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Sample records for cholestasis

  1. Intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    Victoria Geenes; Catherine Williamson

    2009-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by maternal pruritus in the third trimester, raised serum bile acids and increased rates of adverse fetal outcomes. The etiology of ICP is complex and not fully understood, but it is likely to result from the cholestatic effects of reproductive hormones and their metabolites in genetically susceptible women. Equally unclear are the mechanisms by which the fetal complications occur. This article reviews the epidemiology, clinical features, diagnosis, etiology and management of ICP.

  2. Progressive familial intrahepatic cholestasis

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    Baussan Christiane

    2009-01-01

    Full Text Available Abstract Progressive familial intrahepatic cholestasis (PFIC refers to heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but 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. PFIC1 and PFIC2 usually appear in the first months of life, whereas onset of PFIC3 may also occur later in infancy, in childhood or even during young adulthood. Main clinical manifestations include cholestasis, pruritus and jaundice. PFIC patients usually develop fibrosis and end-stage liver disease before adulthood. Serum gamma-glutamyltransferase (GGT activity is normal in PFIC1 and PFIC2 patients, but is elevated in PFIC3 patients. Both PFIC1 and PFIC2 are caused by impaired bile salt secretion due respectively to defects in ATP8B1 encoding the FIC1 protein, and in ABCB11 encoding the bile salt export pump protein (BSEP. Defects in ABCB4, encoding the multi-drug resistant 3 protein (MDR3, impair biliary phospholipid secretion resulting in PFIC3. Diagnosis is based on clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests for excluding other causes of childhood cholestasis. MDR3 and BSEP liver immunostaining, and analysis of biliary lipid composition should help to select PFIC candidates in whom genotyping could be proposed to confirm the diagnosis. Antenatal diagnosis can be proposed for affected families in which a mutation has been identified. Ursodeoxycholic acid (UDCA therapy should be initiated in all patients to prevent liver damage. In some PFIC1 or PFIC2 patients, biliary diversion can also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation

  3. Intrahepatic cholestasis without jaundice

    Institute of Scientific and Technical Information of China (English)

    Thomas Namdar; Andreas Raffel; Stefan Andreas Topp; Jan Schulte am Esch; Günther Fürst; Wolfram Trudo Knoefel; Claus Ferdinand Eisenberger

    2009-01-01

    BACKGROUND: Cholangiocarcinoma (CC), the most common biliary tract malignancy, is frequently seen in advanced unresectable stages and is typically localized extrahepatically. Early diagnosis is unusual because of nonspeciifc symptoms. Painless jaundice is usually the ifrst sign of tumor. METHOD: We present a patient with a CC (Klatskin tumor) with a complete biliary drainage by an aberrant bile duct without jaundice. RESULTS: A 67-year-old woman presented with persisting elevation of liver parameters. Diagnostic tests showed a Klatskin tumor typeⅡ. A curative right hepatic trisegmentectomy was performed after liver volume augmentation by preoperative vein embolization. CONCLUSIONS: A direct drainage of the right posterior bile duct into the common bile duct as an aberrant hepatic duct is a rare variation and is present in less than 5% of the population. In case of persistently perturbed liver function tests, an aberrant bile duct can cover up severe intrahepatic cholestasis and even obscure the diagnosis of a Klatskin tumor. Up to now it has not been described in the literature.

  4. Pruritus and dermographism due to intrahepatic cholestasis of infancy.

    Science.gov (United States)

    Evans, J; Beer, W; Davies, R

    1978-04-01

    A case report of intrahepatic cholestasis of infancy presenting with chronic severe pruritus is described. This presentation is compared with similar cases attending this unit. Intrahepatic cholestasis of infancy and the pathogenesis of puritus associated with cholestasis are briefly discussed.

  5. Sepsis as a cause of intrahepatic cholestasis

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    Rudić Jelena

    2009-01-01

    Full Text Available Introduction. The causes of intrahepatic cholestasis include cholestatic viral hepatitis, primary biliary cirrhosis, benign recurrent cholestasis, primary sclerosing cholangitis and sepsis. During sepsis, proinflammatory cytokines and nitric oxide cause cholestasis by impairing hepatocellular and ductal bile formation. Case Outline. We report a 48-year-old woman who was admitted to hospital due to malaise, jaundice, fever and pain in the neck. Physical examination revealed jaundice, tachycardia (pulse rate was 120/min, hypotension 90/60 mm Hg. Laboratory findings showed normocytic normochromic anaemia, inflammatory syndrome and abnormal liver function tests indicating cholestasis and hepatocellular necrosis. Abdominal ultrasonography detected hepatosplenomegaly. Chest computed tomography showed bronchopneumonic infiltrates. Percutaneous liver biopsy was performed using a Menghini needle of 1.4 mm. Pathohystological analysis of the liver tissue confirmed reactive, intrahepatic cholestasis. Blood cultures isolated Staphylococcus aureus. After the diagnosis was established the treatment with broad-spectrum antibiotics was carried out, resulting in the improvement of general condition of the patient, regression of inflammatory syndrome, disappearance of cholestasis and regression of pulmonary infiltrates. Abdominal ultrasonography after antibiotic treatment did not show hepatosplenomegaly. Conclusion. Concerning patients with cholestasis of uncertain origin, we should always think of sepsis as a possible cause in order to start antibiotic treatment in time.

  6. Genetics Home Reference: benign recurrent intrahepatic cholestasis

    Science.gov (United States)

    ... All Close All Description Benign recurrent intrahepatic cholestasis (BRIC) is characterized by episodes of liver dysfunction called ... a lack of appetite. A common feature of BRIC is the reduced absorption of fat in the ...

  7. Renal elimination of organic anions in cholestasis

    Institute of Scientific and Technical Information of China (English)

    Adriana Mónica Tortes

    2008-01-01

    The disposition of most drugs is highly dependent on specialized transporters.OAT1 and OAT3 are two organic anion transporters expressed in the basolateral membrane of renal proximal tubule cells,identified as contributors to xenobiotic and endogenous organic anion secretion.It is well known that cholestasis may cause renal damage.Impairment of kidney function produces modifications in the renal elimination of drugs.Recent studies have demonstrated that the renal abundance of OAT1 and OAT3 plays an important role in the renal elimination of organic anions in the presence of extrahepatic cholestasis.Time elapsed after obstructive cholestasis has an important impact on the regulation of both types of organic anion transporters.The renal expression of OAT1 and OAT3 should be taken into account in order to improve pharmacotherapeutic efficacy and to prevent drug toxicity during the onset of this hepatic disease.

  8. Genetic cholestasis : Lessons from the molecular physiology of bile formation

    NARCIS (Netherlands)

    Jansen, PLM; Muller, M

    2000-01-01

    Progressive familial intrahepatic cholestasis (PFIC) is a group of severe genetic cholestatic liver diseases of early life. PFIC types 1 and 2 are characterized by cholestasis and a low to normal serum gamma-glutamyltransferase (GGT) activity, whereas in PFIC type 3, the serum GGT activity is elevat

  9. New Insights on Intrahepatic Cholestasis of Pregnancy.

    Science.gov (United States)

    Floreani, Annarosa; Gervasi, Maria Teresa

    2016-02-01

    Intrahepatic cholestasis of pregnancy (ICP) is characterized by maternal pruritus, and elevated serum transaminases and bile acids. Genetic defects in at least 6 canalicular transporters have been found. Association studies stress the variability of genotypes, different penetrance, and influence of environmental factors. Serum autotaxin is a sensitive, specific, and robust diagnostic marker. Elevated maternal bile acids correlate with fetal complications. Long-term sequelae for mothers include the gallstone risk and chronic liver disease. There is an association between ICP and hepatitis C. Current treatment is ursodeoxycholic acid, owing to benefits on pruritus, liver function, safety, and decreased rates of adverse effects.

  10. Prolonged cholestasis and ductopenia associated with tenoxicam.

    Science.gov (United States)

    Trak-Smayra, Viviane; Cazals-Hatem, Dominique; Asselah, Tarik; Duchatelle, Veronique; Degott, Claude

    2003-07-01

    Cholestatic liver diseases leading to progressive destruction of intra-hepatic bile ducts and ductopenia encompass multiple etiologies. Pathophysiology and natural history of drug-induced cholangiopathies remain unclear. We report a case of prolonged ductopenia attributed to Tenoxicam (Tilcotil o--a non-steroidal anti-inflammatory drug of the oxicam family) ingested at therapeutic dose. A 36 year-old male patient was admitted for jaundice and Lyell syndrome starting 1 week after the ingestion of Tenoxicam. Liver biopsy showed cholestasis, non-suppurative cholangitis and polymorphous inflammatory infiltrate of the portal tracts (round cells, macrophages an eosinophils). Treatment with ursodesoxycholic acid and cholestyramine was instituted and the patient was asymptomatic 1 year after. Three years later mild biological cholestasis persisted and ductopenia was evidenced on liver biopsy. In this report we found that: (1) The toxicity of tenoxicam was probably mediated by an immunoallergic mechanism (Lyell syndrome and eosinophils on histology); (2) ductopenia was secondary to inflammatory cholangitis. Factors responsible for this chronic evolution are still unknown (genetic predisposition, vascular factors, etc.); and (3) the presence of ductopenia contrasted with the "clinical recovery" of the disease suggesting accessory bile drainage by cholangioles or partial reconstruction of the biliary tree.

  11. Prolonged cholestasis after raloxifene and fenofibrate interaction: A case report

    Institute of Scientific and Technical Information of China (English)

    M Isabel Lucena; Raúl J Andrade; Luis Vicioso; F Jesús González; Ketevan Pachkoria; Beatriz García-Mu(n)oz

    2006-01-01

    Assigning causality in drug-induced liver injury is challenging particularly when more than one drug could be responsible. We report a woman on long-term therapy with raloxifen who developed acute cholestasis shortly after starting fenofibrate. The picture evolved into chronic cholestasis. We hypothesized that an interaction at the metabolic level could have triggered the presentation of hepatotoxicity after a very short time of exposure to fenofibrate in this patient. The findings of an overexpression of vascular endothelial growth factor in the liver biopsy suggest that angiogenesis might play a role in the persistance of toxic cholestasis.

  12. Genetic Cholestasis: Lessons from the Molecular Physiology of Bile Formation

    Directory of Open Access Journals (Sweden)

    Peter LM Jansen

    2000-01-01

    Full Text Available Progressive familial intrahepatic cholestasis (PFIC is a group of severe genetic cholestatic liver diseases of early life. PFIC types 1 and 2 are characterized by cholestasis and a low to normal serum gamma-glutamyltransferase (GGT activity, whereas in PFIC type 3, the serum GGT activity is elevated. PFIC types 1 and 2 occur due to mutations in loci at chromosome 18 and chromosome 2, respectively. The pathophysiology of PFIC type 1 is not well understood. PFIC types 2 and 3 are caused by transport defects in the liver affecting the hepatobiliary secretion of bile acids and phospholipids, respectively. Benign recurrent intrahepatic cholestasis (BRIC is linked to a mutation in the same familial intrahepatic cholestasis 1 locus at chromosome 18. Defects of bile acid synthesis may be difficult to differentiate from these transport defects.Intrahepatic cholestasis of pregnancy (ICP appears to be related to these cholestatic diseases. For example, heterozygosity in families with PFIC type 3 is associated with ICP, but ICP has also been reported in families with BRIC.In Dubin-Johnson syndrome there is no cholestasis; only the hepatobiliary transport of conjugated bilirubin is affected. This, therefore, is a mild disease, and patients have a normal lifespan.

  13. Late-Onset Drug-Induced Cholestasis in a Living-Related Liver Transplant Donor With Progressive Familial Intrahepatic Cholestasis.

    Science.gov (United States)

    Harmancı, Özgür; Ensaroğlu, Fatih; Özçay, Figen; Öcal, Serkan; Korkmaz, Murat; Özdemir, B Handan; Selçuk, Haldun; Moray, Gökhan; Haberal, Mehmet

    2015-11-01

    We present a rare case of progressive familial intrahepatic cholestasis within a family. A 34-yearold female became a living-related liver transplant donor for her son, who had the disease. Nine years after the transplant, the mother developed severe intrahepatic cholestasis, for which she was evaluated after using an oral contraceptive drug. She presented with jaundice, pruritus, and increased bilirubin levels, together with elevated gamma glutamyl transferase and alkaline phosphatase levels. A liver biopsy revealed findings consistent with intrahepatic cholestasis. However, despite follow-up management and cessation of the insulting drug, her total bilirubin count continuously increased to 20 mg/dL and was accompanied by intractable pruritus. A total of 9 plasmapheresis sessions were performed, and she was started on a regimen of ursodeoxycholic acid (13 mg/kg/d) and cholestyramine (4 g, 3 times daily). The clinical and laboratory picture dramatically improved following cessation of the oral contraceptive, plasmapheresis sessions, and drug treatment. The patient's cholestasis normalized within 3 months, and she recovered uneventfully. A genetic analysis of the whole family revealed that both parents were heterozygous for the mutation c.124G>A in ABCB11, and the son was homozygous for this mutation. These findings supported varying degrees of bile salt export pump deficiency in the family members. Defective bile salt excretory system function can result in a wide spectrum of clinical presentations, ranging from progressive familial intrahepatic cholestasis requiring liver transplant to late-onset drug-induced cholestasis. Our findings suggest that, in a heterozygous carrier of a progressive familial intrahepatic cholestasis mutation, drug-induced cholestasis is responsive to treatment, after which the clinical picture can normalize within 3 months.

  14. A newborn presented with cholestasis and diagnosed with congenital pituitary hormone deficiency

    OpenAIRE

    ÖZALKAYA, ELİF; Akdağ, Arzu; DENİZ PAPATYA, ESRA; TOPÇUOĞLU, Sevilay

    2016-01-01

    An infrequent reason of neonatal cholestasis is congenital pituitary hormone deficiency. Clinical manifestations of cholestasis and hypoglycaemia in the neonatal period. Gestational week 37, 3700 grams, girl baby born with cesarean sectioning. Hypoglicemia symptoms developed at postnatal first and cholestasis at postnatal third week. Multiple pituitary hormone deficiency was identified.  Cholestasis symptoms recovered with growth hormone therapy. Congenital pituitary hormone deficiency should...

  15. Intrahepatic cholestasis in subclinical and overt hyperthyroidism: two case reports

    Directory of Open Access Journals (Sweden)

    Soylu Aliye

    2008-04-01

    Full Text Available Abstract Introduction Non-specific abnormalities in liver function tests might accompany the clinical course of hyperthyroidism. Hyperthyroidism can cause the elevation of hepatic enzymes and bilirubin. Jaundice is rare in overt hyperthyroidism, especially in subclinical hyperthyroidism. On the other hand, the use of anti-thyroid drugs has rarely been associated with toxic hepatitis and cholestatic jaundice. Case presentation Here we present two cases of cholestasis that accompanied two distinct forms of clinical hyperthyroidism. The first patient had a clinical presentation of severe cholestasis in the absence of congestive failure related to hyperthyroidism. The second case had developed intrahepatic cholestasis in the presence of subclinical hyperthyroidism, and improved with rifampicin treatment. Conclusion Hyperthyroidism should be a consideration in non-specific liver dysfunction.

  16. Septic candidasis with intrahepatic cholestasis and immunoglobuline deficiency after renal transplantation.

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    Zazgornik, J; Schmidt, P; Kopsa, H; Fill, W; Deutsch, E

    1975-10-01

    Two renal allograft recipients with acquired immunoglobulin deficiency had a disseminated infection with candida albicans. Septic fever, intrahepatic cholestasis and pulmonary mycotic disease were the prominent clinical symptoms. Recurrence of septic fever during the clinical course was associated with increase of intrahepatic cholestasis. On the other hand there was an amelioration of cholestasis when effective antimycotic therapy was instituted. In our patients there was no evidence that intrahepatic cholestasis was drug-related. It was assumed that toxic metabolits of candida albicans were responsible for intrahepatic cholestasis.

  17. Nuclear receptors : mediators and modifiers of inflammation-induced cholestasis

    NARCIS (Netherlands)

    Mulder, Jaap; Karpen, Saul J.; Tietge, Uwe J. F.; Kuipers, Folkert

    2009-01-01

    Inflammation-induced cholestasis (IIC) is a frequently occurring phenomenon. A central role in its pathogenesis is played by nuclear receptors (NRs). These ligand-activated transcription factors not only regulate basal expression of hepatobiliary transport systems, but also mediate adaptive response

  18. Neonatal cholestasis – differential diagnoses, current diagnostic procedures and treatment

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    Thomas eGötze

    2015-06-01

    Full Text Available Cholestatic jaundice in early infancy is a complex diagnostic problem. Misdiagnosis of cholestasis as physiologic jaundice delays the identification of severe liver diseases. In the majority of infants it may represent benign cases of breast milk jaundice, but few among them are masked and caused by neonatal cholestasis that requires a prompt diagnosis and treatment. Therefore, a prolonged neonatal jaundice longer than two weeks after birth must always be scrutinized because an early diagnosis is essential for appropriate management. To rapidly identify the cholestatic cases, the conjugated bilirubin needs to be determined in any infant presenting with prolonged jaundice at 14 days of age with or without depigmented stool. Once neonatal cholestasis is confirmed, a systematic approach is the key to reliably achieve the diagnosis in order to promptly initiate the specific, and in many cases, life saving therapy. This strategy is most important to promptly identify and treat infants with biliary atresia, the most common cause of neonatal cholestasis that requires a hepatoportoenterostomy as soon as possible.Here, we provide a detailed work-up approach including initial treatment recommendations and a clinically oriented overview of possible differential diagnoses in order to facilitate an early recognition and a timely diagnosis. This warrants a broad spectrum of diagnostic procedures and investigations including new methods that are described in this review.

  19. Intrahepatic cholestasis of pregnancy: When should you look further?

    NARCIS (Netherlands)

    Hardikar, W.; Kansal, S.; Oude Elferink, R.P.J.; Angus, P.

    2009-01-01

    Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy (ICP), a condition associated with significant fetal complications. Although the etiology of ICP is unclear in many cases, certain features of the clinical presentation should alert the

  20. Intrahepatic cholestasis of pregnancy: When should you look further?

    Institute of Scientific and Technical Information of China (English)

    Winita Hardikar; Shivani Kansal; Ronald P J Oude Elferink; Peter Angus

    2009-01-01

    Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy (ICP), a condition associated with significant fetal complications. Although the etiology of ICP is unclear in many cases, certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect,which may not only affect subsequent pregnancies,but may be an indicator of more serious subsequent liver disease. We report a kindred of Anglo-Celtic descent, among whom many members present with ICP, gallstones or cholestasis related to use of oral contraception. Genetic studies revealed a novel mutation in the ABCB4 gene, which codes for a phospholipid transport protein. The clinical significance of this mutation and the importance of identifying such patients are discussed.

  1. Intrahepatic cholestasis in subclinical and overt hyperthyroidism: two case reports

    OpenAIRE

    2008-01-01

    Abstract Introduction Non-specific abnormalities in liver function tests might accompany the clinical course of hyperthyroidism. Hyperthyroidism can cause the elevation of hepatic enzymes and bilirubin. Jaundice is rare in overt hyperthyroidism, especially in subclinical hyperthyroidism. On the other hand, the use of anti-thyroid drugs has rarely been associated with toxic hepatitis and cholestatic jaundice. Case presentation Here we present two cases of cholestasis that accompanied two disti...

  2. An exclusively based parenteral fish-oil emulsion reverses cholestasis

    OpenAIRE

    Junco, Miryam Triana; García Vázquez, Natalia; Zozaya, Carlos; Ybarra Zabala, Marta; Abrams, Steven; García de Lorenzo, Abelardo; Sáenz de Pipaón Marcos, Miguel

    2015-01-01

    Prolonged parenteral nutrition (PN) leads to liver damage. Recent interest has focused on the lipid component of PN. A lipid emulsion based on w-3 fatty acids decrease conjugated bilirubin. A mixed lipid emulsion derived from soybean, coconut, olive, and fish oils reverses jaundice. Here we report the reversal of cholestasis and the improvement of enteral feeding tolerance in 1 infant with intestinal failure-associated liver disease. Treatment involved the substitution...

  3. Experimental obstructive cholestasis: the wound-like inflammatory liver response

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    Aller María-Angeles

    2008-11-01

    Full Text Available Abstract Obstructive cholestasis causes hepatic cirrhosis and portal hypertension. The pathophysiological mechanisms involved in the development of liver disease are multiple and linked. We propose grouping these mechanisms according to the three phenotypes mainly expressed in the interstitial space in order to integrate them. Experimental extrahepatic cholestasis is the model most frequently used to study obstructive cholestasis. The early liver interstitial alterations described in these experimental models would produce an ischemia/reperfusion phenotype with oxidative and nitrosative stress. Then, the hyperexpression of a leukocytic phenotype, in which Kupffer cells and neutrophils participate, would induce enzymatic stress. And finally, an angiogenic phenotype, responsible for peribiliary plexus development with sinusoidal arterialization, occurs. In addition, an intense cholangiocyte proliferation, which acquires neuroendocrine abilities, stands out. This histopathological finding is also associated with fibrosis. It is proposed that the sequence of these inflammatory phenotypes, perhaps with a trophic meaning, ultimately produces a benign tumoral biliary process – although it poses severe hepatocytic insufficiency. Moreover, the persistence of this benign tumor disease would induce a higher degree of dedifferentiation and autonomy and, therefore, its malign degeneration.

  4. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Sagnik, E-mail: Sagnik.Chatterjee@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Richert, Lysiane, E-mail: l.richert@kaly-cell.com [KaLy-Cell, 20A rue du Général Leclerc, 67115 Plobsheim (France); Augustijns, Patrick, E-mail: Patrick.Augustijns@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Annaert, Pieter, E-mail: Pieter.Annaert@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium)

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug

  5. Relative Frequency of Peptic Ulcer and Erosion in Patients with Different Types of Cholestasis

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    F Joukar

    2008-04-01

    Full Text Available Introduction: Cholestasis is impairment of normal bile excretion into the duodenum and classified as mechanical and non mechanical cholestasis. Mechanical Cholestasis presents with increase in bile duct diameter or obstruction in bile duct in an ERCP. Cholestasis leads to different complications. One of these complications is mucosal peptic erosion leading to gastrointestinal bleeding, perforation and even obstruction due to stricture. We therefore carried out this study to assess the relative frequency of peptic ulcer and erosion in patients with different type of cholestasis. Methods: In a case control study, 170 patients with mechanical cholestasis on the basis of physical examination, liver function tests, radiologic and serologic assay were candidates for ERCP as final therapeutic and diagnostic test. Collected data was registered in questionnaire and evaluated by the Fisher Test. Later, sonography (common bile duct diameter in the two groups: mechanical (85 patients and non mechanical (85 patients and endoscopy was done for exact survey and location of mucosal erosions. Results: Frequency of mucosal peptic erosions in mechanical cholestatic groups was42.6% ( 36 patients and significantly more than frequency of mucosal peptic erosion in non mechanical cholestatic groups (15 patients, 17.6% (P=0.02. 51 patients (30% of the total patients with cholestasis had mucosal erosion. From these patients, 25 patients had peptic ulcer [frequency of duodenal ulcer was 17 patients (68% and gastric ulcer was 8 patients (32% ](P=0.01. There was significant difference in prevalence of duodenal ulcer in patients with mechanical (12 cases, 70.6% and non mechanical (5 cases, 29.4% cholestasis(P=0.01. There was a significant difference between prevalence of duodenal ulcer (12 cases, 70.6% and gastric ulcer(5 cases, 29.4% in patients with mechanical cholestasis (P=0.01 but this was not so in patients with non mechanical cholestasis. Conclusion: According to

  6. Lithocholic acid disrupts phospholipid and sphingolipid homeostasis leading to cholestasis

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    Matsubara, Tsutomu; Tanaka, Naoki; Patterson, Andrew D.; Cho, Joo-Youn; Krausz, Kristopher W.; Gonzalez, Frank J.

