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.

Extrahepatic cholestasis associated with paracoccidioidomycosis:Challenges in the differential diagnosis of biliopancreatic neoplasia

BACKGROUND Paracoccidioidomycosis(PCM)may involve the hepatic pedicle and peripan creatic lymph nodes,cause damage to the bile duct and manifest,exceptionally,in combination with extrahepatic cholestasis(EHC),making investigation and treatment challenging.AIM To investigate the management of patients with visceral PCM admitted with EHC.METHODS All patients diagnosed with PCM treated in a public,tertiary teaching hospital between 1982 and 2020 were retrospectively evaluated.Those also identified with EHC were allocated to two groups according to the treatment approach for the purpose of comparing clinical,laboratory,and imaging findings,resources used for etiological diagnosis,treatment results,and prognosis.Statistical analyses were performed using the linear mixed-effects model(random and fixed effects),which was adjusted using the PROC MIXED procedure of the SAS®9.0 software,and Fisher’s exact test.RESULTS Of 1645 patients diagnosed with PCM,40(2.4%)had EHC.Of these,20(50.0%)lived in the rural area and 29(72.5%)were men,with a mean age of 27.1 years(3-65 years).Jaundice as first symptom and weight loss of at least 10 kg were observed in 16 patients(40.0%),and a mass in the head of the pancreas was observed in 8(20.0%).The etiological diagnosis was made by tissue collection during surgery in 4 cases(10.0%)and by endoscopic methods in 3 cases(7.5%).Twenty-seven patients(67.5%)received drug treatment alone(Group 1),whereas 13(32.5%)underwent endoscopic and/or surgical procedures in combination with drug treatment(Group 2).EHC was significantly reduced in both groups(40.7% in Group 1,with a mean time of 3 months;and 38.4% in Group 2,with a mean time of 7.5 months),with no statistically significant difference between them.EHC recurrence rates,associated mainly with treatment nonadherence,were similar in both groups:37% in Group 1 and 15.4% in Group 2.The mortality rate was 18.5% in Group 1 and 23% in Group 2,with survival estimates of 71.3% and 72.5%,respectively,with no statistically significant difference.CONCLUSION Although PCM-related EHC is rare,it needs to be included in the differential diagnosis of malignancies,as timely treatment can prevent hepatic and extrahepatic sequelae.

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.

罕见抗-Di^(b)致严重胎儿新生儿溶血病的实验室检测与相关研究

目的对1例高频抗体导致的胎儿新生儿溶血病(hemolytic disease of the fetus and newborn,HDFN)进行检测、鉴定及配血。方法对患儿进行新生儿溶血试验,对母亲进行血清学意外抗体鉴定,并对母亲红细胞进行常见高频抗原鉴定;对检出抗体进行IgG分型检测,并用流式细胞术进行单核细胞体外吞噬致敏红细胞试验,以检测抗体相关的吞噬率;对患儿母亲、父亲及舅舅进行相关红细胞血型基因测序;利用稀释的母亲血浆和抗人球卡法,在献血者中进行大规模相合血液的筛选。结果产妇鉴定为Di(b-)稀有血型,产生了抗-Di b(效价512)并导致了严重的HDFN;抗-Di b亚型分型为IgG1和IgG2型,单核细胞体外吞噬效率为88.83%(74.7/84.09);产妇亲属中没有相合献血者,后续从5520名献血者中筛选到2例Di(b-)相合血液,患儿接收输血治疗后康复出院。后续在51334名献血者中筛查到17名Di(b-)献血者,该数据表明Di(b-)在广州地区献血者中的分布频率约为三千分之一(0.033%,17/51334)。结论综合利用血型血清学及分子生物学方法诊断了抗-Di b所致的严重HDFN,建立了1种有效大规模筛查Di(b-)稀有血型的方法并找到相合血液,为建立Di(b-)稀有血型库奠定了基础。

4DI110型空压机的技术改造与操作优化

文章通过介绍新引进的4DI110型离心式空压机(以下简称“空压机”)试运行阶段开始以来的运行情况和气温变化对空压机出口流量造成的影响,分析空压机出口流量随气温变化而变化的规律,指出空压机防喘阀V3004阀不能自动调节出口压力,影响空分装置工况的稳定。为实现空压机出口压力的稳定,对其防喘阀V3004阀采取增设自动旁路阀V3008阀的技术改造,同时优化和完善相关逻辑控制并阐述了空压机经技术改造后的操作优化和取得的实际效果。

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.

