Cholestasis Of Pregnancy Research Articles

İntrahepatik Gebelik Kolestazında Plazma Lipid Düzeylerinin Değerlendirilmesi

Objective: To investigate the total cholesterol, triglyceride, LDL, VLDL, and HDL levels of pregnant women diagnosed with intrahepatic cholestasis of pregnancy and to examine the association with disease severity.
 Material and Method: A total of 80 pregnant women, 40 of whom were diagnosed with intrahepatic cholestasis of pregnancy, and 40 age-matched controls, were prospectively enrolled in this study. Lipid levels were compared among the case and controls, and their association with disease severity was analyzed. Birth weight, birth week, and neonatal outcomes were studied.
 Results: LDL and VLDL were significantly higher, and HDL levels were lower in the intrahepatic cholestasis of the pregnancy group than in the healthy pregnancies (p

Obeticholic acid alleviates intrauterine growth restriction induced by di-ethyl-hexyl phthalate in pregnant female mice by improving bile acid disorder.

Di-(2-ethylhexyl)-phthalate (DEHP) is a ubiquitous environmental pollutant and is widely used in industrial plastics. Intrahepatic cholestasis of pregnancy (ICP), distinguished by maternal pruritus and elevated serum bile acid levels, is linked to unfavorable pregnancy consequences. Few studies have investigated the potential effect of gestational DEHP exposure on the cholestasis in pregnant female mice, and the underlying mechanisms remain unclear. In the present study, a mouse model of cholestasis during pregnancy was established by DEHP exposure. We found that DEHP induces elevated bile acid levels by affecting bile acid synthesis and transporter receptor expression in the maternal liver and placenta of pregnant female mice, ultimately leading to intrauterine growth restriction (IUGR). In addition, DEHP changed the bile acid composition of maternal serum and liver as well as placenta and amniotic fluid in pregnant female mice; Importantly, we found that DEHP down-regulates the expression of farnesoid X receptor (FXR), which is considered to be a bile acid receptor. FXR agonist obeticholic acid (OCA) effectively alleviated the adverse effects of DEHP on pregnant female mice. While, OCA itself had no adverse effects on normal pregnant female mice. In summary, DEHP could induces bile acid disorder and IUGR in pregnant female mice by affect FXR, which was reversed by OCA.

Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy

BackgroundThe pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP.MethodsWe recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites.ResultsAn increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP.ConclusionsWomen with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.

The effect of disease severity and response to treatment on perinatal outcomes in intrahepatic cholestasis of pregnancy

Amaç: Gebeliğin intrahepatik kolestazı (GİHK) ile komplike olan gebeliklerde, serum safra asiti (SA) düzeyleri ve ursodeoksikolik asit (UDKA) tedavisine verilen cevabın perinatal sonuçlar üzerine etkisini araştırmaktır.
 Gereçler ve Yöntem: Bu çalışmada Ocak 2013 ile Ocak 2018 tarihleri arasında üçüncü basamak bir merkezde GİHK nedeniyle takip edilen gebelikler retrospektif olarak analiz edildi. GİHK şiddeti, serum SA seviyelerine göre hafif (10–40 μmol/L), orta (40-80 μ mol/L) ve şiddetli (>80 μ mol/L) olarak gruplandırıldı. GİHK’nın şiddeti ve UDKA tedavisine verilen olumlu veya olumsuz yanıtın perinatal sonuçlar üzerine etkisi araştırıldı.
 Bulgular: GİHK tanısı koyulan toplamda 200 gebe çalışmaya dahil edildi. Hastaların %65 (n=130)’inde hafif GİHK, %20 (n=40)’sinde orta şiddetli GİHK ve %15 (n=30)’inde şiddetli GİHK saptandı. GİHK tanısıyla takip edilen hastaların 4 (%2.0)’ünde ölü doğum gerçekleşti. Şiddetli GİHK hastalarında spontan preterm doğum oranı, orta ve hafif GİHK hastalarına kıyasla anlamlı olarak daha yüksekti (p=0.001). Şiddetli GİHK hastalarında ve UDKA tedavisine yanıt vermeyen hastalarda, ortalama doğum haftası, ortalama doğum ağırlığı, 1. ve 5. dakika Apgar skorları daha düşük, amniyosta mekonyum varlığı, yenidoğan yoğun bakım ünitesi ihtiyacı ve ölü doğum oranları daha yüksekti.
 Sonuç: GİHK ile komplike olan gebelikler fetal ve neonatal olumsuz sonuçlar açısından artmış riske sahiptir. Maternal serum SA düzeyleri hastalığın siddeti ve olumsuz perinatal sonuçlarla ilişkilidir. Bununla birlikte, UDKA tedavisine verilen klinik cevap, fetal ve neonatal sonuçları öngörmede etkili olabilir.

