Clinical Values of Elevated Serum Cytokeratin-18 Levels in Hepatitis: a Meta-Analysis

Yang, Zhao; Yang, Su Xian; Qin, Chuanjiang; Chen, Yun Xiu

doi:10.5812/hepatmon.15(5)2015.25328

Cited by 12 publications

(12 citation statements)

References 28 publications

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“…Serum CK-18 levels showed high sensitivity and specificity in diagnosing non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease and reflected clinical disease more accurately than ALT levels [46, 47]. A meta-analysis of elevated serum cytokeratin-18 levels in hepatitis showed its clinical value for identifying the development of hepatitis [48]. The biomarkers such as CK-18, caspase 3/7 activity, sPD-1, and serum miR-122 levels could be used as adjunctive criteria to diagnose acute hepatitis C more definitively and to provide a sharper case definition for acute hepatitis C.…”

Section: Discussionmentioning

confidence: 99%

Elevation of Alanine Aminotransferase Activity Occurs after Activation of the Cell-Death Signaling Initiated by Pattern-Recognition Receptors ‎but before Activation of Cytolytic Effectors in NK or CD8+ T Cells in the Liver During Acute HCV Infection

et al. 2016

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Pattern-recognition receptors (PRRs) promote host defenses against HCV infection by binding to their corresponding adapter molecules leading to the initiation of innate immune responses including cell death. We investigated the expression of PRR genes, biomarkers of liver cell-death, and T cell and NK cell activation/inhibition-related genes in liver and serum obtained from three experimentally infected chimpanzees with acute HCV infection, and analyzed the correlation between gene expression levels and clinical profiles. Our results showed that expression of hepatic RIG-I, TLR3, TLR7, 2OAS1, and CXCL10 mRNAs was upregulated as early as 7 days post-inoculation and peaked 12 to 83 days post-inoculation. All of the three HCV infected chimpanzees exhibited significant elevations of serum alanine aminotransferase (ALT) activity between 70 and 95 days after inoculation. Elevated levels of serum cytokeratin 18 (CK-18) and caspases 3 and 7 activity coincided closely with the rise of ALT activity, and were preceded by significant increases in levels of caspase 3 and caspase 7 mRNAs in the liver. Particularly we found that significant positive auto-correlations were observed between RIG-I, TLR3, CXCL10, 2OAS1, and PD-L1 mRNA and ALT activity at 3 to 12 days before the peak of ALT activity. However, we observed substantial negative auto-correlations between T cell and NK cell activation/inhibition-related genes and ALT activity at 5 to 32 days after the peak of ALT activity. Our results indicated cell death signaling is preceded by early induction of RIG-I, TLR3, 2OAS1, and CXCL10 mRNAs which leads to elevation of ALT activity and this signaling pathway occurs before the activation of NK and T cells during acute HCV infection. Our study suggests that PRRs and type I IFN response may play a critical role in development of liver cell injury related to viral clearance during acute HCV infection.

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Section: Discussionmentioning

confidence: 99%

Elevation of Alanine Aminotransferase Activity Occurs after Activation of the Cell-Death Signaling Initiated by Pattern-Recognition Receptors ‎but before Activation of Cytolytic Effectors in NK or CD8+ T Cells in the Liver During Acute HCV Infection

et al. 2016

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“…A value of 25% -50% for I 2 indicates a low degree of heterogeneity, a value of 50% -75% indicates a moderate heterogeneity, and a value of > 75% indicates a high heterogeneity. When the I 2 value was > 50%, a random-effects model was used to pool the data; otherwise, a fixed-effects model was selected (20). The association between serum CK-18 M30 levels and CHB was estimated by the standard mean difference (SMD) with 95% confidence interval (CI).…”

Section: Data Extraction and Quality Assessmentmentioning

confidence: 99%

“…Accumulated evidence suggests that hepatocyte apoptosis plays a vital role in chronic liver disorders (17,19). Yang et al found that the serum CK-18 levels might be a risk factor for non-alcoholic steatohepatitis (NASH), chronic hepatitis C (CHC), and chronic hepatitis B (CHB) (all P < 0.05) through conducting a meta-analysis of eight case-control studies (20). Some reports also showed that the plasma levels of CK-18 M30 were associated with the progression of non-alcoholic steatohepatitis (NASH) in non-alcoholic fatty liver disease (NAFLD) patients (21,22).…”

Section: Introductionmentioning

confidence: 99%

Association between Serum Cytokeratin-18 Neoepitope M30 (CK-18 M30) Levels and Chronic Hepatitis B: A Meta-Analysis