    2011-01-01

    Lithocholic acid (LCA) is an endogenous compound associated with hepatic toxicity during cholestasis. LCA exposure in mice resulted in decreased serum lysophosphatidylcholine (LPC) and sphingomyelin levels due to elevated lysophosphatidylcholine acyltransferase (LPCAT) and sphingomyelin phosphodiesterase (SMPD) expression. Global metabolome analysis indicated significant decreases in serum palmitoyl-, stearoyl-, oleoyl- and linoleoyl-LPC levels after LCA exposure. LCA treatment also resulted in decreased serum sphingomyelin levels and increased hepatic ceramide levels, and induction of LPCAT and SMPD mRNAs. Transforming growth factor-β TGF-β) induced Lpcat2/4 and Smpd3 gene expression in primary hepatocytes and the induction was diminished by pretreatment with the SMAD3 inhibitor SIS3. Furthermore, alteration of the LPC metabolites and Lpcat1/2/4 and Smpd3 expression was attenuated in LCA-treated farnesoid X receptor-null mice that are resistant to LCA-induced intrahepatic cholestasis. This study revealed that LCA induced disruption of phospholipid/sphingolipid homeostasis through TGF-β signaling and that serum LPC is a biomarker for biliary injury. PMID:21480330

  7. Lipid profiling of lipoprotein X: Implications for dyslipidemia in cholestasis.

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    Heimerl, Susanne; Boettcher, Alfred; Kaul, Harald; Liebisch, Gerhard

    2016-08-01

    Lipoprotein X (Lp-X) is an abnormal lipoprotein that may typically be formed in intra- and extrahepatic cholestasis and potentially interfere with lipid analysis in the routine lab. To gain insight into lipid class and species composition, Lp-X, LDL and HDL from cholestatic and control serum samples were subjected to mass spectrometric analysis including phospholipids (PL), sphingolipids, free cholesterol (FC), cholesteryl esters (CE) and bile acids. Our analysis of Lp-X revealed a content of 46% FC, 49% PL with 34% phosphatidylcholine (PC) as main PL component. The lipid species pattern of Lp-X showed remarkable high fractions of mono-unsaturated species including PC 32:1 and PC 34:1 and phosphatidylethanolamine (PE) 32:1 and 34:1. LDL and HDL lipid composition in the same specimens strongly reflected the lipid composition of Lp-X with increased PC 32:1, PC 34:1, PE 32:1, PE 34:1 and FC accompanied by decreased CE compared to controls. Comparison of Lp-X and biliary lipid composition clearly indicates that Lp-X does not originate from a sole release of bile lipids. Moreover, these data present evidence for increased hepatic fatty acid and PL synthesis which may represent a reaction to high hepatic FC level observed during cholestasis.

  8. Neonatal cholestasis mimicking biliary atresia: Could it be urinary tract infection?

    Science.gov (United States)

    Pereira, Noella Maria Delia; Shah, Ira

    2017-01-01

    Cholestasis can occur in newborns due to infections. However, the manifestations of the underlying infections usually dominate the presentation. We present a 2-month-old infant who presented with jaundice and no fever or signs of systemic illness. Liver biopsy was suggestive of cholangitis. He was subsequently detected to have urinary tract infection with Klebsiella pneumoniae. The child was treated with appropriate antibiotics for 2 weeks following which the cholestasis resolved. Thus, neonatal cholestasis due to infections can also occur in the post-neonatal period without clinical manifestations of an underlying infection.

  9. Prolonged cholestasis and ductopenia following gold salt therapy.

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    Basset, Céline; Vadrot, Jacqueline; Denis, Jacques; Poupon, Joël; Zafrani, Elie Serge

    2003-04-01

    Hepatotoxicity, predominantly cholestatic, is a rare adverse effect of gold salt therapy, which usually completely resolves within a few months. We report the case of a female patient treated for rheumatoid arthritis, who had gold salt overdose, and in whom acute cholestatic hepatitis occurred three weeks after beginning of therapy. Evolution of gold concentration was followed in plasma and urine, as well as in cutaneous and liver dry tissue. Liver biopsy showed marked inflammatory changes of interlobular bile ducts that evolved towards ductopenia, which was responsible for prolonged cholestasis still present 15 months later. In addition, sialadenitis with sicca syndrome was noted six months after onset of the disease. The mechanism of hepatotoxicity was probably immunoallergic since liver lesions were associated with hypersensitivity syndrome including dermatitis and blood and tissue eosinophilia. This is the first report of gold salt hepatotoxicity with histological demonstration of cholangitis followed by ductopenia.

  10. Intrahepatic cholestasis of pregnancy-current achievements and unsolved problems

    Institute of Scientific and Technical Information of China (English)

    Jurate Kondrackiene; Limes Kupcinskas

    2008-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disorder. Maternal effects of ICP are mild; however, there is a clear association between ICP and higher frequency of fetal distress, preterm delivery, and sudden intrauterine fetal death. The cause of ICP remains elusive, but there is evidence that mutations in genes encoding hepatobiliary transport proteins can predispose for the development of ICP. Recent data suggest that ursodeoxycholic acid is currently the most effective pharmacologic treatment, whereas obstetric management is still debated. Clinical trials are required to identify the most suitable monitoring modalities that can specifically predict poor perinatal outcome. This article aims to review current achievements and unsolved problems of ICP.

  11. A clinical approach to intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    Diken, Zaid; Usta, Ihab M; Nassar, Anwar H

    2014-01-01

    Intrahepatic cholestasis of pregnancy (ICP) has a varying prevalence worldwide. The etiology behind this disease remains not fully understood with multiple factors influencing its development including genetic variations, dietary factors, hormonal changes, and environmental influences. Presenting mainly during the third trimester with generalized itching and resolving spontaneously postpartum, this condition is still associated with fetal morbidity and mortality. The diagnosis is based on clinical presentation in association with biochemical abnormalities. Elevation in total bile acid levels is the most frequent laboratory abnormality and seems to be the most important for gauging further management of the disease. The most appropriate gestational age for the delivery of women with ICP is yet to be determined. In this review we discuss the epidemiology, clinical features, diagnosis, etiology, and management of ICP, trying to shed light on some controversial aspects of the disease.

  12. An exclusively based parenteral fish-oil emulsion reverses cholestasis.

    Science.gov (United States)

    Triana Junco, Miryam; García Vázquez, Natalia; Zozaya, Carlos; Ybarra Zabala, Marta; Abrams, Steven; García de Lorenzo, Abelardo; Sáenz de Pipaón Marcos, Miguel

    2014-10-25

    Prolonged parenteral nutrition (PN) leads to liver damage. Recent interest has focused on the lipid component of PN. A lipid emulsion based on w-3 fatty acids decrease conjugated bilirubin. A mixed lipid emulsion derived from soybean, coconut, olive, and fish oils reverses jaundice. Here we report the reversal of cholestasis and the improvement of enteral feeding tolerance in 1 infant with intestinal failure-associated liver disease. Treatment involved the substitution of a mixed lipid emulsion with one containing primarily omega-3 fatty acids during 37 days. Growth and biochemical tests of liver function improved significantly. This suggests that fat emulsions made from fish oils may be more effective means of treating this condition compared with an intravenous lipid emulsion containing soybean oil, medium -chain triglycerides, olive oil, and fish oil.

  13. Role of ABCC2 common variants in intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    Silvia Sookoian; Gustavo Castano; Carlos J Pirola

    2008-01-01

    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.

  14. Lipoprotein Abnormalities in Cholestasis I. Electro-phoretic and Ultracentrifugal Analyses

    Directory of Open Access Journals (Sweden)

    Watanabe,Makoto

    1979-08-01

    Full Text Available The alterations of lipid composition in sera of patients with liver diseases, particularly intrahepatic cholestasis and biliary obstruction, were studied by ultracentrifugation and polyacrylamide-gel disc-electrophoresis of lipoproteins and apoproteins. The elevation of serum cholesterol in intrahepatic cholestasis was greater than in biliary obstruction. The appearance of lipoprotein X in obstructive disease accounted for most of the increased cholesterol. The level of non-lipoprotein X cholesterol in intrahepatic cholestasis was significantly elevated, this being in part ascribed to the appearance of a new class of cholestatic lipoprotein, Slow-migrating HDL. The electrophoretic pattern of lipoprotein in cholestasis was generally characterized by a decrease in alpha band intensity and, in some types of cholestasis, by the appearance of Slow-migrating HDL. In addition, other abnormal lipoproteins exhibiting the characteristics of triglyceride-rich LDL (LP-Y, LP-X-like HDL and LDL-like HDL were found in some cases of intrahepatic cholestasis and biliary obstruction.

  15. Cholestasis progression effects on long-term memory in bile duct ligation rats

    Directory of Open Access Journals (Sweden)

    Nasrin Hosseini

    2014-01-01

    Full Text Available Background : There is evidence that cognitive functions are affected by some liver diseases such as cholestasis. Bile duct ligation induces cholestasis as a result of impaired liver function and cognition. This research investigates the effect of cholestasis progression on memory function in bile duct ligation rats. Materials and Methods: Male Wistar rats were randomly divided into five groups, which include: control group for BDL-7, control group for BDL-21, sham group (underwent laparotomy without bile duct ligation, BDL-7 group (7 days after bile duct ligation, and BDL-21 group (21 days after bile duct ligation. Step-through passive avoidance test was employed to examine memory function. In all groups, short-term (7 days after foot shock and long-term memories (21 days after foot shock were assessed. Results: Our results showed that liver function significantly decreased with cholestasis progression (P < 0.01. Also our findings indicated BDL-21 significantly impaired acquisition time (P < 0.05. Memory retrieval impaired 7 (P < 0.05 and 21 days (P < 0.001 after foot shock in BDL-7 and BDL-21 groups, respectively. Conclusion: Based on these findings, liver function altered in cholestasis and memory (short-term and long-term memory impaired with cholestasis progression in bile duct ligation rats. Further studies are needed to better insight the nature of progression of brain damage in cholestatic disease.

  16. Urinary reducing substances in neonatal intrahepatic cholestasis caused by citrin deficiency

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    Ajmal Kader

    2014-06-01

    Full Text Available Neonatal cholestasis due to citrin deficiency is an autosomal recessive metabolic disorder caused by mutations in SLC25A13 gene. Mutations in this gene have a relatively high prevalence in East-Asian races compared to European or Afro-Caribbean races. Mutations in both sets of chromosomes often lead to self-limiting early onset cholestasis and growth retardation referred as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD. It is associated with a wide range of metabolic derangements including galactosemia and aminoacidemia, which can be detected on the newborn blood spot screening. Galactose, being a reducing sugar, can also be detected using Clinitest® (Clinitest® Reagent Tablets, Bayer Corporation, Diagnostics Division, Elkhart, IN, USA, a common screening test used in the work up of metabolic and hepatic diseases. In the western population classical galactosemia is often suspected when non glucose reducing substances are detected in the urine of infants with cholestasis. However in East-Asian races the prevalence of classical galactosemia is very low whilst galactosemia due to altered uridine diphosphate-galactose epimerase activity in NICCD is more common. We present a case of NICCD in an East-Asian infant with cholestasis and persistently positive urine reducing substance. Conclusion: NICCD deficiency should be considered as a differential diagnosis in any infant with cholestasis and persistently positive urinary reducing substances.

  17. Cholestasis sepsis at neonatology ward and neonatal Intensive Care Unit Cipto Mangunkusumo Hospital 2007 : incidence, mortality rate and associated risk factors

    Directory of Open Access Journals (Sweden)

    Kadim S. Bachtiar

    2008-06-01

    Full Text Available Cholestatic jaundice represents serious pathological condition. Septic-cholestasis is a kind of hepato-cellular cholestasis that occured during or after sepsis caused by biliary flow obstruction. This is a cohort study from February to June 2007 on neonatal sepsis patients at Neonatology ward Department of Child Health Faculty of Medicine University of Indonesia-Cipto Mangunkusumo General National Hospital. Aim of this study is to find out the incidence of intrahepatic cholestasis in neonatal sepsis, associated risk factors, and mortality rate in neonatal cholestasis-sepsis. From 138 neonatal sepsis patients, the incidence of intrahepatic cholestasis is 65.9%. None of the risk factors tested in this study showed statistically significant result. Mortality rate of neonatal cholestasis-sepsis is 52.8%. (Med J Indones 2008; 17: 107-13Keywords: cholestasis intrahepatic, neonatal sepsis, cholestasis sepsis, conjugated hyperbilirubinemia

  18. Excessive bilirubin elevation in a patient with hereditary spherocytosis and intrahepatic cholestasis.

    Science.gov (United States)

    Wree, A; Canbay, A; Müller-Beissenhirtz, H; Dechêne, A; Gerken, G; Dührsen, U; Lammert, F; Nückel, H

    2011-08-01

    Hereditary spherocytosis is a common hemolytic anemia with an estimated incidence of 1 / 2500 births. It is caused by a molecular defect in one or more of the proteins of the red blood cell cytoskeleton. Mutations in the ABCB11 gene, encoding the bile salt export pump, can entail progressive familial intrahepatic cholestasis and benign recurred intrahepatic cholestasis. A 18 year old Turkish patient with hereditary spherocytosis was admitted to hospital with pruritus and severe jaundice. Ultrasound examination presented stones in gallbladder and bile duct. After endoscopic retrograde cholangiography with extraction of small bile duct stones abdominal pain resolved and liver enzymes normalized within a few days, but bilirubin and bile acids remained highly elevated. Liver biopsy revealed a severe canalicular cholestasis. Genetic analysis showed the compound heterozygous variants ABCB11 A 444V and 3084A > G. Treatment with ursodesoxycholic acid and intermittent therapy with prednisone reduced pruritus and jaundice with concomitant improvement of blood test. Here we report the first case of a patient with combined hereditary spherocytosis and compound heterozygous ABCB11 gene variants predisposing to intrahepatic cholestasis. Therefore, patients with hemolytic disorders should be investigated for bile acid transporter diseases in case of hyperbilirubinemia and severe cholestasis.

  19. Extrahepatic complications of chronic cholestasis: current diagnosis and treatment.

    Science.gov (United States)

    Prelipcean, Cristina Cijevschi; Mihai, Cătălina; Gogălniceanu, P; Mihai, B

    2012-01-01

    Pruritus, fatigue and osteoporosis are the main symptoms of the extra hepatic manifestations of chronic cholestasis that affect patients' quality of life. Pruritus affects more often female patients, varies as intensity during a day and for longer period of time, typically can be localized on the palms of hands and soles of feet or can be generalized. Pruritus can be treated with anions resines exchange--cholestiramine, the pregnanne X receptor agonist Rifampicine, Naltrexone. Liver transplantation can be considered if severe pruritus remains refractory to all medical treatments. Fatigue is the most disabling complain in chronic colestasis. No specific therapies are available for fatigue and liver transplantation doesn't improve it. Osteoporosis and the risk of fractures are more severe with the duration and severity of hepatic disease. For treatment are recommended regular physical exercise, vitamin D and Ca supplimentation and bisphosphonates (Alendronate 70 mg/week) in severe cases. Only patients with atherosclerotic risk and hyperlipemia can be treated with statines. Fat soluble vitamin supplementation can be administrated only in symptomatic and proved vitamin deficiency.

  20. Prolonged cholestasis following successful removal of common bile duct stones: Beware patients on estrogen therapy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    There are various well described forms of chronic cholestatic jaundice in adults, such as autoimmune cholangitis, drug-induced cholangitis and intrahepatic cholestasis of pregnancy. We present two cases of prolonged cholestasis following removal of gallstones at endoscopic retrograde cholangiopancreatography (ERCP) and subsequent clear cholangiography. Both patients were taking oral estrogens at the time of presentation, which were subsequently withdrawn. The first case responded rapidly to corticosteroid treatment,and the second case had a much slower resolution with ursodeoxycholic acid. Both cases highlighted the significance of estrogen-induced cholestasis in female patients with protracted jaundice following ERCP and removal of intra-ductal stones. After oral estrogens are discontinued, a short course of steroids needs to be considered.

  1. Cholestasis and Hepatic Failure in a Neonate: A Case Report of Severe Pyruvate Kinase Deficiency.

    Science.gov (United States)

    Olivier, François; Wieckowska, Anna; Piedboeuf, Bruno; Alvarez, Fernando

    2015-11-01

    Unexpected severe cholestasis is part of the presentation in some neonates with hemolytic anemia but is usually self-resolving. Here we report the case of a neonate with pyruvate kinase deficiency (PKD) who presented severe hemolytic anemia at birth, characterized by a rapidly progressive and severe cholestasis with normal γ-glutamyl transpeptidase level associated with hepatic failure. After an extensive investigation to rule out contributing conditions explaining the severity of this patient's clinical presentation, PKD has remained the sole identified etiology. The patient abruptly died of sepsis at 3 months of age before a planned splenectomy and ongoing evaluation for liver transplantation. To the best of our knowledge, only a few similar cases of severe neonatal presentation of PKD complicated with severe hepatic failure and cholestasis have been reported.

  2. Thyrotoxicosis-Associated Cholestasis in a Patient with Hepatitis B Cirrhosis

    Directory of Open Access Journals (Sweden)

    Mohamed Osama Hegazi

    2008-12-01

    Full Text Available Abnormalities in liver function tests were reported in association with hyperthyroidism. Intrahepatic cholestasis is one form of this association. Reversal of hyperbilirubinemia upon correction of hyperthyroidism supports the causal relationship. Most reported cases have occurred in patients without previous liver disease. We report a case of marked cholestatic jaundice associated with hyperthyroidism caused by toxic adenoma in a patient with hepatitis B cirrhosis. Serum bilirubin returned to baseline level after correcting hyperthyroidism with radioiodine therapy. Hyperthyroidism should be considered in the differential diagnosis of cholestasis in association with chronic liver disease.

  3. Unusual case of drug-induced cholestasis due to glucosamine and chondroitin sulfate

    Institute of Scientific and Technical Information of China (English)

    Stephen; Ip; Rachel; Jeong; David; F; Schaeffer; Eric; M; Yoshida

    2015-01-01

    Glucosamine(GS) and chondroitin sulfate(CS) are common over-the-counter(OTC) supplements used in the treatment of osteoarthritis. These medications are seemingly safe, but there are increasing reports of hepatotoxicity with these supplements. We reported a unique case of drug-induced cholestasis caused by GS and CS in a combination tablet. The etiology of the jaundice was overlooked despite extensive investigations over a three-month period. Unlike drug-induced hepatocellular injury, drug-induced cholestatic jaundice with GS and CS has only been reported twice before. This case emphasizes the importance of a complete medication history, especially OTC supplements, in the assessment of cholestasis.

  4. [Value of injection hepato-lymphography during percutaneous transhepatic cholangiography in patients with cholestasis].

    Science.gov (United States)

    Sharipov, V Sh

    2000-01-01

    Injection hepatography (IH) was made in 278 patients with cholestasis to study the drainage function of the liver. In 208 cases. IH was performed as a test during percutaneous transhepatic cholangiography (PTHC). The hepatic lymph pathways were imaged in 167 (60%) patients. Images of the biliary tract were obtained in 245 (88.1%) patients with cholestasis, it being not dilated in 34 (12.2%) patients. The fact that hepatolymphography may be performed during PTHC as an independent test permits verification of hepatic lymph circulatory disorders that are an index of the rate of inflammation in the organ.

  5. Immaturity of the biliary excretory system predisposes neonates to intrahepatic cholestasis.

    Science.gov (United States)

    Abernathy, C O; Utili, R; Zimmerman, H J

    1979-06-01

    Intrahepatic cholestasis associated with both gram-negative bacterial infections and total parenteral nutrition (TPN) is observed more frequently in neonates than in older children or adults. Factors involved in the pathogenesis of this syndrome are uncertain. The cholestatic effects of gram-negative bacterial infections appear to result from the inhibitory effects of endotoxin on bile flow. Since the adverse effects of both endotoxin and TPN on bile flow involve primarily the bile acid-independent portion, the immaturity of the neonatal hepatic excretory system which an inadequate bile acid-dependent fraction of bile would explain the increased susceptibility of the neonate to endotoxin- and, perhaps, to TPN-induced cholestasis.

  6. [A case of sustained cholestasis caused by acute A viral hepatitis in Dubin-Johnson syndrome].

    Science.gov (United States)

    Ra, Sang Ho; Sung, Se Yong; Jung, Ho Yeon; Cha, Jae Hwang; Baik, Soon Koo; Cho, Mee Yon; Kim, Moon Young

    2012-04-01

    Dubin-Johnson syndrome is a rare clinical entity. It shows intermittent symptoms such as chronic or intermittent jaundice, abdominal pain, weakness, nausea, vomiting, anorexia and diarrhea. Symptoms are precipitated or aggravated by pregnancy, alcoholism, surgical procedures and intercurrent disease. Chronic idiopathic jaundice is typical of Dubin-Johnson syndrome and its prognosis is good. We describe a case of prolonged cholestasis for more than 10 months caused by acute A viral hepatitis in a patient with Dubin-Johnson syndrome. It is a first report of cholestasis complicated by acute A viral hepatitis in a patient with Dubin-Johnson syndrome.

  7. Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis

    NARCIS (Netherlands)

    Thébaut, Alice; Nemeth, Antal; Le Mouhaër, Jeannie; Scheenstra, René; Baumann, Ulrich; Koot, Bart; Gottrand, Fredéric; Houwen, Roderick; Monard, Laure; de Micheaux, Sylvie Lafaye; Habes, Dalila; Jacquemin, Emmanuel

    2016-01-01

    OBJECTIVES: D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic ch

  8. Enteral obeticholic acid prevents hepatic cholestasis in total parenteral nutrition-fed neonatal pigs

    Science.gov (United States)

    Total parenteral nutrition (TPN) is a vital support for neonatal infants with congenital or acquired gastrointestinal (GI) disorders and requiring small bowel resection. An adverse outcome associated with prolonged TPN use is parenteral nutrition associated cholestasis (PNAC). We previously showed t...

  9. Effect of surgically induced cholestasis on the levels of hepatic zinc and metallothionein in rat liver.

    Science.gov (United States)

    Brambila, E; Munoz-Sanchez, J L; Waalkes, M P; Albores, A

    2000-01-01

    Early effects of experimental cholestasis on the homeostasis of zinc (Zn) and metallothionein (MT) were studied in rats which had undergone bile duct ligation for 0, 3, 6, 9, 12, 16, 20, and 24 h. Transient increases in hepatic Zn levels were observed at 9 h but returned to control values at 12 h. Serum Zn levels increased at 24 h. Cholestasis was confirmed by increased serum alkaline phosphatase (AP) activity. MT increased at 3 h and reached a maximum level at 12 h and remained elevated even at 24 h after the onset of experimental cholestasis. No hepatocellular damage was detected according to the results of alanine aminotransferase (ALT) activities in serum. These results shown that the increases in Zn observed in liver are related to bile stagnation rather than to a hepatocellular damage and that increased MT occurs concurrently with increased hepatic Zn. These observations suggest that the cellular levels of Zn in cholestasis is regulated by homeostatic mechanisms, of which one could be mediated by MT.

  10. Partial External Biliary Diversion in Children With Progressive Familial Intrahepatic Cholestasis and Alagille Disease

    NARCIS (Netherlands)

    Yang, Huiqi; Porte, Robert J.; Verkade, Henkjan J.; De Langen, Zacharias J.; Hulscher, Jan B. F.

    2009-01-01

    Background: Partial external biliary diversion (PEBD) is a promising treatment for children with progressive familial intrahepatic cholestasis (PFIC) and Alagille disease. Little is known about long-term Outcomes. Patients and Methods: A retrospective chart review of all patients undergoing PEBD in

  11. Bile Acid Pool Dynamics in Progressive Familial lntrahepatic Cholestasis With Partial External Bile Diversion

    NARCIS (Netherlands)

    Jericho, Hilary S.; Kaurs, Elizabeth; Boverhof, Renze; Knisely, Alex; Shneider, Benjamin L.; Verkade, Henkjan J.; Whitington, Peter F.

    2015-01-01

    Objectives: Partial external bile diversion (PEBD) is an established therapy for low-gamma-glutamyl transferase (GGT) progressive familial intrahepatic cholestasis (PFIC). This study sought to determine whether the dynamics of the cholic acid (CA) and chenodeoxycholic acid (CDCA) pools in subjects w

  12. Male sex predisposes the newborn surgical patient to parenteral nutrition-associated cholestasis and to sepsis

    NARCIS (Netherlands)

    Albers, MJIJ; de Gast-Bakker, DAH; van Dam, NAM; Madern, GC; Tibboel, D

    2002-01-01

    Hypothesis: Sepsis is an epiphenomenon of parenteral nutrition-associated cholestasis (PNAC) and not a causative factor, and the incidence of sepsis is not affected by the presence or absence of PNAC. Design: Observational cohort study. Setting: Pediatric surgery department in a tertiary referral ch

  13. Effect of L-arginine on metabolism of polyamines in rat's brain with extrahepatic cholestasis.

    Science.gov (United States)

    Sokolovic, Dusan; Bjelakovic, Gordana; Nikolic, Jelenka; Djindjic, Boris; Pavlovic, Dusica; Kocic, Gordana; Stojanovic, Ivana; Pavlovic, Voja

    2010-01-01

    Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic cholestasis and the effects of L-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with L-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with L-arginine. Increased plasma gamma-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin levels in BDL rats were reduced by administration of L-arginine (P < 0.001). Cholestasis increased the brain's putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of L-arginine in BDL rats prevents metabolic disorders of polyamines and establishes a neuroprotective role in the brain during cholestasis.

  14. Intestinal capacity to digest and absorb carbohydrates is maintained in a rat model of cholestasis

    NARCIS (Netherlands)

    Los, E. Leonie; Wolters, Henk; Stellaard, Frans; Kuipers, Folkert; Verkade, Henkjan J.; Rings, Edmond H. H. M.

