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Gardenia extract protects against intrahepatic cholestasis by regulating bile acid enterohepatic circulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestasis is the main manifestation of cholestatic liver disease, which has a risk of progression to end-stage liver disease. Gardeniae Fructus is the dried fruit of Gardeniae jasminoides Ellis, a plant of the Rubiaceae family. Gardeniae Fructus has shown therapeutic potential in cholestasis-related liver diseases and it is generally believed that Gardeniae Fructus ameliorates cholestasis, which could be related to its influence on bile acids (BAs) metabolism. However, the specific targets of Gardeniae Fructus and its impact on enterohepatic circulation of BAs…

Plasma exchange treats severe intrahepatic cholestasis caused by dacomitinib: A case report.

RATIONALE: Dacomitinib-induced liver injury is often manifested by mild elevations of transaminases and bilirubin, and severe intrahepatic cholestasis caused by dacomitinib for simultaneous taking orally cytochrome P450 2D6 (CYP2D6) competitive substrates has been rarely reported. PATIENT CONCERNS: The patient was a 69-year-old woman with non-small cell lung cancer (NSCLC) who was prescribed oral dacomitinib for a month; she was given oral loratadine due to "allergic rhinitis" and metoprolol extended action tablets due to "tachycardia" separately for a few days during the course of dacomitini…

Systemic ASBT inactivation protects against liver damage in obstructive cholestasis in mice.

BACKGROUND & AIMS: Non-absorbable inhibitors of the apical sodium-dependent bile acid transporter (ASBT; also called ileal bile acid transporter [IBAT]) are recently approved or in clinical development for multiple cholestatic liver disorders and lead to a reduction in pruritus and (markers for) liver injury. Unfortunately, non-absorbable ASBT inhibitors (ASBTi) can induce diarrhoea or may be ineffective if cholestasis is extensive and largely precludes intestinal excretion of bile acids. Systemically acting ASBTi that divert bile salts towards renal excretion may alleviate these issues. METH…

Neonatal cholestasis: development of a diagnostic decision algorithm from multivariate predictive models.

Despite the recent advances involving molecular studies, the neonatal cholestasis (NC) diagnosis still relays on the expertise of medical teams. Our aim was to develop models of etiological diagnosis and unfavourable prognosis which may support a rationale diagnostic approach. We retrospectively analysed 154 patients born between January 1985 and October 2019. The cohort was divided into two main groups: (A) transient cholestasis and (B) other diagnosis (with subgroups) and also in two groups of outcomes: (I) unfavourable and (II) favourable. Multivariate logistic regression analysis identifie…

Cartilage-hair Hypoplasia Complicated with Liver Cirrhosis Due to Chronic Intrahepatic Cholestasis.

We herein report a rare case of cartilage-hair hypoplasia (CHH) complicated with liver cirrhosis. A 20-year-old Japanese man with CHH was found incidentally to have liver cirrhosis and an esophageal varix. This patient had been treated for infections due to immunodeficiency since early childhood. He ultimately died of liver failure at 31 years of age. An autopsy revealed an abnormality of the interlobular bile ducts and intrahepatic cholestasis. Liver cirrhosis was thought to have been caused by chronic intrahepatic cholestasis due to biliary duct hypoplasia and changes in the intestinal micro…

A Molecular Mechanism Underlying Genotype-Specific Intrahepatic Cholestasis Resulting From MYO5B Mutations.

BACKGROUND AND AIMS: Progressive familial intrahepatic cholestasis (PFIC) 6 has been associated with missense but not biallelic nonsense or frameshift mutations in MYO5B, encoding the motor protein myosin Vb (myoVb). This genotype-phenotype correlation and the mechanism through which MYO5B mutations give rise to PFIC are not understood. The aim of this study was to determine whether the loss of myoVb or expression of patient-specific myoVb mutants can be causally related to defects in canalicular protein localization and, if so, through which mechanism. APPROACH AND RESULTS: We demonstrate th…

Progressive familial intrahepatic cholestasis type-3 and multiple sclerosis: lessons from comorbidity.

