The Clinical Significance of Serum Apoptotic Cytokeratin 18 Neoepitope M30 (CK-18 M30) and Matrix Metalloproteinase 2 (MMP-2) Levels in Chronic Hepatitis B Patients with Cirrhosis

Sümer, Şua; Demir, Nazlım Aktuğ; Kölgelier, Servet; İnkaya, Ahmet Çağkan; Arpacı, Abdullah; Demir, Lütfi Saltuk; Ural, Onur

doi:10.5812/hepatmon.10106

Cited by 27 publications

(30 citation statements)

References 31 publications

(40 reference statements)

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“…Our data are also in agreement with several observations by several authors who found increasing MMP-2 levels in chronic HCV patients where the most significant elevations were detected in those developing cirrhosis and HCC (27)(28)(29) .…”

Section: Discussionsupporting

confidence: 83%

Hepatitis C Virus as risk factor for development of hepatocellular carcinoma in Egypt: II-Enhancement role of matrix metalloproteinases-2 in dissemination of HCC

2017

AJOCRR

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Hepatitis C virus (HCV) infection is a major public health problem all over the world. Egypt has the highest prevalence of HCV worldwide (17-26%) with subsequent high morbidity from chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). Matrix metalloproteinase are proteolytic enzymes that play a role in the degradation of extracellular matrix (ECM) which is necessary for invasion and metastasis of tumor cells. The present work was designed to study the relationship between HCV infection and circulating MMP-2 level in chronic HCV patients (either without or with hepatic complication) and compared to that of non-HCV cirrhotic patients as well as healthy controls, in order to clarify the role of HCV in changing microenvironment and underlying mechanisms associated with dissemination of malignancy. The level of MMP-2 was estimated in sera collected at different stages of HCV infections as well as in ascetic fluids collected from those developing either HCC or cirrhosis. Statistical analysis of their results revealed that MMP-2 levels were significantly elevated in all patient groups as compared to healthy controls. The level of MMP-2 in HCV patients with HCC was significantly elevated when compared to other HCV patients. Meanwhile MMP-2 in ascetic fluids of cirrhotic patients were similar to that detected in their sera, while in HCC patients there were 2.4 times elevations in serum level of MMP-2 as compared to that in ascetic fluids. These results revealed that HCV infection is not only responsible for biochemical and hematological abnormalities recorded at chronic stages of infection but also creating a microenvironmental change by enhancing MMP-2 release, which effect on infected cell by obliging them to modify their phenotype in order to survive, thus increasing the invasion potential and facilitate tumor progression.

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Section: Discussionsupporting

confidence: 83%

Hepatitis C Virus as risk factor for development of hepatocellular carcinoma in Egypt: II-Enhancement role of matrix metalloproteinases-2 in dissemination of HCC

2017

AJOCRR

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“…53,54 Thus, MMP-2-deficient mice show enhanced fibrosis after CCL 4 treatment and MMP-2 could be therefore critical for inhibiting type I collagen synthesis by activated HSCs, which strongly express this MMP. 55,56 MMP-9 and MMP-2 are elevated in serum and livers of patients with chronic hepatitis type B and C. [57][58][59] Elevated expression of MMPs in the mentioned fibrotic conditions was shown both in liver parenchyma 60 and portal macrophages. 57,61 Especially, MMP-9 seems to be involved in ongoing liver inflammation, 62 and its level drops after antiviral treatment.…”

Section: Metalloproteinases In the Development Of Liver Fibrosismentioning

confidence: 99%

Metalloproteinases in liver fibrosis: current insights

Zbodakova¹,

Chalupský²,

Turečková³

et al. 2017

MNM

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Liver fibrosis is defined by excessive deposition of extracellular matrix. The fibrotic conditions result from the imbalance between synthesis and deposition of fibrous tissues and decomposition of these matrix proteins. This process can be reversed as a regular part of the healing process after hepatic damage or can become chronic. When the protein matrix synthesis predominates and the decomposition is suppressed, fibrosis will progress into irreversible cirrhosis or steatosis. Among the molecular players involved in fibrotic liver diseases, metalloproteinases of matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase (ADAM) families are critical in the development of liver fibrosis and its resolution. Previously, MMPs were recognized as extracellular matrix degrading enzymes. Currently, they are also known as mediators in a variety of processes related to immunity and tissue repair. In this article, we have reviewed the models of liver fibrosis and findings on MMPs and ADAMs in hepatic fibrosis conditions.

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“…The susceptibility to apoptotic cell death may depend on the HBV genotype, as well (22). Not only apoptotic cell death, but also autophagic cell death, may be good predictors for defining the level of liver injury at the beginning of treatment and during the follow-up period (23). …”

Section: Discussionmentioning

confidence: 99%

The Role of M30 in Predicting the Severity of Liver Fibrosis and Inflammation in Chronic Hepatitis B Patients

et al. 2016

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BackgroundLiver biopsy is an invasive procedure that is currently still necessary for predicting underlying hepatic injury related to chronic viral hepatitis B (CVHB). To date, none of the studied non-invasive methods have been able to replace liver biopsy. An apoptotic serum marker, M30, which has been reported to indicate ongoing liver fibrosis, has been popular in recent years.ObjectivesWe aimed to investigate the possible role of M30 in predicting CVHB-associated hepatic injury and its severity.MethodsForty-eight patients undergoing liver biopsy for evaluation of the severity of CVHB-related liver injury and 40 healthy controls were included in this cross-sectional study. M30 levels were determined for all CVHB patients and controls, and other laboratory parameters and demographic features were obtained from our hospital’s database.ResultsThe mean ages of patients and controls were 39.7 and 45.7 years, respectively, and 35% of the controls and 52% of the patients were male. In contrast to lower platelet counts, transaminase and M30 levels were both higher in the patient group than in the controls. Among the investigated parameters, only transaminase increased as the fibrosis stage changed from mild to moderate; however, none of the laboratory parameters, including M30, differed as the histological activity index (HAI) score increased.ConclusionsM30 levels were higher in CVHB patients compared to healthy controls. However, M30 levels were similar in the mild and moderate stages of fibrosis, so they did not indicate the severity of underlying fibrotic or inflammatory processes in CVHB patients.

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The Clinical Significance of Serum Apoptotic Cytokeratin 18 Neoepitope M30 (CK-18 M30) and Matrix Metalloproteinase 2 (MMP-2) Levels in Chronic Hepatitis B Patients with Cirrhosis

Cited by 27 publications

References 31 publications

Hepatitis C Virus as risk factor for development of hepatocellular carcinoma in Egypt: II-Enhancement role of matrix metalloproteinases-2 in dissemination of HCC

Hepatitis C Virus as risk factor for development of hepatocellular carcinoma in Egypt: II-Enhancement role of matrix metalloproteinases-2 in dissemination of HCC

Metalloproteinases in liver fibrosis: current insights

The Role of M30 in Predicting the Severity of Liver Fibrosis and Inflammation in Chronic Hepatitis B Patients

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