    2007-01-01

    Cholestasis is associated with systemic accumulation of bile salts and with deficiency of bile in the intestinal lumen. During the past years bile salts have been identified as signaling molecules that regulate lipid, glucose, and energy metabolism. Bile salts have also been shown to activate signal

  15. Genetics and Molecular Modeling of New Mutations of Familial Intrahepatic Cholestasis in a Single Italian Center.

    Directory of Open Access Journals (Sweden)

    Isabella Giovannoni

    Full Text Available Familial intrahepatic cholestases (FICs are a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. Three distinct forms are described: FIC1 and FIC2, associated with low/normal GGT level in serum, which are caused by impaired bile salt secretion due to defects in ATP8B1 encoding the FIC1 protein and defects in ABCB11 encoding bile salt export pump protein, respectively; FIC3, linked to high GGT level, involves impaired biliary phospholipid secretion due to defects in ABCB4, encoding multidrug resistance 3 protein. Different mutations in these genes may cause either a progressive familial intrahepatic cholestasis (PFIC or a benign recurrent intrahepatic cholestasis (BRIC. For the purposes of the present study we genotyped 27 children with intrahepatic cholestasis, diagnosed on either a clinical or histological basis. Two BRIC, 23 PFIC and 2 BRIC/PFIC were identified. Thirty-four different mutations were found of which 11 were novel. One was a 2Mb deletion (5'UTR- exon 18 in ATP8B1. In another case microsatellite analysis of chromosome 2, including ABCB11, showed uniparental disomy. Two cases were compound heterozygous for BRIC/PFIC2 mutations. Our results highlight the importance of the pathogenic role of novel mutations in the three genes and unusual modes of their transmission.

  16. Hepatobiliary scintigraphy in chronic intrahepatic cholestasis. Diagnosis of primary sclerosing cholangitis

    Energy Technology Data Exchange (ETDEWEB)

    Aburano, Tamio; Takayama, Teruhiko; Shuke, Noriyuki

    1987-05-01

    Primary sclerosing cholangitis (PSC) is a rare disease of unknown origin, leading to chronic intermittent cholestasis. Due to its low incidence, insidious clinical onset and varied clinical picture, the diagnosis is often delayed by years. PSC is sometimes diagnosed falsely as another disease of chronic intermittent cholestasis, primary biliary cirrhosis (PBC). In the present study, the hepatobiliary imaging with Tc-99m diethyl IDA was done in a total of 14 patients with chronic intermittent cholestasis including 3 patients with PSC and 11 patients with PBC, in order to decide its clinical usefulness as a noninvasive method for the differentiation between PSC and PBC. All three patients with PSC showed a typical pattern of radionuclide stasis within the area of intrahepatic and/or extrahepatic ductal system, representing the stenosis on endoscopic retrograde cholangiogram. On the other hand, none of 11 patients with PBC showed any radionuclide stasis within the area of intrahepatic and/or extrahepatic ductal system. This result suggests that the radionuclide hepatobiliary imaging may be a noninvasive method for investigating patients with chronic intermittent cholestasis, leading to earlier differentiation between PSC and PBC.

  17. Urinary excretion of bile acid glucosides and glucuronides in extrahepatic cholestasis.

    Science.gov (United States)

    Wietholtz, H; Marschall, H U; Reuschenbach, R; Matern, H; Matern, S

    1991-04-01

    Recently the formation of bile acid glucosides has been described as a novel conjugation mechanism in vitro and in vivo. In 10 patients with extrahepatic cholestasis caused by carcinoma of the head of the pancreas we investigated excretion rates and profiles of urinary bile acid glucosides. Urinary bile acid glucosides and, for comparison, bile acid glucuronides were extracted and characterized according to established methods. In controls total urinary bile acid glucoside excretion was 0.22 +/- 0.03 mumol/24 hr (mean +/- S.E.M.)-in the range of bile acid glucuronide excretion (0.41 +/- 0.06 mumol/24 hr; mean +/- S.E.M.). A gas chromatography-mass spectrometry-characterized trihydroxy bile acid glucoside of still-unknown hydroxyl positions accounted for 65% of total urinary bile acid glucosides. In extrahepatic cholestasis total urinary bile acid glucoside excretion was 0.52 +/- 0.13 mumol/24 hr (mean +/- SEM), yet significantly lower than bile acid glucuronide excretion (1.53 +/- 0.13 mumol/24 hr; mean +/- SEM; p less than 0.001). In cholestasis the primary bile acid derivatives cholic and chenodeoxycholic acid glucosides amounted to 90%, whereas the trihydroxy bile acid glucoside had decreased to 5% of total bile acid glucoside excretion, indicating its alteration during enterohepatic circulation. The data establish the composition and quantity of urinary bile acid glucosides in healthy controls and cholestasis and constitute a quantitative comparison with another glycosidic conjugation reaction, bile acid glucuronidation.

  18. Hydrolysed Formula Is a Risk Factor for Vitamin K Deficiency in Infants With Unrecognised Cholestasis

    NARCIS (Netherlands)

    van Hasselt, P. M.; de Vries, W.; de Vries, E.; Kok, K.; Cranenburg, E. C. M.; de Koning, T. J.; Schurgers, L. J.; Verkade, H. J.; Houwen, R. H. J.; Havinga, Rick

    2010-01-01

    Objectives: Vitamin K deficiency (VKD) may cause life-threatening haemorrhages, especially in breast-fed infants with unrecognised cholestasis. Interestingly, hypoallergenic formulas appear overrepresented in reported cases of VKD bleeding (VKDB) in formula-fed infants. We therefore assessed whether

  19. Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis

    NARCIS (Netherlands)

    Thebaut, Alice; Nemeth, Antal; Le Mouhaer, Jeannie; Scheenstra, Rene; Baumann, Ulrich; Koot, Bart; Gottrand, Frederic; Houwen, Roderick; Monard, Laure; de Micheaux, Sylvie Lafaye; Habes, Dalila; Jacquemin, Emmanuel

    2016-01-01

    Objectives:d-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cho

  20. Analysis of the histologic features in the differential diagnosis of intrahepatic neonatal cholestasis

    Institute of Scientific and Technical Information of China (English)

    Maria Angela Bellomo-Brandao; Cecilia AF Escanhoela; Luciana R Meirelles; Gilda Porta; Gabriel Hessel

    2009-01-01

    AIM: To compare the histologic features of the liver in intrahepatic neonatal cholestasis (IHNC) with infectious,genetic-endocrine-metabolic, and idiopathic etiologies.METHODS: Liver biopsies from 86 infants with IHNC were evaluated. The inclusion criteria consisted of jaundice beginning at 3 mo of age and a hepatic biopsy during the 1st year of life. The following histologic features were evaluated: cholestasis, eosinophilia, giant cells, erythropoiesis, siderosis, portal fibrosis, and the presence of a septum.RESULTS: Based on the diagnosis, patients were classified into three groups: group 1 (infectious; n = 18),group 2 (genetic-endocrine-metabolic; n = 18), and group 3 (idiopathic; n = 50). There were no significant differences with respect to the following variables:cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and presence of a septum. A significant difference was observed with respect to erythropoiesis,which was more severe in group 1 (Fisher's exact test,P = 0.016).CONCLUSION: A significant difference was observed in IHNC of infectious etiology, in which erythropoiesis was more severe than that in genetic-endocrine-metabolic and idiopathic etiologies, whereas there were no significant differences among cholestasis, eosinophilia,giant cells, siderosis, portal fibrosis, and the presence of a septum.

  1. Genetics and Molecular Modeling of New Mutations of Familial Intrahepatic Cholestasis in a Single Italian Center

    Science.gov (United States)

    Giovannoni, Isabella; Callea, Francesco; Bellacchio, Emanuele; Torre, Giuliano; De Ville De Goyet, Jean; Francalanci, Paola

    2015-01-01

    Familial intrahepatic cholestases (FICs) are a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. Three distinct forms are described: FIC1 and FIC2, associated with low/normal GGT level in serum, which are caused by impaired bile salt secretion due to defects in ATP8B1 encoding the FIC1 protein and defects in ABCB11 encoding bile salt export pump protein, respectively; FIC3, linked to high GGT level, involves impaired biliary phospholipid secretion due to defects in ABCB4, encoding multidrug resistance 3 protein. Different mutations in these genes may cause either a progressive familial intrahepatic cholestasis (PFIC) or a benign recurrent intrahepatic cholestasis (BRIC). For the purposes of the present study we genotyped 27 children with intrahepatic cholestasis, diagnosed on either a clinical or histological basis. Two BRIC, 23 PFIC and 2 BRIC/PFIC were identified. Thirty-four different mutations were found of which 11 were novel. One was a 2Mb deletion (5’UTR- exon 18) in ATP8B1. In another case microsatellite analysis of chromosome 2, including ABCB11, showed uniparental disomy. Two cases were compound heterozygous for BRIC/PFIC2 mutations. Our results highlight the importance of the pathogenic role of novel mutations in the three genes and unusual modes of their transmission. PMID:26678486

  2. Assessing the risk of drug-induced cholestasis using unbound intrahepatic concentrations.

    Science.gov (United States)

    Riede, Julia; Poller, Birk; Huwyler, Jorg; Camenisch, Gian

    2017-03-02

    Inhibition of the bile salt export pump (BSEP) has been recognized as a key factor in the development of drug-induced cholestasis (DIC). The risk of DIC in human has previously been assessed using in vitro BSEP inhibition data (IC50) and unbound systemic drug exposure under assumption of the "free drug hypothesis". This concept, however, is unlikely valid as unbound intrahepatic drug concentrations are affected by active transport and metabolism. To investigate this hypothesis we experimentally determined the in vitro liver-to-blood partition coefficients (Kp,uu) for 18 drug compounds using the hepatic Extended Clearance Model (ECM). In vitro-in vivo translatability of Kp,uu values was verified for a subset of compounds in rat. Consequently, unbound intrahepatic concentrations were calculated from clinical exposure (systemic and hepatic inlet) and measured Kp,uu data. Using these values, corresponding safety margins against BSEP IC50 values were determined and compared to the clinical incidence of DIC. Depending on the ECM class of a drug, in vitro Kp,uu values deviated up to 14-fold from unity and unbound intrahepatic concentrations were affected accordingly. The use of in vitro Kp,uu-based safety margins allowed to separate clinical cholestasis frequency into three classes (no cholestasis, cholestasis in ≤ 2%, and in > 2% of subjects) for 17 out of 18 compounds. This assessment was significantly superior compared to using unbound extracellular concentrations as a surrogate for intrahepatic concentrations. Furthermore, the assessment of Kpuu according to ECM provides useful guidance for the quantitative evaluation of genetic and physiological risk factors for the development of cholestasis.

  3. Syndrome of Inappropriate Secretion of Antidiuretic Hormone Cholestasis and Pericardial Effusion Due to Brucellosis Infection: A Case Report

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    Ahmet Cumhur Dülger

    2010-01-01

    Full Text Available Syndrome of inappropriate secretion of antidiuretic hormone (SIADH is an extremely rare complication of infectious diseases. A rare case of brucellosis complicated by syndrome of inappropriate secretion of antidiuretic hormone (SIADH cholestasis and pericardial involvement is reported. A 27-year-old woman was admitted for fever, abdominal pain, and scleral icterus. Her medical history revealed no recent use of diuretic agents. In addition to cholestasis and elevated liver enzymes, euvolemic hyponatremia, hypouricemia, low plasma osmolality, and high urinary osmolality were also detected. Surrenal and thyroid tests were also within normal range. Echocardiography revealed minimal pericardial effusion with normal cardiac functions. The final diagnosis was SIADH due to Brucellosis. Hyponatremia, cholestasis, and pericardial disease were resolved with effective antibrucellar treatment with streptomycine and doxycycline. After completing treatment of brucellosis, there was not any more evidence of cholestasis and pericardial fluid.

  4. Hepatic expression of detoxification enzymes is decreased in human obstructive cholestasis due to gallstone biliary obstruction.

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    Jin Chai

    Full Text Available Levels of bile acid metabolic enzymes and membrane transporters have been reported to change in cholestasis. These alterations (e.g. CYP7A1 repression and MRP4 induction are thought to be adaptive responses that attenuate cholestatic liver injury. However, the molecular mechanisms of these adaptive responses in human obstructive cholestasis due to gallstone biliary obstruction remain unclear.We collected liver samples from cholestatic patients with biliary obstruction due to gallstones and from control patients without liver disease (n = 22 per group. The expression levels of bile acid synthetic and detoxification enzymes, membrane transporters, and the related nuclear receptors and transcriptional factors were measured.The levels of bile acid synthetic enzymes, CYP7B1 and CYP8B1, and the detoxification enzyme CYP2B6 were increased in cholestatic livers by 2.4-fold, 2.8-fold, and 1.9-fold, respectively (p<0.05. Conversely, the expression levels of liver detoxification enzymes, UGT2B4/7, SULT2A1, GSTA1-4, and GSTM1-4, were reduced by approximately 50% (p<0.05 in human obstructive cholestasis. The levels of membrane transporters, OSTβ and OCT1, were increased 10.4-fold and 1.8-fold, respectively, (p<0.05, whereas those of OSTα, ABCG2 and ABCG8 were all decreased by approximately 40%, (p<0.05 in human cholestatic livers. Hepatic nuclear receptors, VDR, HNF4α, RXRα and RARα, were induced (approximately 2.0-fold, (p<0.05 whereas FXR levels were markedly reduced to 44% of control, (p<0.05 in human obstructive cholestasis. There was a significantly positive correlation between the reduction in FXR mRNA and UGT2B4/7, SULT2A1, GSTA1, ABCG2/8 mRNA levels in livers of obstructive cholestatic patients (p<0.05.The levels of hepatic detoxification enzymes were significantly decreased in human obstructive cholestasis, and these decreases were positively associated with a marked reduction of FXR levels. These findings are consistent with impaired

  5. Successful Outcome of Chronic Intrahepatic Cholestasis in an Adult Patient with Sickle Cell/β+ Thalassemia

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    Efthymia Vlachaki

    2014-01-01

    Full Text Available Sickle cell/β+ thalassemia (Hb S/β+thal is considered as a variant form of sickle cell disease. Acute episodes of vasoocclusive pain crisis are characteristic for sickle cell disorders and may be complicated by an acute or chronic life-threatening organ dysfunction. Chronic intrahepatic cholestasis is a rare and severe complication in sickle cell disease, characterized by marked hyperbilirubinemia and acute hepatic failure with an often fatal course. Despite the fact that patients with Hb S/β+thal usually have a mild type of disease, herein we describe an interesting case of chronic intrahepatic cholestasis with successful outcome in an adult patient with Hb S/β+thal.

  6. Short-term variability of fetal heart rate in cholestasis of pregnancy.

    Science.gov (United States)

    Ammälä, P; Kariniemi, V

    1981-09-15

    Maternal cholestasis affects about 1% of pregnancies in Finland. Although maternal prognosis in obstetric cholestasis is always good, an increased fetal risk has been reported by several authors. In this paper the differential index (DI), describing the short-term variability of fetal heart rate, was measured in 64 pregnancies with colestasis of pregnancy by a microprocessor-based "on-line" method, which uses abdominal fetal electrocardiogram as a triggering signal. The analysis was successfull in 117 of 131 trials. In five pregnancies no successful analysis was obtained. Fetal distress developed in five fetuses of 59 but not perinatal deaths occurred. The sensitivity of the antepartum DI in predicting fetal distress in labor was 80% and the predictive value was 44%. The relative risk for intrapartum fetal distress in labor after a pathologic antepartal DI compared with normal DI was 22, which is highly significant (p less than 0.001).

  7. Thyrotoxicosis-Associated Cholestasis in a Patient with Hepatitis B Cirrhosis

    OpenAIRE

    2008-01-01

    Abnormalities in liver function tests were reported in association with hyperthyroidism. Intrahepatic cholestasis is one form of this association. Reversal of hyperbilirubinemia upon correction of hyperthyroidism supports the causal relationship. Most reported cases have occurred in patients without previous liver disease. We report a case of marked cholestatic jaundice associated with hyperthyroidism caused by toxic adenoma in a patient with hepatitis B cirrhosis. Serum bilirubin returned to...

  8. Fasciola hepatica infestation as a very rare cause of extrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Ahmet Dobrucali; Rafet Yigitbasi; Yusuf Erzin; Oguzhan Sunamak; Erdal Polat; Hakan Yakar

    2004-01-01

    Fasciola hepatica, an endemic parasite in Turkey, is still a very rare cause of cholestasis worldwide. Through ingestion of contaminated water plants like watercress, humans can become the definitive host of this parasite. Cholestatic symptoms may be sudden but in some cases they may be preceeded by a long period of fever, eosinophilia and vague gastrointestinal symptoms. We report a woman with cholangitis symptoms of sudden onset which was proved to be due to Fasciola hepatica infestation by an endoscopic retrograde cholangiography.

  9. Ursodeoxycholic acid for treatment of cholestasis in patients with hepatic amyloidosis

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    Faust Dominik

    2009-01-01

    Full Text Available Background. Amyloidosis represents a group of different diseases characterized by extracellular accumulation of pathologic fibrillar proteins in various tissues and organs. Severe amyloid deposition in the liver parenchyma has extrahepatic involvement predominantly in the kidney or heart. We evaluated the effect of ursodeoxycholic acid, in four patients with severe hepatic amyloidosis of different etiologies, who presented with increased alkaline phosphatase and γ-glutamyl transferase. Case report. The study included four patients who presented with amyloidosis-associated intrahepatic cholestasis. Three of them had renal amyloidosis which developed 1-3 years before cholestasis occurred, the remaining one having intrahepatic cholestasis as the primary sign of the disease. Amyloidosis was identified from liver biopsies in all patients by its specific binding to Congo red and green birefringence in polarized light. The biochemical nature and the class of amyloid deposits were identified immunohistochemically. In addition to their regular treatment, the patients received 750 mg ursodeoxycholic acid per day. After 2-4 weeks all patients had a significant decrease of serum alkaline phosphatase and γ-glutamyl transferase, and their general status significantly improved. Conclusion. Treatment with ursodeoxycholic acid may be beneficial in patients with hepatic amyloidosis, and do extend indications for the use of ursodeoxycholic acid in amyloidotic cholestatic liver disease.

  10. Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Anabel Brandoni; María Herminia Hazelhoff; Romina Paula Bulacio; Adriana Mónica Torres

    2012-01-01

    Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.

  11. ABC gene-ranking for prediction of drug-induced cholestasis in rats

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    Yauheniya Cherkas

    2016-01-01

    Full Text Available As legacy toxicogenomics databases have become available, improved data mining approaches are now key to extracting and visualizing subtle relationships between toxicants and gene expression. In the present study, a novel “aggregating bundles of clusters” (ABC procedure was applied to separate cholestatic from non-cholestatic drugs and model toxicants in the Johnson & Johnson (Janssen rat liver toxicogenomics database [3]. Drug-induced cholestasis is an important issue, particularly when a new compound enters the market with this liability, with standard preclinical models often mispredicting this toxicity. Three well-characterized cholestasis-responsive genes (Cyp7a1, Mrp3 and Bsep were chosen from a previous in-house Janssen gene expression signature; these three genes show differing, non-redundant responses across the 90+ paradigm compounds in our database. Using the ABC procedure, extraneous contributions were minimized in comparisons of compound gene responses. All genes were assigned weights proportional to their correlations with Cyp7a1, Mrp3 and Bsep, and a resampling technique was used to derive a stable measure of compound similarity. The compounds that were known to be associated with rat cholestasis generally had small values of this measure relative to each other but also had large values of this measure relative to non-cholestatic compounds. Visualization of the data with the ABC-derived signature showed a very tight, essentially identically behaving cluster of robust human cholestatic drugs and experimental cholestatic toxicants (ethinyl estradiol, LPS, ANIT and methylene dianiline, disulfiram, naltrexone, methapyrilene, phenacetin, alpha-methyl dopa, flutamide, the NSAIDs–—indomethacin, flurbiprofen, diclofenac, flufenamic acid, sulindac, and nimesulide, butylated hydroxytoluene, piperonyl butoxide, and bromobenzene, some slightly less active compounds (3′-acetamidofluorene, amsacrine, hydralazine, tannic acid, some

  12. Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis

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    Spahr Laurent

    2011-10-01

    Full Text Available Abstract Background Alcoholic steatohepatitis (ASH is a serious complication of alcoholic liver disease. The diagnosis of ASH requires the association of steatosis, evidence of hepatocellular injury with ballooning degeneration, and polynuclear neutrophil infiltration on liver biopsy. Whether these lesions, in addition to other histological features observed in liver tissue specimens, have prognostic significance is unclear. Methods We studied 163 patients (age 55 yrs [35-78], male/female 102/61 with recent, heavy (> 80 gr/day alcohol intake, histologically-proven ASH (97% with underlying cirrhosis, Maddrey's score 39 [13-200], no sepsis, who had a liver biopsy performed 3 days [0-10] after hospital admission for clinical decompensation. A semi-quantitative evaluation of steatosis, hepatocellular damage, neutrophilic infiltration, periportal ductular reaction, intraparenchymal cholestasis, and iron deposits was performed by two pathologists. All patients with a Maddrey's score ≥ 32 received steroids. The outcome at 3 months was determined. Statistical analysis was performed using the Wilcoxon and Fisher's exact tests, Kaplan-Meier method, and the Cox proportional hazard model. Results 43 patients died after 31 days [5-85] following biopsy. The 3-month survival rate was 74%. Mean kappa value for histological assessment by the two pathologists was excellent (0.92. Univariate analysis identified age, the Maddrey's score, the Pugh's score, the MELD score and parenchymal cholestasis, but not other histological features, as factors associated with 3-month mortality. At multivariate analysis, age (p = 0.029, OR 2.83 [1.11-7.2], intraparenchymal cholestasis (p = 0.001, OR 3.9 [1.96-7.8], and the Maddrey's score (p = 0.027, OR 3.93 [1.17-13.23] were independent predictors of outcome. Intraparenchymal cholestasis was more frequent in non survivors compared to survivors (70% versus 25%, p Conclusions In this large cohort of patients with histologically

  13. Omega-3-enriched lipid emulsion for liver salvage in parenteral nutrition-induced cholestasis in the adult patient.

    Science.gov (United States)

    Jurewitsch, Brian; Gardiner, Geoffrey; Naccarato, Mark; Jeejeebhoy, Khursheed N

    2011-05-01

    The intrahepatic cholestasis attributed to parenteral nutrition (PN) in the adult patient is relatively rare and usually occurs in patients receiving long-term PN. This article reports the first case of an adult patient with cholestatic PN-associated liver disease without sepsis who received almost all her nutrition requirements through PN. Administration of an ω-3-enriched lipid emulsion added to the PN regimen reversed cholestasis and demonstrated histologic improvement on serial liver biopsy. The patient had failed to respond to other modalities of treatment for this condition and was deeply jaundiced. Liver biochemistry profiles returned to baseline, and follow-up liver biopsy showed that cholestasis had resolved and that the only residual changes were mild portal inflammation with no histochemical or ultrastructural progression. The PN regimen for the patient was restored to provide total estimated energy requirements and remains the principle source of the patient's nutrition to date.

  14. Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in cholestasis and intervention effect of Paeonia lactiflora Pall.

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    Xiao eMa

    2016-02-01

    Full Text Available Background: The dried root of Paeonia lactiflora Pall. (PLP is a classical Chinese herbal medicine that has been used to treat hepatic disease for thousands of years. Our previous work suggested that PLP can be used to treat hepatitis with severe cholestasis. This study explored the mechanism by which PLP affects ANIT-induced cholestasis in rats using a metabolomics approach.Methods: The effects of PLP on serum indices (TBIL, DBIL, AST, ALT, ALP and TBA and the histopathology of the liver were analyzed. Moreover, UHPLC-Q-TOF was performed to identify the possible effect of PLP on metabolites. The pathway analysis was conducted to illustrate the pathways and network by which PLP treats cholestasis. Result: High-dose PLP remarkably down-regulated the serum indices and alleviated histological damage to the liver. Metabolomics analyses showed that the therapeutic effect of high-dose PLP is mainly associated with the regulation of several metabolites, such as glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, L(D-arginine and L-tryptophan. A pathway analysis showed that the metabolites were related to bile acid secretion and amino acid metabolism. In addition, the significant changes in bile acid transporters also indicated that bile acid metabolism might be involved in the therapeutic effect of PLP on cholestasis. Moreover, a principal component analysis indicated that the metabolites in the high-dose PLP group were closer to those of the control, whereas those of the moderate dose or low-dose PLP group were closer to those of the ANIT group. This finding indicated that metabolites may be responsible for the differences between the effects of low-dose and moderate-dose PLP. Conclusions: The therapeutic effect of high-dose PLP on cholestasis is possibly related to regulation of bile acid secretion and amino acid metabolism. Moreover, these findings may help better understand the mechanisms of disease and provide a potential therapy for

  15. Intestinal capacity to digest and absorb carbohydrates is maintained in a rat model of cholestasis.

    Science.gov (United States)

    Los, E Leonie; Wolters, Henk; Stellaard, Frans; Kuipers, Folkert; Verkade, Henkjan J; Rings, Edmond H H M

    2007-09-01

    Cholestasis is associated with systemic accumulation of bile salts and with deficiency of bile in the intestinal lumen. During the past years bile salts have been identified as signaling molecules that regulate lipid, glucose, and energy metabolism. Bile salts have also been shown to activate signaling routes leading to proliferation, apoptosis, or differentiation. It is unclear, however, whether cholestasis affects the constitution and absorptive capacity of the intestinal epithelium in vivo. We studied small intestinal morphology, proliferation, apoptosis, expression of intestine-specific genes, and carbohydrate absorption in cholestatic (1 wk bile duct ligation), bile-deficient (1 wk bile diversion), and control (sham) rats. Absorptive capacity was assessed by determination of plasma [(2)H]- and [(13)C]glucose concentrations after intraduodenal administration of [(2)H]glucose and naturally enriched [(13)C]sucrose, respectively. Small intestinal morphology, proliferation, apoptosis, and gene expression of intestinal transcription factors (mRNA levels of Cdx-2, Gata-4, and Hnf-1alpha, and Cdx-2 protein levels) were similar in cholestatic, bile-deficient, and control rats. The (unlabeled) blood glucose response after intraduodenal administration was delayed in cholestatic animals, but the absorption over 180 min was quantitatively similar between the groups. Plasma concentrations of [(2)H]glucose and [(13)C]glucose peaked to similar extents in all groups within 7.5 and 30 min, respectively. Absorption of [(2)H]glucose and [(13)C]glucose in plasma was similar in all groups. The present data indicate that neither accumulation of bile salts in the body, nor their intestinal deficiency, two characteristic features of cholestasis, affect rat small intestinal proliferation, differentiation, apoptosis, or its capacity to digest and absorb carbohydrates.

