Classification of patients with non‐alcoholic fatty liver disease using rapid immunoassay of serum type IV collagen compared with liver histology and other fibrosis markers

Mizuno, Masayuki; Shima, Toshihide; Oya, Hirohisa; Mitsumoto, Yasuhide; Mizuno, Chiemi; Isoda, Satoshi; Kuramoto, Mizue; Taniguchi, M; Noda, Masahiro; Sakai, Kyoko; Koyama, Noriyuki; Okanoue, Takeshi

doi:10.1111/hepr.12710

Cited by 39 publications

(39 citation statements)

References 40 publications

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“…7 Such particle-enhanced turbidimetric immunoassays (PETIAs) have been used since the 1920’s, and currently PETIAs for a variety of analytes are commercially available. 8–10 Turbidimetric assays have the advantages of being label-free, fast (<20 min), and easy to perform on commonplace equipment (i.e., microwell plate readers). 11,12 One disadvantage of common turbidimetric assays is that they require the use of antibodies, which have poor environmental stability, and the routine methods for antibody production are associated with high cost.…”

Section: Introductionmentioning

confidence: 99%

Charged poly(N-isopropylacrylamide) nanogels for use as differential protein receptors in a turbidimetric sensor array

Culver

Sharma

Wechsler

et al. 2017

Analyst

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Due to the high cost and environmental instability of antibodies, there is precedent for developing synthetic molecular recognition agents for use in diagnostic sensors. While these materials typically have lower specificity than antibodies, their cross-reactivity makes them excellent candidates for use in differential sensing routines. In the current work, we design a set of charge-containing poly(N-isopropylacrylamide) (PNIPAM) nanogels for use as differential protein receptors in a turbidimetric sensor array. Specifically, NIPAM was copolymerized with methacrylic acid and modified via carbodiimide coupling to introduce sulfate, guanidinium, secondary amine, or primary amine groups. Modification of the ionizable groups in the network changed the physicochemical and protein binding properties of the nanogels. For high affinity protein-polymer interactions, turbidity of the nanogel solution increased, while for low affinity interactions minimal change in turbidity was observed. Thus, relative turbidity was used as input for multivariate analysis. Turbidimetric assays were performed in two buffers of different pH (i.e., 7.4 and 5.5), but comparable ionic strength, in order to improve differentiation. Using both buffers, it was possible to achieve 100% classification accuracy of eleven model protein biomarkers with as few as two of the nanogel receptors. Additionally, it was possible to detect changes in lysozyme concentration in a simulated tear fluid using the turbidimetric sensor array.

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Section: Introductionmentioning

confidence: 99%

Charged poly(N-isopropylacrylamide) nanogels for use as differential protein receptors in a turbidimetric sensor array

Culver

Sharma

Wechsler

et al. 2017

Analyst

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“…However, current histologic staging systems are not continuous quantitative measures of hepatic fibrosis . Previous studies have suggested that noninvasive or minimally invasive biomarkers, including platelet counts, serum levels of the type IV collagen 7s domain (7s collagen) and Wisteria floribunda agglutinin‐positive Mac‐2 binding protein, fibrosis‐4 (FIB‐4) index, and liver stiffness computed by imaging technologies, are surrogate measurements for estimating the degree of liver fibrosis in patients with NAFLD . Emerging evidence attests to a possible role of fibrosis‐targeted therapy against progressive fibrotic diseases, including NAFLD .…”

Section: Introductionmentioning

confidence: 99%

Quantitative assessment of liver fibrosis reveals a nonlinear association with fibrosis stage in nonalcoholic fatty liver disease

