Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy.Short-chain fatty acids(SCFAs),prominent metabolites of the gut microbiota,have significant connections with various pregnancy complications,and some SCFAs hold potential for treating such complications.However,the metabolic profile of SCFAs in patients with ICP remains unclear.AIM To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.METHODS Maternal serum and cord blood samples were collected from both patients with ICP(ICP group)and normal pregnant women(NP group).Targeted metabolomics was used to assess the SCFA levels in these samples.RESULTS Significant differences in maternal SCFAs were observed between the ICP and NP groups.Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group,mirroring the pattern seen in maternal serum.Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs[r(Pearson)=0.88,P=7.93e-95].In both maternal serum and cord blood,acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups(variable importance for the projection>1).Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP,with caproic acid exhibiting the highest diagnostic efficacy(area under the curve=0.97).CONCLUSION Compared with the NP group,significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group,although they displayed distinct patterns of change.Furthermore,the SCFA levels in maternal serum and cord blood were significantly positively correlated.Notably,certain maternal serum SCFAs,specifically caproic and acetic acids,demonstrated excellent diagnostic efficiency for ICP.

Bile Acid Effects on Placental Damage in Intrahepatic Cholestasis of Pregnancy

Aims: The abnormal increase of bile acid is found in intrahepatic cholestasis of pregnancy (ICP). It also can be observed the damage of placental tissue in ICP. The aim of this study was to find the associations of the bile acid in umbilical vein and the damage of placental tissue. Methods: Thirty women diagnosed with ICP and fifty normal pregnant women between September 2015 and September 2017 at Nanshan District Maternity & Child Healthcare Hospital of Shenzhen were included in this study. The glycocholic acid (GA), total bile acids (TBA), total bilirubin (TB), direct bilirubin (DB) and albumin level in umbilical vein were measured by cycle enzyme method in ICP and control group. The placental damage was analyzed by morphologic study using hematoxylin dyes in two groups. The correlation between the level of the bile acid in the umbilical vein and the damage of the placenta was assessed using SPSS software. Results: The GA, TBA, TB, DB and albumin level in umbilical vein were significantly higher in ICP than those of pregnant women, respectively. The placental villis were expanded and the structure was destroyed in ICP. The vessel was damaged and the cell trophoblast hyperplasia in ICP. It also can be seen that there was obvious nodules and a typical fibrous necrotic substance in ICP but not in control group. There is a positive correlation between the level of the TBA in the umbilical vein and the damage of the placenta in ICP. Conclusion: The TBAs were significantly higher in umbilical vein and were related to the placental damage in ICP.

Effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine on pregnancy outcomes in intrahepatic cholestasis

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a liver disorder that occurs in pregnant women and can lead to a range of adverse pregnancy outcomes.The condition is typically marked by pruritus(itching)and elevated levels of liver enzymes and bile acids.The standard treatment for ICP has generally been ursodeoxycholic acid and ademetionine 1,4-butanedisulfonate,but the efficacy of this approach remains less than optimal.Recently,polyene phosphatidylcholine has emerged as a promising new therapeutic agent for ICP due to its potential hepatoprotective effects.AIM To evaluate the effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate on bile acid levels,liver enzyme indices,and pregnancy outcomes in patients with ICP.METHODS From June 2020 to June 2021,600 patients with ICP who were diagnosed and treated at our hospital were recruited and assigned at a ratio of 1:1 via randomnumber table method to receive either ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate(control group,n=300)or polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate(combined group,n=300).Outcome measures included bile acids levels,liver enzyme indices,and pregnancy outcomes.RESULTS Prior to treatment,no significant differences were observed between the two groups(P>0.05).Post-treatment,patients in both groups had significantly lower pruritus scores,but the triple-drug combination group had lower scores than the dual-drug combination group(P<0.05).The bile acid levels decreased significantly in both groups,but the decrease was more significant in the triple-drug group(P<0.05).The triple-drug group also exhibited a greater reduction in the levels of certain liver enzymes and a lower incidence of adverse pregnancy outcomes compared to the dual-drug group(P<0.05).CONCLUSION Polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate effectively relieves pruritus and reduces bile acid levels and liver enzyme indices in patients with ICP,providing a positive impact on pregnancy outcome and a high safety profile.Further clinical trials are required prior to clinical application.