  16. Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis.

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    Yu Yamaura

    Full Text Available MicroRNAs (miRNAs are small RNA molecules that function to modulate the expression of target genes, playing important roles in a wide range of physiological and pathological processes. The miRNAs in body fluids have received considerable attention as potential biomarkers of various diseases. In this study, we compared the changes of the plasma miRNA expressions by acute liver injury (hepatocellular injury or cholestasis and chronic liver injury (steatosis, steatohepatitis and fibrosis using rat models made by the administration of chemicals or special diets. Using miRNA array analysis, we found that the levels of a large number of miRNAs (121-317 miRNAs were increased over 2-fold and the levels of a small number of miRNAs (6-35 miRNAs were decreased below 0.5-fold in all models except in a model of cholestasis caused by bile duct ligation. Interestingly, the expression profiles were different between the models, and the hierarchical clustering analysis discriminated between the acute and chronic liver injuries. In addition, miRNAs whose expressions were typically changed in each type of liver injury could be specified. It is notable that, in acute liver injury models, the plasma level of miR-122, the most abundant miRNA in the liver, was more quickly and dramatically increased than the plasma aminotransferase level, reflecting the extent of hepatocellular injury. This study demonstrated that the plasma miRNA profiles could reflect the types of liver injury (e.g. acute/chronic liver injury or hepatocellular injury/cholestasis/steatosis/steatohepatitis/fibrosis and identified the miRNAs that could be specific and sensitive biomarkers of liver injury.

  17. The role of imaging methods in identifying the causes of extrahepatic cholestasis.

    Science.gov (United States)

    Rogoveanu, Ion; Gheonea, Dan Ionut; Saftoiu, Adrian; Ciurea, Tudorel

    2006-09-01

    Transabdominal ultrasonography is the first choice examination used for the etiological diagnosis of extrahepatic cholestasis because it is a noninvasive, rapid method and presently widely accessible. In this article we discuss the accuracy of transabdominal ultrasonography, computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasonography (EUS) in detecting the main causes of extrahepatic colestasis. Although in bile duct pathology, and especially in the evaluation of patients with jaundice, transabdominal ultrasonography is the first choice exploration, helicoidal CT, ERCP and MRCP are often required to establish the local cause of jaundice, local and distant consequences evaluation, appreciation of surgical intervention opportunity and choice of the right therapeutic method.

  18. Impaired Hepatic Adaptation to Chronic Cholestasis induced by Primary Sclerosing Cholangitis

    Science.gov (United States)

    Milkiewicz, Malgorzata; Klak, Marta; Kempinska-Podhorodecka, Agnieszka; Wiechowska-Kozlowska, Anna; Urasinska, Elzbieta; Blatkiewicz, Malgorzata; Wunsch, Ewa; Elias, Elwyn; Milkiewicz, Piotr

    2016-01-01

    Pathogenesis of primary sclerosing cholangitis (PSC) may involve impaired bile acid (BA) homeostasis. We analyzed expressions of factors mediating enterohepatic circulation of BA using ileal and colonic (ascending and sigmoid) biopsies obtained from patients with PSC with and without ulcerative colitis (UC) and explanted PSC livers. Two-fold increase of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid colon of PSC patients with correspondingly decreased apical sodium-dependent BA transporter (ASBT) gene expression. This was associated with increased OSTβ protein levels in each part of analyzed gut. An intestinal fibroblast growth factor (FGF19) protein expression was significantly enhanced in ascending colon. Despite increased hepatic nuclear receptors (FXR, CAR, SHP), and FGF19, neither CYP7A1 suppression nor CYP3A4 induction were observed. The lack of negative regulation of BA synthesis may be accountable for lower levels of cholesterol observed in PSC in comparison to primary biliary cholangitis (PBC). In conclusion, chronic cholestasis in PSC induces adaptive changes in expression of BA transporters and FXR in the intestine. However hepatic impairment of expected in chronic cholestasis downregulation of CYP7A1 and upregulation of CYP3A4 may promote BA-induced liver injury in PSC. PMID:28008998

  19. The role of steroid hormones in the development of intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    Pařízek, A; Dušková, M; Vítek, L; Šrámková, M; Hill, M; Adamcová, K; Šimják, P; Černý, A; Kordová, Z; Vráblíková, H; Boudová, B; Koucký, M; Malíčková, K; Stárka, L

    2015-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is a disorder of liver function, commonly occurring in the third trimester but sometimes also as soon as the end of the second trimester of pregnancy. Symptoms of this disorder include pruritus, plus abnormal values of bile acids and hepatic transaminases. After birth, symptoms disappear and liver function returns to normal. Though ICP is relatively non-complicated and often symptomatically mild from the point-of-view of the mother, it presents a serious risk to the fetus, making this disease the subject of great interest. The etiology and pathogenesis of ICP is multifactorial and as yet not fully elucidated. Hormonal factors likely play a significant role, along with genetic as well as exogenous factors. Here we summarize the knowledge of changes in steroid hormones and their role in the development of intrahepatic cholestasis of pregnancy. In addition, we consider the role of exogenous factors as possible triggers of steroid hormone changes, the relationship between metabolic steroids and bile acids, as well as the combination of these factors in the development of ICP in predisposed pregnant women.

  20. Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients.

    Science.gov (United States)

    Tazawa, Yusaku; Kobayashi, Keiko; Abukawa, Daiki; Nagata, Ikuo; Maisawa, Shunichi; Sumazaki, Ryo; Iizuka, Toshiyuki; Hosoda, Yoshito; Okamoto, Manabu; Murakami, Jun; Kaji, Shunsaku; Tabata, Ayako; Lu, Yao Bang; Sakamoto, Osamu; Matsui, Akira; Kanzaki, Susumu; Takada, Goro; Saheki, Takeyori; Iinuma, Kazuie; Ohura, Toshihiro

    2004-11-01

    A deficiency of citrin, which is encoded by the SLC25A13 gene, causes both adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis (NICCD). We analyzed 16 patients with NICCD to clarify the clinical features of the disease. Severe intrahepatic cholestasis with fatty liver was the most common symptom, but the accompanying clinical features were variable, namely; suspected cases of neonatal hepatitis or biliary atresia, positive results from newborn screening, tyrosinemia, failure to thrive, hemolytic anemia, bleeding tendencies and ketotic hypoglycemia. Laboratory data showed elevated serum bile acid levels, hypoproteinemia, low levels of vitamin K-dependent coagulation factors, and hypergalactosemia. Hypercitrullinemia was detected in 11 out of 15 patients examined. Most of the patients were given a lactose-free and/or medium chain triglycerides-enriched formula and lipid-soluble vitamins. The prognosis of the 16 patients is going fairy well at present, but we should observe these patients carefully to see if they manifest any symptom of CTLN2 in the future.

  1. Seasonal cryptogenic organising pneumonia with biochemical cholestasis: a new clinical entity.

    Science.gov (United States)

    Spiteri, M A; Klenerman, P; Sheppard, M N; Padley, S; Clark, T J; Newman-Taylor, A

    1992-08-01

    The term cryptogenic organising pneumonia has been used for the combination of dyspnoea, cough, pleuritic pain, widespread shadows on chest radiographs, and histological evidence of intra-alveolar organisation with buds of granulation tissue within the alveoli. We report 12 patients with seasonal recurrence of this disorder for between 3 and 11 years. In all 12 patients, symptoms recurred between late February and early May every year, tending to increase in severity each year, and resolved between June and January. Chest radiography and computed tomography showed bilateral consolidation. Lung biopsy samples showed intra-alveolar buds of granulation tissue. There were many neutrophils within the lumina of medium-sized airways and terminal bronchioles showed evidence of obstruction by granulation tissue. Functionally, the predominant defect was restrictive and only 2 patients (life-long non-smokers) had airflow limitation. All 12 patients had very high activities of liver enzymes, suggesting intrahepatic cholestasis, but no other evidence of liver disease. Cultures of blood, sputum, lung tissue, and bronchoalveolar lavage fluid, viral screening, and complement fixation tests were consistently negative. In all patients all abnormalities responded rapidly to oral steroid therapy. These findings suggest a seasonal syndrome of organising pneumonia and biochemical abnormalities indicative of intrahepatic cholestasis. No aetiological factor has been identified, but the nature and periodicity of the illness point to an inhaled agent present in the environment for a limited period every year.

  2. [Clinical significance of dissociated cholestasis as a biological syndrome (author's transl)].

    Science.gov (United States)

    Cardellach, F; Sierra, J; Coca, A; Villalta, J; Martinez-Orozco, F; Ingelmo, M; Balcells-Gorina, A

    1981-10-10

    The case histories of 1200 patients admitted to our hospital over a 20 month period were reviewed to determine the degree, frequency and cause of dissociated cholestasis as a biological syndrome. Patients were divided into two groups: group I with 80 cases, included all patients whose gamma-GT levels were more than 30 mU/ml and serum-bilirubin less than 1.2 mg/ml, with alkaline phosphatase levels between 90-180 mU/ml. Group II included those with alkaline phosphatase levels higher than 180 mU/ml (57 cases). All over incidence of dissociated cholestasis was 13.82%. Main causes in group I were infectious diseases, mainly pneumonias and urinary infections and congestive cardiac failure. In group II, neoplasias such as Hodgkin's disease and epithelial metastases and obstructions of the biliary tract such as vesicular or choledocal litiasis were the main causes. Transaminase levels underwent variable increases according to the different entities, without there being any difference between the two groups. The physiopathology as well as the anatomopathological aspects which could originate the syndrome are discussed.

  3. The peculiarities of morphological damages of the liver during obstructive cholestasis in clinic and experiment.

    Directory of Open Access Journals (Sweden)

    Gaydar Yu.A.

    2007-01-01

    Full Text Available The purpose of work was to study of the liver depending on blood level of bilirubine during obstructive cholestasis. 35 patients of 4 groups were examined: I - with the level of blood bilirubine lower 50 mM/l; II - 50-100 mM/l; III - 100-200 mM/l; IV - over 200 mM/l. The biopsies of liver were received during operation. The thin sections were stained by hematoxilin-eosin and Malori-Slinchenco. The immunohistochemical study of PCNA, p-53 and estrogen receptors markers was carried. The ligation of the common bile duct in 21 adult Vistar rats was carried and biopsies of liver were examined by the same methods on 7th and 16-18th day. The increases of inflammatory processes in the liver according to the increase of bilirubine level in the patient’s blood, and also the growth of PCNA expression were observed. The intracanalicular cholestasis was typical in III and IV groups of patients. The expression PCNA proved the activation of the reparative regeneration processes. We also observed the expression of estrogen receptors in hepatic parenchyme and intrahepatic billiar ducts. The ligation of the common bile duct in rats has resulted in acute hepatic necrobiosis by 7th day. The nodular cirrhosis has formed by the16-18th days.

  4. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

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    Natalia Nuño-Lámbarri

    2016-01-01

    Full Text Available Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.

  5. Nervous and Neuroendocrine regulation of the pathophysiology of cholestasis and of biliary carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Marco Marzioni; Giammarco Fava; Antonio Benedetti

    2006-01-01

    Cholangiocytes, the epithelial cells lining the biliary ducts, are the target cells in several liver diseases.Cholangiopathies and cholangiocarcinoma generate interest in many scientists since the genesis. The developing mechanisms, and the therapeutic tools of these diseases are still undefined. Several studies demonstrate that many hormones, neuropeptides and neurotransmitters regulate malignant and non-malignant cholangiocyte pathophysiology in the course of chronic biliary diseases. The aim of this review is to present the findings of several studies published in the recent years that contributed to clarifying the role of nervous and neuroendocrine regulation of the pathophysiologic events associated with cholestasis and cholangiocarcinoma development. This manuscript is organized into two parts. The first part offers an overview of the innervation of the liver and the origin of neuroendocrine hormones,neurotransmitters and neuropeptides affecting cholangiocyte function and metabolism. The first section also reviews the effects played by several neuroendocrine hormones and nervous system on cholangiocyte growth,survival and functional activity in the course of cholestasis. In the second section, we summarize the results of some studies describing the role of nervous system and neuroendocrine hormones in the regulation of malignant cholangiocyte growth.

  6. [Stevens-Johnson syndrome plus intrahepatic cholestasis caused by clindamycin or chlorpheniramine].

    Science.gov (United States)

    Sahagún Flores, J E; Soto Ortiz, J A; Tovar Méndez, C E; Cárdenas Ochoa, E C; Hernández Flores, G

    2009-05-15

    A 48-year-old woman was hospitalized with the diagnosis of hepatitis. She presented with symptoms of jaundice, headache, elevated bilirubin, and elevated hepatic enzymes. She related a recent episode of a bronchial infection that was treated during the previous eight days with paracetamol (500mg, 2 doses only), chlorpheniramine, betamethasone and clindamycin. After an initial clinical and laboratorial improvement, she began to complain of pruritus of the palms and soles. Thereafter, vesicles evolving to blisters developed and a deterioration of her general health ensued. Serologies for hepatitis A, B, and C viruses were negative. Intrahepatic cholestasis and Stevens Johnson Syndrome (SJS) were the final diagnosis. The association of the Stevens Johnson Syndrome and intrahepatic cholestasis simultaneously, related to adverse drug reactions, is very rare. The drugs reportedly involved are mainly antibiotics, such as ampicillin, vancomycin, amoxicillin/clavulinic acid and erythromycin. Other drugs involved are non-steroidal anti-inflamatory drugs, such as mefenamic acid, ibuprofen, and sulindac. The reactions can be minor or severe and can even cause death, an outcome that has been reported in patients of all races and ethnic groups, but appears to be more rare in patients of Latin origin. We present a discussion of this case and review the main characteristics of the Stevens Johnson Syndrome.

  7. Dermatological Diseases Associated with Pregnancy: Pemphigoid Gestationis, Polymorphic Eruption of Pregnancy, Intrahepatic Cholestasis of Pregnancy, and Atopic Eruption of Pregnancy

    OpenAIRE

    Christine Sävervall; Freja Lærke Sand; Simon Francis Thomsen

    2015-01-01

    Dermatoses unique to pregnancy are important to recognize for the clinician as they carry considerable morbidity for pregnant mothers and in some instances constitute a risk to the fetus. These diseases include pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy. This review discusses the pathogenesis, clinical importance, and management of the dermatoses of pregnancy.

  8. A novel phenotype of a hepatocyte nuclear factor homeobox A (HNF1A) gene mutation, presenting with neonatal cholestasis

    NARCIS (Netherlands)

    de Vries, Aleida G. M.; Bakker-van Waarde, Willie M.; Dassel, Anne C. M.; Losekoot, Monique; Duiker, Evelien W.; Gouw, Annette S. H.; Bodewes, Frank A. J. A.

    2015-01-01

    We report a novel phenotype of a hepatocyte nuclear factor homeobox A (HNF1A) mutation (heterozygote c.130dup, p.Leu44fs) presenting with transient neonatal cholestasis, subsequently followed by persistent elevation of transaminases, maturity-onset diabetes of the young (MODY) type 3 and hepatocellu

  9. CCBE1 mutation in two siblings, one manifesting lymphedema-cholestasis syndrome, and the other, fetal hydrops.

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    Sohela Shah

    Full Text Available BACKGROUND: Lymphedema-cholestasis syndrome (LCS; Aagenaes syndrome is a rare autosomal recessive disorder, characterized by 1 neonatal intrahepatic cholestasis, often lessening and becoming intermittent with age, and 2 severe chronic lymphedema, mainly lower limb. LCS was originally described in a Norwegian kindred in which a locus, LCS1, was mapped to a 6.6cM region on chromosome 15. Mutations in CCBE1 on chromosome 18 have been reported in some cases of lymphatic dysplasia, but not in LCS. METHODS: Consanguineous parents of Mexican ancestry had a child with LCS who did not exhibit extended homozygosity in the LCS1 region. A subsequent pregnancy was electively terminated due to fetal hydrops. We performed whole-genome single nucleotide polymorphism genotyping to identify regions of homozygosity in these siblings, and sequenced promising candidate genes. RESULTS: Both siblings harbored a homozygous mutation in CCBE1, c.398 T>C, predicted to result in the missense change p.L133P. Regions containing known 'cholestasis genes' did not demonstrate homozygosity in the LCS patient. CONCLUSIONS: Mutations in CCBE1 may yield a phenotype not only of lymphatic dysplasia, but also of LCS or fetal hydrops; however, the possibility that the sibling with LCS also carries a homozygous mutation in an unidentified gene influencing cholestasis cannot be excluded.

  10. Minimal role of hepatic transporters in the hepatoprotection against LCA-induced intrahepatic cholestasis.

    Science.gov (United States)

    Beilke, Lisa D; Besselsen, David G; Cheng, Quiqiong; Kulkarni, Supriya; Slitt, Angela L; Cherrington, Nathan J

    2008-03-01

    The multidrug resistance-associated proteins (Mrps) are a family of adenosine triphosphate-dependent transporters that facilitate the movement of various compounds, including bile acids, out of hepatocytes. The current study was conducted to determine whether induction of these transporters alters bile acid disposition as a means of hepatoprotection during bile acid-induced cholestasis. Lithocholic acid (LCA) was used to induce intrahepatic cholestasis. C57BL/6 mice were pretreated with corn oil (CO) or known transporter inducers, phenobarbital (PB), oltipraz (OPZ), or TCPOBOP (TC) for 3 days prior to cotreatment with LCA and inducer for 4 days. Histopathology revealed that PB and TC pretreatments provide a protective effect from LCA-induced toxicity, whereas OPZ pretreatment did not. Both PB/LCA and TC/LCA cotreatment groups also had significantly lower alanine aminotransferase values than the LCA-only group. In TC/LCA cotreated mice compared with LCA only, messenger RNA (mRNA) expression of uptake transporters Ntcp and Oatp4 was significantly increased, as were sinusoidal efflux transporters Mrp3 and Mrp4. Although in PB/LCA cotreated mice, the only significant change compared with LCA-only treatment was an increase in uptake transporter Oatp4. Oatp1 was reduced in all groups compared with CO controls. No significant changes in mRNA expression were observed in Oatp2, Bsep, Mrp2, Bcrp, Mrp1, Mrp5, or Mrp6. Mrp4 protein expression was induced in the OPZ/LCA and TC/LCA cotreated groups, whereas Mrp3 protein levels remained unchanged between groups. Protein expression of Mrp1 and Mrp5 was increased in the unprotected LCA-only and OPZ/LCA mice. Thus, transporter expression did not correlate with histologic hepatoprotection, however, there was a correlation between hepatoprotection and significantly reduced total liver bile acids in the PB/LCA and TC/LCA cotreated mice compared with LCA only. In conclusion, changes in transporter expression did not correlate with

  11. Infection by cytomegalovirus in patients with neonatal cholestasis Infecção por cytomegalovirus em pacientes com colestase neonatal

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    Nara Léia Gelle de OLIVEIRA

    2002-04-01

    Full Text Available Background - Neonatal cholestasis syndrome with an intra or extrahepatic origin has been associated to viral infections. The participation of the cytomegalovirus in the etiopathogenesis of neonatal hepatitis has been already known for some time, but only recently there have been indications that this virus may be one of the possible etiological factors for extrahepatic biliary atresia. Aims - To assess the prevalence of infection by cytomegalovirus in patients with intrahepatic cholestasis and extrahepatic cholestasis. To compare the clinical characteristics of the intrahepatic cholestasis and extrahepatic cholestasis groups with the cytomegalovirus serological results. Patients and Methods - This study consisted of 76 patients with neonatal cholestasis who were admitted between January 1980 and January 1999 when they underwent a cytomegalovirus serologic study using the ELISA method. A case note was kept on each patient with the following data: age of patient at admission, serologic result for cytomegalovirus, history of maternal infection, prematurity, fetal distress, birth weight, ponderal gain, choluria and fecal acholia. The final anatomic diagnosis of cholestasis was based on the results of an abdominal ultrasonography, a liver biopsy and its evolution. The patients were then divided into two groups: group I - intrahepatic cholestasis and group II - extrahepatic cholestasis. Each of these groups were then divided into two subgroups: subgroup A - positive serology (IgM for cytomegalovirus and subgroup B - negative serology (IgM for cytomegalovirus. Results - The frequency of positive serology (IgM for cytomegalovirus was 29.4% in children with intrahepatic cholestasis and 28.5% in children with extrahepatic cholestasis. In comparison with group IIB, group IIA presented a higher rate of maternal infection history. The patients in group IIA demonstrated a delayed access to the service in comparison with group IA. The groups did not

  12. [Intrahepatic cholestasis associated with parenteral nutrition: an experimental study in rats].

    Science.gov (United States)

    Salas Martínez, J; Morán Penco, J M; Mahedero Ruiz, G; García Gamito, F; Limón Mora, M; Maciá Botejara, E; Vinagre Velasco, L M

    1989-01-01

    Intrahepatic cholestasis is a condition often observed in patients receiving parenteral nutrition, especially in new born babies who are underweight (taurina. This makes it impossible to achieve a correct conjugation of toxic biliary acids. The access of nutrients to the liver may have an effect on this. An experimental study on rats was performed, administering an oral diet at the expense of lipids (20% Intralipid, 60% of caloric needs) and glucose (40% of caloric needs) in one group, another group received amino acid supplements to this diet (16N) at a proteic rate of 2 gr/kg of weight and day orally, with an identical diet to the above, except that the proteic intake was intraperitoneal. Two control groups were established. We found a microvacuolization in hepatic fat with the help of an electronic microscope in the groups lacking proteins and those with oral or intraperitoneal supplements of amino acids, as well as an increase in plasmatic AST.

  13. Hypervitaminosis A inducing intra-hepatic cholestasis--a rare case report.

    Science.gov (United States)

    Ramanathan, Vivek S; Hensley, Gary; French, Samuel; Eysselein, Victor; Chung, David; Reicher, Sonya; Pham, Binh

    2010-04-01

    The use of over-the-counter supplements is commonplace in today's health conscious society. We present an unusual case of intrahepatic cholestasis caused by vitamin A intoxication. The patient consumed one Herbalife shake with two multivitamin tablets of the same brand for 12 years. When calculated this equated to more than the recommended daily allowance for vitamin A consumption. Deranged liver function tests were consistent with a cholestatic process. Liver biopsy was obtained and revealed features pathognomonic of vitamin A toxicity, without the usual fibrosis. When the supplements were ceased, his jaundice and alkaline phosphatase completely normalized. This case highlights the importance of health care providers documenting non-prescribed dietary supplements and considering them in the etiology of cholestatic liver disease.

  14. Adrenal haemorrhage with cholestasis and adrenal crisis in a newborn of a diabetic mother.

    Science.gov (United States)

    Koklu, Esad; Kurtoglu, Selim; Akcakus, Mustafa; Koklu, Selmin

    2007-03-01

    The large hyperaemic foetal adrenal gland is vulnerable to vascular damage. This may occur in the neonatal period as a consequence of difficult labour, or its aetiology may not be apparent. The spectrum of presentation is considerable, ranging from asymptomatic to severe life-threatening intra-abdominal haemorrhage. The presentation of adrenal insufficiency may be delayed but the regenerative capacity of the adrenal is great, and most adrenal haemorrhage is not associated with significantly impaired function. Some reports showed that cholestatic hepatopathy with congenital hypopituitarism reversed by hydrocortisone treatment is considered in the context of the endocrine syndrome, probably as a consequence of the adrenal failure. We describe a case of bilateral adrenal haemorrhage with hepatitis syndrome and persistent hypoglycaemia in a newborn male with striking features of neonatal cholestasis and adrenal crisis.

