Serum keratin 19 (CYFRA21-1) links ductular reaction with portal hypertension and outcome of various advanced liver diseases

Hamesch, Karim; Güldiken, Nurdan; Aly, M. M.; Hueser, Norbert; Rufat, Pierre; Ziol, Marianne; Lurje, Georg; Mandorfer, Mattias; Scheiner, Bernhard; Reiberger, T; Mueller, Sebastian; Bruns, Tony; Nahon, Pierre; Strnad, Pavel

doi:10.1055/s-0040-1716032

Cited by 3 publications

(9 citation statements)

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“…Interestingly, CYFRA21‐1 levels display a significant association with 90‐day mortality and a superior discriminative ability than other epithelial products such as K18 M30 and M65 or serum transferrin which were previously assessed and reported in this cohort 19,37 . This observation extends an earlier report on the predictive capability of CYFRA21‐1 in advanced liver fibrosis 17 . In line with the above CYFRA21‐1 may more specifically reflect the severity of injury within the hepatic progenitor compartment.…”

Section: Discussionsupporting

confidence: 85%

“…In the present manuscript, the significance of CYFRA21‐1 serum levels in individuals with a clinical diagnosis of severe AH was evaluated by assessing their relationship with histological features, clinicodemographic variables, other serum biomarkers and clinical outcomes. These data indicate that serum CYFRA21‐1 levels in patients with the clinical syndrome of severe AH i) are somewhat higher than concentrations detected in advanced liver fibrosis 17 ; ii) predict the presence of ASH and severe inflammation on biopsy; and iii) are significantly independently associated with 90‐day mortality and predict outcomes with performance similar to clinical scoring systems.…”

Section: Discussionmentioning

confidence: 74%

“…It is employed clinically as a tumour marker and is routinely available in many clinical laboratories 16 . Evaluation of serum CYFRA21‐1 as a biomarker in cirrhosis demonstrated that serum levels correlate with hepatic expression of KRT19 and predict adverse outcomes including death and the development of hepatocellular carcinoma 17 . In contrast to that, serum levels of total (M65) or apoptosis‐specific keratin 18 ( KRT18 /K18) fragments (M30) serve as hepatocellular injury markers 16,18 and in AH, correlate with histological disease activity and response to prednisolone 19 …”

Section: Introductionmentioning

confidence: 99%

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Serum keratin 19 (CYFRA21‐1) is a prognostic biomarker in severe alcoholic hepatitis

Atkinson

Aly

Remih

et al. 2022

Liver International

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Background and Aims Up to 30% of patients with severe alcoholic hepatitis (sAH) die within 3 months of presentation. The degree of ductular reaction, characterized by accumulation of biliary and liver progenitor cells, confers a poor prognosis. Keratin fragments are established serological surrogates of liver injury and keratin 19 (K19) is a histological marker of the ductular reaction. We assessed the relationship between serum K19 levels (viz. CYFRA21‐1), histology and outcome in patients with sAH. Methods Serum CYFRA21‐1 was quantified in pre‐treatment serum samples from 824 patients enrolled in the STOPAH trial. The cohort was randomly divided into two groups to test mortality associations; histological analyses were performed using the 87 cases with suitable samples. Results CYFRA21‐1 levels were elevated in sAH and strongly predicted alcoholic steatohepatitis (ASH) on biopsy (area under the receiver operated characteristic [AUROC] 0.785 [95% Confidence Interval 0.602–0.967]) and 90‐day survival (AUROC 0.684/0.693). The predictive ability of CYFRA21‐1 was comparable with the model of end‐stage liver disease (MELD) score and was independently associated with survival in multivariable analysis. CYFRA21‐1 moderately correlated with hepatocellular injury markers M30/M65 but displayed a more robust predictive ability. A combination of MELD and CYFRA21‐1 conferred a modest improvement in the AUROC value (0.731/0.743). Conclusions In sAH serum, CYFRA21‐1 levels associate with the presence of ASH on biopsy and independently predict 90‐day survival. As a single marker performance is comparable to established scoring systems. Therefore, CYFRA21‐1, which is available in many clinical laboratories, may become a useful component of prognostic models.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

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Serum keratin 19 (CYFRA21‐1) is a prognostic biomarker in severe alcoholic hepatitis