Liu

et al. 2018

Hepat Mon

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Background: Cytokeratin-18 Neoepitope M30 (CK-18 M30) has been reported to be associated with chronic HBV infection and severity of liver injury; however, the results of these studies are inconsistent. Objectives: We sought to investigate the association between serum CK-18 M30 levels and the severity of liver injury in chronic hepatitis B (CHB) patients. Methods: A systematic literature search was performed in PubMed, Embase, and Cochrane Library databases for relevant studies published in English up to August 2017. Heterogeneity among individual studies was investigated for summarizing all the studies. The standard mean difference (SMD) and 95% confidence interval (CI) were calculated using a random-effects model or fixed-effects model. Finally, the sensitivity analysis and publication bias were performed to evaluate the accuracy of this meta-analysis. Statistical analysis was conducted using Review Manager 5.3 and Stata 12.0. Results: Five case-control studies were included in the ultimate analysis, recruiting 488 CHB patients, 276 inactive carriers, and 193 healthy controls. The major results of the meta-analysis revealed significantly elevated serum CK-18 M30 levels in chronic HBV infected patients including CHB patients with severe liver injury and inactive HBV carriers when compared to healthy controls (SMD = 1.13, 95% CI: 0.75-1.50, P < 0.001; SMD = 0.63, 95% CI: 0.38-0.89, P < 0.001, respectively). Furthermore, the serum CK-18 M30 levels were significantly higher in CHB patients with severe liver injury than in inactive carriers (SMD =1.29, 95% CI: 0.60-1.98, P < 0.001). The sensitivity and publication bias analysis verified the stability and reliability of our analysis. Conclusions: The elevated serum CK-18 M30 levels could be regarded as a useful non-invasive biomarker for the diagnosis of chronic HBV infection, and were associated with the severity of liver injury in chronic Hepatitis B patients. The serum CK-18 M30 levels could reflect the liver inflammation in inactive carriers, representing the early stage of chronic HBV infection.

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“…Also, Yang et al found high serum CK‐18 in patients with liver disease compared to controls. More than that, increased serum CK‐18 was related to fibrosis progression ignoring family characteristics (Asians, Africans and Caucasians) and cause of liver disease (chronic hepatitis C, chronic hepatitis B and NASH).…”

Section: Discussionmentioning

confidence: 98%

Diagnostic value of serum cytokeratin‐18 in children with chronic liver disease

Shalby

Ibrahim

Behairy

et al. 2019

J Paediatrics Child Health

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EgyptAim: This study aimed to assess the diagnostic value of serum cytokeratin-18 in children with chronic liver diseases (CLD) and correlate its serum level with liver histology and other liver biomarkers. Methods: This study included two groups, the first group included children with CLD and the second group included healthy matched age and gender subjects as a control group, complete history and clinical examination, and serum CK-18 was measured using the sandwich enzyme-linked immunosorbent assay technique. Results: Serum concentrations of CK-18 were significantly elevated in CLD patients with mean AE standard deviation (1070.63 AE 699.2 ng/mL) compared to healthy controls mean AE standard deviation (203.95 AE 83.57 ng/mL). CK-18 levels were associated with a change in hepatocyte and portal tract (P = 0.005) as it was elevated with cirrhosis and fibrosis stage (P = 0.02) as it was elevated with moderate and severe fibrosis than mild fibrosis, also it showed a gradual increase in accordance with child Pugh score. There was a positive correlation between CK-18 levels and Total IgG, paediatric end-stage liver disease score and model for end-stage liver disease scores, the best cutoff point of CK-18 was 624 ng/mL, with sensitivity 93.06%, specificity 62.5% and diagnostic accuracy 90.0% for detection of fibrosis. Conclusion: CK-18 could be used as a non-invasive diagnostic marker in children with CLD.

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Clinical Values of Elevated Serum Cytokeratin-18 Levels in Hepatitis: a Meta-Analysis

Cited by 12 publications

References 28 publications

Elevation of Alanine Aminotransferase Activity Occurs after Activation of the Cell-Death Signaling Initiated by Pattern-Recognition Receptors ‎but before Activation of Cytolytic Effectors in NK or CD8+ T Cells in the Liver During Acute HCV Infection

Elevation of Alanine Aminotransferase Activity Occurs after Activation of the Cell-Death Signaling Initiated by Pattern-Recognition Receptors ‎but before Activation of Cytolytic Effectors in NK or CD8+ T Cells in the Liver During Acute HCV Infection

Association between Serum Cytokeratin-18 Neoepitope M30 (CK-18 M30) Levels and Chronic Hepatitis B: A Meta-Analysis

Diagnostic value of serum cytokeratin‐18 in children with chronic liver disease

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