  15. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Woolbright, Benjamin L.; Dorko, Kenneth [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Clarke, Joanna I. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Gholami, Parviz [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Li, Feng [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS (United States); Fan, Fang [Department of Pathology, University of Kansas Medical Center, Kansas City, KS (United States); Jenkins, Rosalind E.; Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Hagenbuch, Bruno [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Olyaee, Mojtaba [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  16. The Effect of Fish Oil-Based Lipid Emulsion and Soybean Oil-Based Lipid Emulsion on Cholestasis Associated with Long-Term Parenteral Nutrition in Premature Infants

    Science.gov (United States)

    Wang, Leilei; Zhang, Jing; Gao, Jiejin; Qian, Yan; Ling, Ya

    2016-01-01

    Purpose. To retrospectively study the effect of fish oil-based lipid emulsion and soybean oil-based lipid emulsion on cholestasis associated with long-term parenteral nutrition in premature infants. Methods. Soybean oil-based lipid emulsion and fish oil-based lipid emulsion had been applied in our neonatology department clinically between 2010 and 2014. There were 61 qualified premature infants included in this study and divided into two groups. Soybean oil group was made up of 32 premature infants, while fish oil group was made up of 29 premature infants. Analysis was made on the gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, age at which feeding began, usage of lipid emulsions, and incidence of cholestasis between the two groups. Results. There were no statistical differences in terms of gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, and age at which feeding began. Besides, total incidence of cholestasis was 21.3%, and the days of life of occurrence of cholestasis were 53 ± 5.0 days. Incidence of cholestasis had no statistical difference in the two groups. Conclusion. This study did not find the different role of fish oil-based lipid emulsions and soybean oil-based lipid emulsions in cholestasis associated with long-term parenteral nutrition in premature infants. PMID:27110237

  17. The Effect of Fish Oil-Based Lipid Emulsion and Soybean Oil-Based Lipid Emulsion on Cholestasis Associated with Long-Term Parenteral Nutrition in Premature Infants

    Directory of Open Access Journals (Sweden)

    Leilei Wang

    2016-01-01

    Full Text Available Purpose. To retrospectively study the effect of fish oil-based lipid emulsion and soybean oil-based lipid emulsion on cholestasis associated with long-term parenteral nutrition in premature infants. Methods. Soybean oil-based lipid emulsion and fish oil-based lipid emulsion had been applied in our neonatology department clinically between 2010 and 2014. There were 61 qualified premature infants included in this study and divided into two groups. Soybean oil group was made up of 32 premature infants, while fish oil group was made up of 29 premature infants. Analysis was made on the gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, age at which feeding began, usage of lipid emulsions, and incidence of cholestasis between the two groups. Results. There were no statistical differences in terms of gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, and age at which feeding began. Besides, total incidence of cholestasis was 21.3%, and the days of life of occurrence of cholestasis were 53±5.0 days. Incidence of cholestasis had no statistical difference in the two groups. Conclusion. This study did not find the different role of fish oil-based lipid emulsions and soybean oil-based lipid emulsions in cholestasis associated with long-term parenteral nutrition in premature infants.

  18. The Effect of Fish Oil-Based Lipid Emulsion and Soybean Oil-Based Lipid Emulsion on Cholestasis Associated with Long-Term Parenteral Nutrition in Premature Infants.

    Science.gov (United States)

    Wang, Leilei; Zhang, Jing; Gao, Jiejin; Qian, Yan; Ling, Ya

    2016-01-01

    Purpose. To retrospectively study the effect of fish oil-based lipid emulsion and soybean oil-based lipid emulsion on cholestasis associated with long-term parenteral nutrition in premature infants. Methods. Soybean oil-based lipid emulsion and fish oil-based lipid emulsion had been applied in our neonatology department clinically between 2010 and 2014. There were 61 qualified premature infants included in this study and divided into two groups. Soybean oil group was made up of 32 premature infants, while fish oil group was made up of 29 premature infants. Analysis was made on the gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, age at which feeding began, usage of lipid emulsions, and incidence of cholestasis between the two groups. Results. There were no statistical differences in terms of gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, and age at which feeding began. Besides, total incidence of cholestasis was 21.3%, and the days of life of occurrence of cholestasis were 53 ± 5.0 days. Incidence of cholestasis had no statistical difference in the two groups. Conclusion. This study did not find the different role of fish oil-based lipid emulsions and soybean oil-based lipid emulsions in cholestasis associated with long-term parenteral nutrition in premature infants.

  19. Treatment of pruritus with Prometheus dialysis and absorption system in a patient with benign recurrent intrahepatic cholestasis.

    Science.gov (United States)

    Ołdakowska-Jedynak, Urszula; Jankowska, Irena; Hartleb, Marek; Jirsa, Milan; Pawłowska, Joanna; Czubkowski, Piotr; Krawczyk, Marek

    2014-10-01

    Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disorder characterized by recurrent episodes of jaundice and itching. Episodes of cholestasis last variously from 1 week to several months, may start at any age and usually resolve spontaneously. No effective treatment has been found as yet. We report a case of genetically proven BRIC in a male patient who developed three episodes of pruritus and jaundice at the age of 14, 16 and 19 years. During the third episode, he did not respond to pharmacological medical therapy, and fractionated plasma separation and absorption (FPSA, Prometheus) was performed to manage intractable pruritus. The treatment immediately alleviated pruritus, lowered serum bilirubin concentration and induced sustained remission in the 5-year follow up. FPSA seems to be a safe and effective way of treatment for BRIC in patients with severe pruritus and prolonged jaundice.

  20. Effects of dopamine receptor agonist and antagonists on cholestasis-induced anxiolytic-like behaviors in rats.

    Science.gov (United States)

    Reza Zarrindast, Mohammad; Eslimi Esfahani, Delaram; Oryan, Shahrbano; Nasehi, Mohammad; Torabi Nami, Mohammad

    2013-02-28

    Dysfunctions in the dopamine transmission system have been suggested to contribute to the pathogenesis of hepatic encephalopathy. In an experimental animal model, cholestasis induction through bile duct ligation may present several main pathological features of hepatic encephalopathy. Dopaminergic systems are shown to play pivotal roles in regulation of anxiety-like behaviors. The main bile duct in male Wistar rats, weighing 220-240 g, was ligated using two ligatures plus duct transection in between. Anxiety-like behaviors were measured using the elevated plus maze task. Cholestasis increased the open arm time percentage (%OAT), 13 but not 10 days after bile duct ligation, indicating an anxiolytic-like effect. Sole intraperitoneal injection of apomorphine (dopamine D1/D2 receptor agonist, 0.25 mg/kg), SCH23390 (dopamine D1 receptor antagonist, 0.005, 0.01 and 0.02 mg/kg) or sulpiride (dopamine D2 receptor antagonist, 0.125, 0.25 and 0.5 mg/kg) did not alter %OAT, open arm entries percentage (%OAE) and locomotor activity in the sham-operated rats. Meanwhile, the higher dose apomorphine (0.5 mg/kg) induced anxiolytic-like behaviors in this group. The subthreshold dose injection of SCH23390 or sulpiride, partially reversed the anxiolytic-like behaviors induced by cholestasis (13 days after bile duct ligation). On the other hand, subthreshold dose of apomorphine in cholestatic rats (10 days post bile duct ligation) induced anxiolytic-like effects which could be blocked by SCH23390 or sulpiride. The effective doses of above drugs did not alter locomotor activity, number of rearings, groomings and defections. These findings suggested that the dopaminergic system may potentially be involved in the modulation of cholestasis-induced anxiolytic-like behaviors in rats.

  1. Colestase neonatal prolongada: estudo prospectivo Prolonged neonatal cholestasis: a prospective study

    Directory of Open Access Journals (Sweden)

    Elizabeth Teixeira Mendes Livramento PRADO

    1999-12-01

    completo e abrangente, evoluindo para a ideal diminuição progressiva dos processos idiopáticos.Due to the urgency in choosing either clinical treatment or immediate surgical intervention, the study of the prolonged neonatal cholestasis involves two basic aims: the differential diagnosis between biliary atresia and neonatal hepatitis and the research into the associated etiological agents. So, in a prospective trial carried out in the 70´s, 77 children with prolonged neonatal cholestasis were studied in order to establish the differential diagnosis between biliary atresia and neonatal hepatitis, followed by the evaluation of 108 children towards a pathogenesis of the prolonged neonatal cholestasis. The results of the differential diagnosis showed that within 18 items examined only 8 proved to be good biliary atresia indicators. They are as follows (in decreasing order: ductular proliferation (portal tracts, fibrosis (portal tracts, cholestasis (portal tracts, stools colour -- acholia, hepatomegaly, canalicular cholestasis (lobule, infiltrate (portal tracts, giant cells (lobule. These eight items were then gathered in a sole indicator of great discriminative power, with a confidence level of 99%. The figures regarding the pathogenesis are: rubella virus 0%, herpes simplex virus 0%, listeriosis 0%, cytomegalovirus 2.2%, hepatitis B virus 2.4%, toxoplasmosis 2.8%, alpha-1-antitrypsin deficiency 13.1%, syphilis 21.1%, autoantibodies against the liver 58.4%. Such work thus revealed that those eight most important factors when differentiating biliary atresia from neonatal hepatitis remain as fundamental indicators and, when employed alongside other diagnostic methods, can help in the assembling of a multifactorial strategy less and less invasive and more precise. The pathogenic study, with its heavy dependency on time and place, has become more complete with the introduction of new diagnostic methods, evolving to the ideal progressive reduction of idiopathic processes.

  2. INCREASE OF GLYCOSAMINOGLYCANS AND METALLOPROTEINASES 2 AND 9 IN LIVER EXTRACELLULAR MATRIX ON EARLY STAGES OF EXTRAHEPATIC CHOLESTASIS

    Directory of Open Access Journals (Sweden)

    Pedro Luiz Rodrigues GUEDES

    2014-12-01

    Full Text Available Context Cholestasis produces hepatocellular injury, leukocyte infiltration, ductular cells proliferation and fibrosis of liver parenchyma by extracellular matrix replacement. Objective Analyze bile duct ligation effect upon glycosaminoglycans content and matrix metalloproteinase (MMPs activities. Methods Animals (6-8 weeks; n = 40 were euthanized 2, 7 or 14 days after bile duct ligation or Sham-surgery. Disease evolution was analyzed by body and liver weight, seric direct bilirubin, globulins, gamma glutamyl transpeptidase (GGT, alkaline phosphatase (Alk-P, alanine and aspartate aminotransferases (ALT and AST, tissue myeloperoxidase and MMP-9, pro MMP-2 and MMP-2 activities, histopathology and glycosaminoglycans content. Results Cholestasis caused cellular damage with elevation of globulins, GGT, Alk-P, ALT, AST. There was neutrophil infiltration observed by the increasing of myeloperoxidase activity on 7 (P = 0.0064 and 14 (P = 0.0002 groups which leads to the magnification of tissue injuries. Bile duct ligation increased pro-MMP-2 (P = 0.0667, MMP-2 (P = 0.0003 and MMP-9 (P<0.0001 activities on 14 days indicating matrix remodeling and establishment of inflammatory process. Bile duct ligation animals showed an increasing on dermatan sulfate and/or heparan sulfate content reflecting extracellular matrix production and growing mitosis due to parenchyma depletion. Conclusions Cholestasis led to many changes on rats’ liver parenchyma, as so as on its extracellular matrix, with major alterations on MMPs activities and glycosaminoglycans content.

  3. Upregulation of PDZK1 by Calculus Bovis Sativus May Play an Important Role in Restoring Biliary Transport Function in Intrahepatic Cholestasis

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    Dong Xiang

    2017-01-01

    Full Text Available Intrahepatic cholestasis is a main cause of hepatic accumulation of bile acids leading to liver injury, fibrosis, and liver failure. Our previous studies proved that Calculus Bovis Sativus (CBS can restore biliary transport function through upregulating the multidrug resistance-associated protein 2 (MRP2 and breast cancer resistance protein (BCRP in 17α-ethynylestradiol- (EE- induced intrahepatic cholestasis rats. The regulation mechanism of CBS on these transporters, however, remains unclear. This study was designed to evaluate the possible relationship between the effect of CBS on transport activities and the regulation of CBS on the expression of PDZK1, a mainly scaffold protein which can regulate MRP2 and BCRP. Intrahepatic cholestasis model was induced in rats with injection of EE for five consecutive days and then the biliary excretion rates and cumulative biliary excretions were measured. The mRNA and protein expression levels of PDZK1 were detected by reverse transcription-quantitative real-time polymerase chain reaction, western blot, and immunohistochemical analysis. When treated with CBS, cumulative biliary excretions and mRNA and protein expressions of PDZK1 were significantly increased in intrahepatic cholestasis rats. This study demonstrated that CBS exerted a beneficial effect on EE-induced intrahepatic cholestasis rats by restoring biliary transport function, which may result from the upregulation of PDZK1 expression.

  4. Role of ciprofloxacin in patients with cholestasis after endoscopic retrograde cholangiopancreatography

    Institute of Scientific and Technical Information of China (English)

    Thawee Ratanachu-ek; Pitchaya Prajanphanit; Kawin Leelawat; Suchart Chantawibul; Sukij Panpimanmas; Somboon Subwongcharoen; Jerasak Wannaprasert

    2007-01-01

    AIM: To determine the role of ciprofloxacin in reducing cholangitis in cholestatic patients with adequate biliary drainage after endoscopic retrograde cholangiopancreatography (ERCP).METHODS: A randomized, controlled trial was performed in 48 cholestatic patients at Rajavithi Hospital (Tertiary Referral Center for ERCP: 600 cases per year). All the 48 patients received 200 mg ciprofloxacin intravenous injection for 30 min before starting any procedures, and then were randomly divided in two groups. Twenty-two patients in study group continually received ciprofloxacin until 48 h after ERCP. Causes of biliary obstruction, bacteriology of bile and blood (in cholangitis) and clinical cholangitis were recorded.RESULTS: Forty-eight patients were enrolled and divided into continuous ciprofloxacin treatment group (n = 22) and discontinuous ciprofloxacin treatment group (n = 26). During ERCP, stones were found in 22 patients,malignant diseases in 24 patients and other pathologic lesions in 5 patients. One (4.5%) of the 22 patients who received ciprofloxacin and 2 (6.3%) of the 26 patients who discontinued ciprofloxacin after ERCP developed cholangitis (relative risk = 0.71; 95% CI = 0.14-3.65;P = 0.88). Bacterobilia was found in 27 (56.3%) out of 48 patients. E. coli and Streptococcus viridans were the most common organisms.CONCLUSION: Continual use of ciprofloxacin in patients with cholestasis after adequate biliary drainage procedures plays no role in reducing cholangitis.

  5. Bile duct ligation in mice: induction of inflammatory liver injury and fibrosis by obstructive cholestasis.

    Science.gov (United States)

    Tag, Carmen G; Sauer-Lehnen, Sibille; Weiskirchen, Sabine; Borkham-Kamphorst, Erawan; Tolba, René H; Tacke, Frank; Weiskirchen, Ralf

    2015-02-10

    In most vertebrates, the liver produces bile that is necessary to emulsify absorbed fats and enable the digestion of lipids in the small intestine as well as to excrete bilirubin and other metabolic products. In the liver, the experimental obstruction of the extrahepatic biliary system initiates a complex cascade of pathological events that leads to cholestasis and inflammation resulting in a strong fibrotic reaction originating from the periportal fields. Therefore, surgical ligation of the common bile duct has become the most commonly used model to induce obstructive cholestatic injury in rodents and to study the molecular and cellular events that underlie these pathophysiological mechanisms induced by inappropriate bile flow. In recent years, different surgical techniques have been described that either allow reconnection or reanastomosis after bile duct ligation (BDL), e.g., partial BDL, or other microsurgical methods for specific research questions. However, the most frequently used model is the complete obstruction of the common bile duct that induces a strong fibrotic response after 21 to 28 days. The mortality rate can be high due to infectious complications or technical inaccuracies. Here we provide a detailed surgical procedure for the BDL model in mice that induce a highly reproducible fibrotic response in accordance to the 3R rule for animal welfare postulated by Russel and Burch in 1959.

  6. Incidence and Risk Factors of Parenteral Nutrition-Associated Cholestasis in Omani Neonates; Single centre experience

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    Sharef W. Sharef

    2015-05-01

    Full Text Available Objectives: Parenteral nutrition-associated cholestasis (PNAC is one of the most challenging complications of prolonged parenteral nutrition (PN in neonates. There is a lack of research investigating its incidence in newborn infants in Oman and the Arab region. Therefore, this study aimed to assess the incidence of PNAC and its risk factors in Omani neonates. Methods: This retrospective study took place between January and April 2014. All neonates who received PN for ≥14 days during a four-year period (June 2009 to May 2013 at the neonatal intensive care unit (NICU in Sultan Qaboos University Hospital, Muscat, Oman, were enrolled. Results: A total of 1,857 neonates were admitted to the NICU over the study period and 135 neonates (7.3% received PN for ≥14 days. Determining the incidence of PNAC was only possible in 97 neonates; of these, 38 (39% had PNAC. The main risk factors associated with PNAC were duration of PN, duration of enteral starvation, gastrointestinal surgeries, blood transfusions and sepsis. Neonates with PNAC had a slightly higher incidence of necrotising enterocolitis in comparison to those without PNAC. Conclusion: This study found a PNAC incidence of 39% in Omani neonates. There were several significant risk factors for PNAC in Omani neonates; however, after logistic regression analysis, only total PN duration remained statistically significant. Preventive strategies should be implemented in NICUs so as to avoid future chronic liver disease in this population.

  7. Antioxidant Effect of Sepia Ink Extract on Extrahepatic Cholestasis Induced by Bile Duct Ligation in Rats

    Institute of Scientific and Technical Information of China (English)

    Hanan Saleh; Amel M Soliman; Ayman S Mohamed; Mohamed-Assem S Marie

    2015-01-01

    Objective The aim of our study was to assess the complications of hepatic fibrosis associated with bile duct ligation and the potential curative role of sepia ink extract in hepatic damage induced by bile duct ligation. Methods Rattus norvegicus rats were divided into 3 groups: Sham-operated group, model rats that underwent common bile duct ligation (BDL), and BDL rats treated orally with sepia ink extract (200 mg/kg body weight) for 7, 14, and 28 d after BDL. Results There was a significant reduction in hepatic enzymes, ALP, GGT, bilirubin levels, and oxidative stress in the BDL group after treatment with sepia ink extract. Collagen deposition reduced after sepia ink extract treatment as compared to BDL groups, suggesting that the liver was repaired. Histopathological examination of liver treated with sepia ink extract showed moderate degeneration in the hepatic architecture and mild degeneration in hepatocytes as compared to BDL groups. Conclusion Sepia ink extract provides a curative effect and an antioxidant capacity on BDL rats and could ameliorate the complications of liver cholestasis.

  8. Effect of Intrahepatic Cholestasis of Pregnancy on Cytokines, Hemorheology and Coagulation Function of Pregnant Women

    Institute of Scientific and Technical Information of China (English)

    YU Cui-ge; LI Lian-xiang; LIU Xiao-qin; SHI Jian-yong

    2015-01-01

    Objective:To explore the effect of intrahepatic cholestasis of pregnancy (ICP) on the cytokines, hemorheology and coagulation function of pregnant women. Methods: A total of 43 singleton pregnant women with ICP delivered in Shaanxi Provincial People’s Hospital from June 2014 to June 2015 were selected as observation group, and 45 singleton healthy pregnant women accompanied by indications of cesarean section were selected as control group. Automatic Viscometer was used to detect the hematological indexes, Automatic Coagulometer to detect the indexes related to coagulation function and radioimmunoassay to determine the levels of cell inflammatory factors, and the pregnancy outcomes were closely observed. Results:The levels of interleukin-12 (IL-12), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), high and low shear rates of whole blood viscosity, hematokrit, plasma viscosity and erythrocyte sedimentation rate (ESR) in observation group were all dramatically higher than those in control group, and all the differences were statistically signiifcant (P0.05). When compared with control group, the levels of D-dimer (D-D) and fibrinogen (FIB) in observation group increased dramatically (P0.05). Conclusion: Both the hemorheology and coagulation function of pregnant women with ICP manifest signiifcantly high viscosity and hypercoagulability, and the release of cell inlfammatory factors increases, which all exert adverse inlfuence on pregnancy outcome.

  9. Leukocytapheresis Therapy Improved Cholestasis in a Patient Suffering from Primary Sclerosing Cholangitis with Ulcerative Colitis

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    Minoru Itou

    2009-04-01

    Full Text Available Primary sclerosing cholangitis (PSC is an autoimmune disease of the hepatobiliary system for which effective therapy has not been established. Leukocytapheresis (LCAP therapy is known to effective in patients with ulcerative colitis (UC. In addition, effects of LCAP therapy were reported on some autoimmune diseases such as Crohn’s disease, rheumatoid arthritis and rapidly progressive glomerulonephritis. Here we report the case of a 29-year-old man with PSC associated with UC who was treated with LCAP therapy. He had a 16-year history of UC and a 12-year history of PSC. Although he was under treatment with prednisolone and ursodeoxycholic acid, exacerbation of UC and PSC-associated cholestasis were seen. Since he showed side effects of prednisolone, he was treated with LCAP. Not only improvement of UC, but also decreased serum alkaline phosphatase, γ-guanosine triphosphate and total bile acids, suggesting improvement of PSC-associated cholestaisis, were seen after treatment with LCAP. Our experience with this case suggests that LCAP therapy could be a new effective therapeutic strategy for patients with PSC associated with UC.

  10. Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Fabio Marra; Carlo Spirli; Mario Strazzabosco; Massimo Pinzani; Maurizio Parola; Raffaella DeFranco; Gaia Robino; Erica Novo; Eva Efsen; Sabrina Pastacaldi; Elena Zamara; Alessandro Vercelli; Benedetta Lottini

    2005-01-01

    AIM: To investigate the effects of troglitazone (TGZ), an anti-diabetic drug which activates peroxisome proliferatoractivated receptor-γ (PPAR-γ), for liver tissue repair, and the development of ductular reaction, following common bile duct ligation (BDL) in rats.METHODS: Rats were supplemented with TGZ (0.2% w/w in the pelleted food) for 1 wk before BDL or sham operation.Animals were killed at 1, 2, or 4 wk after surgery.RESULTS: The development of liver fibrosis was reduced in rats receiving TGZ, as indicated by significant decreases of procollagen type Ⅰ gene expression and liver hydroxyproline levels. Accumulation of α-smooth-muscle actin (SMA)-expressing cells surrounding newly formed bile ducts following BDL, as well as total hepatic levels of SMA were partially inhibited by TGZ treatment, indicating the presence of a reduced number and/or activation of hepatic stellate cells (HSC) and myofibroblasts. Development of the ductular reaction was inhibited by TGZ, as indicated by histochemical evaluation and hepatic activity of γ-glutamyltransferase (GGT).CONCLUSION: Treatment with thiazolidinedione reduces ductular proliferation and fibrosis in a model of chronic cholestasis, and suggests that limiting cholangiocyte proliferation may contribute to the lower development of scarring in this system.

  11. Predictors of premature delivery in patients with intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    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.

  12. Growth evaluation in infants with neonatal cholestasis Antropometria em crianças com colestase neonatal

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    Camila Carbone Prado

    2006-12-01

    Full Text Available BACKGROUD: Chronic liver diseases in childhood often cause undernutrition and growth failure. To our knowledge, growth parameters in infants with neonatal cholestasis are not available AIM: To evaluate the nutritional status and growth pattern in infants with intrahepatic cholestasis and extrahepatic cholestasis. PATIENTS AND METHODS: One hundred forty-four patients with neonatal cholestasis were followed up at the Pediatric Gastroenterology Service of the Teaching Hospital, State University of Campinas, Campinas, SP, Brazil, in a 23-year period, from 1980 to 2003. The records of these patients were reviewed and patients were classified into two groups, according to their anatomical diagnosis: patients with intrahepatic cholestasis - group 1, and patients with extrahepatic cholestasis - group 2. Records of weight and height measurements were collected at 4 age stages of growth, in the first year of life: 1 from the time of the first medical visit to the age of 4 months (T1; 2 from the 5th to the 7th month (T2; 3 from the 8th to the 10th month (T3; and 4 from the 11th to the 13th month (T4. The weight-by-age and height-by-age Z-scores were calculated for each patient at each stage. In order for the patient to be included in the study it was necessary to have the weight and/or height measurements at the 4 stages. Analyses of variance and Tukey's tests were used for statistical analysis. Repeated measurement analyses of variance of the weight-by-age Z-score were performed in a 60-patient sample, including 29 patients from group 1 and 31 patients from group 2. The height-by-age data of 33 patients were recorded, 15 from group 1 and 18 from group 2 RESULTS: The mean weight-by-age Z-scores of group 1 patients at the 4 age stages were: T1=-1.54; T2=-1.40; T3=-0.94; T4=-0.78. There was a significant difference between T2 X T3 and T1 X T4. The weight-by-age Z-scores for group 2 patients were :T1=-1.04; T2=-1.67; T3=-1.93 and T4=-1.77, with a significant

  13. Effects of curcumin on cyclosporine-induced cholestasis and hypercholesterolemia and on cyclosporine metabolism in the rat.

