Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Diagnostic performance of Liver FibraChek Dx©, a blood-based test for the non-invasive detection of liver cirrhosis and cancer
Fernando Siguencia, Michitaka Matsuda, Vijay Pandyarajan, Sunao Tanaka, Steven M Smith, Catherine Bresee, Ekihiro Seki, Charles J Rosser, Hideki Furuya
Fernando Siguencia, Sunao Tanaka, Steven M Smith, Charles J Rosser, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Michitaka Matsuda, Vijay Pandyarajan, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Catherine Bresee, Department of Biostatistics Shared Resources, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Ekihiro Seki, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Hideki Furuya, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Co-first authors: Fernando Siguencia and Michitaka Matsuda.
Author contributions: Siguencia F and Matsuda M wrote the manuscript; Siguencia F, Matsuda M, Pandyarajan V, Tanaka S, and Smith S performed the research; Matsuda M, Pandyarajan V, Bresee C, and Furuya H analyzed the data and performed investigation, resources; Seki E, Rosser CJ and Furuya H reviewed and edited the manuscript; Rosser CJ and Furuya H designed the research study; all authors have read and agreed to the published version of the manuscript.
Institutional review board statement: This study received approval and a waiver of consent to use previously banked de-identified serum samples from the Cedars-Sinai Medical Center Institutional Review Board, Los Angeles, CA, United States (No. 00002172). Study performance complied with the tenets of the Declaration of Helsinki.
Informed consent statement: This study was conducted using previously banked, de-identified serum samples. The Cedars-Sinai Medical Center Institutional Review Board reviewed the study protocol and granted a waiver of informed consent.
Conflict-of-interest statement: Charles J Rosser is an officer at Nonagen Bioscience Corporation (Los Angeles, CA, United States), which has patent interests in and development rights to the Liver FibraChek Dx© assay. The remaining authors have no potential conflicts of interest to disclose, financial or otherwise.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Hideki Furuya, PhD, Associate Professor, Department of Biomedical Science, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, United States.
hideki.furuya@cshs.org
Received: February 27, 2025
Revised: April 24, 2025
Accepted: May 29, 2025
Published online: June 27, 2025
Processing time: 118 Days and 19 Hours
BACKGROUND
Metabolic dysfunction-associated steatotic liver disease (MASLD), hepatic fibrosis, and cirrhosis are major risk factors for hepatocellular carcinoma (HCC), yet current blood-based diagnostic assays lack sufficient accuracy for routine clinical use. Identifying a non-invasive molecular signature that accurately detects liver disease could improve early diagnosis and monitoring. We hypothesized that the Liver FibraChek Dx© serum assay could discriminate MASLD and HCC from healthy controls using a multiplex biomarker-based algorithm.
AIM
To evaluate the diagnostic performance of the Liver FibraChek Dx© assay for detecting MASLD and HCC.
METHODS
This was a prospective, single-center study conducted in a United States tertiary care setting. Serum samples were collected from 45 participants (14 MASLD, 19 HCC, 12 healthy controls) with liver histology confirmed by biopsy. The Liver FibraChek Dx© algorithm integrates weighted values of aspartate aminotransferase, alanine aminotransferase, taurocholic acid, L-tyrosine, platelet count, and patient age to generate a risk score. Wilcoxon rank sum tests were used to assess associations with histologic diagnosis, and receiver operating characteristic (ROC) curves quantified diagnostic performance.
RESULTS
Liver FibraChek Dx© risk scores were significantly elevated in MASLD and HCC compared to controls (median: 6.92 ± 3.86 vs 3.61 ± 1.67, P < 0.001). The area under the ROC curve was 0.890 (95%CI: 0.776–1.000) for distinguishing diseased from healthy individuals. Sensitivity was 93.9%, specificity 75.0%, positive predictive value 91.1%, negative predictive value 81.8%, and overall accuracy 88.9%.
CONCLUSION
The Liver FibraChek Dx© assay accurately detects liver disease and shows promise as a non-invasive tool for diagnosing and monitoring MASLD and HCC.
Core Tip: This retrospective observational study assessed the diagnostic accuracy of Liver FibraChek Dx©, a non-invasive serum assay for detecting metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). The test algorithm integrates five serum biomarkers and age to produce a risk score. Among 45 participants with biopsy-confirmed diagnoses (MASLD, HCC, or healthy), Liver FibraChek Dx© achieved an area under the receiver operating characteristic curve of 0.890, with 93.9% sensitivity and 88.9% accuracy. Risk scores significantly distinguished individuals with liver disease from healthy controls. These findings support the potential clinical utility of Liver FibraChek Dx© in diagnosing and monitoring liver pathogenesis via blood-based testing.
