scholarly journals Alterations of the Human Gut Microbiota in Intrahepatic Cholestasis of Pregnancy

2021 ◽  
Vol 11 ◽  
Author(s):  
Qitao Zhan ◽  
Xuchen Qi ◽  
Ruopeng Weng ◽  
Fangfang Xi ◽  
Yuan Chen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Real Time ◽  
Ribosomal Rna ◽  
Intrahepatic Cholestasis ◽  
Unsaturated Fatty Acids ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Fetal Complications ◽  
Polymerase Chain ◽  
Cholestasis Of Pregnancy

Background and AimsWomen with severe intrahepatic cholestasis of pregnancy (ICP) are at higher risks of fetal complications and without effective treatments. Changes in gut microbiota in pregnancy were found to be related to the altered intestinal bile acid composition, so we aimed to explore the alterations of microbiota in the gut of ICP patients.MethodsA total of 90 women were recruited, including 45 ICP patients and 45 healthy controls. The gut microbiota communities of ICP group were compared to control group through 16S ribosomal RNA gene sequencing. The results were then confirmed by real-time polymerase chain reaction (PCR) and generalized linear model (GLM). Furthermore, we analyzed the relationships between microbiota and the severity of ICP.ResultsA total of seven genera and nine taxa with differential abundances between the ICP patients and the controls were identified. All of the seven genera were verified through real-time PCR, and three key genera Parabacteroides, Flavonifractor, and Megamonas were confirmed by using the GLM model. Further analysis found that the genera Escherichia_Shigella, Olsenella, and Turicibacter were enriched in the severe ICP group, the microbial gene function related to biosynthesis of unsaturated fatty acids and propanoate metabolism were also increased in them.ConclusionsOverall, our study was the first in Asia to demonstrate an association between gut microbiota and ICP. Our findings would contribute to a better understanding of the occurrence of ICP.

scholarly journals The relationship of bile acid with biochemical tests in the diagnosis of intrahepatic cholestasis of pregnancy

2021 ◽  
Vol 38 (4) ◽  
pp. 485-489
Author(s):  
Cuma TAŞIN ◽  
Revan Sabri ÇİFTÇİ
Keyword(s):  
Bile Acid ◽  
Preterm Delivery ◽  
Sensitivity And Specificity ◽  
Intrahepatic Cholestasis ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Biochemical Tests ◽  
Increased Risk ◽  
Fetal Complications ◽  
Cholestasis Of Pregnancy

Intrahepatic pregnancy cholestasis (ICP) is associated with increased fetal complications. It is linked to an increased risk. Early diagnosis of this disease reduces these fetal complications. In this study, it was aimed to determine the sensitivity and specificity of biochemical tests according to cut off values. The values of 14 patients with bile acid ≥40 μmol / L diagnosed with intrahepatic cholestasis of pregnancy and 40 patients with bile acid <40 μmol / L were compared retrospectively with 60 control patients. In ICP patients, the ALT and AST values in patients with group 1 with bile acid ≥40 μmol / L and group 2 with bile acid <40 μmol / L were significantly higher than the control group (p = 0.0001 for both markers). Groups 1 and 2 with ICP patients have high sensitivity and specificity compared to the cut off value of ALT and AST. In our study, it was found that increased the risk of preterm delivery in ICP patients. Especially in cases where bile acid was ≥ 40 μmol / L, complications such as preterm delivery and low birth weight increased in proportion to the increase in bile acid. In the ICP patients, AST and especially ALT values increased in proportion to the increase in bile acid.

