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.

Diagnosis and management of benign recurrent intrahepatic cholestasis and psychosocial stressors in an adolescent:A case report

BACKGROUND Benign recurrent intrahepatic cholestasis(BRIC)is a rare autosomal recessive disorder,characterized by episodes of intense pruritus,elevated serum levels of alkaline phosphatase and bilirubin,and near-normal-glutamyl transferase.These episodes may persist for weeks to months before spontaneously resolving,with patients typically remaining asymptomatic between occurrences.Diagnosis entails the evaluation of clinical symptoms and targeted genetic testing.Although BRIC is recognized as a benign genetic disorder,the triggers,particularly psychosocial factors,remain poorly understood.CASE SUMMARY An 18-year-old Chinese man presented with recurrent jaundice and pruritus after a cold,which was exacerbated by self-medication involving vitamin B and paracetamol.Clinical and laboratory evaluations revealed elevated levels of bilirubin and liver enzymes,in the absence of viral or autoimmune liver disease.Imaging excluded biliary and pancreatic abnormalities,and liver biopsy demonstrated centrilobular cholestasis,culminating in a BRIC diagnosis confirmed by the identification of a novel ATP8B1 gene mutation.Psychological assessment of the patient unveiled stress attributable to academic and familial pressures,regarded as potential triggers for BRIC.Initial relief was observed with ursodeoxycholic acid and cetirizine,followed by an adjustment of the treatment regimen in response to elevated liver enzymes.The patient's condition significantly improved following a stress-related episode,thanks to a comprehensive management approach that included psychosocial support and medical treatment.CONCLUSION Our research highlights genetic and psychosocial influences on BRIC,emphasizing integrated diagnostic and management strategies.

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.

Novel ABCB4 mutations in an infertile female with progressive familial intrahepatic cholestasis type 3:A case report

BACKGROUND Mutations that occur in the ABCB4 gene,which encodes multidrug-resistant protein 3,underlie the occurrence of progressive familial intrahepatic cholestasis type 3(PFIC3).Clinical signs of intrahepatic cholestasis due to gene mutations typically first appear during infancy or childhood.Reports of PFIC3 occurring in adults are rare.CASE SUMMARY This is a case study of a 32-year-old infertile female Chinese patient with a 15-year history of recurrent abnormal liver function.Her primary clinical signs were elevated levels of alkaline phosphatase andγ-glutamyl transpeptidase.Other possible reasons for liver dysfunction were eliminated in this patient,resulting in a diagnosis of PFIC3.The diagnosis was confirmed using gene detection and histological analyses.Assessments using genetic sequencing analysis indicated the presence of two novel heterozygous mutations in the ABCB4 gene,namely,a 2950C>T;p.A984V mutation(exon 24)and a 667A>G;p.I223V mutation(exon 7).After receiving ursodeoxycholic acid(UDCA)treatment,the patient's liver function indices improved,and she successfully became pregnant by in vitro fertilization.However,the patient developed intrahepatic cholestasis of pregnancy in the first trimester.Fortunately,treatment with UDCA was safe and effective.CONCLUSION These novel ABCB4 heterozygous mutations have a variety of clinical phenotypes.Continued follow-up is essential for a comprehensive understanding of PFIC3.

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.

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.

Role of ABCC2 common variants in intrahepatic cholestasis of pregnancy

The pathogenesis of intrahepatic cholestasis of pregnancy (ICP), a disorder that adversely affects maternal wellbeing and fetal outcome, is unclear. However, multiple factors probably interact along with a genetic predisposition. We would like to add some comments on a paper recently published concerning the role of ABCB11 and ABCC2 polymorphisms in both ICP and contraceptive-induced cholestasis, especially in the light of our recently published findings about a positive association between ICP and ABCC2 common variants.