    Science.gov (United States)

    Deters, Michael; Klabunde, Til; Meyer, Hartmut; Resch, Klaus; Kaever, Volkhard

    2003-04-01

    Former studies have shown that curcumin, which can be extracted from different Curcuma species, is able to stimulate bile flow and to reduce hypercholesterolemia. We investigated in a subchronic bile fistula model the ability of curcumin to reduce cyclosporine-induced cholestasis and hypercholesterolemia. Male Wistar rats were daily treated with curcumin (100 mg/kg p. o.), cyclosporine (10 mg/kg i. p.), and a combination of curcumin with cyclosporine. After two weeks a bile fistula was installed into the rats to measure bile flow and biliary excretion of bile salts, cholesterol, bilirubin, cyclosporine and its main metabolites. Blood was taken to determine the concentration of these parameters in serum or blood. Cyclosporine reduced bile flow (-14 %) and biliary excretion of bile salts (-10 %) and cholesterol (-61 %). On the other hand, cyclosporine increased serum concentrations of cholesterol and triglycerides by 32 % and 82 %, respectively. Sole administration of curcumin led to a slight decrease of bile flow (-7 %) and biliary bile salt excretion (-12 %), but showed no effect on biliary excretion of cholesterol and serum lipid concentration. When curcumin was given simultaneously with cyclosporine, the cyclosporine-induced cholestasis was enhanced but the cyclosporine-induced hyperlipidemia was not affected. Neither the biliary excretion nor the blood concentration of cyclosporine was influenced by curcumin. The blood concentration of the main cyclosporine metabolites, however, was lowered by half while their biliary excretion was strongly increased by curcumin. From these results we conclude that curcumin is not able to prevent cyclosporine-induced cholestasis and hyperlipidemia after prolonged administration in bile fistula rats.

  14. Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic Bile Acid Signaling.

    Science.gov (United States)

    McMillin, Matthew; Frampton, Gabriel; Quinn, Matthew; Divan, Ali; Grant, Stephanie; Patel, Nisha; Newell-Rogers, Karen; DeMorrow, Sharon

    2015-12-01

    Suppression of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to occur during cholestatic liver injury. Furthermore, we have demonstrated that in a model of cholestasis, serum bile acids gain entry into the brain via a leaky blood brain barrier and that hypothalamic bile acid content is increased. Therefore, the aim of the current study was to determine the effects of bile acid signaling on the HPA axis. The data presented show that HPA axis suppression during cholestatic liver injury, specifically circulating corticosterone levels and hypothalamic corticotropin releasing hormone (CRH) expression, can be attenuated by administration of the bile acid sequestrant cholestyramine. Secondly, treatment of hypothalamic neurons with various bile acids suppressed CRH expression and secretion in vitro. However, in vivo HPA axis suppression was only evident after the central injection of the bile acids taurocholic acid or glycochenodeoxycholic acid but not the other bile acids studied. Furthermore, we demonstrate that taurocholic acid and glycochenodeoxycholic acid are exerting their effects on hypothalamic CRH expression after their uptake through the apical sodium-dependent bile acid transporter and subsequent activation of the glucocorticoid receptor. Taken together with previous studies, our data support the hypothesis that during cholestatic liver injury, bile acids gain entry into the brain, are transported into neurons through the apical sodium-dependent bile acid transporter and can activate the glucocorticoid receptor to suppress the HPA axis. These data also lend themselves to the broader hypothesis that bile acids may act as central modulators of hypothalamic peptides that may be altered during liver disease.

  15. Fetal outcomes in pregnancies complicated by intrahepatic cholestasis of pregnancy in a Northern California cohort.

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    Michelle Rook

    Full Text Available BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP has important fetal implications. There is increased risk for poor fetal outcomes, including preterm delivery, meconium staining of amniotic fluid, respiratory distress, fetal distress and demise. METHODS: One hundred and one women diagnosed with ICP between January 2005 and March 2009 at San Francisco General Hospital were included in this study. Single predictor logistic regression models were used to assess the associations of maternal clinical and biochemical predictors with fetal complications. Clinical predictors analyzed included age, race/ethnicity, gravidity, parity, history of liver or biliary disease, history of ICP in previous pregnancies, and induction. Biochemical predictors analyzed included serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, albumin, total protein, and total bile acids (TBA. RESULTS: The prevalence of ICP was 1.9%. Most were Latina (90%. Labor was induced in the majority (87% and most were delivered by normal spontaneous vaginal delivery (84%. Fetal complications occurred in 33% of the deliveries, with respiratory distress accounting for the majority of complications. There were no statistically significant clinical or biochemical predictors associated with an increased risk of fetal complications. Elevated TBA had little association with fetal complications until reaching greater than 100 µmoL/L, with 3 out of 5 having reported complications. ICP in previous pregnancies was associated with decreased risk of fetal complications (OR 0.21, p = 0.046. There were no cases of late term fetal demise. CONCLUSIONS: Maternal clinical and laboratory features, including elevated TBA, did not appear to be substantial predictors of fetal complications in ICP.

  16. RIP3 Inhibits Inflammatory Hepatocarcinogenesis but Promotes Cholestasis by Controlling Caspase-8- and JNK-Dependent Compensatory Cell Proliferation

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    Mihael Vucur

    2013-08-01

    Full Text Available For years, the term “apoptosis” was used synonymously with programmed cell death. However, it was recently discovered that receptor interacting protein 3 (RIP3-dependent “necroptosis” represents an alternative programmed cell death pathway activated in many inflamed tissues. Here, we show in a genetic model of chronic hepatic inflammation that activation of RIP3 limits immune responses and compensatory proliferation of liver parenchymal cells (LPC by inhibiting Caspase-8-dependent activation of Jun-(N-terminal kinase in LPC and nonparenchymal liver cells. In this way, RIP3 inhibits intrahepatic tumor growth and impedes the Caspase-8-dependent establishment of specific chromosomal aberrations that mediate resistance to tumor-necrosis-factor-induced apoptosis and underlie hepatocarcinogenesis. Moreover, RIP3 promotes the development of jaundice and cholestasis, because its activation suppresses compensatory proliferation of cholangiocytes and hepatic stem cells. These findings demonstrate a function of RIP3 in regulating carcinogenesis and cholestasis. Controlling RIP3 or Caspase-8 might represent a chemopreventive or therapeutic strategy against hepatocellular carcinoma and biliary disease.

  17. [A difficult and complicated case study: neonatal intrahepatic cholestasis caused by citrin deficiency].

    Science.gov (United States)

    Song, Yuan-Zong; Hao, Hu; Ushikai, Miharu; Liu, Guo-Sheng; Xiao, Xin; Saheki, Takeyori; Kobayashi, Keiko; Wang, Zi-Neng

    2006-04-01

    Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a kind of inborn errors of metabolism, with the main clinic manifestations of jaundice, hepatomegaly, and abnormal liver function indices. As a mitochondrial solute carrier protein, citrin plays important roles in aerobic glycolysis, gluconeogenesis, urea cycle, and protein and nucleotide syntheses. Therefore citrin deficiency causes various and complicated metabolic disturbances, such as hypoglycemia, hyperlactic acidemia, hyperammonemia, hypoproteinemia, hyperlipidemia, and galactosemia. This paper reported a case of NICCD confirmed by mutation analysis of SLC25A13, the gene encoding citrin. The baby (male, 6 months old) was referred to the First Affiliated Hospital with the complaint of jaundice of the skin and sclera, which it had suffered from for nearly 6 months. Physical examination showed obvious jaundice and a palpable liver 5 cm below the right subcostal margin. Liver function tests revealed elevated enzymatic activities, like GGT, ALP, AST, and ALT, together with increased levels of TBA, bilirubin (especially conjugated bilirubin), and decreased levels of total protein/albumin and fibrinogen. Blood levels of ammonia, lactate, cholesterol, and triglyceride were also increased, and in particular, the serum AFP level reached 319,225.70 microg/L, a extremely elevated value that has rarely been found in practice before. Tandem mass analysis of a dried blood sample revealed increased levels of free fatty acids and tyrosine, methionine, citrulline, and threonine as well. UP-GC-MS analysis of the urine sample showed elevated galactose and galactitol. The baby was thus diagnosed with suspected NICCD based on the findings. It was then treated with oral arginine and multiple vitamins (including fat-soluble vitamins A, D, E, and K), and was fed with lactose-free and medium-chain fatty acids enriched formula instead of breast feeding. After half a month of treatment, the jaundice disappeared

  18. Effect of Intrahepatic Cholestasis of Pregnancy on Cytokines, Hemorheology and Coagulation Function of Pregnant Women

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    Cui-ge YU

    2015-12-01

    Full Text Available Abstract Objective: To explore the effect of intrahepatic cholestasis of pregnancy (ICP on the cytokines, hemorheology and coagulation function of pregnant women. Methods: A total of 43 singleton pregnant women with ICP delivered in Shaanxi Provincial People’s Hospital from June 2014 to June 2015 were selected as observation group, and 45 singleton healthy pregnant women accompanied by indications of cesarean section were selected as control group. Automatic Viscometer was used to detect the hematological indexes, Automatic Coagulometer to detect the indexes related to coagulation function and radioimmunoassay to determine the levels of cell inflammatory factors, and the pregnancy outcomes were closely observed. Results: The levels of interleukin-12 (IL-12, interleukin-18 (IL-18, tumor necrosis factor-α (TNF-α, high and low shear rates of whole blood viscosity, hematokrit, plasma viscosity and erythrocyte sedimentation rate (ESR in observation group were all dramatically higher than those in control group, and all the differences were statistically significant (P<0.01. There was no statistical significance between two groups with regard to prothrombin When compared with control group, the levels of D-dimer (D-D and fibrinogen (FIB in observation group increased dramatically (P<0.01, but platelet (PLT decreased markedly (P<0.01. The incidence of amniotic fluid pollution and premature delivery in observation group was higher than in control group (P<0.05 or P<0.01, and that of fetal distress, neonatal asphyxia and low birth weight tended to be higher than in control group, but there was no statistical significance (P>0.05. Conclusion: Both the hemorheology and coagulation function of pregnant women with ICP manifest significantly high viscosity and hypercoagulability, and the release of cell inflammatory factors increases, which all exert adverse influence on pregnancy outcome. time (PT and activated

  19. Changes of hemorheological indeses, coagulation function and cytokines in women with intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    Li Zhang; Xiao-Li Li; Yuan-Xia Lan

    2015-01-01

    Objective:To explore the changes of hemorheological indexes, coagulation function and cytokines of women with intrahepatic cholestasis of pregnancy ICP.Methods: A total of 54 cases of ICP in our hospital were collected as study group, 54 cases of normal pregnancy period were collected as the control group. The changes of coagulation function, inflammatory cytokines and D- two dimer of two groups were observed and compared.Results: The blood rheology indexes such as whole blood viscosity at high shear, whole blood viscosity at low shear, plasma viscosity, hematocrit and erythrocyte sedimentation rate of study group were (4.73±0.81) mPa•s, (6.67±1.40) mPa•s, (1.93±0.38) mPa•s, (46.34±4.25)%, and the (68.92±7.93) mm/h, respectively; they were significantly higher than those of control group (P0.05). FIB, D-D of the study group respectively were (5.62±0.78) g/L, (0.45±0.11) mg/L, significantly higher than the control group. PLT was (168.44±16.35)í109/L, and was significantly reduced compared with the control group (P<0.05). The levels of IL-18, IL-12, TNF-α of the study Group were (70.22±5.33) ng/L,(47.55±4.23) ng/L and (40.45±3.45) ng/L, respectively. Compared with normal pregnancy control they was significantly increased (P<0.05). The rates of premature delivery, amniotic fluid contamination, fetal distress, neonatal asphyxia and low birth weight infants were 20.37%, 37.04%, 18.52%, 11.11% and 9.26%, significantly higher than the control group (P<0.05).Conclusion: ICP patients have significantly high viscosity changes, high coagulation and has adverse effects on pregnancy outcome, which play important roles in the clinical diagnosis.

  20. Activation of the renin-angiotensin system stimulates biliary hyperplasia during cholestasis induced by extrahepatic bile duct ligation.

    Science.gov (United States)

    Afroze, Syeda H; Munshi, Md Kamruzzaman; Martínez, Allyson K; Uddin, Mohammad; Gergely, Maté; Szynkarski, Claudia; Guerrier, Micheleine; Nizamutdinov, Damir; Dostal, David; Glaser, Shannon

    2015-04-15

    Cholangiocyte proliferation is regulated in a coordinated fashion by many neuroendocrine factors through autocrine and paracrine mechanisms. The renin-angiotensin system (RAS) is known to play a role in the activation of hepatic stellate cells and blocking the RAS attenuates hepatic fibrosis. We investigated the role of the RAS during extrahepatic cholestasis induced by bile duct ligation (BDL). In this study, we used normal and BDL rats that were treated with control, angiotensin II (ANG II), or losartan for 2 wk. In vitro studies were performed in a primary rat cholangiocyte cell line (NRIC). The expression of renin, angiotensin-converting enzyme, angiotensinogen, and angiotensin receptor type 1 was evaluated by immunohistochemistry (IHC), real-time PCR, and FACs and found to be increased in BDL compared with normal rat. The levels of ANG II were evaluated by ELISA and found to be increased in serum and conditioned media of cholangiocytes from BDL compared with normal rats. Treatment with ANG II increased biliary mass and proliferation in both normal and BDL rats. Losartan attenuated BDL-induced biliary proliferation. In vitro, ANG II stimulated NRIC proliferation via increased intracellular cAMP levels and activation of the PKA/ERK/CREB intracellular signaling pathway. ANG II stimulated a significant increase in Sirius red staining and IHC for fibronectin that was blocked by angiotensin receptor blockade. In vitro, ANG II stimulated the gene expression of collagen 1A1, fibronectin 1, and IL-6. These results indicate that cholangiocytes express a local RAS and that ANG II plays an important role in regulating biliary proliferation and fibrosis during extraheptic cholestasis.

  1. Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice

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    Woolbright, Benjamin L. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Jenkins, Rosalind E. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Bajt, Mary Lynn [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2013-12-15

    Cholestasis is a pathological common component of numerous liver diseases that results in hepatotoxicity, inflammation, and cirrhosis when untreated. While the predominant hypothesis in cholestatic liver injury remains hepatocyte apoptosis due to direct toxicity of hydrophobic bile acid exposure, recent work suggests that the injury occurs through inflammatory necrosis. In order to resolve this controversy, we used novel plasma biomarkers to assess the mechanisms of cell death during early cholestatic liver injury. C57Bl/6 mice underwent bile duct ligation (BDL) for 6–72 h, or sham operation. Another group of mice were given D-galactosamine and endotoxin as a positive control for apoptosis and inflammatory necrosis. Plasma levels of full length cytokeratin-18 (FL-K18), microRNA-122 (miR-122) and high mobility group box-1 protein (HMGB1) increased progressively after BDL with peak levels observed after 48 h. These results indicate extensive cell necrosis after BDL, which is supported by the time course of plasma alanine aminotransferase activities and histology. In contrast, plasma caspase-3 activity, cleaved caspase-3 protein and caspase-cleaved cytokeratin-18 fragments (cK18) were not elevated at any time during BDL suggesting the absence of apoptosis. In contrast, all plasma biomarkers of necrosis and apoptosis were elevated 6 h after Gal/End treatment. In addition, acetylated HMGB1, a marker for macrophage and monocyte activation, was increased as early as 12 h but mainly at 48–72 h. However, progressive neutrophil accumulation in the area of necrosis started at 6 h after BDL. In conclusion, these data indicate that early cholestatic liver injury in mice is an inflammatory event, and occurs through necrosis with little evidence for apoptosis. - Highlights: • The mechanism of cell death during cholestasis remains a controversial topic. • Plasma biomarkers offer new insight into cell death after bile duct ligation. • Cytokeratin-18, microRNA-122 and HMGB

  2. Proteomic analysis of polypeptides captured from blood during extracorporeal albumin dialysis in patients with cholestasis and resistant pruritus.

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    Marina Gay

    Full Text Available Albumin dialysis using the molecular adsorbent recirculating system (MARS is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis.

  3. The state of membrane of the hepatocytes and the blood erytrocytes in pations with chronic hepatitis with signs of cholestasis.

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    Zakharash A.D.

    2007-01-01

    Full Text Available The purpose of work was to give morphological and morphometric characteristic of the hepatocytes and the blood erytrocytes against a background to determine the state of lipid peroxidation and antioxidant system of protection in case chronic cryptogenic hepatitis. Morphological and morphometric liver parameters were measured at the icteris in 5 patients (control – 5 patients. It was found that in patients with chronic hepatitis square of hepatocytes, square of their nuclei have been decreased, their relationship change for the better of cytoplasm. The hepatocytes and their nuclei have been deformed. The modifications of morphological and morphometric characteristic of the hepatocytes and the blood erytrocytes have been determined, drastic increase of the level CD95+ lymphocytes is evidence of the system reaction of apoptosis of the cells were studied in case chronic hepatitis with signs of cholestasis. In same patients with chronic hepatitis of non-virus etiology there were determined changes of area, perimeter and deformity of erythrocytes both on the basis of free radical reactions disorder and antioxidate protection system disorders; it induces us to quest their pathogenetically substantiated treatment.

  4. Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diet.

    Science.gov (United States)

    Flowers, Matthew T; Groen, Albert K; Oler, Angie Tebon; Keller, Mark P; Choi, Younjeong; Schueler, Kathryn L; Richards, Oliver C; Lan, Hong; Miyazaki, Makoto; Kuipers, Folkert; Kendziorski, Christina M; Ntambi, James M; Attie, Alan D

    2006-12-01

    Stearoyl-coenzyme A desaturase 1-deficient (SCD1(-/-)) mice have impaired MUFA synthesis. When maintained on a very low-fat (VLF) diet, SCD1(-/-) mice developed severe hypercholesterolemia, characterized by an increase in apolipoprotein B (apoB)-containing lipoproteins and the appearance of lipoprotein X. The rate of LDL clearance was decreased in VLF SCD1(-/-) mice relative to VLF SCD1(+/+) mice, indicating that reduced apoB-containing lipoprotein clearance contributed to the hypercholesterolemia. Additionally, HDL-cholesterol was dramatically reduced in these mice. The presence of increased plasma bile acids, bilirubin, and aminotransferases in the VLF SCD1(-/-) mice is indicative of cholestasis. Supplementation of the VLF diet with MUFA- and PUFA-rich canola oil, but not saturated fat-rich hydrogenated coconut oil, prevented these plasma phenotypes. However, dietary oleate was not as effective as canola oil in reducing LDL-cholesterol, signifying a role for dietary PUFA deficiency in the development of this phenotype. These results indicate that the lack of SCD1 results in an increased requirement for dietary unsaturated fat to compensate for impaired MUFA synthesis and to prevent hypercholesterolemia and hepatic dysfunction. Therefore, endogenous MUFA synthesis is essential during dietary unsaturated fat insufficiency and influences the dietary requirement of PUFA.

  5. High incidence of rickets in extremely low birth weight infants with severe parenteral nutrition-associated cholestasis and bronchopulmonary dysplasia.

    Science.gov (United States)

    Lee, Soon Min; Namgung, Ran; Park, Min Soo; Eun, Ho Sun; Park, Kook In; Lee, Chul

    2012-12-01

    Risk factors for rickets of prematurity have not been re-examined since introduction of high mineral formula, particularly in ELBW infants. We analyzed the incidence and the risk factors of rickets in extremely low birth weight (ELBW) infants. As a retrospective case-control study from 2004 to 2008, risk factors were analyzed in 24 patients with rickets versus 31 patients without. The frequency of rickets in ELBW infants was 24/55 (44%). Infants with rickets were diagnosed at 48.2 ± 16.1 days of age, and improved by 85.3 ± 25.3 days. By radiologic evaluation, 29% were grade 1 rickets, 58% grade 2 and 13% grade 3. In univariate analysis, infants with rickets had significantly higher incidence of patent ductus arteriosus, parenteral nutrition associated cholestasis (PNAC), severe PNAC and moderate/severe bronchopulmonary dysplasia (BPD). In multiple regression analysis, after adjustment for gestation and birth weight, rickets significantly correlated with severe PNAC and with moderate/severe BPD. Serum peak alkaline phosphatase levels were significantly elevated in rickets (P rickets of prematurity remains high and the incidence of severe PNAC and moderate/severe BPD was significantly increased 18 and 3 times, respectively.

  6. Proteomic analysis of polypeptides captured from blood during extracorporeal albumin dialysis in patients with cholestasis and resistant pruritus.

    Science.gov (United States)

    Gay, Marina; Pares, Albert; Carrascal, Montserrat; Bosch-i-Crespo, Pau; Gorga, Marina; Mas, Antoni; Abian, Joaquin

    2011-01-01

    Albumin dialysis using the molecular adsorbent recirculating system (MARS) is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX) cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone) were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis.

  7. Intrahepatic Cholestasis of Pregnancy with Severe Elevation of Bile Acids in the Setting of Acute Hepatitis C Infection

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    Megan L. Lawlor

    2016-01-01

    Full Text Available Intrahepatic cholestasis of pregnancy (ICP is a complication of pregnancy resulting in elevation of serum bile acid levels. ICP is often associated with underlying liver disease, including hepatitis C. Bile acids in relationship to the acute infection of hepatitis C virus have not yet been delineated in the literature. A 26-year-old gravida 4 para 2103 with dichorionic, diamniotic twin gestation and history of intravenous drug abuse developed ICP in the setting of acute hepatitis C infection. In addition to clinical symptoms of pruritus and right upper quadrant pain, she developed severe elevation in bile acids, 239 micromol/L, and transaminitis aspartate aminotransferase 1033 U/L, and alanine aminotransferase 448 U/L. She received ursodeoxycholic acid and antenatal testing was performed. Patient delivered vaginally at 33-week gestation following preterm rupture of membranes. Neonates were admitted to NICU and had uncomplicated neonatal courses. In the setting of ICP with significant transaminitis and severe elevation of bile acids, consideration of acute viral hepatitis is important, especially considering the worsening opioid epidemic and concurrent increase in intravenous drug use in the United States. Further study is needed regarding the acute form of HCV infection and its effect on ICP and associated bile acids.

  8. Pediatric parenteral nutrition-associated liver disease and cholestasis: Novel advances in pathomechanisms-based prevention and treatment.

    Science.gov (United States)

    Orso, Giuseppe; Mandato, Claudia; Veropalumbo, Claudio; Cecchi, Nicola; Garzi, Alfredo; Vajro, Pietro

    2016-03-01

    Parenteral nutrition constitutes a life-saving therapeutic tool in patients unable to ingest/absorb oral or enteral delivered nutrients. Liver function tests abnormalities are a common therapy-related complication, thus configuring the so-called Parenteral Nutrition Associated Liver Disease (PNALD) or cholestasis (PNAC). Although the damage is frequently mild, and resolves after discontinuation of parenteral nutrition, in some cases it progresses into cirrhotic changes, especially in neonates and infants. We present a literature review focusing on the pathogenetic mechanisms-driven prevention and therapies for the cases where parenteral nutrition cannot be discontinued. Ursodeoxycholic acid has been proposed in patients with cholestatic hepatopathy, but its efficacy needs to be better established. Little evidence is available on efficacy of anti-oxidants, antibiotics, probiotics and anti TNFα. Lipid emulsions based on fish oil with a high content of long-chain polyunsaturated fatty acids ω-3 appear effective both in decreasing intrahepatic inflammation and in improving biliary flow. Most recent promising variations such as soybean/MCT/olive/fish oil emulsion [third generation lipid emulsion (SMOFlipid)] are under investigation. In conclusion, we remark the emergence of a number of novel pathomechanisms underlying the severe liver impairment damage (PNALD and PNAC) in patients treated with parenteral nutrition. Only few traditional and innovative therapeutic strategies have hitherto been shown promising.

  9. Swertianlarin, an Herbal Agent Derived from Swertia mussotii Franch, Attenuates Liver Injury, Inflammation, and Cholestasis in Common Bile Duct-Ligated Rats

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    Liangjun Zhang

    2015-01-01

    Full Text Available Swertianlarin is an herbal agent abundantly distributed in Swertia mussotii Franch, a Chinese traditional herb used for treatment of jaundice. To study the therapeutic effect of swertianlarin on cholestasis, liver injury, serum proinflammatory cytokines, and bile salt concentrations were measured by comparing rats treated with swertianlarin 100 mg/kg/d or saline for 3, 7, or 14 days after bile duct ligation (BDL. Serum alanine aminotransferase (ATL and aspartate aminotransferase (AST levels were significantly decreased in BDL rats treated with swertianlarin for 14 days (P<0.05. The reduced liver injury in BDL rats by swertianlarin treatment for 14 days was further confirmed by liver histopathology. Levels of serum tumor necrosis factor alpha (TNFα were decreased by swertianlarin in BDL rats for 3 and 7 days (P<0.05. Moreover, reductions in serum interleukins IL-1β and IL-6 levels were also observed in BDL rats treated with swertianlarin (P<0.05. In addition, most of serum toxic bile salt concentrations (e.g., chenodeoxycholic acid (CDCA and deoxycholic acid (DCA in cholestatic rats were decreased by swertianlarin (P<0.05. In conclusion, the data suggest that swertianlarin derived from Swertia mussotii Franch attenuates liver injury, inflammation, and cholestasis in bile duct-ligated rats.