Effects of low molecular heparin combined with ursodeoxycholic acid on liver function, immunologic function and pregnancy outcome in patients with intrahepatic cholestasis of pregnancy

Objective: To investigate the effects of low molecular heparin (LMWH) combined with ursodeoxycholic acid (UDCA) on liver function, immunologic function and pregnancy outcome in patients with intrahepatic cholestasis of pregnancy (ICP). Methods: A total of 110 patients with ICP were randomly divided into the observation group (n=55) and the control group (n=55). Patients in the control group received conventional therapy, while patients in the observation group were treated with LMWH hypodermic injection and UDCA orally on the basis of the treatment plan of the control group. Before and after treatment, the levels of serum total bile acid (TBA), glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP) and immunoglobulin (IgG, IgA, IgM) between the two groups were compared. The changes of T lymphocyte subsets of peripheral blood in the two groups were analyzed, and the pregnancy outcomes of the two groups were observed. Results: After treatment, the serum levels of TBA, ALT, AST, TBIL, DBIL and ALP in the two groups were significantly lower than those before treatment, and the change of each index in the observation group was more obvious than that in the control group. The serum levels of IgG, IgA and IgM in the observation group after treatment were significantly higher than those before treatment and those in the control group after treatment. However, the percentage of CD4+T cells and the ratio of CD4+/CD8+ in the observation group after treatment were significantly lower than those before treatment and those in the control group after treatment. Conclusions: LMWH combined with UDCA could effectively reduce serum bile acid level, improve liver function and regulate immune balance in patients with ICP, and improve outcomes of maternal and fetal.

Intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by maternal pruritus in the third trimester, raised serum bile acids and increased rates of adverse fetal outcomes. The etiology of ICP is complex and not fully understood, but it is likely to result from the cholestatic effects of reproductive hormones and their metabolites in genetically susceptible women. Equally unclear are the mechanisms by which the fetal complications occur. This article reviews the epidemiology, clinical features, diagnosis, etiology and management of ICP.

Intrahepatic Cholestasis of Pregnancy: Biochemical Predictors of Adverse Perinatal Outcomes

Summary： This study aimed to identify biochemical predictors of adverse perinatal outcomes in in- trahepatic cholestasis of pregnancy （ICP）. A total of 106 ICP cases were analyzed retrospectively by the combination of receiver operating characteristic curve and binary logistic regression analysis. ＂Adverse perinatal outcomes＂ included spontaneous preterm labor, meconium-staining of amniotic fluid, stillbirth and Apgar score ≤7 at 1 or 5 min. Total bile acid （TBA） [AUC=0.658, 95%CI （0.536, 0.781）, P=0.031] was a valuable predictor for adverse perinatal outcomes. The critical value of TBA above which adverse perinatal outcomes were observed was 40.15 μmol/L （Youden＇s index=0.3）. Binary multivariate logistic regression analysis revealed that the risk of adverse perinatal outcomes increased when TBA ≥40.15 /.tmol/L [OR=3.792, 95%CI （1.226, 11.727）, P=0.021]. It is concluded that the risk of adverse perinatal outcomes in ICP increases when maternal TBA ≥40.15 gmol/L.

Effect of Cholic Acid on Fetal Cardiac Myocytes in Intrahepatic Choliestasis of Pregnancy

This study examined the effect of cholic acid （CA） on cultured cardiac myoeytes （CMs） from neonatal rats with an attempt to explore the possible mechanism of sudden fetal death in intra- hepatic cholestasis of pregnancy （ICP）. Inverted microscopy was performed to detect the impact of CA on the beating rates of rat CMs. MTT method was used to study the effect of CA on the viability of CMs. CMs cultured in vitro were incubated with 10 ~maol/L Ca2＋-sensitive fluorescence indicator fluo-3/AM. The fluorescence signals of free calcium induced by CA were measured under a laser scanning confocal microscope. The results showed that CA decreased the beating rates of the CMs in a dose-dependent manner. CA could suppress the activities of CMs in a time- and dose-dependent manner. CA increased the concentration of intracellular free calcium in a dose-dependent manner. Our study suggested that CA could inhibit the activity of CMs by causing calcium overload, thereby leading to the sudden fetal death in ICP.