Lipid profile and pregnancy associated pathologies

Throughout pregnancy, maternal lipid metabolism changes substantially, all of which can be seen by analysing the lipid profile. Determination of serum total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels may have a predictive role in the subsequent development of pregnancyspecific pathologies such as preeclampsia, intrahepatic cholestasis of pregnancy and gestational diabetes. Also, disorders present in the lipid profile may influence the weight of the newborn at birth. Early dyslipidaemia during pregnancy, manifested by elevated triglycerides and low-density lipoprotein cholesterol serum levels, has been associated with the development of preeclampsia. In laboratory tests, pregnant women diagnosed with intrahepatic cholestasis have significantly higher plasma triglycerides levels and reduced high-density lipoprotein cholesterol concentrations compared to healthy pregnant women. In case of foetal intrauterine growth restriction in the newborn, literature data report significantly increased triglycerides levels. Women who during pregnancy developed gestational diabetes had higher plasma triglycerides levels and lower high-density lipoprotein cholesterol levels, with no statistically significant difference between serum triglycerides or high-density lipoprotein cholesterol levels.

EP01.32: Fetal cardiac profile using speckle‐tracking echocardiography in intrahepatic cholestasis of pregnancy and its association with perinatal outcome

EP01.32: Fetal cardiac profile using speckle‐tracking echocardiography in intrahepatic cholestasis of pregnancy and its association with perinatal outcome

Obstetric Cholestasis among Pregnant Women Visiting a Tertiary Care Centre.

Obstetric cholestasis is one of the most frequent hepatic disorders specific to pregnancy. It occurs commonly during the latter half of pregnancy. The data regarding this issue is rare in our settings. The aim of this study was to find out the prevalence of obstetric cholestasis among pregnant women visiting a tertiary care centre. A descriptive cross-sectional study was conducted among pregnant women, who attended a tertiary care centre from 24 July 2022 to 24 January 2023. Ethical approval was taken from the Institutional Review Committee of the same institute. Convenience sampling method was used. The point estimate was calculated at a 99% Confidence Interval. The prevalence of obstetric cholestasis was 80 (1.38%) (1-1.80, 99% Confidence Interval). A total of 40 (50%) were in the age group 21-30 years, with a mean age of 28.06±6.39 years. A total of 48 (60%) were multigravida and 73 (91.30%) had singleton pregnancies. Pruritus of the whole body was complained of by 56 (70%) patients. Previous history of obstetric cholestasis was present in 21 (26.30%). The prevalence of obstetric cholestasis among pregnant women is lower than other studies done in similar settings. Nepal; obstetric cholestasis; pregnancy.

The Impact of the Association Between Nonalcoholic Fatty Liver Disease and Intrahepatic Cholestasis of Pregnancy on Maternal and Fetal Outcomes.