The comorbidity between multiple sclerosis (MS) and progressive familial intrahepatic cholestasis type-3 (PFIC3) has never been described yet. ABCB4 gene encodes the multidrug resistant protein 3 (MDR3) and its mutations induce PFIC3 as well as intrahepatic cholestasis of pregnancy (ICP) and drug-induced liver injury (DILI). We describe the case of a 32-year-old female with MS and PFIC3 who was effectively treated with natalizumab and ursodeoxycholic acid (UCDA), in contrast to glatiramer acetate, dimethylfumarate, and IFNb1a associated with DILI. Our findings clarify the pharmacodynamics of M…

Comprehensive bile acid profiling in hereditary intrahepatic cholestasis: Genetic and clinical correlations.

BACKGROUND & AIMS: Genetic defects causing dysfunction in bile salt export pump (BSEP/ABCB11) lead to liver diseases. ABCB11 mutations alter the bile acid metabolome. We asked whether profiling plasma bile acids could reveal compensatory mechanisms and track genetic and clinical status. METHODS: We compared plasma bile acids in 17 ABCB11-mutated patients, 35 healthy controls and 12 genetically undiagnosed cholestasis patients by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC/MRM-MS). We developed an index to rank bile acid hydrophobicity, and…

Preventive effect of artemisinin extract against cholestasis induced via lithocholic acid exposure.

Obstructive cholestasis characterized by biliary pressure increase leading to leakage of bile back that causes liver injury. The present study aims to evaluate the effects of artemisinin in obstructive cholestasis in mice. The present study was carried out on 40 adult healthy mice that were divided into 4 groups, 10 mice each; the negative control group didn't receive any medication. The normal group was fed normally with 100 mg/kg of artemisinin extract orally. The cholestatic group fed on 1% lithocholic acid (LCA) mixed into control diet and cholestatic group co-treated with 100 mg/kg of art…

В результате патологии холестаза, вызванной печенью, происходит неэффективная иммунная реакция после артериальной инфекции.

Неуменные реакции имеют решающее значение для защиты от патогенов. Однако продолжительная вирусная инфекция может привести к дефектному иммунитету клеток Т, что приведет к хронической вирусной инфекции. Мы изучали иммунную активацию в ответ на аренывирусную инфекцию во время холестаза с помощью желчного протока (BDL). Мы отслеживали реакцию Т клеток, вирусную нагрузку и патологические маркеры печени после инфекции вирусом лимфоцита (LCMV). Мыши BDL не смогли вызвать противовирусный иммунитет против ЛКМВ и, следовательно, продемонстрировали хроническую вирусную инфекцию. Мыши BDL продемонстриро

Совпадение в аннотации оригинала
Immune responses are critical for defense against pathogens. However, prolonged viral infection can result in defective T cell immunity, leading to chronic viral infection. We studied immune activation in response to arenavirus infection during cholestasis using bile duct ligation (BDL). We monitored T cell responses, virus load and liver pathology markers a…

CCBE1 mutation causing sclerosing cholangitis: Expanding the spectrum of lymphedema-cholestasis syndrome.

A 52-year old patient presented with lymphedema, protein loosing enteropathy, and sclerosing cholangitis and was diagnosed with lymphedema cholestasis syndrome (LCS). Cholangioscopy revealed dilated lymphatic vessels obstructing the bile duct and compound heterozygosity for collagen and calcium-binding epidermal growth factor domain-containing protein 1 (CCBE1) mutations was identified defining a novel type of LCS. (Hepatology 2017;66:286-288).

Cross-Sectional Analysis of Progressive Familial Intrahepatic Cholestasis in Puerto Rican Children.

OBJECTIVE: Specific inherited disorders may be more common in island communities. Prior case reports suggest that cholestatic liver diseases may constitute a group of these inherited disorders in Puerto Rico. A cross-sectional survey of liver diseases in children was conducted to assess this hypothesis. METHODS: A cross-sectional analysis was performed in patients with chronic cholestasis at "Hospital Pediátrico Universitario" in San Juan, Puerto Rico. Ten potential participants with high gamma-glutamyl transpeptidase (GGTP) cholestasis were identified. Therapeutic response to ursodeoxycholic…

Regulation of hepatic EAAT-2 glutamate transporter expression in human liver cholestasis.

