Evaluation of dithiothreitol-oxidizing capacity (DOC) as a serum biomarker for chronic hepatitis B in patients exhibiting normal alanine aminotransferase levels: a pilot study towards better monitoring of disease

Yang, Lumin; Zhang, Yafei; Zhang, Ke; Liu, Zhongping; He, Tao; Zheng, Xiaowei; Li, Lei; Arnér, Elias S.J.; Zhen-hua, Zhang; Zhang, Jinsong

doi:10.1016/j.eclinm.2021.101180

Cited by 2 publications

(4 citation statements)

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“…QSOX1 may impair Nrf2 activation in hepatocellular carcinoma cells [ 40 ], suggesting that the over-expression of hepatic QSOX1 may promote oxidative stress. QSOX1 was initially found to be a specific biomarker for indentifying acute decompensated heart failure [ 41 ], while more recently it was revealed to be a biomarker for CLDs [ 19 , 21 ]. Contrary to the trajectory, serum gamma glutamyl transferase concentration, a non-specific liver test, has evolved to be a biomarker of cardiometabolic health [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Contrary to the trajectory, serum gamma glutamyl transferase concentration, a non-specific liver test, has evolved to be a biomarker of cardiometabolic health [ 42 ]. We have found that the DOC test could not be used for indentifying acute myocardial infarction [ 21 ]. In addition, QSOX1 is only sensitive in the case of acute decompensated heart failure, but not stable chronic heart failure [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…DOC activity was measured according to our previously validated assay [ 21 ] with slight modification. Briefly, serum (15 μL) was diluted with saline (85 μL) and was mixed with 50 μL of the reaction mixture with or without 1 mM dithiothreitol (DTT).…”

Section: Methodsmentioning

confidence: 99%

“…D ithiothreitol- o xidizing c apacity (DOC) in human serum is predominantly contributed by QSOX1 [ 20 ]. We have recently shown that DOC is a promising biomarker for disease monitoring in HBV-infected patients with normal serum ALT levels [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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

Yang,

Zhang,

Hong

et al. 2024

BMC Med

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Background APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). Methods Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. Results Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). Conclusions This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.

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