Placental expressions of estrogen receptor α,estrogen receptor β in intrahepatic cholestasis of pregnancy

To investigate the association of the expression of estrogen receptor ct, estrogen receptor 13 in placenta with intrahepatic cholestasis of pregnancy （ICP） susceptibility. Methods： In 14 cases of mild ICP, 14 cases of severe ICP and 14 cases of normal cases （control group） with corresponding age and gestation weeks, the expressions of ERa and ERD were detected by means of immunohistochemical method S-P. Results： The mean grey numbers of ERa in each group mentioned above were 151.684±3.76, 149.854±3.69, 153.184±3.18, without significant difference （P〉0.05） The mean grey numbers of ERβ in each group mentioned above were 146.51±3.81, 139.434±9.97, 149.87±4.17, with significant difference （P〉0.05）; the expression of ERI3 of severe ICP group was significantly higher than that of the mild ICP group and the control group （P〈0.05）. The expression of ERβ in every group was higher than that of ERa （P〈0.05）. Conclusion： ERβ maybe play an important part in the etiology and development 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.

Effect of the maternal-fetal interface immunoregulation on the occurrence of intrahepatic cholestasis of pregnancy

Maternal immune tolerance of the fetus is indispensable for a healthy pregnancy. Currently, the study of the immune microenvironment of the maternal-fetal interface has been a heated topic in reproductive immunology research. More and more studies show that the immune imbalance in the maternal-fetal interface plays a very important role in the incidence of intrahepatic cholestasis of pregnancy(ICP). However, the precise etiology and mechanism of immune imbalance in the occurrence of ICP is still unknown. In order to clarify the potential immunologic mechanisms of ICP, this review summarizes the recent studies of the decidual immunology microenvironment and the potential immunologic mechanisms related to the development of 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.

Analysis on Therapeutic Effect of Western and Chinese Drug in Treating Intrahepatic Cholestasis of Pregnancy

Objective: To evaluate the therapeutic effect of Yinchenghao decoction (YCHD, 茵陈蒿汤) and S-adenosy-L-methionine (SAM) in treating intra-hepatic cholestasis of pregnancy (TCP) and improving prognosis of perinatal newborn babies. Methods: Sixty in-patients of TCP were randomly divided into two groups, the group A treated with YCHD and the group B treated with SAM. The symptom of itching and serum biochemical indexes, including glycocholic acid, bilirubin and transaminase, were observed after 3 weeks treat-ment, and the prognosis of perinatal newborn babies between the two groups was compared after delivery. Results: After treatment, the symptom of itching, serum levels of glycocholic acid, bilirubin and transaminase improved significantly (P< 0.05) in both groups, and the prognosis of newborn in the two groups was similar (P>0. 05). Conclusion: Both YCHD and SAM could effectively treat ICP. The former is rather cheaper, so it is more feasible for spreading.Original article on CJITWM (Chin) 2004 ;24(4): 309

Review of a challenging clinical issue:Intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy(ICP) is a reversible pregnancy-specific cholestatic condition characterized by pruritus, elevated liver enzymes, and increased serum bile acids. It commences usually in the late second or third trimester, and quickly resolves after delivery. The incidence is higher in South American and Scandinavian countries(9.2%-15.6% and 1.5%, respectively) than in Europe(0.1%-0.2%). The etiology is multifactorial where genetic, endocrine, and environmental factors interact. Maternal outcome is usually benign, whereas fetal complications such as preterm labor, meconium staining, fetal distress, and sudden intrauterine fetal demise not infrequently lead to considerable perinatal morbidity and mortality. Ursodeoxycholic acid is shown to be the most efficient therapeutic agent with proven safety and efficacy. Management of ICP consists of careful monitoring of maternal hepatic function tests and serum bile acid levels in addition to the assessment of fetal well-being and timely delivery after completion of fetal pulmonary maturity. This review focuses on the current concepts about ICP based on recent literature data and presents an update regarding the diagnosis and management of this challenging issue.