AIM: To investigate the activity and expression of EAAT2 glutamate transporter in both in vitro and in vivo models of cholestasis. METHODS: This study was conducted on human hepatoblastoma HepG2 cell cultures, the liver of bile duct ligated rats and human specimens from cholestatic patients. EAAT2 glutamate transporter activity and expression were analyzed using a substrate uptake assay, immunofluorescence, reverse transcription-polymerase chain reaction, and immunohistochemistry, respectively. RESULTS: In HepG2 cells, cholestasis was mimicked by treating cells with the protein kinase C acti…

Glucagon-Like Peptide 2 Improves Cholestasis in Parenteral Nutrition--Associated Liver Disease.

BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) remains a significant cause of morbidity and mortality in neonates with in … ets (group 3, n = 8) were used for comparison. RESULTS: Both groups 1 and 2 receiving PN developed cholestasis relative to sow-reared controls, as evidenced by a decrease in bile flow and increase in serum total bilirubin. However, group 2 had improved bile flow (1.35 vs 0.73 µL/g; P = .02) and diminished bilirubin (38.0 vs 78.5 µmol/L; P = .008) compared wi …

Ursodeoxycholyl lysophosphatidylethanolamide inhibits cholestasis- and hypoxia-induced apoptosis by upregulating antiapoptosis proteins.

An increase of toxic bile acids such as glycochenodeoxycholic acid occurs during warm ischemia reperfusion causing cholestasis and damage in hepatocytes and intrahepatic biliary epithelial cells. We aim to test antiapoptosis effects of ursodeoxycholyl lysophosphatidylethanolamide under cholestatic induction by glycochenodeoxycholic acid treatment of mouse hepatocytes and hypoxia induction by cobalt chloride treatment of intrahepatic biliary epithelial cancer Mz-ChA-1cell line. Such treatments caused marked increases in apoptosis as evidenced by activation of caspase 3, caspase 8 and poly (ADP-…

Haematological manifestations of arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome: a case report.

Arthrogryposis multiplex congenita, renal dysfunction, and cholestasis (ARC) syndrome is a rare, fatal, multisystem disorder. Bleeding problems, which occur spontaneously and post organ biopsies, have been reported in these patients. We report the case of an infant who had life-threatening spontaneous nasal bleeding. A detailed assessment of her platelet function and morphology is presented.

Parenteral nutrition-associated cholestasis--what do we know, what can we do?

In the early days of parenteral nutrition of children liver disease resulting in steatosis and cholestasis was assumed to be an inevitable complication of the procedure. Since then, the management of parenteral nutrition has improved so much that nowadays adolescents have a fair chance of surviving more than 15 to 20 years without severe liver disease. Nevertheless, we still see cases of parenteral nutrition-associated cholestasis (PNAC) due to various conditions such as recurrent infections, inflammatory response, inappropriate composition of the nutrient mixture, contaminants of the nutrient…

Relationship between apoptosis, tumour necrosis factor, and cell proliferation in chronic cholestasis.

BACKGROUND: Target of the immune response in chronic autoimmune cholestasis, is the bile duct epithelium. Lymphocytic infiltration and apoptosis have both been suggested to mediate the destruction of hepatocytes and biliary epithelium in primary biliary cirrhosis. AIMS: To further address this issue in two cholestatic liver diseases characterized by an autoimmune pathogenesis and, furthermore, evaluate the relationship between apoptosis and both tumour necrosis factor alpha and cell proliferation. METHODS: Liver tissue specimens from 16 patients with primary biliary cirrhosis, 15 with primar…

[Acute intracranial hypertension and anicteric cholestasis revealing Whipple's disease without digestive involvement].

Whipple's disease is a rare infectious disease with potential central nervous system manifestations and a poor prognosis. We report the case of a young woman who presented with acute intracranial hypertension associated with cholestasis which revealed Whipple's disease without digestive involvement. The diagnosis was supported by the presence of PAS-diastase positive hepatic granulomas. A long course of antibiotics resulted in complete remission of the disease without relapse. An acute neurologic syndrome associated with cholestasis should suggest Whipple's disease.