Ursodeoxycholic Acid in the Treatment of Intraheptic Cholestasis of Pregnancy

In order to observe the effect of ursodeoxycholic acid （UDCA） in the treatment of intrahepatic cholestasis of pregnancy （ICP）, 68 patients with ICP were equally divided into treatment group and control group at random. The patients in treatment group were administered with UDCA 300 mg three times every day and those in control group received a combination of 10 % glucose, Vitamin C and Inosine. Itching scores, serum ALT and total bile acids （TBA） were measured before, during and after treatment. The results showed that as compared with those before treatment, itching scores, serum ALT and TBA were significantly reduced after treatment （P〈0.05）. The occurrences of premature labor, fetal asphyxia and meconium staining in amniotic fluid were significantly lower in treatment group than in control group （P〈0. 05）. It was suggested that UDCA was an effective drug in the treatment of ICP.

Fetal lung surfactant and development alterations in intrahepatic cholestasis of pregnancy

AIM: To investigate the association between total bile acid(TBA) level during intrahepatic cholestasis of pregnancy(ICP) and fetal lung surfactant alteration. METHODS: We recruited 42 ICP and 32 normal pregnancy women in this study. The maternal blood, fetal blood and amniotic fluid TBA level were detected using a circulating enzymatic method. Umbilical blood pulmonary surfactant protein A(SP-A) was evaluated with enzyme-linked immunosorbent assay. High performance liquid chromatography was used for the determination of phosphatidyl choline(PC), phosphatidyl inositol(PI), lysolecithin(LPC) and sphingomyelin(SM). Amniotic fluid lamellar body was counted with a fully automatic blood cell counter. Fetal lung area and fetal body weight were calculated from data obtained with an iu22 color supersonic diagnostic set. Clinical information of a nonstress test, amniotic fluid properties and neonatal Apgar score, and birth weight were recorded for review. RESULTS: The TBA level in maternal blood, fetal blood and amniotic fluid in the ICP group were significantly higher than that in the control group(maternal blood: 34.11 ± 6.75 mmol/L vs 4.55 ± 1.72 mmol/L, P < 0.05; fetal blood: 11.9 ± 2.23 mmol/L vs 3.52 ± 1.56 mmol/L, P < 0.05; amniotic fluid: 3.89 ± 1.99 mmol/L vs 1.43 ± 1.14 mmol/L, P < 0.05). Amniotic fluid PC and PI in the ICP group were significantly lower than that in the control group(PC: 65.71 ± 7.23 μg/m L vs 69.70 ± 6.68 μg/m L, P < 0.05; PI: 3.87 ± 0.65 μg/m L vs 4.28 ± 0.74 μg/m L, P < 0.05). PC/LPC ratio of the ICP group was lower than that of the control group(14.40 ± 3.14 vs 16.90 ± 2.52, P < 0.05). Amniotic LB in the ICP group was significantly lower than that of the control group((74.13 ± 4.37) × 109/L vs(103.0 ± 26.82) × 109/L, P < 0.05). Fetal umbilical blood SP-A level in the ICP group was significantly higher than that of the control group(30.26 ± 7.01 ng/m L vs 22.63 ± 7.42 ng/m L, P < 0.05). Fetal lung area/body weight ratio of the ICP group was significantly lower than that of the control group(5.76 ± 0.63 cm2/kg vs 6.89 ± 0.48 cm2/kg, P < 0.05). In the ICP group, umbilical cord blood TBA concentration was positively correlated to the maternal blood TBA concentration(r = 0.746, P < 0.05) and umbilical blood SP-A(r = 0.422, P < 0.05), but it was negatively correlated to the amniotic fluid lamellar corpuscle(r = 0.810, P < 0.05) and fetal lung area/body weight ratio(r = 0.769, P < 0.05). Furthermore, umbilical blood TBA showed a negative correlation to PC, SM and PI(r pc = 0.536, r sm = 0.438, r pi = 0.387 respectively, P < 0.05). The neonatal asphyxia, neonatal respiratory distress syndrome, fetal distress and perinatal death rates in the ICP group are higher than that of theCONCLUSION: ICP has higher TBA in maternal and fetal blood and amniotic fluid. The high concentration of TBA may affect fetal pulmonary surfactant production and fetal lung maturation.

