ABSTRACT
Children with infantile cholestatic liver disease are often accompanied by malnutrition, which in turn can affect its progression and prognosis. There are many factors causing malnutrition and various methods for malnutrition assessment, but there is still a lack of uniform standard for nutritional assessment in patients with liver diseases, and a variety of indicators and methods are required for comprehensive analysis and assessment. This article analyzes the common causes of malnutrition in children with cholestatic liver disease, introduces the different methods for nutritional assessment, including anthropometric measurements, laboratory examination, and nutritional assessment tools, and elaborates on nutritional intervention treatment, so as to improve the understanding of nutritional problems in children with cholestatic liver disease. Early identification and rational interventions can help to improve the quality of life and prognosis of children.
ABSTRACT
Objective To investigate the clinical and pathological features of progressive familial intrahepatic cholestasis type 3 (PFIC3). Methods A retrospective analysis was performed for 1326 patients with unexplained liver disease who attended Nanjing Second Hospital from January 2017 to December 2019, among whom 8 patients were diagnosed with PFIC3 based on clinical/pathological manifestation and gene sequencing results (1 patient did not undergo liver biopsy due to contraindication). Clinical, laboratory, imaging, and pathological findings were analyzed and a literature review was performed for the pathology of ABCB4-related diseases to summarize the clinical and pathological features of PFIC-3. Results Among the 8 patients with PFIC3, there were 5 male patients and 3 female patients, with a median age of 29.5 years. Of all 8 patients, 4 (50%) manifested as chronic cholestasis and 4 (50%) manifested as biliary cirrhosis, among whom 3 (75%) had the manifestation of portal hypertension. As for biochemical examination, 75% (6/8) had an increase in alkaline phosphatase, and 100% (8/8) had an increase in gamma-glutamyl transpeptidase. As for imaging examination, 50% (4/8) had cholecystitis, 25% (2/8) had gallstones, 25% (2/8) had bile duct dilatation, 75% (6/8) had splenomegaly, and 25% (2/8) had liver cirrhosis. As for liver biopsy, all 7 patients manifested as bile duct injury and/or reduction, and 57.1% (5/7) had absence of the bile duct. Multidrug resistance P-glycoprotein 3 (MDR3) immunohistochemical staining showed normal expression in 42.9% (3/7) of the patients and reduced expression in 57.1% (4/7) of the patients. Literature review obtained 17 articles with a description of the bile duct or MDR3 immunohistochemistry. Among the 7 patients with low phospholipid-associated cholelithiasis, 71.4% (5/7) had normal bile duct, 14.3% (1/7) had bile duct reduction, and 14.3% (1/7) had absence of the bile duct; among the 6 patients with intrahepatic cholestasis of pregnancy, 16.7% (1/6) had normal bile duct, 50% (3/6) had bile duct reduction, and 33.3% (2/6) had absence of the bile duct; among the 8 patients with PFIC3, 25% (2/8) had bile duct reduction and 75% (6/8) had absence of bile duct; among the 21 patients with PFIC3, 9.5% (2/21) had normal expression of MDR3, 23.8% (5/21) had a reduction in the expression of MDR3, and 66.7% (14/21) had absence of the expression of MDR3. Conclusion PFIC3 mainly manifests as cholestasis, cholelithiasis, and hepatic fibrosis. Pathological manifestation includes bile duct injury and bile duct reduction or absence of the bile duct in severe cases, and the degree of injury is associated with disease severity. MDR3 immunohistochemistry may show normal expression, reduced expression, or absence of expression, and diagnosis cannot be excluded in patients with normal expression. Genetic testing can be performed for diagnosis when necessary.