Backgroundː Intrahepatic cholestasis of pregnancy (ICP), a hepatic condition that causes severe itching in late pregnancy, is linked to nonalcoholic fatty liver disease (NAFLD) due to disrupted bile acid balance. It poses maternal risks such as preterm labor and gestational diabetes and fetal risks such as preterm birth and respiratory distress. The study examined NAFLD's impact on ICP in pregnant women, highlighting management and research implications. Methodsː This retrospective study examined pregnant women (≥18 years) with ICP, assessing fatty liver with follow-up ultrasounds. Participants were divided into ICP only and ICP with fatty liver (FL) groups, excluding heavy alcohol users and incomplete data. Maternal age, medical history, and comorbidities were evaluated alongside abdominal ultrasounds to identify FL. Resultsː In this study of 43 pregnant women, the mean maternal age was 27 years. Patients with ICP and FL had significantly higher bile acid levels than those with ICP alone. However, no significant differences were found between the two groups regarding the history of gestational diabetes mellitus (GDM), dyslipidemia, polycystic ovarian syndrome (PCOS), parity, and hypothyroidism. Among women with ICP and FL, 51.85% underwent lower segment cesarean section (LSCS), while 43.75% with ICP without FL underwent LSCS. Conclusionsː ICP with FL did not show significant adverse effects on maternal and neonatal outcomes, including mode of delivery, gestational age, maternal complications, neonatal intensive care unit (NICU) admissions, and low birth weight (LBW) with asphyxia. However, additional research is required to fully comprehend the relationship between ICP, NAFLD, and their impact on pregnancy outcomes.

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

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. 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. 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 random-number 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. 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). 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 Pregnancy on Plasma Sphingolipids Using a Metabolomic and Quantitative Analysis Approach.

Changes in the maternal metabolome, and specifically the maternal lipidome, that occur during pregnancy are relatively unknown. The objective of this investigation was to evaluate the effects of pregnancy on sphingolipid levels using metabolomics analysis followed by confirmational, targeted quantitative analysis. We focused on three subclasses of sphingolipids: ceramides, sphingomyelins, and sphingosines. Forty-seven pregnant women aged 18 to 50 years old participated in this study. Blood samples were collected on two study days for metabolomics analysis. The pregnancy samples were collected between 25 and 28 weeks of gestation and the postpartum study day samples were collected ≥3 months postpartum. Each participant served as their own control. These samples were analyzed using a Ultra-performance liquid chromatography/mass spectroscopy/mass spectroscopy (UPLC/MS/MS) assay that yielded semi-quantitative peak area values that were used to compare sphingolipid levels between pregnancy and postpartum. Following this lipidomic analysis, quantitative LC/MS/MS targeted/confirmatory analysis was performed on the same study samples. In the metabolomic analysis, 43 sphingolipid metabolites were identified and their levels were assessed using relative peak area values. These profiled sphingolipids fell into three categories: ceramides, sphingomyelins, and sphingosines. Of the 43 analytes measured, 35 were significantly different during pregnancy (p < 0.05) (including seven ceramides, 26 sphingomyelins, and two sphingosines) and 32 were significantly higher during pregnancy compared to postpartum. Following metabolomics, a separate quantitative analysis was performed and yielded quantified concentration values for 23 different sphingolipids, four of which were also detected in the metabolomics study. Quantitative analysis supported the metabolomics results with 17 of the 23 analytes measured found to be significantly different during pregnancy including 11 ceramides, four sphingomyelins, and two sphingosines. Fourteen of these were significantly higher during pregnancy. Our data suggest an overall increase in plasma sphingolipid concentrations with possible implications in endothelial function, gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy, and fetal development. This study provides evidence for alterations in maternal sphingolipid metabolism during pregnancy.

Diagnostic Approach to Elevated Liver Function Tests during Pregnancy: A Pragmatic Narrative Review.

Liver disease is not uncommon during pregnancy and is associated with increased maternal and fetal/neonatal morbidity and mortality. Physiological changes during pregnancy, including a hyperestrogenic state, increase in circulating plasma volume and/or reduction in splanchnic vascular resistance, and hemostatic imbalance, may mimic or worsen liver disease. For the clinician, it is important to distinguish among the first presentation or exacerbation of chronic liver disease, acute liver disease non-specific to pregnancy, and pregnancy-specific liver disease. This last group classically includes conditions such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, liver disorders associated with the pre-eclampsia spectrum, and an acute fatty liver of pregnancy. All of these disorders often share pathophysiological mechanisms, symptoms, and laboratory findings (such as elevated liver enzymes), but a prompt and correct diagnosis is fundamental to guide obstetric conduct, reduce morbidity and mortality, and inform upon the risk of recurrence or development of other chronic diseases later on in life. Finally, the cause of elevated liver enzymes during pregnancy is unclear in up to 30-40% of the cases, and yet, little is known on the causes and mechanisms underlying these alterations, or whether these findings are associated with worse maternal/fetal outcomes. In this narrative review, we aimed to summarize pragmatically the diagnostic work-up and the management of subjects with elevated liver enzymes during pregnancy.

