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      Identification of Matrix Metalloproteinase-2 and 9 as Biomarker of Intrahepatic Cholestasis of Pregnancy

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          Abstract

          ABSTRACT Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disease uniquely occurring during pregnancy. In this study we aimed to identify novel biomarker for the diagnosis of ICP in Chinese population. 50 healthy pregnant women, 50 mild ICP patients and 48 severe ICP patients were enrolled for this study. Liver function tests, including serum total bilirubin, direct bilirubin, alanine transaminase, aspartate aminotransferase and cholyglycine, were performed in all participants. After an overnight fast serum levels of total bile acids (TBA), matrix metalloproteinase (MMP)-2 and MMP-9 were measured, and their correlation with liver function tests were analyzed. The observed increase in serum TBA in ICP patients was not statistically significant which made it unreliable for diagnosis of ICP in Chinese population. On the other hand, both MMP-2 and MMP-9 serum levels exhibited a progressive and significant elevation in mild and severe ICP patients compared with healthy pregnant women, which also positively correlated with liver function tests. Serum levels of both MMP-2 and MMP-9 could be reliably used as laboratory abnormalities for accurate diagnosis and sensitive grading of ICP in Chinese population.

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          Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management.

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            Reversal of IFN-gamma, oxLDL and prolactin serum levels correlate with clinical improvement in patients with peripartum cardiomyopathy.

            Peripartum cardiomyopathy (PPCM) is characterized by acute onset of heart failure of unknown aetiology. We aimed to identify mechanisms involved in initiation and progression of the disease. Serum markers related to cardiac function, apoptosis, oxidative stress, remodelling, inflammation and the nursing hormone prolactin were analyzed in PPCM patients and healthy controls. The kinetics of these markers were compared between patients who improved cardiac function (IMP) and those patients who did not improve (NIMP), over 6 months follow-up. All patients received ACE-inhibitors, beta-blockers and diuretics. Baseline levels of TGF-beta-1 were significantly lower, MMP-9 and VEGF were not different; all other markers were significantly higher in PPCM compared with controls. Only baseline NT-proBNP levels were higher in NIMP compared with IMP. After 6 months, NT-proBNP, oxLDL and IFN-gamma were significantly lower in IMP and the decrease in oxLDL, IFN-gamma and prolactin was significant in IMP but not in NIMP. Significant correlations were observed between the kinetics of NT-proBNP, oxLDL, prolactin and IFN-gamma in PPCM patients. Baseline NT-proBNP and the failure to decrease oxLDL, IFN-gamma and prolactin are associated with poor outcome in PPCM, suggesting a potential role of these factors in the pathophysiology of PPCM and for risk stratification of PPCM patients.
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              Intrahepatic cholestasis of pregnancy

              Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder characterized by (i) pruritus with onset in the second or third trimester of pregnancy, (ii) elevated serum aminotransferases and bile acid levels, and (iii) spontaneous relief of signs and symptoms within two to three weeks after delivery. ICP is observed in 0.4–1% of pregnancies in most areas of Central and Western Europe and North America, while in Chile and Bolivia as well as Scandinavia and the Baltic states roughly 5–15% and 1–2%, respectively, of pregnancies are associated with ICP. Genetic and hormonal factors, but also environmental factors may contribute to the pathogenesis of ICP. Intrahepatic cholestasis of pregnancy increases the risk of preterm delivery (19–60%), meconium staining of amniotic fluid (27%), fetal bradycardia (14%), fetal distress (22–41%), and fetal loss (0.4–4.1%), particularly when associated with fasting serum bile acid levels > 40 μmol/L. The hydrophilic bile acid ursodeoxycholic acid (10–20 mg/kg/d) is today regarded as the first line treatment for intrahepatic cholestasis of pregnancy. Delivery has been recommended in the 38th week when lung maturity has been established.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                ah
                Annals of Hepatology
                Ann. Hepatol.
                Asociación Mexicana de Hepatología, A.C. (Ciudad de México, Ciudad de México, Mexico )
                1665-2681
                April 2017
                : 16
                : 2
                : 291-296
                Affiliations
                [2] Suzhou Jiangsu orgnameSoochow University orgdiv1Department of Obstetrics and Gynecology China
                [3] Suzhou Jiangsu orgnameSoochow University orgdiv1Department of Pathology China
                [1] Wuxi orgnameNanjing Medical University orgdiv1Wuxi Maternity and Child Health Hospital
                Article
                S1665-26812017000200291
                10.5604/16652681.1231589
                041d2e3d-f147-4ad7-8cac-d935a025f00b

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 05 May 2016
                : 31 July 2016
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 33, Pages: 6
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                SciELO Mexico


                Matrix metalloproteinase,Intrauterine fetal death,Liver function tests,Intrahepatic cholestasis of pregnancy,Total bile acid

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