Liver stiffness in pregnant women with intrahepatic cholestasis of pregnancy:A case control study

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a rare but severe complication for both the mother and the unborn child.The diagnosis is primarily based on elevated serum levels of bile acids.In a large ICP cohort,we here study in detail liver stiffness(LS)using transient elastography(TE),now widely used to noninvasively screen for liver cirrhosis within minutes.AIM To specifically explore LS in a large cohort of women with ICP compared to a control group with uncomplicated pregnancy.METHODS LS and hepatic steatosis marker controlled attenuation parameter(CAP)were measured in 100 pregnant women with ICP using TE(Fibroscan,Echosens,Paris,France)between 2010 and 2020.In 17 cases,LS could be measured postpartum.450 women before and 38 women after delivery with uncomplicated pregnancy served as control group.Routine laboratory,levels of bile acids and apoptosis marker caspase-cleaved cytokeratin 18 fragment(M30)were also measured.RESULTS Women with ICP had significantly elevated transaminases but normal gammaglutamyl transferase(GGT).Mean LS was significantly increased at 7.3±3.0 kPa compared to the control group at 6.2±2.3 kPa(P<0.0001).Postpartum LS decreased significantly in both groups but was still higher in ICP(5.8±1.7 kPa vs 4.2±0.9 kPa,P<0.0001),respectively.In ICP,LS was highly significantly correlated with levels of bile acids and M30 but not transaminases.No correlation was seen with GGT that even increased significantly after delivery in the ICP group.Bile acids were mostly correlated with the liver apoptosis marker M30,LS and levels of alanine aminotransferase,aspartate aminotransferase,and bilirubin.In multivariate analysis,LS remained the sole parameter that was independently associated with elevated bile acids.CONCLUSION In conclusion,LS is significantly elevated in ICP which is most likely due to toxic bile acid accumulation and hepatocyte apoptosis.In association with conventional laboratory markers,LS provides additional non-invasive information to rapidly identify women at risk for ICP.

Why more attentions to fetus in cases of intrahepatic cholestasis of pregnancy?

Intrahepatic cholestasis of pregnancy(ICP) is a peculiar disease in middle-late pregnancy with the pathological characteristics of hepatic capillary bile duct silts and is accompanied by clinical presentations of pruritus and bile acid(BA) elevation in serum. Maternal outcomes for patients diagnosed with ICP are usually good. However, fetal outcomes can be devastating with high frequencies of perinatal complications. Patients with ICP generally have an early delivery due to fetal complications. The current hypothesis is that ICP has higher frequencies of fetal complications due to high concentrations of BA which has toxic cellular effects to many organs. In lungs, it destroys the AT-II cells, decreasing phospholipids synthesis leading to the alveolar capillary permeability to increase and pulmonary surfactant to decrease. In heart, cholate can cross into the fetal compartment and causing fetal arrhythmias and decreased contractility. In the nervous system, high BAs can cause nerve cell denaturation and necrosis, mitochondria edema and membrane dissolve. In the placenta, high BA concentration can cause edema of the villous, decrease number of villous, intervillous thickening and balloon formation.In addition, high total BA can result in chorionic vein constriction and impaired fetal adrenal function.

Expanding etiology of progressive familial intrahepatic cholestasis

BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.