Non-alcoholic steatohepatitis in pregnancy: a case report

BackgroundDyslipidemia and non-alcoholic fatty liver disease are well-known diseases and are part of a very broad spectrum evolving toward non-alcoholic steatohepatitis (NASH). This entity has not been described in pregnant women and could have obstetrical repercussions.Case presentationA 26-year-old woman with 28 + 5 weeks of pregnancy presented with preterm labor. At admission, a significant hepatic cytolysis was detected (AST/ALT 265/485 U/L—GGT/alkaline phosphatase 60/164 U/L). She had normal blood pressure and negative 24-h proteinuria. She did not have intrahepatic cholestasis of pregnancy (bile acid at 7) and also no organic hepatic etiology (negative serologies and imaging). This cytolysis worsened until a more detailed history revealed a potential etiology: a diet very rich in sugars and fatty acids corresponding to a NASH syndrome. Dietary rebalancing improved the cytolysis. Complications such as intrahepatic cholestasis of pregnancy and preterm birth favored by significant dyslipidemia could not be avoided.ConclusionsIt is important to consider the lipid profile of our patients. This will allow for a more personalized follow-up given the possible obstetrical repercussions that can arise from this pathology. It should also be considered in the differential diagnosis of liver test alterations during pregnancy. A healthy diet seems to help control the disease.

Evaluation of maternal serum vascular endothelial growth factor C and D levels in intrahepatic cholestasis of pregnancy.

This study aimed to investigate maternal serum vascular endothelial growth factor (VEGF) C and D levels in patients with intrahepatic cholestasis of pregnancy (ICP). A total of 83 patients, including 41 patients with ICP and 42 healthy pregnant women, were included in the study. We first compared the maternal serum VEGF-C and VEGF-D levels between the ICP and control groups and then examined the correlation between the serum VEGF-C level and the bile acid level in patients with severe ICP. We observed statistically significantly higher serum VEGF-C levels and lower VEGF-D levels in the ICP group compared with the healthy controls (P < 0.001 and P = 0.015, respectively). According to receiver operating characteristic analysis, the optimal cutoff value for ICP was 147 ng/mL in the determination of the VEGF-C level (specificity and sensitivity: 76%). In patients with severe ICP, the serum VEGF-C statistically significantly correlated with the bile acid level (P = 0.019). This study showed that the maternal serum VEGF-C level was higher and the VEGF-D level was lower in patients with ICP compared with healthy pregnant women. We also found that the VEGF-C level was correlated with the serum bile acid level in patients with severe ICP. Serum VEGF-C level can be used in the diagnosis and follow-up of intrahepatic pregnancy cholestasis.

To study the maternal and fetal outcome in women presenting with jaundice in pregnancy: A prospective observational study

To study the maternal and fetal outcome in women presenting with jaundice in pregnancy: A prospective observational study

Hepatoprotective agents in the management of intrahepatic cholestasis of pregnancy: current knowledge and prospects.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by unexplained distressing pruritus in the mother and poses significant risk to the fetus of perinatal mortality. Occurring in the second and third trimester, the serum bile acid and aminotransferase are usually elevated in ICP patients. Ursodeoxycholic acid (UDCA) is the first line drug for ICP but the effectiveness for hepatoprotection is to a certain extent. In ICP patients with severe liver damage, combination use of hepatoprotective agents with UDCA is not uncommon. Herein, we reviewed the current clinical evidence on application of hepatoprotective agents in ICP patients. The underlying physiological mechanisms and their therapeutic effect in clinical practice are summarized. The basic pharmacologic functions of these hepatoprotective medications include detoxification, anti-inflammation, antioxidation and hepatocyte membrane protection. These hepatoprotective agents have versatile therapeutic effects including anti-inflammation, antioxidative stress, elimination of free radicals, anti-steatohepatitis, anti-fibrosis and anti-cirrhosis. They are widely used in hepatitis, non-alcoholic fatty liver disease, drug induced liver injury and cholestasis. Evidence from limited clinical data in ICP patients demonstrate reliable effectiveness and safety of these medications. Currently there is still no consensus on the application of hepatoprotective agents in ICP pregnancies. Dynamic monitoring of liver biochemical parameters and fetal condition is still the key recommendation in the management of ICP pregnancies.