Assessment of Mechanical Fetal PR Interval in Intrahepatic Cholestasis of Pregnancy and Its Relationship with the Severity of the Disease

2019 ◽  
Vol 37 (14) ◽  
pp. 1476-1481
Author(s):  
Kadriye Yakut ◽  
Fatma Doğa Öcal ◽  
Merve Öztürk ◽  
Filiz Halici Öztürk ◽  
Yüksel Oğuz ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Intrahepatic Cholestasis ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Positive Correlation ◽  
Severity Of Disease ◽  
Pr Interval ◽  
Fetal Complications ◽  
Severity Of The Disease ◽  
Cholestasis Of Pregnancy

Abstract Objective This study aimed to investigate the fetal atrioventricular conduction system in intrahepatic cholestasis of pregnancy (ICP) by measuring the fetal mechanical PR interval and to explore the significance of predicting the severity of the disease. Study Design Forty pregnant women diagnosed with ICP, classified as severe and mild, and 40 healthy pregnant women participated in the study. Fetal mechanical PR interval was calculated, and fetal mechanical PR interval and neonatal outcome were compared between the groups. The relationship between the mechanical PR interval and the severity of ICP was analyzed. Results The fetal mechanical PR interval was significantly longer in the ICP group than in the control group (p < 0.005). Likewise, laboratory parameters such as transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) and total bilirubin levels were significantly higher in the ICP group (p < 0.005).There were no statistically significant differences in the fetal complications. There was a positive correlation between the severity of disease and fetal PR interval. Conclusion A prolonged fetal mechanical PR interval in fetuses of mothers with ICP was demonstrated in this study. It was also shown that there was a positive correlation between fetal PR interval and severity of the disease. The study concluded that fetal mechanical PR interval measurement can be used to predict the severity of disease in ICP.

scholarly journals Characterization of gut microbiota associated with clinical parameters in intrahepatic cholestasis of pregnancy

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Rong Li ◽  
Xuehai Chen ◽  
Zhongzhen Liu ◽  
Yan Chen ◽  
Chuan Liu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Pregnant Women ◽  
Intrahepatic Cholestasis ◽  
Premature Delivery ◽  
Clinical Parameters ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Control Groups ◽  
And Control ◽  
Cholestasis Of Pregnancy

Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that specifically occurs in pregnancy. Elevated levels of liver transaminases aspartate aminotransferase, alanine aminotransferase and serum bilirubin levels are common biochemical characteristics in ICP. The disorder is associated with an increased risk of premature delivery and stillbirth. The characterization of the potential microbiota in ICP could go a long way in the prevention and treatment of this pregnancy disease. Methods A total of 58 patients were recruited for our study: 27 ICP patients and 31 healthy pregnant subjects with no ICP. The V3 and V4 regions of the 16S rDNA collected from fecal samples of both diseased and control groups were amplified. 16S rRNA gene amplicon sequencing was then performed on gut microbiota. Sequencing data were analyzed and the correlation between components of microbiota and patient ICP status was found. Related metabolic pathways, relative abundance and significantly different operational taxonomic units (OTUs) between ICP and controls were also identified. Results Elevated levels of total bile acid, ALT, AST, Dbil and Tbil were recorded or observed in ICP subjects as compared to the control. Gut microbiota in pregnant women was dominated by four major phyla and 27 core genera. PCoA analysis results indicated that there was no significant clustering in Bray–Curtis distance matrices. Our results showed that there was a correlation between specific OTUs and measured clinical parameters of pregnant women. Comparison at the different taxonomy levels revealed high levels of abundance of Blautia and Citrobacter in ICP patients. At the family level, Enterobacteriaceae and Leuconostocaceae were higher in ICP patients. 638 KEGG Orthologs and 138 pathways significantly differed in the two groups. PLS-DA model with VIP plots indicated a total of eight genera and seven species were key taxa in ICP and control groups. Conclusions Our research indicated that although there was no significant clustering by PCoA analysis, patients with ICP have increased rare bacteria at different phylogenetic levels. Our results also illustrated that all 638 KEGG Orthologs and 136 in 138 KEGG pathways were less abundant in ICP patients compared to the controls.