Atkinson

Aly

Remih

et al. 2022

Liver International

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“…While most of these novel proteins have not been directly linked to fibrosis, their expression by biliary epithelial cells, endothelial cells, and immune cells within the fibrotic tissue points to a potential role in the pathogenesis of PHT by matrix deposition or modulation of endothelial function. Their increased expression in biliary epithelial cells supports the theory that ductular reaction is not only associated with the severity of liver disease but also correlates with PHT, as recently suggested by Hamesch et al (27) The increased expression of BMX was unexpected given the decrease in the serum concentration in cPHT. The precise mechanism of this divergence is yet to be determined and may relate to posttranslational processing that may influence its release to the blood.…”

Section: Discussionsupporting

confidence: 72%

Serum Proteomics Uncovers Biomarkers of Clinical Portal Hypertension in Children With Biliary Atresia

et al. 2021

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Children with biliary atresia (BA) often develop portal hypertension (PHT) and its complications, which are associated with high morbidity and mortality. The goal of this study was to identify serum biomarkers of PHT by using large‐scale proteomics. We applied the slow off‐rate modified aptamer scan (SOMAscan) to measure 1,305 proteins in serum samples of children with BA with and without clinical evidence of PHT in validation and discovery cohorts enrolled in the Biliary Atresia Study of Infants and Children. Serum proteomics data was analyzed using logistic regression to identify protein(s) with an area under the receiver operating characteristic curve (AUROC) ≥ 0.90. Immunostaining was used to characterize the cellular localization of the new biomarker proteins in liver tissues. We identified nine proteins in the discovery cohort (n = 40 subjects) and five proteins in the validation cohort (n = 80 subjects) that individually or in combination predicted clinical PHT with AUROCs ≥ 0.90. Merging the two cohorts, we found that semaphorin 6B (SEMA6B) alone and three other protein combinations (SEMA6B+secreted frizzle protein 3 [SFRP3], SEMA6B+COMM domain containing 7 [COMMD7], and vascular cell adhesion molecule 1 [VCAM1]+BMX nonreceptor tyrosine kinase [BMX]) had AUROCs ≥ 0.90 in both cohorts, with high positive‐ and negative‐predictive values. Immunostaining of the new protein biomarkers showed increased expression in hepatic endothelial cells, cholangiocytes, and immune cells within portal triads in BA livers with clinical PHT compared to healthy livers. Conclusion: Large‐scale proteomics identified SEMA6B, SFRP3, COMMD7, BMX, and VCAM1 as biomarkers highly associated with clinical PHT in BA. The expression of the biomarkers in hepatic epithelial, endothelial, and immune cells support their potential role in the pathophysiology of PHT.

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“…Its soluble segments could specifically combine with two monoclonal antibodies -Ks19.1 and BM19.21, thus being called CYFRA 21-1. CYFRA 21-1 exists in malignant lung cancer tissues, and has full content, especially a high expression in squamous cell lung cancer [30] .…”

Section: Cyfra 21-1mentioning

confidence: 99%

Research Progress of the Clinical Application of Small Cell Lung Cancer Related Tumor Markers and Biochemical Indicators

Wang

Qin

2021

PAR

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With continual advances in medicine, more studies on early diagnosis, therapeutic evaluation, and prognosis of lung cancer have emerged in recent years, particularly in regard to small cell lung cancer (SCLC), which is a pathological type of lung cancer with the highest grade. In the era of medical treatment scarcity, early diagnosis of SCLC, evaluation of treatment effect, recurrence factors, and prognosis are important to treat patients with SCLC, prolong their survival, and improve their life quality. The research on the changes of serum tumor markers and biochemical indicators in the early diagnosis and treatment of SCLC has gradually become a hot topic. Therefore, this article reviews the research progress of serum tumor markers and biochemical indicators of SCLC.

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Serum keratin 19 (CYFRA21-1) links ductular reaction with portal hypertension and outcome of various advanced liver diseases

Cited by 3 publications

References 0 publications

Serum keratin 19 (CYFRA21‐1) is a prognostic biomarker in severe alcoholic hepatitis

Serum keratin 19 (CYFRA21‐1) is a prognostic biomarker in severe alcoholic hepatitis

Serum Proteomics Uncovers Biomarkers of Clinical Portal Hypertension in Children With Biliary Atresia

Research Progress of the Clinical Application of Small Cell Lung Cancer Related Tumor Markers and Biochemical Indicators

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