Predictors of Adverse Fetal Outcomes in Intrahepatic Cholestasis of Pregnancy (ICP): a Narrative Review.

Intrahepatic cholestasis of pregnancy (ICP) is a hepatic disorder in pregnancy linked with adverse fetal outcomes, which primarily manifests in the late second and third trimesters of pregnancy. This review aims to recapitulate the existing evidence on factors that can predict detrimental perinatal outcomes in pregnant women diagnosed with intrahepatic cholestasis of pregnancy. We searched PubMed, Web of Science, Cochrane Library, Scopus, Medline, and Embase databases and selected studies related to predictors of fetal outcome in intrahepatic cholestasis of pregnancy. Studies of the articles showed that predictors of an adverse fetal outcome include in vitro fertilization (IVF) pregnancy, multifetal pregnancy, biochemical markers, gestational age of ICP onset, presence of comorbidities (preeclampsia and gestational diabetes mellitus), maternal history of ICP, and hepatobiliary disease.Intrahepatic cholestasis of pregnancy (ICP) complicates the pregnancy. Hence, early assessment of low-risk and high-risk groups will help to administer definite management protocols and strategies to prevent adverse neonatal outcomes. Further research should concentrate on the number of conditions/factors and the predictive power of different factors to determine the most reliable predictors and biomarkers that can predict adverse fetal outcomes and improve the assessment of risk in pregnancy complicated with ICP.

Expression and Significance of Galectin-1 and Galectin-3 in the Serum and Placental Tissues of Patients with Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease, usually occurring in the third trimester of pregnancy. Its typical clinical manifestations are itching and elevated serum total bile acid levels, which are more harmful to the fetus, and can lead to a variety of adverse pregnancy outcomes. This paper discusses the expressions of galectin -1 and 3 in the serum and placenta of ICP patients and their relationship with the effect of the incidence of ICP. Galectin-1 and 3 in serum and placenta were detected in 22 pregnant women with ICP and 20 healthy pregnant women admitted to the obstetrics Department of Northern Jiangsu People's Hospital from May 2021 to February 2022. Serum levels of galectin-1 and galectin-3 in ICP pregnant women were significantly higher than those in controls, with significant differences (P<0.05). Placental galectin-1 and 3 were higher in normal pregnant women, and there were statistical differences between groups (P<0.05). In ICP, the maternal serum and placental galectin-1 and 3 levels were significantly increased, both of which may play an important role in the development of ICP, which may be the initiation factor of ICP pathophysiology, a marker of ICP prediction, and a target of ICP prevention strategies.

Rational use of drugs to alleviate adverse outcomes caused by COVID-19 quarantine in women with intrahepatic cholestasis of pregnancy.

This study aimed to investigate the impacts of home quarantine on pregnancy outcomes of women with intrahepatic cholestasis of pregnancy (ICP) during the COVID-19 outbreak and whether the rational use of drugs will change these impacts. This multi-center study was conducted to compare the pregnancy outcomes in women with ICP between the home quarantine group and the non-home quarantine group in southwest China. Propensity score matching was performed to confirm the pregnancy outcomes of the medication group and the non-medication group in women with ICP during the epidemic period. A total of 3,161 women with ICP were enrolled in this study, including 816 in the home quarantine group and 2,345 in the non-home quarantine group. Women with ICP in the home quarantine group had worse pregnancy outcomes, such as a growing risk of gestational diabetes mellitus A1, fetal growth restriction, pre-eclampsia, preterm delivery, and even stillbirth. Drug therapy could alleviate some adverse pregnancy outcomes caused by home quarantine, including pre-eclampsia, preterm delivery, and meconium-stained amniotic fluid. COVID-19 quarantine would increase the incidence of ICP and lead to adverse pregnancy outcomes in women with ICP. The rational use of drugs reduced some obstetrical complications and improved partial pregnancy outcomes. Our findings suggested that the government and hospitals should enhance their management and life guidance for women with ICP and speed up developing home quarantine guidelines.