Different regional distribution of SLC25A13 mutations in Chinese patients with neonatal intrahepatic cholestasis

AIM: To investigate the differences in the mutation spectra of the SLC25A13 gene mutations from specific regions of China. METHODS: Genetic analyses of SLC25A13 mutations were performed in 535 patients with neonatal intrahepatic cholestasis from our center over eight years. Unrelated infants with at least one mutant allele were enrolled to calculate the proportion of SLC25A13 mutations in different regions of China. The boundary between northern and southern China was drawn at the historical border of the Yangtze River.RESULTS: A total of 63 unrelated patients (about 11% of cases with intrahepatic cholestasis) from 16 provinces or municipalities in China had mutations in the SLC25A13 gene, of these 16 (25%) were homozygotes, 28 (44%) were compound heterozygotes and 19 (30%) were heterozygotes. In addition to four well described common mutations (c.851_854del, c.1638_1660dup23, c.615+5G>A and c.1750+72_17514dup17insNM_138459.3:2667 also known as IVS16ins3kb), 13 other mutation types were identified, including three novel mutations: c.985_986insT, c.287T>C and c.1349A>G. According to the geographical division criteria, 60 mutant alleles were identified in patients from the southern areas of China, 43 alleles were identified in patients from the border, and 4 alleles were identified in patients from the northern areas of China. The proportion of four common mutations was higher in south region (56/60, 93%) than that in the border region (34/43, 79%, χ 2 = 4.621, P = 0.032) and the northern region (2/4, 50%, χ 2 = 8.288, P = 0.041). CONCLUSION: The SLC25A13 mutation spectra among the three regions of China were different, providing a basis for the improvement of diagnostic strategies and interpretation of genetic diagnosis.

Computed tomography findings for predicting severe acute hepatitis with prolonged cholestasis

AIM: To evaluate the significance of computed tomography (CT) findings in relation to liver chemistry and the clinical course of acute hepatitis. METHODS: Four hundred and twelve patients with acute hepatitis who underwent enhanced CT scanning were enrolled retrospectively. Imaging findings were analyzed for the following variables: gallbladder wall thickness (GWT), arterial heterogeneity, periportal tracking, number and maximum size of lymph nodes, presence of ascites, and size of spleen. The serum levels of alanine aminotransferase, alkaline phosphatase, bilirubin, albumin, and prothrombin time were measured on the day of admission and CT scan, and laboratory data were evaluated every 2-4 d for all subjects during hospitalization. RESULTS: The mean age of patients was 34.4 years, and the most common cause of hepatitis was hepatitis A virus (77.4%). The mean GWT was 5.2 mm. The number of patients who had findings of arterial heterogeneity, periportal tracking, lymph node enlargement > 7 mm, and ascites was 294 (80.1%), 348 (84.7%), 346 (84.5%), and 56 (13.6%), respectively. On multivariate logistic regression, male gender [odds ratio (OR) = 2.569, 95%CI: 1.477-4.469, P = 0.001], toxic hepatitis (OR = 3.531, 95%CI: 1.444-8.635, P = 0.006), level of albumin (OR = 2.154, 95%CI: 1.279-3.629, P = 0.004), and GWT (OR = 1.061, 95%CI: 1.015-1.110, P = 0.009) were independent predictive factors for severe hepatitis. The level of bilirubin (OR = 1.628, 95%CI: 1.331-1.991, P < 0.001) and GWT (OR = 1.172, 95%CI: 1.024-1.342,P = 0.021) were independent factors for prolonged cholestasis in multivariate analysis. CONCLUSION: In patients with acute hepatitis, GWT on CT scan was an independent predictor of severe hepatitis and prolonged cholestasis.

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.

