A novel rapid immunoassay of serum type IV collagen 7S for the diagnosis of fibrosis stage of nonalcoholic fatty liver diseases

Abstract

Aim: Type IV collagen 7S (T4C7S) is a valuable biomarker for detecting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). The conventional T4C7S measurement via radioimmunoassay (T4C7S RIA) has shortcomings of radioisotope usage and longer assay periods. We compared T4C7S RIA with a newly developed, fast T4C7S chemiluminescent enzyme immunoassay (T4C7S CLEIA) and examined the diagnostic accuracies of and correlation between the two techniques. Methods: We evaluated 170 biopsy-confirmed patients with NAFLD. T4C7S was measured via both T4C7S RIA and T4C7S CLEIA. The correlation between T4C7S RIA and T4C7S CLEIA was analyzed in 305 total serum samples via exploratory research and 47 validation samples. The diagnostic accuracies of T4C7S CLEIA and T4C7S RIA were compared in the sera of patients with NAFLD and test samples. Results: Sera T4C7S levels of T4C7S CLEIA and T4C7S RIA significantly correlated in patients' samples via exploratory (r ¼ 0.914, P ¼ 0.000) and validation (r ¼ 0.929, P ¼ 0.000) research. At a 10% coefficient, T4C7S CLEIA concentration was 0.26 ng/ml in the serum samples, indicating high accuracy at even low concentrations. T4C7S CLEIA revealed distinct changes between each stage and high sensitivity in detecting the F2 stage, indicating a higher sensitivity in detecting low fibrosis stages than T4C7S RIA in patients with NAFLD. Conclusions: The T4C7S CLEIA correlated well with the T4C7S RIA. Favorably, the T4C7S CLEIA has a higher sensitivity and rapid measurement time and requires a small sample volume; thus, it is a promising and popular biomarker for fibrosis stage diagnosis in NAFLD. Abbreviations: AUROC, the area under the receiver operator characteristic curve; CLEIA, chemiluminescent enzyme immunoassay; CV, coefficient of variation; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD activity score; NASH, non-alcoholic steatohepatitis; RIA, radioimmunoassay; T4C7S, type IV collagen 7S; T4C7S CLEIA, type IV collagen 7S with chemiluminescent enzyme immunoassay; T4C7S RIA, type IV collagen 7S with radioimmunoassay. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Comparison of thrombocytopenia between patients with non‐alcoholic fatty liver disease and those with hepatitis C virus‐related chronic liver disease

“…Recently, we have published artificial intelligence systems for screening NASH 2 and staging liver fibrosis 3 using 11 clinical values 2 and a fibrosis marker (type 4 collagen 7S [T4C7S]), 3 respectively. In addition, we have reported the novel immunoassay of T4C7S for diagnosing NASHrelated fibrosis 4 and noninvasive scoring systems containing T4C7S. [5][6][7] Many other biomarkers for detecting liver fibrosis have been proposed.…”

A 3-step approach to predict advanced fibrosis in nonalcoholic fatty liver disease: impact on diagnosis, patient burden, and medical costs

“…The T4C7S is a fragment of type IV collagen and is used as a biomarker of liver fibrosis in NAFLD 12 , 13 . It can be measured as a single parameter in serum using a chemiluminescent enzyme immunoassay 14 . T4C7S has an area under the receiver operating characteristic curve of 0.83–0.91 15 , 16 .…”

Novel artificial intelligent/neural network system for staging of nonalcoholic steatohepatitis

“…One of the reasons of its lack of approval is the handling of the radioisotope substance and prolonged assay period in the conventional T4C7S RIA. Recently the novel rapid T4C7S by chemiluminescent enzyme immunoassay technique was developed by Fujirebio 13 . It correlated well with T4C7S RIA and has a higher sensitivity and rapid measurement time 13 .…”

“…Recently the novel rapid T4C7S by chemiluminescent enzyme immunoassay technique was developed by Fujirebio 13 . It correlated well with T4C7S RIA and has a higher sensitivity and rapid measurement time 13 . Imaging tests such as transient elastography 14,15 and MRE 16–18 have become widely known for the detection of steatosis and liver fibrosis in patients diagnosed with NAFLD; however, these techniques are costly and time‐consuming.…”