  10. Effect of betaine supplementation on changes in hepatic metabolism of sulfur-containing amino acids and experimental cholestasis induced by alpha-naphthylisothiocyanate.

    Science.gov (United States)

    Kim, Young C; Jung, Young S; Kim, Sang K

    2005-05-01

    Alterations in the hepatic metabolism of sulfur amino acids in experimental cholestasis induced by alpha-naphthylisothiocyanate (ANIT) (100 mg/kg, po) were monitored in male mice for 1 week. We also examined the effects of betaine supplementation (1% in drinking water) for 2 weeks on the hepatotoxicity and changes in the sulfur amino acid metabolism induced by ANIT treatment. Acute ANIT challenge elevated the serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, and total bilirubin contents from 5 h after the treatment, reaching a peak at t = 48-72 h. Hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels were decreased significantly in a manner almost inversely proportional to the changes in serum parameters measured to determine the ANIT-induced toxicity. Hepatic glutathione and cysteine levels were elevated at t = 120 h after the treatment. Betaine supplementation blocked or significantly attenuated induction of the hepatotoxicity by ANIT. The decrease in SAM and SAH levels was also inhibited by betaine intake. The results indicate that betaine supplementation may antagonize the induction of experimental cholestasis and changes in the metabolism of sulfur amino acids associated with ANIT treatment. The underlying mechanism and pharmacological significance of its action are discussed.

  11. Paeonia lactiflora Pall. protects against ANIT-induced cholestasis by activating Nrf2 via PI3K/Akt signaling pathway

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    Ma X

    2015-09-01

    Full Text Available Xiao Ma,1,2 Yan-ling Zhao,2 Yun Zhu,3 Zhe Chen,1,2 Jia-bo Wang,4 Rui-yu Li,1,4 Chang Chen,1,2 Shi-zhang Wei,1,2 Jian-yu Li,3 Bing Liu,5 Rui-lin Wang,3 Yong-gang Li,3 Li-fu Wang,3 Xiao-he Xiao4 1Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Pharmacy, 302 Military Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 3Department of Integrative Medical Center, 302 Military Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 4China Military Institute of Chinese Medicine, 302 Military Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 5School of Chinese Medicine, The University of Hong Kong, Hong Kong Background: Paeonia lactiflora Pall. (PLP, a traditional Chinese herbal medicine, has been used for hepatic disease treatment over thousands of years. In our previous study, PLP was shown to demonstrate therapeutic effect on hepatitis with severe cholestasis. The aim of this study was to evaluate the antioxidative effect of PLP on alpha-naphthylisothiocyanate (ANIT-induced cholestasis by activating NF-E2-related factor 2 (Nrf2 via phosphatidylinositol 3-kinase (PI3K/Akt signaling pathway. Materials and methods: Liquid chromatography-mass spectrometry (LC-MS was performed to identify the main compounds present in PLP. The mechanism of action of PLP and its therapeutic effect on cholestasis, induced by ANIT, were further investigated. Serum indices such as total bilirubin (TBIL, direct bilirubin (DBIL, aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, γ-glutamyl transpeptidase (γ-GT, and total bile acid (TBA were measured, and histopathology of liver was also performed to determine the efficacy of treatment with PLP. Moreover, in order to illustrate the underlying signaling pathway, liver glutathione (GSH content and mRNA or protein levels of glutamate

  12. Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Qiang; Chen, Xin-li; Wang, Chang-yuan; Liu, Qi; Sun, Hui-jun; Sun, Peng-yuan; Huo, Xiao-kui; Liu, Zhi-hao; Yao, Ji-hong; Liu, Ke-xin, E-mail: kexinliu@dlmedu.edu.cn

    2015-03-15

    Intrahepatic cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Appropriate regulation of bile acids in hepatocytes is critically important for protection against liver injury. In the present study, we characterized the protective effect of alisol B 23-acetate (AB23A), a natural triterpenoid, on alpha-naphthylisothiocyanate (ANIT)-induced liver injury and intrahepatic cholestasis in mice and further elucidated the mechanisms in vivo and in vitro. AB23A treatment dose-dependently protected against liver injury induced by ANIT through reducing hepatic uptake and increasing efflux of bile acid via down-regulation of hepatic uptake transporters (Ntcp) and up-regulation of efflux transporter (Bsep, Mrp2 and Mdr2) expression. Furthermore, AB23A reduced bile acid synthesis through repressing Cyp7a1 and Cyp8b1, increased bile acid conjugation through inducing Bal, Baat and bile acid metabolism through an induction in gene expression of Sult2a1. We further demonstrate the involvement of farnesoid X receptor (FXR) in the hepatoprotective effect of AB23A. The changes in transporters and enzymes, as well as ameliorative liver histology in AB23A-treated mice were abrogated by FXR antagonist guggulsterone in vivo. In vitro evidences also directly demonstrated the effect of AB23A on FXR activation in a dose-dependent manner using luciferase reporter assay in HepG2 cells. In conclusion, AB23A produces protective effect against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes. - Highlights: • AB23A has at least three roles in protection against ANIT-induced liver injury. • AB23A decreases Ntcp, and increases Bsep, Mrp2 and Mdr2 expression. • AB23A represses Cyp7a1 and Cyp8b1 through inducing Shp and Fgf15 expression. • AB23A increases bile acid metabolism through inducing Sult2a1 expression. • FXR activation is involved

  13. Diagnóstico diferencial de colestase neonatal: parâmetros clínicos e laboratoriais Differential diagnosis of neonatal cholestasis: clinical and laboratory parameters

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    Maria Angela Bellomo-Brandao

    2010-02-01

    Full Text Available OBJETIVO: Avaliar se os parâmetros clínicos e laboratoriais poderiam auxiliar no diagnóstico diferencial da colestase neonatal (CN intra- e extra-hepática. MÉTODOS: Estudo retrospectivo de pacientes com CN hospitalizados na Clínica de Hepatologia Pediátrica do Hospital de Clínicas da Universidade Estadual de Campinas (UNICAMP, Campinas (SP, entre dezembro de 1980 e março de 2005. A abordagem para o diagnóstico da CN foi padronizada. De acordo com o diagnóstico, os pacientes foram classificados em dois grupos: I (colestase neo natal intra-hepática e II (colestase neonatal extrahepática. Para verificar se havia associação com a variável categórica, os testes de qui-quadrado e Mann-Whitney foram utilizados com correções para idade para a análise de covariância (ANCOVA. A determinação da precisão das variáveis clínicas e laboratoriais para a diferenciação dos grupos foi realizada através da análise da curva ROC. RESULTADOS: Cento e sessenta e oito pacientes foram avaliados (grupo I = 54,8% e grupo II = 45,2%. Nos pacientes com menos de 60 dias de vida, houve predominância de causas intra-hepáticas, enquanto que naqueles com mais de 60 dias, houve predominância de etiologia extrahepática (p OBJECTIVE: To evaluate if clinical and laboratory parameters could assist in the differential diagnosis of intra and extra-hepatic neonatal cholestasis (NC. METHODS: Retrospective study of NC patients admitted at the Pediatric Hepatology Outpatient Clinic of the teaching hospital of Universidade Estadual de Campinas (UNICAMP, Campinas, Brazil, between December 1980 and March 2005. The approach to the diagnosis of NC was standardized. According to diagnosis, patients were classified into two groups: I (intra-hepatic neonatal cholestasis and II (extra-hepatic neonatal cholestasis. In order to verify if there was association with the categorical variable, the chi-square and Mann-Whitney tests were used, with corrections for age for

  14. Heterozygous Inactivation of the Nuclear Receptor PXR/NR1I2 in a Patient With Anabolic Steroid-Induced Intrahepatic Cholestasis

    Science.gov (United States)

    Liebe, Roman; Krawczyk, Marcin; Raszeja-Wyszomirska, Joanna; Kruk, Beata; Preis, Rebecca; Trottier, Jocelyn; Barbier, Olivier; Milkiewicz, Piotr; Lammert, Frank

    2016-01-01

    Introduction The incidence of liver damage due to steroid consumption is increasing due to the omnipresence of the idealized body image and the widespread availability of drugs via the Internet. The genetic factors underlying individual susceptibility are not presently known. Case Presentation A male patient developed cholestatic liver injury two weeks after a two-month course of anabolic steroids. Next-generation sequencing (NGS) of 24 cholestasis-related genes revealed a heterozygous two-basepair deletion in exon 1 of the pregnane X receptor gene (PXR). Serum bile salt levels showed marked imbalances, strongly resembling the changes observed in patients with biliary obstruction. Conclusions This case of PXR haploinsufficiency reveals transcriptional regulatory functions activated in the liver under xenobiotic stress by steroids, which appear to require two functional copies of the nuclear receptor gene. Deranged bile salt levels outline the central role of PXR in bile acid synthesis, modification, and export. PMID:27799961

  15. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis

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    Blazquez, Alba G., E-mail: albamgb@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Briz, Oscar, E-mail: obriz@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Gonzalez-Sanchez, Ester, E-mail: u60343@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); Perez, Maria J., E-mail: mjperez@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); University Hospital of Salamanca, IECSCYL-IBSAL, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Ghanem, Carolina I., E-mail: cghanem@ffyb.uba.ar [Instituto de Investigaciones Farmacologicas, Facultad de Farmacia y Bioquimica, CONICET, Universidad de Buenos Aires, Buenos Aires (Argentina); Marin, Jose J.G., E-mail: jjgmarin@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain)

    2014-05-15

    Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48 h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis. - Highlights: • Acetaminophen induces changes in placental BCRP expression in vitro. • This drug reduces the ability of placental cells to export BCRP substrates. • Acetaminophen induces changes in Bcrp expression in rat placenta. • Placental barrier to bile acids is impaired in rats treated with this drug.

  16. Ultrasonography of Neonatal Cholestasis

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    Cheon, Jung Eun [Seoul National University Hospital, Seoul (Korea, Republic of)

    2012-06-15

    Ultrasonography (US) is as an important tool for differentiation of obstructive and non-obstructive causes of jaundice in infants and children. Beyond two weeks of age, extrahepatic biliary atresia and neonatal hepatitis are the two most common causes of persistent neonatal jaundice: differentiation of extrahepatic biliary atresia, which requires early surgical intervention, is very important. Meticulous analysis should focus on size and configuration of the gallbladder and anatomical changes of the portahepatis. In order to narrow the differential diagnosis, combined approaches using hepatic scintigraphy, MR cholangiography, and, at times, percutaneous liver biopsy are necessary. US is useful for demonstrating choledochal cyst, bile plug syndrome, and spontaneous perforation of the extrahepatic bile duct

  17. Coinfection of hepatitis A virus genotype IA and IIIA complicated with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive immunoglobulin M anti-hepatitis E virus: a case report.

    Science.gov (United States)

    Kim, Hee Sup; Jeong, Sook Hyang; Jang, Je Hyuck; Myung, Hyung Joon; Kim, Jin Wook; Bang, Soo Mee; Song, Sang Hoon; Kim, Haeryoung; Yun, Hae Sun

    2011-12-01

    A 37-year-old male presented with fever and jaundice was diagnosed as hepatitis A complicated with progressive cholestasis and severe autoimmune hemolytic anemia. He was treated with high-dose prednisolone (1.5 mg/kg), and eventually recovered. His initial serum contained genotype IA hepatitis A virus (HAV), which was subsequently replaced by genotype IIIA HAV. Moreover, at the time of development of hemolytic anemia, he became positive for immunoglobulin M (IgM) anti-hepatitis E virus (HEV). We detected HAV antigens in the liver biopsy specimen, while we detected neither HEV antigen in the liver nor HEV RNA in his serum. This is the first report of hepatitis A coinfected with two different genotypes manifesting with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive IgM anti-HEV.

  18. The research advancement of pathogenesis of intrahepatic cholestasis jaundice related to chronic hepatits B%慢性乙型肝炎肝内胆汁淤积性黄疸发病机制的研究概况

    Institute of Scientific and Technical Information of China (English)

    杨宗国; 陈晓蓉; 刘成

    2011-01-01

    慢性乙型肝炎致肝内胆汁淤积性黄疸的发病机制极其复杂,其中肝细胞凋亡、氧化应激及脂质过氧化、巨噬细胞介导的炎症反应等途径均参与肝内胆汁淤积性黄疸的发病.明确肝内胆汁淤积性黄疸的发病机制对临床靶点治疗有重要意义.%The pathogenesis of intrahepatic cholestasis jaundice caused by chronic hepatite B is extremely complicated, and the following pathways such as hepatocytes apoptosis, oxidative stress, lipid peroxidation and inflammatory response mediated by macrophage have a close link with the pathogenesis of intrahepatic cholestasis jaundice. To have a clear and complete definition on the pathogenesis of intrahepatic cholestasis jaundice is of great significance for its clinical target therapy.

  19. 妊娠期肝内胆汁淤积症与胎儿损伤%Intrahepatic cholestasis of pregnancy and fetal injury

    Institute of Scientific and Technical Information of China (English)

    张丽娟; 张凤华; 汤丽丽; 杨伟红; 张雪

    2013-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is an unique complication in pregnancy,which usually manifests in the second or third trimester,and mainly harms the fetus.Its pathogenesis is not yet clear,and placental pathological changes are insufficient to explain the clinical phenomenon.Recent studies had shown that the important cause ofperinatal deaths may be the damage to the placental structure and function caused by the high bile acid level.In addition,the change of placental structure and function,unbilical cord factors,and endocrine changes can also cause the fetal development and intrauterine hypoxia.In recent years related researches focus on the toxic effect of bile acid on fetus heart,lungs,brain,liver,and other important organs,the placental vascular pathology,hemodynamic changes,umbilical cord blood vessel factors and the endocrine changes.%妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,Icp)是妊娠中晚期特有的并发症,主要危害胎儿,其发病机制尚不清楚,胎盘的病变不足以解释临床现象.近年研究发现,ICP患者母体高胆酸水平对胎儿脏器组织结构和功能的损害是围产儿死亡的重要原因.另外,ICP胎盘结构及功能改变,脐带因素及内分泌变化等也可导致胎儿发育受损及宫内缺氧.近年来有关胆汁酸对胎儿心、肺、脑、肝等重要脏器的毒性作用、ICP胎盘病理及血流动力学改变、胎盘血管及脐带血管因素和内分泌变化的研究有了长足的进展.

  20. 基于上海市住院慢性肝病患者胆汁淤积患病率的调查研究%Cholestasis morbidity rate in first-hospitalized patients with chronic liver disease in Shanghai

    Institute of Scientific and Technical Information of China (English)

    曹旬旬; 高月求; 张文宏; 徐萍; 傅青春; 陈成伟; 李成忠; 杨长青; 马光斌

    2015-01-01

    Objective To investigate the epidemiological status of cholestasis in first-hospitalized patients with chronic liver disease in Shanghai,and to provide a scientific basis for developing prevention and treatment measures.Methods From April 2005 to September 2014,5 146 first-hospitalized patients in Shanghai with a diagnosis of chronic liver disease were enrolled in this study.Clinical data of the 4 660 patients who fit the study criteria for participation were collected for retrospective analysis.Diagnosis of cholestasis was made according to serum alkaline phosphatase (ALP) levels higher than 1.5 times the upper limit normal (ULN) and gamma-glutamyltransferase (GGT) levels higher than 3 times the ULN.The incidence rate of cholestasis was assessed for relation to age,sex,etiology,and type of liver disease,and statistically compared to the general clinical data and specific biochemical indicators with potential sexrelated differences.T-test and chi-square test were performed for the statistical analyses.Results Of the 4 660 study participants,10.26% had cholestasis;the prevalence of cholestasis increased with increasing age in male patients.The distribution of the cholestasis incidence according to the type of chronic liver disease was:75.00%,primary sclerosing cholangitis;42.86%,primary biliary cirrhosis;35.97%,hepatic tumor;30.77%,autoimmune hepatitis;28.31%,drug-induced liver disease;16.46%,alcoholic hepatitis;13.98%,cryptogenic cirrhosis;12.99%,schistosomal cirrhosis;7.53%,alcoholic cirrhosis;7.32%,mixed cirrhosis;5.94%,viral liver cirrhosis;2.70%,nonalcoholic fatty liver disease.There was no significant difference in the prevalence of cholestasis between the two sexes.In the patients with cholestasis,the levels of GGT and total bilirubin were significantly different between the two sexes.Conclusion The incidence rate of cholestasis in firsthospitalized patients with chronic liver disease was 10.26%,and the rate increased with

  1. The Role of e-NOS in Chronic Cholestasis-Induced Liver and Renal Injury in Rats: The Effect of N-Acetyl Cysteine

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    Yusuf Gunay

    2014-01-01

    Full Text Available Introduction. The role of chronic cholestasis (CC in liver injury and fibrosis remains unclear. The aims of this study were to define the role of endothelial nitric oxide synthase (e-NOS in CC and the protective effect of N-acetyl-L-cysteine (NAC in liver and kidney injury. Materials and Methods. Group A (sham group; Group B (CBDL; and Group C (CBDL + NAC. Group C received daily dosage of NAC (100 mg/kg intraperitoneally for up to 4 weeks. Results. The rate of bridging fibrosis was higher (100% versus 20%, P=.025, but the intensity of e-NOS in liver was lower in rats that received NAC (1.3 versus 2.7, P=.046. The necrotic area in the kidneys among rats that received NAC was lower at week 4 (48% versus 57%; P<.001. The numbers of e-NOS stained cells in kidney were similar in sham group and the two groups with CBDL. Discussion. NAC reduced the stimulus for liver fibrosis in this rat model of CC and attenuated liver and kidney injury. Our study showed that e-NOS expression increased in liver tissue of rats with CC and that this was reversed by NAC. Treatment with NAC might restore e-NOS protein expression and prevent liver injury in CC.

  2. Screening for the inherited metabolic diseases in infants with cholestasis and changing pattern of diagnosis%遗传代谢病的筛查与婴儿胆汁淤积病因诊断的变化

    Institute of Scientific and Technical Information of China (English)

    李晓瑜; 马华梅; 陈红珊; 李燕虹; 沈振宇; 杜敏联

    2010-01-01

    Objective To investigate the changing pattern of diagnosis of infantile cholestasis after screening the inherited metabolic diseases in infants with cholestasis. Methods Infants under 12 months with cholestasis were identified retrospectively from hospital records from Jan. 1996 to Dec. 2007. The data were retrieved from the medical records and analyzed by focusing particularly on the changing etiology of cholestasis and inherited metabolic diseases in these infants after performing routine screening and diagnostic procedures. Results Among 421 infants identified as having cholestasis during 12-years study period, the common causes of infantile cholestasis were cytomegalovirus (CMV) infection (36. 11% ), bile duct hypoplasia or congenital biliary atresia (31.59%), metabolic disease (8.08%), miscellaneous (10.69%), and unknown ( 13.54% ). The proportion of infants with metabolic diseases after screening increased 16 folds compared with before screening( 15.76% vs 0. 92% ,P<0. 01 ), whereas the proportion of infants with unknown cause decreased from 17.43% to 9.36% (P<0.05). There was no significant change in the proportions of CMV infection, congenital biliary atresia, and miscellaneous causes. The major metabolic diseases of 34 infants included citrin deficiency (41. 18% ) and tyrosinemia (23.53%), followed by galactosemia and progressive familial intrahepatic cholestasis (8. 82% )etc. Conclusions Inherited metabolic disease has become an important cause of infantile cholestasis, which is mainly due to citrin deficiency. Therefore, it is necessary to set a routing screening of citrin deficiency in infants with cholestasis.%目的 了解开展遗传代谢病筛查后婴儿胆汁淤积的病因谱变化及与之相关的遗传代谢病种类.方法 回顾性总结1996年1月至2007年12月本院收治的婴儿胆汁淤积病例的临床资料,分析进行遗传代谢病筛查前后婴儿胆汁淤积病因的年代变迁及与胆汁淤积相关的遗

  3. Progress in study on the cellular and molecular level of intrahepatic chole-stasis of pregnancy%妊娠期肝内胆汁淤积症在细胞分子水平上的认识进展

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    胡海军; 李佳平

    2015-01-01

    妊娠期肝内胆汁淤积症( intrahepatic cholestasis of pregnancy,ICP)为高危妊娠,是妊娠期特有疾病。虽然对孕妇预后良好,仍会出现早产、羊水胎粪污染、胎儿宫内窘迫、无明显先兆的胎死宫内等不良妊娠结局,故近年来越来越受到重视。然而ICP发生机制仍不清楚,可能与遗传因素,生殖激素,免疫耐受失衡以及环境因素有关,有待于进一步深入研究与探求。%Intrahepatic cholestasis of pregnancy ( ICP) is a high-risk pregnancy and it is specific. Although the prognosis is good for pregnant women,there are bad results such as premature birth,meconium stained amniotic fluid,fetal distress and no obvious sign of fetal death,etc. So in recent years more and more attentions are paid to ICP. The ICP mechanism,however,remains unclear and may be associated with genetic factors, reproductive hormones, immune tolerance instability, as well as environmental factors, which needs further research and exploration.

  4. Clinical characteristics of twin pregnancy with intrahepatic cholestasis%双胎妊娠合并妊娠期肝内胆汁淤积症临床特点分析

    Institute of Scientific and Technical Information of China (English)

    吴星光

    2012-01-01

    目的 分析双胎合并妊娠期肝内胆汁淤积症的临床特点.方法 我院产科诊治的双胎妊娠患者515例,其中双胎妊娠合并妊娠期肝内胆汁淤积症17例为观察组,随机选取18例未合并肝内胆汁淤积症的双胎妊娠患者为对照组.观察并比较两组患者围生儿预后情况、孕妇生产方式及并发症发生情况.结果 双胎妊娠合并妊娠期肝内胆汁淤积症的发病率为3.30%;观察组中发生胎儿窘迫、胎儿窒息及胎儿死亡的比例分别为41.2%、52.9%和35.3%,显著高于对照组的5.6%、11.1%和0(P< 0.05);观察组患者中剖宫产比例为70.6%,显著高于对照组的33.3%(P<0.05);观察组患者发生妊高症及产后出血并发症的比例分别为58.8%和41.2%,均明显高于对照组的16.7%和5.6%(P<0.05).结论 双胎妊娠合并妊娠期肝内胆汁淤积症发病率高,胎儿预后较差,孕妇并发症多,临床工作中应该积极应对.%Objective To analyze the clinical characteristics of the twin pregnancy with intrahepatic cholestasis. Methods Five hundred and fifteen patients of twin pregnancy were chosen. Seventeen of the patients complicated with intrahepatic cholestasis were chosen as the study group, and 18 of the patients without intrahepatic cholestasis were chosen as the control group. The prognosis, maternal mode of production and occurrence of complications were compared between the two groups. Results The incidence of twin pregnancy complicated with gestational intrahepatic cholestasis were 3.30%. The occurrence of fetal distress, fetal asphyxia and fetal death in the study group were 41.2%, 52.9% and 35.3%, respectively, significantly higher than those in the control group (5.6%, 11.1% and 0%, respectively), P<0.05. The incidence of cesarean section, the pregnancy induced hypertension and postpartum hemorrhage of the study group were 70.6%, 58.8% and 41.2%, respectively, significantly higher than those in the

  5. EFFECTS OF INTRAHEPATIC CHOLESTASIS OF PREGNANCY COMBINED GESTATIONAL DIABETES MELLITUS ON MATERNAL AND FETAL OUTCOMES%ICP合并GDM对母儿结局的影响

    Institute of Scientific and Technical Information of China (English)

    周冬梅; 杨如

    2014-01-01

    目的:探讨妊娠期肝内胆汁淤积症(ICP)合并妊娠期糖尿病(GDM)对母儿结局的影响。方法:分析15例ICP合并GDM孕妇和50例单纯ICP孕妇的临床资料。结果:ICP合并GDM组新生儿窒息率、羊水污染率、小于胎龄儿发生率均显著高于ICP组(P<0.05)。ICP合并GDM组新生儿出生体重较单纯ICP患者轻,分娩孕周较单纯ICP患者小(P<0.05)。结论:ICP合并GDM对围产儿的影响较大,应加强产前和产时母儿监护,合理评估病情,必要时促进胎肺成熟,适时终止妊娠,以改善围生儿不良结局。%Objective:To investigate the effects of intrahepatic cholestasis of pregnancy (ICP) combined gestational diabetes mellitus (GDM) on maternal and fetal outcomes.Methods:The clinical data of 15 cases ICP combined GDM and 50 cases ICP pregnant women were analyzed.Results:The neonatal asphyxia rate, incidence of amniotic lfuid contamination and incidence of small for gestationel age infants of ICP combined GDM pregnant women were all obviously higher than that of ICP pregnant women (P<0.05). The newborn birth weight of ICP combined GDM group was signiifcantly lower,andtheterminationtimeofpregnancyofICPcombinedGDMgroupwassigniifcantlyearlierthanthatofICPgroup(P<0.05). Conclusions:ICP combined GDM has great inlfuence on perinatal infant. We should strengthen antenatal and intrapartum maternal and perinatal care, evaluate the disease reasonably, timely termination of pregnancy, so to improve the adverse outcome of perinatal infant.