Pharmacokinetic Characteristics of Baicalin in Rats with 17α-ethynylestradiol-induced Intrahepatic Cholestasis

Baicalin is one of the main active ingredients of choleretic traditional Chinese medicine drug Radix Scutellariae.The aim of this study was to explore the pharmacokinetic characteristics of baicalin in rats with 17α-ethynylestradiol（EE）-induced intrahepatic cholestasis（IC） based on its choleretic effects.Firstly,rats were subcutaneously injected with EE solution（5 mg/kg,0.25 m L/100 g） for 5 consecutive days to construct an IC model.Then the bile excretion rate,serum levels of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,alkaline phosphatase（ALP） and total bile acid（TBA） and pathological changes of the liver were detected.Secondly,after successfully modeling,the rats were intragastrically given baicalin solution（200 mg/kg）（n=6）.Blood samples were collected from the tail vein at different time points after intragastric administration.The protective effects of low-（50 mg/kg）,medium-（100 mg/kg） and high-dose（200 mg/kg） baicalin on the liver in IC rats were evaluated.The content of baicalin in plasma was detected by liquid chromatography-mass spectrometry/mass spectrometry and pharmacokinetics parameters were calculated.Pharmacodynamic results showed that low-,medium-and high-dose baicalin all significantly increased the average excretion rate of bile（P〈0.05）,and significantly decreased serum levels of ALT,AST and ALP and TBA（P〈0.05）.Meanwhile,HE staining showed that baicalin significantly relieved EEinduced hepatocyte edema and necrosis.Pharmacokinetic results exhibited that the absorption of baicalin in both IC and normal control rats showed bimodal phenomenon.Cmax,AUC（0-t） and AUC（0-∞） of baicalin in IC rats were significantly higher than those of the normal control group（P〈0.01）.T1/2 of plasma baicalin in the model group was significantly extended to（11.09±1.84） h,with clearance dropping to 61.78% of that of the normal control group（P〈0.01）.The above results suggested that baicalin had protective effects on the liver of IC rats,accompanied by significantly increased in vivo exposure,delayed in vivo clearance and markedly alterative pharmacokinetic characteristics.This study provides a theoretical basis for further development of baicalin as a feasible drug for treating IC.Key words

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.

Clinical Assessment of Differential Diagnostic Methods in Infants with Cholestasis due to Biliary Atresia or Non-Biliary Atresia

The different methods in differentiating biliary atresia(BA)from non-BA-related cholestasis were evaluated in order to provide a practical basis for a rapid,early and accurate differential diagnosis of the diseases.396 infants with cholestatic jaundice were studied prospectively during the period of May 2007 to June 2011.The liver function in all subjects was tested.All cases underwent abdominal ultrasonography and duodenal fluid examination.Most cases were subjected to hepatobiliary scintigraphy,magnetic resonance cholangiopancreatography(MRCP)and a percutaneous liver biopsy.The diagnosis of BA was finally made by cholangiography or histopathologic examination.The accuracy,sensitivity,specificity and predictive values of these various methods were compared.178 patients(108 males and 70 females with a mean age of 58±30 days)were diagnosed as having BA.218 patients(136 males and 82 females with a mean age of 61±24 days)were diagnosed as having non-BA etiologies of cholestasis jaundice during the follow-up period in which jaundice faded after treatment with medical therapy.For diagnosis of BA,clinical evaluation,hepatomegaly,stool color,serum gamma-glutamyltranspeptidase(GGT),duodenal juice color,bile acid in duodenal juice,ultrasonography(gallbladder),ultrasonography(griangular cord or strip-apparent hyperechoic foci),hepatobiliary scintigraphy,MRCP,liver biopsy had an accuracy of 76.0%,51.8%,84.3%,70.0%,92.4%,98.0%,90.4%,67.2%,85.3%,83.2%and 96.6%,a sensitivity of 83.1%,87.6%,96.1%,73.7%,90.4%,100%,92.7%,27.5%,100%,89.0%and 97.4%,a specificity of 70.2%,77.5%,74.8%,67.0%,94.0%,96.3%,88.5%,99.5%,73.3%,75.4%and 94.3%,a positive predictive value of 69.0%,72.6%,75.7%,64.6%,92.5%,95.7%,86.8%,98.0%,75.4%,82.6%and 98.0%,and a negative predictive value of 83.6%,8.5%,95.9%,75.7%,92.3%,100%,84.2%,93.7%,100%,84.0%and 92.6%,respectively.It was concluded that all the differential diagnosis methods are useful.The test for duodenal drainage and elements is fast and accurate.It is helpful in the differential diagnosis of BA and non-BA etiologies of cholestasis.It shows good practical value clinically.