ABSTRACT
Objective To investigate the influence of intrahepatic cholestasis of pregnancy (ICP) on adverse pregnancy outcomes of hepatitis B virus (HBV)-infected pregnant women. Methods A retrospective analysis was performed for 232 pregnant women with chronic HBV infection who were admitted to Beijing YouAn Hospital, Capital Medical University, from March 2018 to March 2021. According to the presence or absence of ICP, the patients were divided into HBV infection group with 100 patients and HBV+ICP group with 132 patients; according to the severity of ICP, the patients in the HBV+ICP group were further divided into HBV+mild ICP group with 86 patients and HBV+severe ICP group with 46 patients. The above groups were compared in terms of the incidence rates of maternal complications during pregnancy, such as premature delivery, premature rupture of membranes, gestational diabetes mellitus, hypertensive disorder complicating pregnancy, and postpartum hemorrhage (PPH), as well as the adverse outcomes of fetus/neonate, such as intrauterine fetal death, neonatal asphyxia, amniotic fluid pollution degree Ⅲ(AFⅢ), neonatal respiratory distress syndrome, small-for-gestational-age (SGA), admission to the neonatal intensive care unit, pneumonia, and mother-to-child transmission (MTCT) of HBV. A one-way analysis of variance was used for comparison between multiple groups; the chi-square test, the chi-square test with continuity correction or the Fisher's exact test was used for comparison of categorical data between multiple groups. Results Compared with the HBV infection group in terms of maternal complications in late pregnancy, the HBV+ICP group had significantly higher incidence rates of premature delivery and PPH ( χ 2 =4.169 and 5.448, P =0.041 and 0.020), and in terms of the adverse outcomes of neonates, the HBV+ICP group had significantly higher incidence rates of neonatal asphyxia, AFⅢ, and SGA than the HBV infection group ( χ 2 =5.448, 16.567, and 11.053, P =0.020, P < 0.001, and P =0.002). In terms of the adverse outcomes of neonates, the HBV+severe ICP group had significantly higher incidence rates of AFⅢ and SGA than the HBV+mild ICP group ( χ 2 =4.200 and 4.511, P =0.040 and 0.034). Conclusion Compared with the pregnant women with HBV infection alone, the pregnant women with HBV infection and ICP have significantly higher incidence rates of adverse pregnancy outcomes in mothers and neonates, and the incidence rate of adverse outcomes in neonates increases with the increase in the severity of ICP. However, ICP has no influence on HBV MTCT.
ABSTRACT
ObjectiveTo investigate the clinical features and gene mutation characteristics of neonatal intrahepatic cholestasis caused citrin deficiency (NICCD) in northern China. MethodsA total of 23 pediatric patients in northern China who were diagnosed with NICCD by blood tandem mass spectrometry and/or gene detection in Department of Gastroenterology, Children’s Hospital Affiliated to Capital Institute of Pediatrics, from January 2015 to December 2018 were enrolled as NICCD group, and 36 pediatric patients with idiopathic neonatal cholestasis (INC) who had unclarified etiology after a series of examinations during the same period of time were enrolled as INC group. A retrospective analysis was performed for the clinical manifestation, laboratory examination, pathology, blood/urine metabolic screening, and gene sequencing results of the pediatric patients in the NICCD group, and follow-up was performed to observe their outcome; biochemical parameters were compared between the two groups. The independent samples t-test was used for comparison of normally distributed continuous data, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data; the chi-square test was used for comparison of categorical data between groups. ResultsAmong the 23 patients in the NICCD group, 10 had hypoglycemia, 13 had hypoalbuminemia, 17 had hyperammonemia, and 15 had hyperlactacidemia; 15 had an increase in low-density lipoprotein, 6 had an increase in cholesterol, and 7 had an increase in triglyceride; 17 had prolonged prothrombin time, and 16 had prolonged activated partial thromboplastin time (APTT). Compared with the INC group, the NICCD group had significantly higher gamma-glutamyl transpeptidase (GGT), total bile acid (TBA), and APTT and a significantly lower albumin (Alb) level (Z=-2.487, Z=-3.528, t=3.532, t=-2.24, all P＜0.05). For the patients with NICCD, blood tandem mass spectrometry showed that the most common abnormalities were the increased levels of arginine, citrulline, methionine, free carnitine, and long-chain acylcarnitine, while urinary gas chromatography showed the increased levels of 4-hydroxyphenyllactic acid, galactose, galactitol, and galactonic acid. Gene detection was performed for all 23 patients and identified 16 pathogenic mutations, among which 7 were newly discovered, namely ivs14-9a＞G, c1640 G＞A, c.762T＞A, c.736delG, c.1098 T del, c.851G＞A, and c.550G＞A. Except for the 2 patients who were lost to follow-up, the levels of aminotransferases and bilirubin gradually returned to normal in 21 patients after 2-6 months of treatment; none of them showed delayed growth and development after being followed up to the age of 1 year, and 2 of them developed dietary preference (they liked fish and meat and did not like staple food). ConclusionAbnormalities of blood GGT, TBA, Alb, and APTT may provide ideas for the differential diagnosis of NICCD and INC. NICCD gene mutations in northern China are heterogeneous and most patients tend to have a good prognosis.