Masugi

Abe

Tsujikawa

et al. 2017

Hepatology Communications

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Accurate staging of liver fibrosis is crucial to guide therapeutic decisions for patients with nonalcoholic fatty liver disease (NAFLD). Digital image analysis has emerged as a promising tool for quantitative assessment of fibrosis in chronic liver diseases. We sought to determine the relationship of histologic fibrosis stage with fiber amounts quantified in liver biopsy specimens for the better understanding of NAFLD progression. We measured area ratios of collagen and elastin fibers in Elastica van Gieson‐stained biopsy tissues from 289 patients with NAFLD from four hospitals using an automated computational method and examined their correlations with Brunt's fibrosis stage. As a secondary analysis, we performed multivariable logistic regression analysis to assess the associations of the combined area ratios of collagen and elastin with noninvasive fibrosis markers. The combined fiber area ratios correlated strongly with Brunt's stage (Spearman correlation coefficient, 0.78; P < 0.0001), but this relationship was nonlinear (P = 0.007) with striking differences between stage 4 (median area ratios, 12.3%) and stages 0‐3 (2.1%, 2.8%, 4.3%, and 4.8%, respectively). Elastin accumulation was common in areas of thick bridging fibrosis and thickened venous walls but not in areas of perisinusoidal fibrosis. The highest tertile of the combined fiber area ratios was associated with the fibrosis‐4 index and serum type IV collagen 7s domain (7s collagen) levels, whereas the upper two tertiles of the fiber amounts significantly associated with body mass index, aspartate aminotransferase, and 7s collagen in the multivariable analysis. Conclusion: Quantitative fibrosis assessment reveals a nonlinear relationship between fibrosis stage and fiber amount, with a marked difference between stage 4 and stage 3 and much smaller differences among stages 0‐3, suggesting a heterogeneity in disease severity within NAFLD‐related cirrhosis. (Hepatology Communications 2018;2:58–68)

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“…The degree of liver fibrosis is associated with long‐term outcomes in NAFLD patients and liver biopsy is recommended as the gold‐standard method for its staging, but this approach has several limitations. There are several non‐invasive biomarkers and scoring systems, involving the use of combinations of clinical laboratory parameters, for the staging of NAFLD . However, these scoring systems also have limitations.…”

Section: Discussionmentioning

confidence: 99%

Autotaxin is a valuable biomarker for the prediction of liver fibrosis in patients with non‐alcoholic fatty liver disease

Honda

Imajo

Kobayashi

et al. 2019

Hepatology Research

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Aim We investigated the characteristics of serum autotaxin (ATX) and its diagnostic performance for liver fibrosis in a large cohort of patients with non‐alcoholic fatty liver disease (NAFLD). Methods We compared the usefulness of ATX and other fibrosis markers in 307 biopsy‐confirmed NAFLD patients. In addition, in 145 participants with NAFLD, we compared the diagnostic performance of ATX with that of non‐invasive imaging methods (vibration‐controlled transient elastography and magnetic resonance elastography [MRE]). Results Serum ATX concentration was significantly correlated with fibrosis stage in male and female NAFLD patients. In male patients, the area under the receiver operating characteristic (AUROC) curve values of ATX for the diagnosis of ≥stage 1, ≥stage 2, ≥stage 3, and ≥stage 4 fibrosis were 0.65, 0.75, 0.81, and 0.95, respectively. In female NAFLD participants, the AUROC values were all >0.81. The sensitivity of ATX was highest for the diagnosis of ≥stage 2 and ≥stage 3 fibrosis in both men and women with NAFLD. In the comparison between ATX and non‐invasive imaging methods, the AUROC for MRE was the highest at every stage of fibrosis. Conclusions Serum ATX concentration is significantly correlated with fibrosis stage in NAFLD patients. The diagnostic accuracy of ATX for liver fibrosis is lower than that of MRE, but the sensitivities of ATX for the diagnosis of ≥stage 2 and ≥stage 3 were highest. We conclude that ATX is useful for the selection of patients requiring further evaluation for liver fibrosis.

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Classification of patients with non‐alcoholic fatty liver disease using rapid immunoassay of serum type IV collagen compared with liver histology and other fibrosis markers

Abstract: Type IV collagen may be a useful measure of NASH severity as latex particle-enhanced turbidimetric immunoassay-based rapid type IV collagen assay can be carried out routinely.

Cited by 39 publications

References 40 publications

Charged poly(N-isopropylacrylamide) nanogels for use as differential protein receptors in a turbidimetric sensor array

Charged poly(N-isopropylacrylamide) nanogels for use as differential protein receptors in a turbidimetric sensor array

Quantitative assessment of liver fibrosis reveals a nonlinear association with fibrosis stage in nonalcoholic fatty liver disease

Autotaxin is a valuable biomarker for the prediction of liver fibrosis in patients with non‐alcoholic fatty liver disease

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