pregnane X receptor and constitutive androstane receptor modulate differently CYp3A-mediated metabolism in earlyand late-stage cholestasis

AIM To ascertain whether cholestasis affects the expression of two CYP3 A isoforms(CYP3 A1 and CYP3 A2) and of pregnane X receptor(PXR) and constitutive androstane receptor(CAR).METHODS Cholestasis was induced by bile duct ligation in 16 male Wistar rats; whereas 8 sham-operated rats were used as controls. Severity of cholestasis was assessed on histological examination of liver sections, and serum concentrations of albumin, AST, ALT, GGT, ALPK and bilirubin. Gene and protein expressions of PXR, CAR, CYP3 A1 and CYP3 A2 were assessed by means of q RT-PCR and Western blot, respectively. Alterations in CYP3 A activity were measured by calculating the kinetic parameters of 4-OH and 1'-OH-midazolam hydroxylation, marker reactions for CYP3 A enzymes.RESULTS The m RNA and protein expression of CYP3 A1 increased significantly in mild cholestasis(P < 0.01). At variance, m RNA and protein expression of CYP3 A2 didn't change in mild cholestasis, whereas the expression and activity of both CYP3 A1 and CYP3 A2 decreased dramatically when cholestasis became severe. Consistently with these observations, the nuclear expression of both PXR and CAR, which was measured because they both translocate into the cell nucleus after their activation, virtually disappeared in the late stage of cholestatic injury, after an initial increase. These results indicate that early-and late-stage cholestasis affects CYP3 Amediated drug metabolism differently, probably as consequence of the different activation of PXR and CAR.CONCLUSION Early-and late-stage cholestasis affects CYP3 Amediated drug metabolism differently. PXR and CAR might be targeted therapeutically to promote CYP3 Amediated liver detoxification.

High prevalence of cholestasis, with increased conjugated bile acids in inflammatory bowel diseases patients

AIM To investigate the prevalence and causes of cholestasis in patients with inflammatory bowel diseases in the Swiss Inflammatory Bowel Diseases Cohort. METHODS A retrospective cohort study was performed of all the patients in the Swiss Inflammatory bowel disease Cohort. Total bile acid was measured for all patients and cholestasis was defined as a concentration > 8 μmol/L. The characteristics of patients with or without cholestasis were compared. Bile acid profiles were then determined for 80 patients with high total bile acid and 80 matched patients with low total bile acid. Bile acid profiles were compared for smokers vs nonsmokers, ileal vs colonic disease, and inflammatory vs non inflammatory diseases.RESULTS Ninety-six patients had more than 8 μmol/L total bile acid, giving a prevalence of 7.15%. Patients with an obvious cause of cholestasis, such as primary sclerosing cholangitis, were then excluded, leaving 1190 participants with total bile acid < 8 μmol/L and 80 with total bile acid > 8 μmol/L. In multivariate analysis, calcium supplementation was significantly associated with cholestasis(odds ratio, 2.36, 95%CI: 1.00-5.21, P = 0.040) whereas current smoking significantly reduced the risk of cholestasis(odds ratio, 0.42, 95%CI: 0.17-0.91, P = 0.041). Levels of all conjugated bile acids were higher in the cholestasis group than in the control group. When we compared patients with ileal vs colonic disease, the former had higher levels of primary, secondary, and tertiary bile acids whereas patients with colonic disease had higher levels of conjugated bile acids.CONCLUSION Prevalence of cholestasis is high. Smoking appears to reduce cholestasis. Conjugated bile acids are higher in cholestasis and in colonic disease whereas unconjugated in ileal disease.