Association of ABCB4 and ABCB11 nucleotide variants with intrahepatic cholestasis of pregnancy

2019 ◽  
Vol 88 (4) ◽  
pp. 209-217
Author(s):  
Milena Gruszczyńska-Losy ◽  
Adrianna Mostowska ◽  
Łukasz Adamczak ◽  
Paweł Jagodziński ◽  
Ewa Wender-Ożegowska ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Intrahepatic Cholestasis ◽  
Clinical Symptoms ◽  
Melting Curve ◽  
Liver Disorder ◽  
Melting Curve Analysis ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Increased Risk ◽  
Cholestasis Of Pregnancy

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder during gestation. The exact pathogenesis of ICP is multifactorial and still unclear. Therefore, our study aimed to check whether the selected ABCB4and ABCB11nucleotide variants are associated with an increased risk of ICP. Methods:ICP was diagnosed based on clinical symptoms characteristic of this disease and confirmed by increase in serum bile acids and transaminases, spontaneous resolution of clinical symptoms and normalization of laboratory tests after delivery. The total of 86 pregnant women meeting the criteria were included into the study. Healthy pregnant women with uncomplicated pregnancy served as control group (n=310). Sixcommon nucleotide variants in theABCB11and ABCB4genes were genotypedwith the use of high-resolution melting curve analysis. Conclusion:Our study did not show any significant association of analysed ABCB4and ABCB11nucleotide variants with the increased risk of intrahepatic cholestasis of pregnancy.

Fetal complications due to intrahepatic cholestasis of pregnancy

2015 ◽  
Vol 43 (2) ◽  
Author(s):  
Patrik Šimják ◽  
Antonín Pařízek ◽  
Libor Vítek ◽  
Andrej Černý ◽  
Karolína Adamcová ◽  
...  
Keyword(s):  
Intrahepatic Cholestasis ◽  
Current Knowledge ◽  
Elevated Serum ◽  
Liver Function Tests ◽  
Liver Disorder ◽  
Intrauterine Fetal Death ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Management Options ◽  
Fetal Complications ◽  
Cholestasis Of Pregnancy

AbstractIntrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder of pregnancy. Diagnosis is based on the clinical picture, particularly the presence of pruritus with a deterioration of liver function tests, and typically elevated serum levels of total bile acids. ICP manifests in the second half of pregnancy, predominantly during the third trimester. Symptoms of the disease resolve spontaneously after delivery. Etiology is still not fully understood. Genetic defects in specific transport proteins, elevated levels of sex hormones, and various environmental factors are thought to play a role in the development of this disorder. Although practically benign for the pregnant woman, ICP represents a serious threat to the fetus. It increases the risk of preterm delivery, meconium excretion into the amniotic fluid, respiratory distress syndrome, and sudden intrauterine fetal death. Identifying fetuses at risk of ICP complications remains challenging. The ideal obstetrical management of ICP needs to be definitively determined. The aim of this review is to summarize the current knowledge on fetal complications of ICP and describe management options for their prevention.

scholarly journals Effect of Histone Deacetylase HDAC3 on Cytokines IL-18, IL-12 and TNF-α in Patients with Intrahepatic Cholestasis of Pregnancy

2017 ◽  
Vol 42 (4) ◽  
pp. 1294-1302 ◽  
Author(s):  
Yong Shao ◽  
Jing Chen ◽  
Jiao Zheng ◽  
Cai-Ru Liu
Keyword(s):  
Protein Expression ◽  
Histone Deacetylase ◽  
Intrahepatic Cholestasis ◽  
Serum Levels ◽  
Hepatic Function ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Tnf Α ◽  
Significant Difference ◽  
Cholestasis Of Pregnancy