Response of gut microbiota to serum metabolome changes in intrahepatic cholestasis of pregnant patients

BACKGROUND Intrahepatic cholestasis in pregnancy(ICP)is the most common liver disease during pregnancy,and its exact etiology and course of progression are still poorly understood.AIM To investigate the link between the gut microbiota and serum metabolome in ICP patients.METHODS In this study,a total of 30 patients were recruited,including 15 patients with ICP(disease group)and 15 healthy pregnant patients(healthy group).The serum nontarget metabolomes from both groups were determined.Amplification of the 16S rRNA V3-V4 region was performed using fecal samples from the disease and healthy groups.By comparing the differences in the microbiota and metabolite compositions between the two groups,the relationship between the gut microbiota and serum metabolites was also investigated.RESULTS The Kyoto Encyclopedia of Genes and Genomes analysis results showed that the primary bile acid biosynthesis,bile secretion and taurine and hypotaurine metabolism pathways were enriched in the ICP patients compared with the healthy controls.In addition,some pathways related to protein metabolism were also enriched in the ICP patients.The principal coordination analysis results showed that there was a distinct difference in the gut microbiota composition(beta diversity)between the ICP patients and healthy controls.At the phylum level,we observed that the relative abundance of Firmicutes was higher in the healthy group,while Bacteroidetes were enriched in the disease group.At the genus level,most of the bacteria depleted in ICP are able to produce short-chain fatty acids(e.g.,Faecalibacterium,Blautia and Eubacterium hallii),while the bacteria enriched in ICP are associated with bile acid metabolism(e.g.,Parabacteroides and Bilophila).Our results also showed that specific genera were associated with the serum metabolome.CONCLUSION Our study showed that the serum metabolome was altered in ICP patients compared to healthy controls,with significant differences in the bile,taurine and hypotaurine metabolite pathways.Alterations in the metabolization of these pathways may lead to disturbances in the gut microbiota,which may further affect the course of progression of ICP.

Presence of Obstetrics Cholestasis in Mothers Presenting with Pruritus in Pregnancy: In a Low Resource South Asian Setting

Obstetric cholestasis (also referred to as intrahepatic cholestasis of pregnancy—ICP) is a pruritic form of reversible cholestasis that is associated with significant fetal risks. There is a paucity of research regarding pregnancy outcomes of the mothers with obstetric cholestasis in the South Asian setting. Hence, the objective of this study was to determine the prevalence of obstetric cholestasis among mothers presenting with pruritus during pregnancy and to describe the characteristics and outcomes for those diagnosed with ICP in comparison with those with pruritus in the absence of ICP. Methods: All mothers presenting with pruritus to De Soyza Maternity hospital in Colombo Sri Lanka, between 1st January 2011 to 1st January 2014, were recruited for the study. A standard set of biochemical tests were used for diagnosis of ICP. An interviewer administered questionnaire and patient records were used for data collection. Presentation, characteristics and pregnancy outcomes were assessed and compared for mothers with ICP against those with pruritus in the absence of ICP. Results: The prevalence of ICP in the study population was found to be 27% (n = 27). Generalized pruritus with pruritus of the palms and soles was identified as the commonest pattern of pruritus for diagnosed with ICP. Delivery before 37 weeks (p = 0.001), meconium stained liquor (p = 0.004), placental abruption (p = 0.005), postpartum hemorrhage (p = 0.005), bleeding manifestation (p = 0.006), preterm labor (p = 0.031) and fetal distress (p = 0.035) were found to be significantly associated with the presence of ICP. Conclusions: Nearly 1/3 of mothers presenting with pruritus in pregnancy in Sri Lanka are affected by ICP which is associated with an increase in a wide range of adverse maternal and fetal outcomes compared to those with pruritus in the absence of ICP.

Targeted metabolomics of sulfated bile acids in urine for the diagnosis and grading of intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy(ICP)is related to cholestatic disorder in pregnancy.Total urinary sulfated bile acids(SBAs)were found increased in ICP.We distinguished the metabolic profiling of urinary SBAs in ICP to find potential biomarkers for the diagnosis and grading of ICP.The targeted metabolomics based on high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to analyze urinary SBAs profiling in mild and severe ICP cases,as well as healthy controls.16 kinds of urinary SBAs were determined by HPLC-MS/MS.Sulfated dihydroxy glycine bile acid(di-GBA-S),glycine cholic acid 3-sulfate(GCA-3S),sulfated dihydroxy taurine bile acid(di-TBA-S)and taurine cholic acid 3-sulfate(TCA-3S)increased significantly in ICP group compared with the control group.Seven kinds of SBAs were significantly different(p<0.05)between the ICP group and the control group,with the variable importance in the projection(VIP)value more than one by the orthogonal partial least squares discriminant analysis(OPLS-DA).GCA-3S was well-suited to be used as the biomarker for the diagnosis of ICP with the sensitivity of 100%and specificity of 95.5%.A multi-variable logistic regression containing GCA-3S and di-GBA-S-1 was constructed to distinguish severe ICP from mild ICP,with the sensitivity of 94.4%and specificity of 100%.The developed HPLC-MS/MS method is suitable for the measurement of urinary SBAs profiling.Moreover,the urinary SBAs in the metabolomic profiling have the potential to be used as non-intrusive biomarkers for the diagnosis and grading of ICP.