ABSTRACT
Objective:To investigate the effects of dexamethasone-assisted ademetionine and ursodeoxycholic acid on pregnancy outcome and serum thyroid peroxidase antibody (TPOAb) and interleukin-12 (IL-12) expressions in patients with intrahepatic cholestasis (ICP) during pregnancy.Methods:A prospective randomized controlled study of 80 patients with ICP in Pingyang Hospital Affiliated of Wenzhou Medical University from April 2017 to April 2020 was selected. The patients were divided into the observation group and the control group using random number table, with 40 cases in each group. On the basis of conventional treatment, the control group was given ademetionine and ursodeoxycholic acid, and the observation group was given dexamethasone-assisted ademetionine and ursodeoxycholic acid. All patients were treated for 1 week. The efficacy, time of disappearance of symptoms, maternal and infant outcomes and liver function indexes aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bile acid (TBA), immune function indexes immunoglobulin M (IgM), immunoglobulin A (IgA), immunoglobulin G (IgG), serum TPOAb and IL-12 levels before and after treatment were compared between the two groups.Results:After treatment, the total effective rate in the observation group was higher than that in the control group: 95.0% (38/40) vs. 80.0%(32/40), the difference was statistically significant ( χ2 = 4.114, P<0.05). The disappearance time of jaundice and itching were shorter than those in the control group ( P<0.05). After treatment, the levels of serum AST, ALT, TBA, TPOAb, and IL-12 in the two groups were lower than before treatment, and the levels of above index in the observation group were lower than those in the control group: (57.49 ± 11.45) U/L vs. (83.70 ± 13.57) U/L, (87.61 ± 29.03) U/L vs. (126.24 ± 33.28) U/L, (13.24 ± 5.48) μmol/L vs. (21.39 ± 7.20) μmol/L, (9.18 ± 2.41) kU/L vs. (12.97 ± 2.73) kU/L, (11.37 ± 2.05) ng/L vs. (18.26 ± 2.54) ng/L; the levels of serum IgM, IgA and IgG in two groups were higher than before treatment, the levels of above index in the observation group were higher than those in the control group: (1.40 ± 0.09) g/L vs. (1.28 ± 0.11) g/L, (1.96 ± 0.14) g/L vs. (1.82 ± 0.12) g/L, (11.53 ± 2.80) g/L vs. (9.37 ± 2.59) g/L, the differences were statistically significant ( P<0.05). The incidence of cesarean section, premature delivery, postpartum hemorrhage, neonatal asphyxia, and intrauterine distress in the observation group were lower than those in the control group. Conclusions:Dexamethasone-assisted ademetionine and ursodeoxycholic acid treatment of ICP patients can improve liver function and immune function, reduce serum TPOAb and IL-12 levels, alleviate clinical symptoms and improve maternal and infant outcomes.
ABSTRACT
Intrahepatic cholestasis (IHC) is a dysfunction of bile production, secretion, and excretion caused by various factors including genetics, immunity, inflammation, stones, and tumors, and therefore, the bile is not normally discharged into the duodenum and reversely flows into blood, which causes a series of clinical diseases with organic damage, metabolic disorders, and dysfunction. In recent years, with the deepening of clinical and basic research, intestinal microecology is found to play an important role in the development and progression of liver diseases. This article reviews the mechanism of action of intestinal microecology and inflammatory factors in intrahepatic cholestasis and explores the research advances in the role of probiotics in regulating intestinal flora stability and improving intestinal microenvironment, so as to provide a basis for clinical treatment, scientific research, and drug research and development.
