarker panel for non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis

Cell Metab. 2024 Oct 29:S1550-4131(24)00404-2. doi: 10.1016/j.cmet.2024.10.008. Online ahead of print.

Authors

Xiang Zhang¹, Ming-Hua Zheng², Dehua Liu¹, Yufeng Lin¹, Sherlot Juan Song¹, Eagle Siu-Hong Chu¹, Dabin Liu¹, Seema Singh³, Michael Berman³, Harry Cheuk-Hay Lau¹, Hongyan Gou¹, Grace Lai-Hung Wong¹, Ni Zhang², Hai-Yang Yuan², Rohit Loomba⁴, Vincent Wai-Sun Wong⁵, Jun Yu⁶

Affiliations

¹ Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shenzhen Research Institute, Hong Kong SAR, China.
² MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ MASLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, San Diego, CA, USA.
⁴ MASLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, San Diego, CA, USA. Electronic address: roloomba@ucsd.edu.
⁵ Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shenzhen Research Institute, Hong Kong SAR, China. Electronic address: wongv@cuhk.edu.hk.
⁶ Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shenzhen Research Institute, Hong Kong SAR, China. Electronic address: junyu@cuhk.edu.hk.

PMID: 39500327
DOI: 10.1016/j.cmet.2024.10.008

Abstract

The current diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe form, metabolic dysfunction-associated steatohepatitis (MASH), is suboptimal. Here, we recruited 700 individuals, including 184 from Hong Kong as a discovery cohort and 516 from San Diego, Wenzhou, and Hong Kong as three validation cohorts. A panel of 3 parameters (C-X-C motif chemokine ligand 10 [CXCL10], cytokeratin 18 fragments M30 [CK-18], and adjusted body mass index [BMI]) was formulated (termed N3-MASH), which discriminated patients with MASLD from healthy controls with an area under the receiver operating characteristic (AUROC) of 0.954. Among patients with MASLD, N3-MASH could identify patients with MASH with an AUROC of 0.823, achieving 90.0% specificity, 62.9% sensitivity, and 88.6% positive predictive value. The diagnostic performance of N3-MASH was confirmed in three validation cohorts with AUROC of 0.802, 0.805, and 0.823, respectively. Additionally, N3-MASH identifies patients with MASH improvement with an AUROC of 0.857. In summary, we developed a robust blood-based panel for the non-invasive diagnosis of MASH, which might help clinicians reduce unnecessary liver biopsies.

Keywords: MASH; MASLD; N3-MASH; diagnosis; markers; multi-cohort; non-invasive; serum.