Kallistatin, a new and reliable biomarker for the diagnosis of liver cirrhosis

Cheng, Zhiyun; Lv, Yinghui; Pang, Su-Qiu; Bai, Ruyu; Wang, Mingxi; Lin, Shuyu; Xu, Tianwen; Spalding, Duncan; Habib, Nagy; Xu, Rui‐hua

doi:10.1016/j.apsb.2015.02.003

Cited by 35 publications

(44 citation statements)

References 39 publications

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“…Also, they declared that SERPINA4 was highly expressed in the normal human tissue, but its expression decreased in cases with liver fibrosis. Furthermore, Chao et al This finding is in a good agreement with that obtained by Cheng et al [17] who found that kallistatin level reduced significantly in the serum of early liver fibrosis patients; however, there was a marked reduction in kallistatin level of cirrhotic patients.…”

Section: ]supporting

confidence: 82%

Evaluation of Kallistatin as a Biomarker in Chronic Hepatitis C Patients

Ragab¹

2017

WJPPS

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Early outcome prediction after hepatitis C viral infections has a great interest. This study aims to evaluate kallistatin in the prediction of liver fibrosis in chronic hepatitis C Egyptian patients. This study included 62 patients with chronic HCV infection (30 patients suffering from early liver fibrosis, 16 with advanced liver fibrosis, 16 with HCC) and 14 healthy subjects. Serum liver function tests were determined by colorimetric methods, HBsAg, HCVAb, AFP, CRP and kallistatin were investigated by ELISA, HCV-RNA and the expression of SERPINA4 gene were determined by qRT-PCR assay, abdominal ultrasound and ultrasonic-guided liver biopsy were done to determine the stage of fibrosis. Serum kallistatin level was significantly lower in patients with chronic liver disease (CLD) than healthy subjects at the gene expression and protein levels (P=0.003 & 0.001, respectively). Also, there was a significant difference in kallistatin concentration in early and advanced fibrosis, (p=0.044).Serum kallistatin had greater sensitivity and NPV values than did AST/ALT ratio (AAR) and AST/platelet ratio index (APRI) in patients with CLD compared with healthy subjects with sensitivity 95.1%, specificity 50%, PPV 89.2%, and NPV 70%. Moreover, Kallistatin could significantly distinguish patients at early stage of liver fibrosis from healthy subjects with sensitivity 96.7% and specificity 50%. Compared with single detection, combined measurement of the AAR, APRI and kallistatin markers showed 90% sensitivity and 78.6% specificity, 90% PPV and 78.6% NPV. These data support that kallistatin may be an efficient

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Section: ]supporting

confidence: 82%

Evaluation of Kallistatin as a Biomarker in Chronic Hepatitis C Patients

Ragab¹

2017

WJPPS

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“…Human kallistatin levels are significantly decreased in liver cirrhosis, sepsis, and inflammatory bowel disease, suggesting kallistatin is consumed in these diseases [5, 24, 25]. We previously demonstrated that patients with severe pneumonia had decreased plasma levels of kallistatin [20].…”

Section: Discussionmentioning

confidence: 99%

Plasma kallistatin in critically ill patients with severe sepsis and septic shock

et al. 2017

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Kallistatin, an endogenous serine proteinase inhibitor, is protective against sepsis in animal models. The aim of this study was to determine the plasma concentration of kallistatin in intensive care unit (ICU) patients with severe sepsis and septic shock and to determine their potential correlation with disease severity and outcomes. We enrolled 86 ICU patients with severe sepsis and septic shock. Their plasma concentrations of kallistatin, kallikrein, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 were measured by enzyme-linked immunosorbent assay. The association of kallistatin levels with disease severity and patient outcomes was evaluated. The relationship between kallistatin and other biomarkers was also analyzed. Plasma kallistatin levels on day 1 of ICU admission were lower in patients with septic shock compared with patients with severe sepsis (p = 0.004). Twenty-nine patients who died in the hospital had significantly lower day 1 kallistatin levels than patients who survived (p = 0.031). Using the optimal cutoff value (4 μg/ml) of day 1 plasma kallistatin determined by receiver operating characteristic curves for 60-day mortality, we found that high kallistatin levels were associated with a preferable 60-day survival (p = 0.012) by Kaplan-Meier analysis and lower Sequential Organ Failure Assessment (SOFA) scores over the first 5 days in the ICU (p = 0.001). High kallistatin levels were also independently associated with a decreased risk of septic shock, the development of acute respiratory distress syndrome, and positive blood cultures. In addition, there were inverse correlations between day 1 kallistatin levels and the levels of TNF-α, IL-1β, IL-6, and C-reactive protein, and SOFA scores on day 1. Our results indicate that during severe sepsis and septic shock, a decrease in plasma concentrations of kallistatin reflects increased severity and poorer outcome of disease.

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“…Plasma kallistatin levels are significantly reduced in patients with prostate and colon cancer [28]. Recent studies highlight the potential of kallistatin as a biomarker for the diagnosis of liver cirrhosis and an independent prognostic indicator for colorectal cancer [106, 107]. Therefore, it is possible that kallistatin’s role as a biomarker can also be applied to diverse human cancers.…”

Section: Discussionmentioning

confidence: 99%

Kallistatin suppresses cancer development by multi-factorial actions

Chao

2017

Critical Reviews in Oncology/Hematology

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Kallistatin was first identified in human plasma as a tissue kallikrein-binding protein and a serine proteinase inhibitor. Kallistatin via its two structural elements regulates differential signaling cascades, and thus a wide spectrum of biological functions. Kallistatin’s active site is essential for: inhibiting tissue kallikrein’s activity; stimulating endothelial nitric oxide synthase and sirtuin 1 expression and activation; and modulating the synthesis of the microRNAs, miR-34a, miR-21 and miR-203. Kallistatin’s heparin-binding site is crucial for antagonizing the signaling pathways of vascular endothelial growth factor, tumor necrosis factor-α, Wnt, transforming growth factor-β and epidermal growth factor. Circulating kallistatin levels are markedly reduced in patients with prostate and colon cancer. Kallistatin administration attenuates angiogenesis, inflammation, tumor growth and invasion in animal models and cultured cells. Therefore, tumor progression may be substantially suppressed by kallistatin’s pleiotropic activities. In this review, we will discuss the role and mechanisms of kallistatin in the regulation of cancer development.

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Kallistatin, a new and reliable biomarker for the diagnosis of liver cirrhosis

Cited by 35 publications

References 39 publications

Evaluation of Kallistatin as a Biomarker in Chronic Hepatitis C Patients

Evaluation of Kallistatin as a Biomarker in Chronic Hepatitis C Patients

Plasma kallistatin in critically ill patients with severe sepsis and septic shock

Kallistatin suppresses cancer development by multi-factorial actions

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