ABSTRACT
Benign recurrent intrahepatic cholestasis (BRIC), a rare cause of cholestasis, is characterized by recurrent episodes of cholestasis without permanent liver damage. BRIC type 2 (BRIC2) is an autosomal recessive disorder caused by ABCB11 mutations. A 6-year-old girl had recurrent episodes of jaundice. At two months of age, jaundice and hepatosplenomegaly developed. Liver function tests showed cholestatic hepatitis. A liver biopsy revealed diffuse giant cell transformation, bile duct paucity, intracytoplasmic cholestasis, and periportal fibrosis. An ABCB11 gene study revealed novel compound heterozygous mutations, including c.2075+3A>G in IVS17 and p.R1221K. Liver function test results were normal at 12 months of age. At six years of age, steatorrhea, jaundice, and pruritus developed. Liver function tests improved following administration of phenylbutyrate and rifampicin. Her younger brother developed jaundice at two months of age and his genetic tests revealed the same mutations as his sister. This is the first report of BRIC2 confirmed by ABCB11 mutations in Korean siblings.
Subject(s)
Child , Female , Humans , Bile Ducts , Biopsy , Cholestasis , Cholestasis, Intrahepatic , Fibrosis , Giant Cells , Hepatitis , Jaundice , Liver , Liver Function Tests , Pruritus , Rifampin , Siblings , SteatorrheaABSTRACT
Abstract Purpose: To investigate the relations of neuropeptide Y (NPY) and heme oxygenase-1 (HO-1) expressions with fetal brain injury in rats with intrahepatic cholestasis of pregnancy (ICP). Methods: Sixty rats pregnant for 15 days were randomly divided into experimental and control groups. The ICP model was established in experimental group. On the 21st day, the blood biochemical test, histopathological examination of pregnant rat liver and fetal brain tissues and immunohistochemical analysis of fetal rat brain tissues were performed. Results: On the 21st day, the alanineaminotransferase, aspartate aminotransferase and total bile acid levels in experimental group were significantly higher than control group (P<0.01). Compared with control group, there was obvious vacuolar degeneration in pregnant rat liver tissue and fetal brain tissue in experimental group. NPY expression in fetal brain tissue was negative in control group and positive in experimental group. HO-1 expression in fetal brain tissue was strongly positive in control group and positive in experimental group. There was significant difference of immunohistochemical staining optical density between two groups (P<0.01). Conclusion: In fetal brain of ICP rats, the NPY expression is increased, and the HO-1 expression is decreased, which may be related to the fetal brain injury.
Subject(s)
Animals , Female , Pregnancy , Rats , Pregnancy Complications/metabolism , Neuropeptide Y/metabolism , Brain Injuries/metabolism , Cholestasis, Intrahepatic/metabolism , Heme Oxygenase-1/metabolism , Pregnancy Complications/pathology , Brain Injuries/etiology , Brain Injuries/pathology , Immunohistochemistry , Cholestasis, Intrahepatic/complications , Cholestasis, Intrahepatic/pathology , Rats, Sprague-Dawley , Disease Models, AnimalABSTRACT
ObjectiveTo investigate the clinical features of cholestatic liver disease (CLD), and to provide a reference for strengthening the diagnosis and treatment of this disease. MethodsA retrospective analysis was performed for the clinical data of 107 patients who were admitted to Chenggong Hospital Affiliated to Xiamen University from January 2015 to December 2017 and were diagnosed with CLD. The t-test was used for comparison of continuous data between groups. ResultsMost patients had the clinical symptoms of weakness, loss of appetite, nausea, abdominal distension, pruritus, and jaundice. According to the site of cholestasis, there were 64 patients (59.8%) with intrahepatic cholestasis and 43 (40.2%) with extrahepatic cholestasis. The cause of the disease was common bile duct stones in 21 patients (19.6%), bile duct parasites in 1 patient (0.9%), primary sclerosing cholangitis in 2 patients (1.9%), primary biliary cirrhosis in 3 patients (2.8%), liver cancer in 8 patients (7.5%), bile duct carcinoma in 5 patients (4.7%), pancreatic cancer in 4 patients (3.7%), pancreatitis in 12 patients (11.2%), viral hepatitis in 28 patients (26.2%), drug-induced liver injury in 11 patients (10.3%), alcoholic hepatitis in 6 patients (5.6%), nonalcoholic fatty liver disease in 4 patients (3.7%), and autoimmune hepatitis in 2 patients (19%). The CLD patients with underlying diseases had a significantly poorer liver function (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, bile acid, and total bilirubin) than those with CLD alone (t=-3.44, -2.99, -2.42, -4.39, -3.34, and -2.49, all P＜0.05). Most of the patients achieved good recovery after liver-protecting, transaminase-lowering, and jaundice clearance treatment. The patients with tumors had poor prognosis. ConclusionCLD has various causes, and its clinical features lack specificity. Clinicians should pay enough attention to this disease.