Predictors of premature delivery in patients with intrahepatic cholestasis of pregnancy

AIM： To evaluate the predictive value of clinical symptoms and biochemical parameters for prematurity in intrahepatic cholestasis of pregnancy （ICP）. METHODS： Sixty symptomatic patients with ICP were included in this retrospective analysis. Preterm delivery was defined as delivery before 37 wk gestation. Predictors of preterm delivery were disclosed by binary multivariate logistic regression analysis. RESULTS： Mean time of delivery was 38.1 ± 1.7 wk. No stillbirths occurred. Premature delivery was observed in eight （13.3%） patients. Total fasting serum bile acids were higher （47.8 ±15.2 vs 41.0 ± 10.0 μmol/L, P 〈 0.05）, and pruritus tended to start earlier （29.0 ± 3.9 vs 31.6 ± 3.3 wk, P = 0.057） in patients with premature delivery when compared to those with term delivery. Binary multivariate logistic regression analysis revealed that early onset of pruritus （OR 1.70, 95% CI 1.23-2.95, P = 0.038） and serum bile acid （OR 2.13, 95% CI 1.13-3.25, P = 0.013） were independent predictors of preterm delivery. CONCLUSION： Early onset of pruritus and high levels of serum bile acids predict preterm delivery in ICP, and define a subgroup of patients at risk for poor neonatal outcome.

Ductopenia and cirrhosis in a 32-year-old woman with progressive familial intrahepatic cholestasis type 3: A case report and review of the literature

Progressive familial intrahepatic cholestasis type 3 is caused by a mutation in the ATP-binding cassette, subfamily B, member 4 (ABCB4) gene encoding multidrug resistance protein 3. A 32-year-old woman with a history of acute hepatitis at age 9 years was found to have jaundice during pregnancy in 2008, and was diagnosed as having intrahepatic cholestasis of pregnancy. In 2009, she underwent cholecystectomy for gallstones and chronic cholecystitis. However, itching and jaundice did not resolve postoperatively. She was admitted to our hospital with fatigue, jaundice, and a recently elevated γ-glutamyl transpeptidase level. Liver biopsy led to the diagnosis of biliary cirrhosis with ductopenia. Genetic testing revealed a pathogenic heterozygous mutation, ex13 c.1531G > A (p.A511 T), in the ABCB4 gene. Her father did not carry the mutation, but her mother's brother carried the heterozygous mutation. We made a definitivediagnosis of familial intrahepatic cholestasis type 3. He symptoms and liver function improved after 3 mo o treatment with ursodeoxycholic acid.

New tight junction protein 2 variant causing progressive familial intrahepatic cholestasis type 4 in adults: A case report

BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)encompasses a group of autosomal recessive disorders with high morbidity and mortality.Variants in the gene encoding tight junction protein-2(TJP2)have been linked to PFIC type 4(PFIC4),which predominantly presents in childhood.However,there are only limited data from adults with TJP2-related PFIC4.We report a family with an autosomal recessive disorder with a novel variant in the TJP2 gene in adults with very variable expression of PFIC4.CASE SUMMARY The index patient presented at 19 years old with liver cirrhosis and variceal bleeding and was treated with endoscopic banding and beta-blockers.In 2018,he developed primary liver cancer that was treated with radiofrequency ablation followed by liver transplantation in 2019.Genetic testing revealed a novel homozygous TJP2 variant causing PFIC4(TJP2([NM_004817.3]:c.[3334C>T];[3334C>T])).The consanguineous family consists of the father and mother(both heterozygous)and their 12 children,of which five carry the variant in a homozygous state;however,these five siblings have highly variable expression of PFIC4.Two homozygous brothers had cirrhosis and portal hypertension at diagnosis at the ages of 19 and 36.Two other homozygous brothers,age 23 and 19,and the homozygous sister,age 21,have elevated liver enzymes but presently no cirrhosis,which may suggest an age-dependent penetrance.In addition,five sisters had severe and mild intrahepatic cholestasis of pregnancy and carry the TJP2 variant in a homozygous and heterozygous state,respectively.CONCLUSION This novel TJP2 variant is associated with PFIC4 causing severe liver disease with cirrhosis and primary liver cancer in adolescents/adults.

