Serum dithiothreitol-oxidizing capacity (DOC) is a promising biomarker for excluding significant liver fibrosis: a proof-of-concept study

Lumin Yang ¹, Yafei Zhang ², Xiaodan Hong ²

¹State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, No. 130 West Changjiang Lane, Hefei, Anhui, 230036, China.
²Department of Infectious Diseases and Institute of Clinical Virology, The Second Hospital of Anhui Medical University, No. 678 Furong Lane, Hefei, Anhui, 230601, China.
³MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China.
⁴Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁵Department of Medicine, University of Verona, Verona, Italy.
⁶Metabolic Diseases Research Unit, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar Di Valpolicella, Italy.
⁷Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton and University of Southampton, Southampton General Hospital, Southampton, UK.
⁸Department of Infectious Diseases and Institute of Clinical Virology, The Second Hospital of Anhui Medical University, No. 678 Furong Lane, Hefei, Anhui, 230601, China. zzh1974cn@163.com.
⁹MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China. zhengmh@wmu.edu.cn.
¹⁰Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China. zhengmh@wmu.edu.cn.
¹¹State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, No. 130 West Changjiang Lane, Hefei, Anhui, 230036, China. zjs@ahau.edu.cn.

⁰State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science, Anhui Agricultural University, No. 130 West Changjiang Lane, Hefei, Anhui, 230036, China.

Bmc Medicine +

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July 3, 2024

View abstract on PubMed

Summary

The serum dithiothreitol-oxidizing capacity (DOC) test shows promise for identifying significant liver fibrosis, outperforming APRI and FIB-4 scores. This non-invasive test could reduce the need for liver biopsies in patients with chronic liver diseases.

Area Of Science

Hepatology
Biomarker Discovery
Diagnostic Accuracy

Background

APRI and FIB-4 scores are commonly used to assess liver fibrosis but have variable cut-offs across patient cohorts.
Significant fibrosis (stage ≥ F2) requires accurate, non-invasive detection methods for patient management.
Quiescin sulfhydryl oxidase-1, a matrix remodeling enzyme, is a potential target for fibrosis assessment.

Purpose Of The Study

To evaluate serum dithiothreitol-oxidizing capacity (DOC) as a non-invasive biomarker for significant liver fibrosis in various chronic liver diseases (CLDs).
To compare the diagnostic performance of DOC against established non-invasive markers APRI and FIB-4.
To determine if DOC can provide a uniform cut-off for fibrosis assessment, independent of CLD etiology and patient age.

Main Methods

Diagnostic performance of DOC, APRI, and FIB-4 was assessed using ROC curve analyses in multiple cohorts: chronic hepatitis B (CHB), metabolic-associated steatotic liver disease (MASLD), and mixed CLDs.
Cut-off values were determined using the Youden index, with analyses stratified by CLD etiology and age.
The variability of cut-offs for DOC, APRI, and FIB-4 was compared to assess uniformity.

Main Results

The DOC test demonstrated superior performance over APRI and FIB-4 in discriminating significant fibrosis in cohorts where APRI/FIB-4 showed poor/modest accuracy.
DOC performance was equivalent to APRI/FIB-4 when the latter exhibited moderate/adequate diagnostic capabilities.
DOC offered a significant advantage in establishing a uniform cut-off (1.7% CV) compared to APRI (22.9% CV) and FIB-4 (47.6% CV) when stratified by etiology, and similarly when stratified by age (2.0% CV for DOC vs. 26.7% for APRI and 29.5% for FIB-4).
A uniform cut-off of 2.13 for DOC, consistent with its upper limit of normal (99% specificity), showed high negative predictive value for excluding significant fibrosis and acceptable positive predictive value for detecting it.

Conclusions

The serum DOC test is a promising non-invasive tool for efficiently ruling in and ruling out significant liver fibrosis across diverse CLDs.
DOC's ability to establish a uniform cut-off reduces variability associated with other non-invasive markers, simplifying clinical application.
This biomarker has the potential to decrease the number of unnecessary liver biopsies and aid clinicians in excluding significant fibrosis in primary care settings.

Keywords:

APRI Cut-off Dithiothreitol-oxidizing capacity (DOC) FIB-4 Liver fibrosis