ABSTRACT
BACKGROUND/AIMS: Although endoscopic bilateral stent-in-stent placement is challenging, many recent studies have reported promising outcomes regarding technical success and endoscopic re-intervention. This study aimed to evaluate the technical accessibility of stent-in-stent placement using large cell-type stents in patients with inoperable malignant hilar biliary obstruction. METHODS: Forty-three patients with inoperable malignant hilar biliary obstruction from four academic centers were prospectively enrolled from March 2013 to June 2015. RESULTS: Bilateral stent-in-stent placement using two large cell-type stents was successfully performed in 88.4% of the patients (38/43). In four of the five cases with technical failure, the delivery sheath of the second stent became caught in the hook-cross-type vertex of the large cell of the first stent, and subsequent attempts to pass a guidewire and stent assembly through the mesh failed. Functional success was achieved in all cases of technical success. Stent occlusion occurred in 63.2% of the patients (24/38), with a median patient survival of 300 days. The median stent patency was 198 days. The stent patency rate was 82.9%, 63.1%, and 32.1% at 3, 6, and 12 months postoperatively, respectively. Endoscopic re-intervention was performed in 14 patients, whereas 10 underwent percutaneous drainage. CONCLUSIONS: Large cell-type stents for endoscopic bilateral stent-in-stent placement had acceptable functional success and stent patency when technically successful. However, the technical difficulty associated with the entanglement of the second stent delivery sheath in the hook-cross-type vertex of the first stent may preclude large cell-type stents from being considered as a dedicated standard tool for stent-in-stent placement.
Subject(s)
Humans , Cholangiopancreatography, Endoscopic Retrograde , Cholestasis, Intrahepatic , Drainage , Klatskin Tumor , Prospective Studies , Self Expandable Metallic Stents , StentsABSTRACT
Objective@#To explore the relationship between genotype and phenotype of ABCB11 deficiency.@*Methods@#Clinical data of two siblings with ABCB11 deficiency were retrospectively analyzed. Related literature from PubMed, CNKI and Wangfang databases was reviewed to date (up to August 2017) with 'ABCB11 gene’ or 'bile salt export pump’, 'cholestasis’ and 'child’ as key words.@*Results@#The patients were siblings. Both of them presented as jaundice, pruritus and hepatosplenomegaly since 3 days after birth. Significant laboratory findings on admission of the older sister included high total bilirubin, 170 µmol/L;conjugated bilirubin, 115.8 µmol/L;alanine aminotransferase, 168 U/L;total bile acid 186.3 µmol/L and normal gamma-glutamyl transpeptidase. While routine laboratory data of the younger brother were as follows: total bilirubin, 148.8 µmol/L;conjugated bilirubin, 96.3 µmol/L;alanine aminotransferase, 232.8 U/L;total bile acid 226 µmol/L, and normal gamma-glutamyl transpeptidase.Both received ursodeoxycholic acid and fat-soluble vitamins. Liver pathology of the younger brother showed giant hepatocytes with ballooning degeneration, focal necrosis and intrahepatic cholestasis. Both the patients harbor the same compound heterozygous mutations in ABCB11 gene, c.145C>T (p.Q49X) and c.1510G>A (p.E504K). The sister is 9 years old now, with normal liver function. Jaundice faded around 3 months after birth, pruritus relieved at age 5, and medications was stopped since then. The brother progressed to liver failure after an operation on perianal abscess when he was 8-month-old, and received living-related liver transplantation when he was 9 month and 20 days old (from his mother). Now he is 1 year and 5 months old, with normal liver function. Both are under our follow-up. Literature review revealed 18 ABCB11 deficiency patients from 7 families who had apparent different prognoses, within each family the siblings had the same ABCB11 gene mutation. Seven cases relieved after ursodeoxycholic acid therapy and/or partial external biliary diversion, 5 received orthotopic liver transplantation, 2 developed hepatocellular carcinoma and 4 cases died in childhood.@*Conclusions@#The clinical manifestations of ABCB11 deficiency may vary greatly in patients carrying the same genotype, even in siblings. Patients should be managed in individualized maner.