Liver transplantation and the management of progressive familial intrahepatic cholestasis in children

Progressive familial intrahepatic cholestasis(PFIC) is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children. The accumulation of bile results in progressive liver damage, and if left untreated leads to end stage liver disease and death. Patients often present with worsening jaundice and pruritis within the first few years of life. Many of these patients will progress to end stage liver disease and require liver transplantation. The role and timing of liver transplantation still remains debated especially in the management of PFIC1. In those patients who are appropriately selected, liver transplantation offers an excellent survival benefit. Appropriate timing and selection of patients for liver transplantation will be discussed, and the short and long term management of patients post liver transplantation will also be described.

Segmental intrahepatic cholestasis as a technical complication of the transjugular intrahepatic porto-systemic shunt

BACKGROUND Segmental intrahepatic cholestasis caused by transjugular intrahepatic portosystemic shunt(TIPS)(SIC-T),is a rare complication of this technique and only referred by case reports.Thus,we conducted a systematic,retrospective analysis to provide evidence regarding prevalence and consequences of this TIPS-induced bile duct compression.AIM To assess prevalence and outcome of SIC-T in a large TIPS-cohort.METHODS In this retrospective cohort study,we screened the institutional databases for all consecutive patients that were treated by TIPS-placement or TIPS-revision between January 2005 and August 2013.We analyzed radiologic images for signs of biliary congestion.Cases that were indicative of SIC-T were reviewed by two independent radiologists and additional patient data was collected.Descriptive statistics of patient demographics,indications for TIPS and procedural details were registered.Logistic regression analysis was performed to identify predictors for the development of SIC-T.RESULTS We analyzed 135 cirrhotic patients who underwent TIPS(mean age 55 years,79%male gender).Etiology of cirrhosis was alcohol in most cases and indications for TIPS were mainly refractory ascites and recurrent variceal bleeding.TIPS revision was necessary in 31 patients.We identified 4 cases(2.9%)of SIC-T in direct proximity of the TIPS-stent.Diagnosis was confirmed by CT-scan,MRI or endoscopic retrograde cholangio pancreaticography(ERCP).In two patients TIPS was implanted via the right and in one through the medial hepatic vein.One patient received TIPS-prolongation by multiple revisions.Most patients were asymptomatic but one cholangitic abscess necessitated a transhepatic drain.Logistic regression analysis identified TIPS-placement other than from medial hepatic vein to right portal vein as risk factor(OR 21.0)for SIC-T.CONCLUSION SIC-T ads to(mostly late)complications in the interventional treatment of cirrhotic portal hypertensions and can lead to cholangitic abscesses.Patients,particularly with multiple interventions,should be screened for SIC-T.

Intrahepatic cholestasis after liver transplantation

Intrahepatic cholestasis occurs commonly after liver transplantation and may be caused by infections, drugs, and acute or chronic rejection. Some disor- ders may be managed medically, but others often re- quire re-transplantation. Prompt recognition and specific treatment can improve the outcome of liver recipients.

Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump

AIM： To study the association of three common ABCB11 and ABCC2 polymorphisms （ABCB11： 1331T〉C→V444A; ABCC2： 3563T〉A → V1188E and 4544G 〉A → C1515Y） with intrahepatic cholestasis of pregnancy （ICP） and contraceptive-induced cholestasis （CIC）. METHODS： ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS： The ABCB11 1331T〉C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls： C allele 76.2% （CI, 58.0-94.4） vs 51.3% （CI 35.8-66.7）, respectively （P = 0.0007）; and CC allele 57.1% （CI 36.0-78.3） vs 20% （CI 7.6-32.4）, respectively （P = 0.0065）. All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION： Our data support a role for the ABCB11 1331T〉C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and 7-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.