Clinical Management Guidelines for Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy(ICP)is a significant gestational complication in late pregnancy,potentially leading to severe perinatal complications such as intrauterine fetal demise and preterm birth.The Obstetrics Group of the Gynecology and Obstetrics Branch and the Perinatal Medicine Branch of the Chinese Medical Association organized a panel of domestic experts to deliberate and propose recommendations based on domestic and international guidelines,recent evidence-based medical evidence about key clinical issues including risk factors,clinical manifestations,perinatal outcomes,diagnosis,severity grading,maternal and fetal monitoring,treatment methods,timing,and methods of pregnancy termination,and postpartum follow-up for ICP,with the aim to guide its clinical diagnosis,treatment,and management.

妊娠期肝内胆汁淤积症与妊娠期糖尿病的相关性研究

目的:探讨妊娠期肝内胆汁淤积症(ICP)与妊娠期糖尿病(GDM)的相关性。方法:选取2013年2月至2021年2月在北京大学深圳医院产科分娩的GDM孕妇5517例(GDM组)和非GDM孕妇5517例(非GDM组),采用单因素、多因素和分层分析法分析ICP与GDM、ICP与血糖水平、总胆汁酸与GDM的相关性。结果:GDM组中ICP比例显著大于非GDM组,差异有统计学意义(P<0.05)。GDM合并ICP患者的OGTT-1h血糖显著高于GDM未合并ICP患者(P<0.05),两组患者OGTT-0h或2h血糖比较,差异无统计学意义(P>0.05)。与非GDM组比较,GDM组中重度ICP占ICP总体的比例显著增高(34.88%vs 9.68%,P<0.001);ICP病例中,与未合并GDM患者比较,合并GDM的患者血清总胆汁酸显著升高(中位数29.10μmol/L vs 20.65μmol/L,P<0.01)。多因素分析提示,ICP与GDM显著相关(OR=1.426,95%CI为1.011~2.011,P=0.043),这与非高龄妊娠、单胎妊娠、经产妇中的分层分析结果一致。结论:ICP与GDM存在显著相关性,并且这种相关性在重度ICP中更明显,ICP可能是GDM的风险因素之一。

HBV感染孕妇早期胆汁酸谱检测在妊娠期肝内胆汁淤积症诊断中的应用

目的探讨HBV感染孕妇早期胆汁酸谱检测在妊娠期肝内胆汁淤积症(ICP)诊断中的应用价值。方法回顾性分析2020年1月—2022年12月无锡市妇幼保健院收治的186例HBV感染孕妇,根据ICP诊断标准将其分为单纯HBV组(124例)和HBV并发ICP组(62例),收集两组孕妇一般资料及妊娠早期围保肝生化指标和胆汁酸谱检测结果,采用单因素分析、多因素logistic回归分析HBV感染孕妇并发ICP的主要影响因素,ROC曲线分析预测诊断效能。结果与HBV组比,HBV并发ICP组AST[(46.60±38.98)U/L比(30.97±31.49)U/L,P=0.004]、ALT[(50.80±36.81)U/L比(40.32±29.45)U/L,P=0.037]、DBil[(6.07±2.34)μmol/L比(4.73±1.83)μmol/L,P<0.001]、TBA[(16.98±2.48)μmol/L比(6.01±2.34)μmol/L,P=0.010]明显升高,CA[(0.59±0.49)μmol/L比(0.40±0.34)μmol/L,P=0.007]、GCA[(2.41±1.04)μmol/L比(1.52±0.70)μmol/L,P<0.001]、GDCA[(0.92±0.35)μmol/L比(0.67±0.37)μmol/L,P<0.001]、GCDCA[(2.14±0.89)μmol/L比(1.67±0.56)μmol/L,P<0.001]也升高,且AST、DBil、GCA、GDCA、GCDCA为HBV并发ICP的主要危险因素(P<0.05);AST、DBil、GCA对HBV并发ICP诊断价值较高(分别AUC 0.747、0.725、0.761);GCDCA、GDCA的诊断价值一般(AUC 0.667、0.688)。结论胆汁酸谱GCA、GCDCA、GDCA亚型升高及AST、DBil升高均是HBV感染孕妇并发ICP发生的主要危险因素,且GCA的预测诊断价值最高,临床应结合肝功能指标综合诊断。