Background/aims: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is poorly understood. Objective: This study aimed to explore the possible effect of HDAC3 (histone deacetylase) on cytokines IL-18, IL-12 and TNF-α in ICP. Methods: Serum levels of cytokines IL-18, IL-12 and TNF-α, bile acids and hepatic function parameters were measured. The expression of HDAC3 in the placenta was determined by immunohistochemistry (IHC), western blotting and RT-PCR. Results: IL-18, IL-12 and TNF-α serum levels were significantly higher in the severe ICP group than in the mild ICP group and the control group, and the difference between the mild ICP group and control group was not significant. HDAC3 protein expression was identified in the nucleus of the placental trophoblast by IHC. HDAC3 mRNA and protein expression were significantly lower in the ICP groups (mild ICP and severe ICP groups) than in the control groups, and no significant difference was found between the mild ICP and severe ICP groups. Conclusions: The low expression of HDAC3 and overexpession of inflammatory cytokines (IL-18, IL-12 and TNF-α) in ICP may be involved in liver cell apoptosis. We suspect that HDAC3 may play an important role in the pathophysiology of ICP.

The Role of Melatonin, IL-8 and IL-10 in Intrahepatic Cholestasis of Pregnancy

2020 ◽  
Author(s):  
Samettin Çelik ◽  
Huri Guve ◽  
Canan Çalışkan ◽  
Sebahattin Çelik
Keyword(s):  
Intrahepatic Cholestasis ◽  
Inflammatory Cytokine ◽  
Elevated Serum ◽  
Interleukin 10 ◽  
Interleukin 8 ◽  
Controlled Study ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Cholestasis Of Pregnancy

Abstract Introduction Intrahepatic cholestasis of pregnancy is a pregnancy-specific liver disease that usually emerges during the third trimester of pregnancy. It is characterized by itching and elevated serum total bile acid levels, and it may lead to severe fetal complications. This study aimed to investigate the role of interleukin-8, a pro-inflammatory cytokine; interleukin-10, an anti-inflammatory cytokine; and melatonin in intrahepatic cholestasis of pregnancy. Materials and Methods This prospective, case-controlled study was conducted with 51 women with intrahepatic cholestasis of pregnancy (40 mild and 11 severe cases) and 43 healthy pregnant women. Serum interleukin-8, interleukin-10, and melatonin levels were evaluated. Results Melatonin and interleukin -10 were significantly lower in subjects with intrahepatic cholestasis of pregnancy (p=0.001; p=0.001, respectively p<0.05). Interleukin-8 levels were found to be significantly higher in the cholestasis group than control group (p=0.001, p<0.05). Conclusions Because interleukin-8, interleukin-10, and melatonin were found to be significantly correlated with intrahepatic cholestasis of pregnancy, we believe this finding could shed light on the etiology of the disease.

scholarly journals Intrahepatic Cholestasis of Pregnancy: Natural History and Current Management

2021 ◽  
Author(s):  
Rebecca Roediger ◽  
Jaquelyn Fleckenstein
Keyword(s):  
Adverse Effects ◽  
Intrahepatic Cholestasis ◽  
Elevated Serum ◽  
Reproductive Hormones ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Current Management ◽  
Immune Mediated ◽  
Increased Risk ◽  
Fetal Complications ◽  
Cholestasis Of Pregnancy

AbstractIntrahepatic cholestasis of pregnancy (ICP) is a common disorder in the second half of pregnancy characterized by pruritus and elevated serum bile acids (BAs) with spontaneous resolution after delivery. ICP carries a risk of adverse effects on the fetus which correlates with the degree of BA elevation. ICP occurs in genetically susceptible women as the reproductive hormones increase during pregnancy. Ursodeoxycholic acid is still considered the first-line treatment for ICP though it is of unproven benefit in preventing adverse effects on the fetus. Fetal complications, such as stillbirth, increase with gestational age, so preterm delivery is generally performed in cases of severe ICP, defined as BA levels above 40 μmol/L. ICP may recur in future pregnancies and is associated with an increased risk for future hepatobiliary, immune mediated, and cardiovascular diseases. Children born of mothers with ICP have normal development but may have a risk for subsequent metabolic disease.

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