ABSTRACT
Objective To explore the correlation between maternal serum total bile acid (TBA) of pregnant women with intrahepatic cholestasis of pregnancy (ICP) and varying degrees of neonatal lung injury.Methods A total of 52 cases of pregnant women with ICP and their corresponding newborns were enrolled into the ICP group from March 2014 to December 2015 in the People's Hospital of Shapingba District.Other 52 cases of pregnant women received cesarean delivery whose gestational age and birth weight of newborns were close to the ICP group and their corresponding newborns were selected as the control group.The conditions of neonatal lung injury were recorded,and the correlations of maternal serum level of TBA and exposure time of high serum level of TBA to degrees of lung injury were analyzed as well.Results The incidence rate of neonatal lung injury in the ICP group (67.3 ％) was higher than that in the control group (17.3 ％),there was statistically significant difference (P＜0.05).The degree of lung injury was positively correlated with maternal serum level of TBA and exposure time of high serum level of TBA (r=0.687,P=0.000;r=0.523,P=0.001).Conclusion The probability of neonatal lung injury of corresponding pregnant women with ICP is significantly increased,and the extent of lung injury is positively correlated with concentration of maternal serum TBA and exposure time of high serum level of TBA.
ABSTRACT
Objective To observe the effect of low molecular weight heparin in the treatment of patients with intrahepatic cholestasis pregnancy(ICP)and regulation of cytokines.Methods 124 patients with ICP were randomly divided into observation group and control group.The control group was treated with SAMe +UDCA therapy,the con-trol group was added low molecular weight heparin.All patients were treated for 10 days.Alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bile acid (TBA),tumor necrosis factor alpha (TNF -α)and IL-18 were observed before and after treatment.Results After treatment,ALT,AST and TBA levels were lower in the two groups(t=64.48,110.14,45.75,40.76,62.54,24.67,all P=0.000),which of the observation group were higher(t=62.42,49.42,23.03,all P=0.000).After treatment,the TNF-αand IL-18 levels were lower in the two groups(t=13.14,25.07,all P=0.000),the TNF-αlevel in the observation group was lower than the control group(t=4.91,P=0.000).After treatment,the incidence rates of neonatal meconium,neonatal asphyxia of the observation group were significantly lower than those of the control group(7.14%vs.20.69%,χ2 =4.33,P=0.037;8.93% vs.24.14%,χ2 =4.75,P=0.029).The incidence rate of fetal and maternal hemorrhage between the two groups had no statistically significant differences (1.79% vs.1.72%,χ2 =0.00,P=0.980;5.17% vs.3.57%,χ2 =0.17,P=0.680).Conclusion The effect of low molecular weight heparin in the treatment of patients with intrahepatic cholestasis of pregnancy is exact,it can reduce the biochemical markers and inflammatory cytokine expression and improve perinatal outcome,which deserves to promote in the clinical treatment application.