Causal association between gut microbiota and intrahepatic cholestasis of pregnancy: mendelian randomization study

BackgroundPrevious observational cohort studies have shown that the composition of the gut microbiota is related to the risk of intrahepatic cholestasis of pregnancy (ICP), although it is unclear if the association is causative. This study used Mendelian randomization (MR) to systematically examine whether the gut microbiota was causally linked to ICP.MethodsWe obtained the genome-wide association study (GWAS) summary statistics of gut microbiota and ICP from published GWASs. Maximum likelihood (ML), MR-Egger regression, weighted median, inverse variance weighted (IVW), and weighted model were used to investigate the causal association between gut microbiota and ICP. We further conducted a series of sensitivity analyses to confirm the robustness of the primary results of the MR analyses. Reverse MR analysis was performed on the bacterial taxa that were reported to be causally linked to ICP risk in forwarding MR analysis to evaluate the possibility of reverse causation.ResultsMR analysis revealed that phylum Tenericutes (OR: 1.670, 95%CI: 1.073–2.598, P = 0.023), class Bacteroidia (OR: 1.644, 95%CI: 1.031–2.622, P = 0.037), class Mollicutes (OR: 1.670, 95%CI: 1.073–2.598, P = 0.023), and order Bacteroidales (OR: 1.644, 95%CI: 1.031–2.622, P = 0.037), and were positively associated with the risk of ICP. And we identified that the relative abundance of genus Dialister (OR: 0.562, 95%CI: 0.323–0.977, P = 0.041), genus Erysipelatoclostridium (OR: 0.695, 95%CI: 0.490–0.987, P = 0.042), genus Eubacterium (brachy group) (OR: 0.661, 95%CI: 0.497–0.880, P = 0.005), genus Eubacterium (hallii group) (OR: 0.664, 95%CI: 0.451–0.977, P = 0.037), genus Holdemania (OR: 0.590, 95%CI: 0.414–0.840, P = 0.003), genus Ruminococcus (torques group) (OR: 0.448, 95%CI: 0.235–0.854, P = 0.015), and genus Veillonella (OR: 0.513, 95%CI: 0.294–0.893, P = 0.018) were related to a lower risk of ICP. Additional sensitivity analyses confirmed the robustness of the association between specific gut microbiota composition and ICP. No evidence of reverse causality from ICP to identified bacterial taxa was found in the findings of the reverse MR analyses.ConclusionsUnder MR assumptions, our findings propose new evidence of the relationship between gut microbiota and ICP risk. Our results show that the gut microbiota may be useful target of intervention for ICP.

Staging and clinical characteristics of pregnant women with chronic hepatitis B virus infection: A retrospective cohort study from Nanjing, China.

To investigate the immune status of Chinese chronic hepatitis B (CHB) pregnant women and their clinical characteristics. About 1544 CHB pregnant women without antiviral therapy from 2013 to 2018 were selected from the hospital records. The definition of immune status is based on American Association for the Study of Liver Diseases (AASLD) 2018 Hepatitis B Guidance, and those who did not meet any criteria of the immune status were referred to in the gray zones (GZ). There were 284 patients in the immune-tolerance phase, 72 patients in the HBeAg-positive immune active phase, 553 patients in the inactive phase, 61 patients in the HBeAg-negative immune active phase. Of note, 574 (37.18%) patients did not fit into any of the above phases were defined as the GZ. Patients with elevated ALT had a higher rate of intrahepatic cholestasis of pregnancy (ICP). Mother to child HBV transmission was rare (only two cases) and occurred in mothers in the immune-tolerant phase. Our data showed that more than one-third of CHB pregnant women were classified into the GZ. In standard stages, advanced age is associated with HBeAg-negative and a higher cesarean rate in the inactive phase. The incidence of ICP was higher in immune active phases, including GB and GD. The probability of mother-to-child transmission in gray zones is low.