Severe cholestasis due to adalimumab in a Crohn's disease patient

Elevation of liver biochemistry has been reported with anti-tumor necrosis factor agents, but overt liver failure rarely reported. Autoimmune hepatitis has been more commonly reported with infliximab than adalimumab(ADA). Our case, however, describes the first reported case of ADA-associated severe cholestatic injury. A 39-year-old female with Crohn's disease developed severe jaundice after initiation of ADA. All serologic tests and imaging studies were normal. Liver biopsy showed prominent pericentral canalicular cholestasis,without features of steatosis or sclerosing cholangitis,consistent with drug-induced cholestasis. The serum total bilirubin peaked at 280 μmol/L, and improvement was seen after 5 wk with eventual normalization of liver enzymes at 10 wk. Our case describes the first reported case of ADA-associated severe cholestatic liver disease and the first histopathologic examination of this adverse drug effect. Clinicians need to be aware of this potential drug-induced liver injury when prescribing this commonly used biologic medication.

Multidrug resistance protein 3 R652G may reduce susceptibility to idiopathic infant cholestasis

AIM:To evaluate the role of genetic factors in the pathogenesis of idiopathic infant cholestasis.METHODS:We performed a case-control study,in-cluding 78 infants with idiopathic infant cholestasis and 113 healthy infants as controls.Genomic DNA was extracted from peripheral venous blood leukocytes us-ing phenol chloroform methodology.Polymerase chain reaction was used to amplify the multidrug resistance protein 3(MDR3)R652G fragment,and products were sequenced using the ABI 3100 Sequencer.RESULTS:The R652G single nucleotide polymorphism(SNP)was significantly more frequent in healthy infants(allele frequency 8.0%)than in patients(allele frequency 2.60%)(P < 0.05),odds ratio,0.29;95% confidence interval,0.12-0.84.The conjugated bilirubin in patients with the AG genotype was significantly lower than in those with the AA genotype(44.70 ± 6.15 μmol/L vs 95.52 ± 5.93 μmol/L,P < 0.05).CONCLUSION:MDR3 R652G is negatively correlated with idiopathic infant cholestasis.Children with the R652G SNP in Guangxi of China may have reduced susceptibility to infant intrahepatic cholestasis.

Increased syndecan-1 and glypican-3 predict poor perinatal outcome and treatment resistance in intrahepatic cholestasis

Background:Intrahepatic cholestasis of pregnancy(ICP)increases the risk of adverse pregnancy outcomes.This study aimed to explore the association between serum syndecan-1 and glypican-3 levels and the adverse perinatal outcome as well as the responses to the treatment of ursodeoxycholic acid(UDCA).Methods:This prospective,case control study included 88 pregnant women(44 women with ICP and 44 healthy controls).The primary end points were the perinatal outcome and the response to UDCA therapy.A logistic regression model was used to identify the independent risk factors of adverse pregnancy outcomes and reduced response to UDCA therapy.Results:Women with ICP had significantly higher serum syndecan-1(1.27±0.36 ng/m L vs.0.98±0.50 ng/m L;P=0.003),glypican-3(1.78±0.13 ng/m L vs.1.69±0.16 ng/m L;P=0.004),AST(128.59±1.44 vs.13.29±1.32 U/L;P<0.001),and ALT(129.84±1.53 vs.8.00±3.67 U/L;P<0.001)levels compared with the controls.The increased levels of syndecan-1(OR=4.715,95%CI:1.554–14.310;P=0.006),glypican-3(OR=8.465,95%CI:3.372–21.248;P=0.007),ALT(OR=1.382,95%CI:1.131–1.690;P=0.002),and postprandial bile acid(PBA)(OR=3.392,95%CI:1.003–12.869;P=0.026)were correlated to ICP.The adverse neonatal outcome was related to increased glypican-3(OR=4.275,95%CI:2.726–5.635;P=0.039),and PBA(OR=3.026,95%CI:1.069–13.569;P=0.037).Increases of syndecan-1(OR=7.464,95%CI:2.130–26.153,P=0.017)and glypican-3(OR=6.194,95%CI:2.951–13.002;P=0.025)were the risk factors of decreased response to UDCA treatment.Conclusion:Syndecan-1 and glypican-3 might be powerful determinants in predicting adverse perinatal outcome in patients with ICP,and they can be used to predict the response to the UDCA treatment.

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.

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.

借助DIS实验突破教学难点——以“磁场对通电导线的作用力”为例

教材中直接得出安培力的公式,该知识点难度较大,传统实验现象不够明显且只能定性探究,学生无法真正理解该物理规律和公式。传统实验加DIS实验可对物理规律进行定性和定量的探究,有利于学生物理学科核心素养的培养。