ABSTRACT
Objective To evaluate the effect of endoplasmic reticulum stress in trophocytes,in patients with intrahepatic cholestasis of pregnancy (ICP).Methods Sixty-one pregnant women who were hospitalized in Women's Hospital,School of Medicine,Zhejiang University from January to December 2015 were recruited.Thirty-one women who were diagnosed as ICP were defined as the ICP group and 30 healthy pregnant women were defined as the control group.The localization and expression intensity of glucose regulated protein 78 (GRP-78) in placental tissues were detected by immunohistochemistry technique.Electronic microscope was used to observe ultra-microstructure change of the endoplasmic reticulum in trophocytes and cell line Swan71.Reverse transcription (RT)-PCR and western blot were used to investigate the expression of GRP-78 mRNA and protein in Swan 71 cell.Results (1) GRP-78 protein was mainly expressed in the cytoplasm of cytotrophoblasts and syncytiotrophoblasts.The protein expression of GRP-78 in placentas of the ICP group (13.2±2.4) was significantly higher than that in the control group (7.8±1.3,P＜0.01).(2) The volume of endoplasmie reticulum did not increase and the microvilli developed well,with no swelling and no expansion of endoplasmic reticulum in the control group.In the ICP group,microvilli injury,endoplasmic reticulum edema were found;the volume of endoplasmic reticulum increased,with dilation,vacuolation and significant degranulation.After treated with 100 μmol/L cholyglycine for 24 hours,universal dilatation of the endoplasmic reticulum were seen in the Swan71 cells.(3) In Swan71 cells,cholylglycine displayed a concentration-dependent up-regulation on the expression of GRP-78.The expressions of GRP-78 mRNA in 0,25,50,100 μmol/L cholylglycine experimental group were 1.01±0.17,2.17±0.16,5.47±0.36,5.65 ± 0.82,respectively.The expression of GRP-78 protein in 0,25,50,100 μmol/L cholylglycine experimental group were 1.01±0.04,1.17±0.15,1.33±0.13,1.73±0.13,respectively.The expression of GRP-78 mRNA and protein in 100 and 50 μ mol/L cholylglycine experimental group were significantly higher than 0 μmol/L (all P＜0.01).Conclusion The obvious expansion of endoplasmic reticulum and the increased expression of GRP-78 in trophocytes indicated that endoplasmic reticulum stress of trophocytes may be involved in the pathogenesis of ICP.
ABSTRACT
Ninety six offspring infants (48 males, 48 females) born by hospitalized patients with intrahepatic cholestasis of pregnancy from January 2010 to February 2013 ( study group) and 108 cases of offspring infants (54 males, 54 females) born by hospitalized healthy pregnant woman ( control group) were enrolled in the study. All offspring infants were followed up for 2 years after birth, physical and neuropsychological development parameters were investigated at 1 month, 1 year and 2 years after birth. There were no significant difference in body weight [ ( 11.94 ±0.89 ) vs.( 13.99 ±0.78 ) kg ] , length [(86.2 ±2.0) vs.(87.0 ±3.1) cm], sitting height, [(51.8 ±2.1) vs.(51.8 ±1.9) cm], head circumference[(47.9 ±1.3) vs.(48.1 ±1.1) cm], development of intelligence quotient index[(99.4 ± 12.9) vs.(100.0 ±12.0)] at 2 years after birth between two groups (P>0.05).Two-year follow up reveals that ursodeoxycholic acid and S-adenosine methionine treatment for women with intrahepatic cholestasis of pregnant has no significant adverse effect on the growth and development of their offspring.
ABSTRACT
Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal-recessive disorders. The estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC-1, PFIC-2, and PFIC-3 are due to mutations in ATP8B1, ABCB11, and ABCB4 genes involved in bile secretion, respectively. Serum gamma-glutamyl transpeptidase is normal in patients with PFIC-1 and PFIC-2, while it is raised in patients with PFIC3. The main clinical manifestation of PFIC is severe intrahepatic cholestasis. PFIC usually appears in infancy or childhood and rapidly progresses to end-stage liver disease before adulthood. Diagnosis of this disease is based on clinical manifestations, liver function tests, liver ultrasonography, liver histology, and genetic testing. Ursodeoxycholic acid therapy is the initial treatment in all PFIC patients to prevent liver damage. In some PFIC1 and PFIC2 patients, biliary diversion may also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation.