不同血清总胆汁酸水平对妊娠肝内胆汁淤积症患者肝功能和母婴结局的影响

目的分析不同血清总胆汁酸(TBA)水平对妊娠肝内胆汁淤积症(ICP)患者肝功能和母婴结局的影响。方法选取2021年1月至12月珠海市妇幼保健院收治的60例ICP患者为研究对象,根据TBA水平分为对照组(30例,TBA<40μmol/L)、观察组(30例,TBA≥40μmol/L)。比较两组血清总胆红素(TBiL)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、γ-谷氨酰基转移酶(γ-GGT)水平和母婴结局。结果观察组血清TBiL、ALT、AST、ALP、γ-GGT水平高于对照组,差异有统计学意义(P<0.05);观察组羊水污染率高于对照组,差异有统计学意义(P<0.05);观察组早产、新生儿窒息率高于对照组,差异有统计学意义(P<0.05);观察组新生儿出生后1、10 min的Apgar评分低于对照组,差异有统计学意义(P<0.05)。结论高水平TBA的ICP患者肝功能损害更加严重,羊水污染、早产、新生儿窒息等不良母婴结局的发生率更高。

血清谷氨酰胺转移酶和甘胆酸对妊娠期肝内胆汁淤积的诊断价值

目的探讨血清谷氨酰胺转移酶(GGT)和甘胆酸(CG)对妊娠期肝内胆汁淤积(ICP)的诊断价值。方法回顾性选择2017年1月—2022年6月于徐州市中心医院妇产科和消化内科初次就诊的157例ICP患者为研究对象(ICP组),另选择同期在徐州市中心医院就诊的正常孕妇119例作为对照。收集并比较2组患者的一般临床资料及实验室指标,logistic回归分析ICP发生的危险因素;受试者工作特征曲线(ROC)分析血清GGT和CG对ICP的诊断价值。结果(1)ICP组与对照组孕妇年龄、孕周、总胆红素(TBil)、国际标准化比值(INR)、碱性磷酸酶(ALP)、天冬氨酸氨基转氨酶(AST)、GGT、总胆汁酸(TBA)、CG等指标差异有统计学意义(P<0.05);(2)logistic回归分析显示:GGT[Exp(B)=1.006,95%CI=1.002,1.010,P=0.004]和CG[Exp(B)=1.046,95%CI=1.032,1.061,P<0.001]与ICP的发生显著相关;(3)ROC曲线分析表明:GGT诊断ICP的曲线下面积(AUC)为0.85(95%CI=0.801,0.901,P<0.001),敏感度及特异度分别为:82.17%和91.60%,约登指数为73.77;CG诊断ICP的AUC为0.95(95%CI=0.932,0.975,P<0.001),敏感度及特异度分别为:90.45%和87.39%,约登指数为77.84。二者联合诊断时的AUC为0.98(95%CI=0.966,0.992,P<0.001),敏感度和特异度分别为93.28%(95%CI=87.180,97.050)和94.74%(95%CI=89.890,97.700),约登指数为88.02。结论ICP患者血清GGT和CG水平明显增高,且与ICP的发生相关,二者联合检测可提高对ICP的诊断效能。