ABSTRACT
Intrahepatic cholestasis is a manifestation of liver damage commonly seen in clinical practice, with a complex etiology and involvement of a wide range of diseases. Its pathogenesis is related to hepatocellular damage and bile capillary cell damage, bile acid transport disorder, and abnormal bile flow. The treatment of intrahepatic cholestasis mainly includes drug therapy, and major drugs include ursodeoxycholic acid, obeticholic acid, S-adenosyl methionine, and traditional Chinese medicine preparations. The pathogenesis and treatment of intrahepatic cholestasis are reviewed in this article.
ABSTRACT
Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal-recessive disorders. The estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC-1, PFIC-2, and PFIC-3 are due to mutations in ATP8B1, ABCB11, and ABCB4 genes involved in bile secretion, respectively. Serum gamma-glutamyl transpeptidase is normal in patients with PFIC-1 and PFIC-2, while it is raised in patients with PFIC3. The main clinical manifestation of PFIC is severe intrahepatic cholestasis. PFIC usually appears in infancy or childhood and rapidly progresses to end-stage liver disease before adulthood. Diagnosis of this disease is based on clinical manifestations, liver function tests, liver ultrasonography, liver histology, and genetic testing. Ursodeoxycholic acid therapy is the initial treatment in all PFIC patients to prevent liver damage. In some PFIC1 and PFIC2 patients, biliary diversion may also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation.
ABSTRACT
Intrahepatic cholestasis is a manifestation of liver damage commonly seen in clinical practice, with a complex etiology and involvement of a wide range of diseases. Its pathogenesis is related to hepatocellular damage and bile capillary cell damage, bile acid transport disorder, and abnormal bile flow. The treatment of intrahepatic cholestasis mainly includes drug therapy, and major drugs include ursodeoxycholic acid, obeticholic acid, S-adenosyl methionine, and traditional Chinese medicine preparations. The pathogenesis and treatment of intrahepatic cholestasis are reviewed in this article.
ABSTRACT
ObjectiveTo investigate the significances of clinical diagnostic approaches to biliary atresia (BA) and intrahepatic cholestasis (IHC) in children, and to improve clinicians′ understanding of BA and reduce the rates of missed diagnosis and false diagnosis. MethodsA total of 133 children diagnosed with cholestasis with persistent jaundice admitted to our department from July 2011 to June 2014 were divided into IHC group with 111 patients and BA group with 22 patients. The general clinical trial data were reviewed and analysed and the significances of clinical manifestations, laboratory examination, and imaging features for differential diagnosis of BA and IHC were evaluated. Comparison of continuous data between the two groups was made by t test and comparison of categorical data between the two groups was made by chi-square test. When the sample characteristics for chi-square test were not suitable, the comparison was made by Fisher′s test. ResultsSignificant differences in clinical manifestations of kaolin stools and enlarged and hardened liver and spleen were observed between the two groups (P＜0.01). Total bilirubin (TB), direct bilirubin (DB), gamma GGT (γ-GT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in BA group were significantly higher than those in IHC group (P＜0.01). The specificity, positive predictive value, and positive likelihood ratio of γ-GT were the highest among them, while TB had the highest sensitivity, the highest negative predictive value, and the lowest negative likelihood ratio. The sensitivity and negative predictive value of TB, DB, and γ-GT in the parallel experiment reached 100%. The specificity and positive predictive value of them in the serial experiment were 98% and 88.9%, respectively. There were significant differences in the hepatic portal fibrous mass and gallbladder hypokinesia detected with ultrasonography of the liver, gallbladder, and spleen and in magnetic resonance cholangiopancreatography (MRCP) features between the two groups (P＜001). The specificity and positive predictive values of them in serial experiment reached 100%. ConclusionKaolin stools, enlarged and hardened liver and spleen, TB, DB, γ-GT, ultrasonography, and MRCP of the liver and gallbladder are important indices to distinguish between BA and IHC and a combined analysis of them can improve the diagnostic accuracy.