  6. ICP围产儿不良结局的高危因素分析%High risk factors for adverse outcomes of perinatal infants of intrahepatic cholestasis pregnancy

    Institute of Scientific and Technical Information of China (English)

    刘翠; 王勇; 楼方

    2015-01-01

    Objective To discuss the high risk factors for adverse outcomes of perinatal infants in intrahepatic cholestasis of pregnancy ( ICP) . Methods The ICP cases were collected from Affiliated Hospital of Chengdu University. The relationship between obstetric factors and adverse outcomes of perinatal infants was retrospectively analyzed with the data of 522 cases of ICP. Results Univariate analysis showed that the time of onset earlier than 34 gestational week, high TBA, high ALT, high TBIL, high DBIL, and complicated hypertension were statistically significant (χ2 value was 35. 079, 15. 140, 12. 155, 6. 142, 9. 988 and 12. 604, respectively, all P <0. 05). Logistic regression analysis indicated that time of onset earlier than 34 gestational week, high TBA and complicated hypertension were high risk factors for adverse outcomes of ICP perinatal infants (OR value was 2. 922, 1. 770 and 1. 861, respectively, all P<0. 05). Conclusion TBA≥40μmol/L, time of onset earlier than 34 gestational week and complicated high hypertension are risk factors for adverse outcomes of ICP perinatal infants.%目的:探讨妊娠期肝内胆汁淤积症( ICP)围产儿不良结局的高危因素。方法收集在成都大学附属医院住院分娩的ICP病例。回顾性分析522例ICP病例的产科因素与围产儿不良结局之间的关系。结果单因素分析发现发病时间≤孕34周、高总胆汁酸( TBA)、高谷丙转氨酶( ALT)、高总胆红素( TBIL)、高直接胆红素( DBIL)、合并高血压对围产儿不良结局均有统计学差异(χ2值分别为35.079、15.140、12.155、6.142、9.988、12.604,均P<0.05);经Logistic回归分析发现ICP的发病时间≤孕34周、高TBA、合并高血压系ICP围产儿不良结局的高危因素,其OR值分别为2.922、1.770、1.861,均P<0.05。结论 TBA≥40μmol/L、发病时间≤孕34周、合并高血压系ICP围产儿不良结局的高危因素。

  7. Clinical Analysis of 32 Patients with Intrahepatic Cholestasis of Pregnancy%32例妊娠期肝内胆汁淤积症临床分析

    Institute of Scientific and Technical Information of China (English)

    白月婷

    2012-01-01

    Objective To investigate the harm of intrahepatic cholestasis of pregnancy( ICP) and the time and manner of delivery in patients with ICP. Methods The clinical data of 32 patients with ICP from 2007 to 2011 in Haidian maternal and child health hospital were analyzed retrospectively. Results There were 13 patients had complications,3 cases were with hypertension in pregnancy,2 with severe pre-eclampsia, 1 with gestational diabetes mellitus,2 with pregnancy impaired glucose tolerance, 1 with thrombocytopenia, 1 with fetal growth restriction, 1 with still birth ,4 with amniotic fluid pollution and 1 with postpartum hemorrhage. 13 patients with the mild ICP had no amniotic fluid pollution,fetal distress or still birth. A premature delivery was seen in 2 patients with mild ICP. 6 patients with the severe ICP had premature cesarean section delivery because of serious condition or complications. Conclusion For the patients with mild ICP a full term trial of vaginal labour can be performed under the close monitoring and a relaxed cesarean section indications. The patients with severe ICP should immediately be cared in hospital with closely monitoring and positive treatment. The cesarean section should be timely carried out to terminate the gestation on the 36th weeks.%目的 探讨妊娠期肝内胆汁淤积症(ICP)的危害、分娩时机及方式.方法 回顾性分析海淀区妇幼保健院2007 ~ 2011年收治的32例ICP患者的临床资料.结果 13例患者出现并发症,其中妊娠期高血压3例,重度子痫前期2例,妊娠期糖尿病1例,妊娠期糖耐量受损2例,血小板减少1例,胎儿生长受限1例,胎死宫内1例,羊水污染4例,产后出血1例.轻度ICP患者13例,无羊水污染、胎儿窘迫、胎死宫内发生,早产2例;重度ICP患者19例,早产6例,均因病情严重、合并症/并发症剖宫产分娩.结论 轻度ICP可观察至妊足月,在密切监护下行阴道试产,并放宽剖宫产指征.一旦诊断重度ICP,需立即

  8. Acute cholestasis related to desloratidine

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    Ramón Pérez; Luis Rodrigo; Rosa Pérez; Ruth de Francisco

    2005-01-01

    @@ TO THE EDITOR Desloratidine (Clarinex, Neoclarytin, Aerius, Azomyr, Opulis,Allex), the principal active metabolite of loratadine is itself a new oral antihistamine drug Its main indications are for the treatment of seasonal allergic rhinitis (SAR) and chronic idiopathic urticaria (CIU). The pharmacologic profile of desloratidine offers particular benefits, in terms of histamine H1-receptor binding potency and H1 selectivity. It has a half-life of 21-27 h, permitting a once-daily dose. No specific precautions are required with respect to its administration in renal or hepatic failure. No clinically relevant racial or gender variations in the disposition of desloratidine have been noted. We present here a clinical case of acute reversible idiosyncratic liver toxicity, related to its administration.

  9. Hepatoprotective effect of water soluble extract of Coleus barbatus on cholestasis on young rats Efeito hepatoprotetor do extrato aquoso de Coleus barbatus na colestase em ratos jovens

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    Ana Paula Ronquesel Battochio

    2008-06-01

    Full Text Available PURPOSE: To test the effects of water extract of Coleus barbatus (WEB on liver damage in biliary obstruction in young rats. METHODS: Forty 21 day-old male Wistar rats were divided into four groups of ten 21 day old (P21 submitted to sham or actual operation (S or L combined with WEB or Water (B or A. At P48 pentobarbital sleeping time (ST was measured. At P49 they were submitted to euthanasia to determine of serum activities of aspartate aminotransferase (AST and alanine aminotransferase (ALT, liver wet weight (PFF and, on hepatic histological slides, the frequency of mitoses (FM, the number of necrotic areas (NN, intensity of fibrosis (IF and intensity of ductal proliferation (IPD. Two Way ANOVA, the S.N.K. test and the Wilcoxon test for paired multiple comparisons were employed to study the effects of cholestasis and those of EAB and their interactions. The Pearson's coefficient of linear correlation of between paired histological variables separately for the groups LA and LD was determined. The test results were considered statistically significant when the p of alpha error OBJETIVO: Testar os efeitos do extrato aquoso de Coleus barbatus (EAB na cirrose biliar secundária por obstrução das vias biliares extra-hepáticas em ratos jovens. MÉTODOS: Quarenta ratos Wistar machos com 21 dias de vida (P21, foram distribuídos em quatro grupos de 10 animais, submetidos a operação simulada ou dupla ligadura e ressecção do ducto biliar (S ou L combinados EAB e a Água (B ou A. No P48, foi medido o tempo de sono com o pentobarbital (TS. No P49, foram submetidos a eutanásia para a determinação das atividades séricas do aspartato aminotransferase (AST e da alanina aminotransferases (ALT; após a eutanásia foram avaliados o peso fresco do fígado (PFF e, em cortes histológicos do fígado, a freqüência de mitoses (FM, o número de áreas de necrose (NN, a intensidade da fibrose (IF e da proliferação ductal (IPD. Os efeitos da colestase, os

  10. Clinical Experience on the Treatment of 89 Cases with Intrahepatic Cholestasis During Pregnancy%治疗89例妊娠期肝内胆汁淤积症的临床体会

    Institute of Scientific and Technical Information of China (English)

    刘展

    2013-01-01

    目的:探讨治疗妊娠期肝内胆汁淤积症的临床特点、治疗方法及母婴预后。方法:选取2006年6月-2012年12月本院妇产科病区收治的89例妊娠期肝内胆汁淤积症患者,回顾性分析其诊治方法、分娩方式、产后出血量及围生儿结局。结果:89例患者阴道分娩25例,剖宫产64例,产后出血量150~670 mL;分娩孕周31~38周,早产儿57例;新生儿体重1900~4100 g,其中低体重儿58例;新生儿中轻度窒息24例,重度窒息5例。所有新生儿外观均无畸形,生后均以高危儿立即转新生儿科治疗,1例患儿因早产、窒息合并多脏器功能衰竭死亡。结论:妊娠期肝内胆汁淤积症为妊娠期严重并发症,应进行早期诊断,早期治疗,加强监护,必要时终止妊娠,从而降低围生儿的致残率、病死率,减少产妇产后出血情况的发生,保障母婴健康。%Objective:To research on the clinical characteristics of intrahepatic cholestasis of pregnancy(ICP)and its negative effects on mother and child.Method:Eighty-nine patients with intrahepatic cholestasis of pregnancy from June 2006 to December 2012 in department of obstetrics were selected.The diagnosis and treatment method,mode of delivery,postpartum hemorrhage and perinatal outcomes were retrospectively analyzed.Result:89 cases were 25 cases of vaginal delivery,cesarean section in 64 cases,the amount of 150-670 mL postpartum hemorrhage;pregnant was 31-38 weeks, 57 cases were premature infants;Neonatal weight was 1900-4100 g,including 58 cases of low birth weight infant;24 cases of newborn asphyxia,5 cases of severe asphyxia neonatorum.All neonates were no abnormal appearance,they were transferred to the Neonatal Department for treatment as high-risk infants,1 case died because of premature birth,asphyxia death combined multiple organ function failure.Conclusion:Intrahepatic cholestasis of pregnancy is a serious complication of pregnancy,should be

  11. Intrahepatic cholestasis of pregnancy characteristics and clinical prognosis of perinatal child%妊娠期肝内胆汁淤积症早期干预措施及对围生儿的影响

    Institute of Scientific and Technical Information of China (English)

    张小燕

    2012-01-01

    目的 探讨妊娠期肝内胆汁淤积症(ICP)患者的临床特点、终止妊娠方式的选择及对围生儿预后的影响.方法 选择2008年3月-2011年3月分娩的100例妊娠期肝内胆汁淤积症患者作为观察组,同期选取住院分娩的正常孕妇120例作为对照组,比较两组孕妇及新生儿情况以及观察组中分娩方式不同对新生儿的影响.结果 两组的早产、胎儿宫内窘迫、死亡及羊水污染明显高于对照组(P<0.05);观察组孕妇血清总胆汁酸值不同对新生儿的影响亦不同.结论 妊娠期肝内胆汁淤积症对母婴,特别是新生儿的危害极大,导致早产、胎儿宫内窘迫、胎死宫内、产后出血等并发症,增加了围生儿发病率和死亡率.因此应加强孕妇的健康教育,高度重视产前检查和中期妊娠胆汁酸的监测,做到早发现、早治疗,对减少母婴并发症有重要作用.%Objective To investigate the clinical features of intrahepatic cholestasis of pregnancy (ICP) in patients, mode of selection and termination of pregnancy on perinatal outcome of children. Methods March 2008-March 2011 in our hospital delivery of 100 cases patients with intrahepatic cholestasis of pregnancy as the observation group, selected hospital delivery over the same period 120 cases of normal pregnant women as the control group, the two groups of pregnant women and newborn as well as the observation group in the different mode of delivery on neonatal effects. Results The observation groups of premature delivery, fetal distress, death and amniotic significantly higher than those of the control group ( P < 0. 05) ; Observation group maternal serum total bile acid have different effects on different newborn. Conclusions Intrahepatic cholestasis of pregnancy on maternal, newborn, especially the great harm, leading to premature delivery, fetal distress, fetal death, postpartum hemorrhage and other complications, increased perinatal incidence and mortality

  12. Cholestasis in a murine experimental model: lesions include hepatocyte ischemic necrosis Colestase em modelo experimental em murinos: lesões incluem necrose isquêmica dos hepatócitos

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    Ivete Bedin Prado

    2003-01-01

    Full Text Available OBJECTIVE: To establish a murine experimental model of bile duct obstruction that would enable controlled observations of the acute and subacute phases of cholestasis. METHODOLOGY: Adult male isogenic BALB/c mice underwent a bile duct ligation (22 animals or a sham operation (10 animals. Fifteen days after surgery, or immediately after the animal's death, macroscopic findings were noted and histological study of the liver, biliary tree, and pancreas was performed (hematoxylin-eosin and Masson trichromic staining. RESULTS: Beginning 24 hours after surgery, all animals from the bile duct ligation group presented progressive generalized malaise. All animals presented jaundice in the parietal and visceral peritoneum, turgid and enlarged liver, and accentuated dilatation of gallbladder and common bile duct. Microscopic findings included marked dilatation and proliferation of bile ducts with accentuated collagen deposits, frequent areas of ischemic necrosis, hepatic microabscesses, and purulent cholangitis. Animals from the sham operation group presented no alterations. CONCLUSION: We established a murine experimental model of induced cholestasis, which made it possible to study acute and subacute tissue lesions. Our data suggests that in cholestasis, hepatic functional ischemia plays an important role in inducing hepatic lesions, and it also suggests that the infectious process is an important factor in morbidity and mortality.OBJETIVO: Realizar um modelo experimental de obstrução do ducto biliar que permita uma observação controlada das fases aguda e subaguda da colestase. MÉTODOS: Submeteram-se camundongos BALB/c, adultos, machos, a ligadura do ducto biliar (22 animais ou a cirurgia-controle (10 animais. Quinze dias após a cirurgia, ou imediatamente após a morte do animal, foram observados os achados macroscópicos e realizado o estudo histológico do fígado, árvore biliar e pâncreas (haematoxylina-eosina e tricrômico de Masson

  13. Clinical analysis on intrahepatic cholestasis of pregnancy: A report of 96 cases%妊娠期肝内胆汁淤积症96例临床治疗体会

    Institute of Scientific and Technical Information of China (English)

    魏秀琴; 孙友红

    2011-01-01

    目的 探讨妊娠期肝内胆汁淤积症(ICP)对母儿的影响.方法 将2008年1月~2010年12月本院住院的96例ICP患者(观察组)与同期其他随机抽取的正常孕妇106名产妇(对照组)进行比较.结果 ICP早产儿(25%);胎儿宫内窘迫(31.58%);低体重儿(19.74%);围产儿死亡(3.95%);明显高于对照组(P<0.01).剖宫产率(87.5%);产后出血(21.88%):明显高于对照组(P<0.01).结论 妊娠期肝内胆汁淤积症对母婴危害极大,应提高认识,加强孕期监护,提高围生儿生存率,降低产科并发症.%Objective To investigate the influences of intrahepatic cholestasis in the course of pregnancy (ICP) on mother and baby. Methods Retrospective analysis was made on the 96 cases of ICP (observation group) and the 106 cases of normal pregnant women (control group) in our hospital, in which the morbidity of premature delivery, fetal distress, low body weight, perinatal fetus and others were measured. Results For those that suffered ICP, the morbidity of premature delivery (25%), fetal distress (31.58%), low body weight (19.74%), and perinatal fetus (3. 95%) were significantly higher than the control group (P<0.01). Furthermore, the percentage of cesarean section (87. 5%) and blood loss after delivery (21. 88%) were also significantly higher than the control group (P<0.01). Conclusion Intrahepatic cholestasis of pregnancy can induce serious damage on mother and baby, which should be paid much attention to. Clinically, we should take intensive care of these patients to increase the survival rate of perinatal outcomes and decrease the obstetrical complications.

  14. 早产儿肠外营养相关性胆汁淤积防治进展%Progress in prevention and treatment of parenteral nutrition associated cholestasis of preterm infants

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    朱峰

    2011-01-01

    In the treatment of parenteral nutrition(PN) of preterm infants, parenteral nutrition associated cholestasis(PNAC) is the most common complication. However, the mechanisms of how this complication happens are unknown. This paper summarizes the research reports about PNAC both at home and aboard in recent years and raises various precautions on premature birth avoiding, reasonable feeding, PN projects optimizing and so on.Ursodeoxycholicacid is the first-line drug in the current treatment for PNAC.%肠外营养相关性胆汁淤积(PNAC)是早产儿肠外营养(PN)治疗过程中最常见的并发症,其病因及发病机制尚不明确.该文总结了近年来国内外有关早产儿PNAC的研究报道,提出了避免早产、合理喂养、优化PN方案等多种预防措施.熊去氧胆酸是目前治疗PNAC的一线药物.

  15. 妊娠期肝内胆汁淤积症对早期新生儿的预后评价%Effect of intrahepatic cholestasis of pregnancy to out-come of early newborns

    Institute of Scientific and Technical Information of China (English)

    陈颖; 李明美; 胡京辉; 吴明远

    2002-01-01

    本文通过对同一时期内患有妊娠期肝内胆汁淤积症(1)(Intrahepatic Chol-estasis of Pregnancy,简称ICP)母亲所娩婴儿及健康孕妇所娩婴儿各159例进行对照分析,发现ICP婴儿早产、低体重儿、羊水粪染及窒息儿患病率、难产率均明显高于对照组(P<0.05~0.0001),而ICP组婴儿高胆红素患病率略高于对照组,但无统计学意义.平均出生体重及体重回复率则明显低于对照组(T检验=0.00046,P<0.05),在疾病中呼吸系统发病最多,占ICP组患病儿的91.1%.本资料说明ICP使新生儿群体体质水平下降,但对胆红素的代谢无异常,呼吸系统患病率增高.

  16. 肝移植术后早期严重肝内胆汁淤积的相关因素分析%Risk factors of severe intrahepatic cholestasis during early period after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    张胜; 周杰; 谭永法; 谭凯; 陈立言

    2012-01-01

    (32/165),两组比较,差异有统计学意义(x2=11.54,P<0.05).结论 纠正受者术前不良的临床因素;术后积极控制感染和抗排斥反应可降低原位肝移植患者术后早期严重肝内胆汁淤积的发生率,并有可能改善早期预后.%Objective To investigate the risk factors of severe intrahepatic cholestasis during early period after liver transplantation.Methods The clinical data of 225 patients who received orthotopic liver transplantation at the Nanfang Hospital of Southern Medical University from August 2004 to February 2011 were retrospectively analyzed.All patients were divided into positive group (60 patients with intrahepatic cholestasis) and negative group (165 patients without intrahepatic cholestasis).Preoperative,intraoperative and postoperative factors of the 2 groups were compared via t test,chi-square test,Wilcoxon test or Logistic regression analysis.Results The proportion of patients with hepatic cirrhosis,hepatic encephalopathy integral,ascites integral,international normalized ratio,and the levels of prothrombin time (PT),total bilirubin (TBil),aspartate aminotransferase of the positive group before operation were significantly higher than those in the negative group (x2 =6.09,Z =2.22,2.60,2.46,2.84,4.81,3.42,P < 0.05),while the levels of albumin,Na +,K +,hemoglobin,platelet (PLT) of the positive group in the operation were significantly higher than those in the negative group (t =2.10,4.97,Z =2.49,t =3.51,Z =3.66,P < 0.05).The ratio of compatible blood type of the donors and recipients,ratio of fatty liver graft,cold ischemia time,relative warm ischemia time,intraoperative blood loss,intraoperative transfusion of red blood cells,PLT,and cryoprecipitate of the positive group after the operation were significantly higher than those in the negative group (x2 =4.29,13.11,Z =2.45,2.61,3.75,3.20,2.89,3.95,P <0.05).The incidences of acute rejection,hepatic artery embolism,pulmonary infection

  17. Influencing factors of parenteral nutrition associated cholestasis in preterm infant%早产儿胃肠外营养相关性胆汁淤积的影响因素分析

    Institute of Scientific and Technical Information of China (English)

    吴雅娟; 吕庆鹏; 李翠霞

    2016-01-01

    Objective To analyze the related factors of parenteral nutrition associated cholestasis in preterm infant and to provide theoretical basis for clinical intervention .Methods Retrospective analysis was conducted on hospitalization data of 146 preterm infants receiving parenteral nutrition (PN) in Second People’s Hospital of Nanhai District during January 2010 to April 2014.The cases were divided into control group (without cholestasis, n=110) and observation group (cholestasis, n=36), and they were compared in birth weight, PN duration, fasting time, hospitalization length, PN nutrient solution ratio, infection, antibiotics and mechanical ventilation .Results There were significant differences between two groups in birth weight , PN duration, fasting time, sugar calories ratio, amino acid calories ratio, fat lactic acid calories ratio, milk calories ratio, and total calories ratio (t value was 5.469, 12.921, 14.802, 8.156, 9.217, 10.108, 19.982 and 14.698, respectively, all P<0.05).The differences in infection incidence and mechanical ventilation rate were significant between two groups (χ2 value was 4.105 and 4.891, respectively, both P<0.05).Multiple stepwise Logistic analysis showed that long duration of PN (OR=2.147, 95%CI:1.040-3.807), long fasting time (OR=2.751,95%CI:1.970-4.408), high glucose calories ratio (OR=2.433, 95%CI:1.583-3.901), high fat lactic acid calories ratio (OR=2.907,95%CI:2.072-5.833), high amino acid calories ratio (OR=2.779,95%CI: 2.018 -4.540), mechanical ventilation (OR=1.511,95%CI:1.067 -3.908) and infection (OR=1.275, 95%CI:1.021-3.460) were risk factors of premature infants with parenteral nutrition associated cholestasis , while high birth weight was the protective factor (OR=0.672,95%CI:0.070-0.759).Conclusion Cholestasis in preterm infants threatens life and health of them.Clinicians should control infection , the use of mechanical ventilation , and opening of milk as early as possible .PN duration needs to be reduced and PN

  18. 妊娠期肝内胆汁淤积症118例的诊治研究及妊娠结局%Clinical research and pregnancy outcome of 118 cases of intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    梁美燕; 罗一平; 欧阳晓红

    2014-01-01

    Objective:To observe the clinical symptoms of intrahepatic cholestasis of pregnancy(ICP).To analyze its harm of maternal and child and the effective treatments of reducing the fetal death,neonatal asphyxia,premature delivery.Methods:118 cases with intrahepatic cholestasis of pregnancy were selected from January 2008 to June 2013.The clinical data were retrospectively analyzed.The clinical characteristics,delivery mode,postpartum hemorrhage and pregnancy outcome were summarized.Results:In the 118 ICP cases,81 cases were cesarean section,and 37 cases were vaginal delivery.25 cases(21.2%) were premature delivery,19cases (16.1%) were fetal distress,and 12 cases(10.2%) were neonatal asphyxia.ICP onset time was more early.The liver damage was more serious,and the harm was more greater.Neonatal appearance had no abnormalities.1 case high risk infant was died because of multiple organ failure after new pediatric treatment.Through the comparison with another 50 cases of the treatment group,it found that the treatment had significant improvement on the maternal and child health.Conclusion:ICP can cause intrauterine fetal anoxia,premature delivery,fetal distress and neonatal asphyxia,which has a great harm to the maternal and child.The early diagnosis,early treatment,and strengthening of fetal heart rate monitoring and timely termination of pregnancy can effectively reduce the neonatal hazards and improve the maternal and child health.%目的:观察妊娠期肝内胆汁淤积症(ICP)的临床症状,分析其对母婴的危害及降低胎儿宫内死亡、新生儿窒息、早产的有效治疗方法。方法:2008年1月-2013年6月收治ICP患者118例,对其临床资料进行回顾性分析,总结其临床特点、分娩方式、产后出血量及妊娠结局。结果:118例ICP患者中,剖宫产81例,阴道分娩37例。其中早产25例(21.2%),胎儿窘迫19例(16.1%),新生儿窒息12例(10.2%)。ICP发病时间越早,其肝损伤越严重,危害

  19. A Retrospective, Multi-Center, Post-Marketing Observational Study to Evaluate the Effectiveness of Ademetionine 1,4-Butanedisulfonate Injection (Transmetil®) Treatment in Chinese Patients with Intrahepatic Cholestasis Caused by Viral Hepatitis

    Institute of Scientific and Technical Information of China (English)

    Wen Xie; Ming-sheng Chen; Cun-jin Mei; Xiao-lin Guo; Xiao-hu Zhao; Jiang-bin Wang; Zheng-qin Fan; Jian-he Gan; Qing Xie; Jun Cheng; Hong Zhao; Yu Chen; Qin Zhang; Wei Lu; Wei Liu; Ai-rong Hu; Han-wei Li; Ping Feng

    2013-01-01

    Obejective Ademetionine 1,4-butanedisulfonate [S-adenosyl-L-methionine (SAMe)/Transmetil®, Abbott] has been available in China for more than 15 years, and it has been shown to reduce serum bilirubin and transaminase levels in patients with viral hepatitis (VH). However, no large-scale studies have focused on the impact of SAMe treatment regimen on reducing the serum total bilirubin (TBil) in VH patients with intrahepatic cholestasis (IHC). The main objective of this study was to evaluate the effectiveness of intravenous SAMe (Transmetil®) treatment in reducing the serum TBil by 50%. Methods This retrospective, multi-center, cross-sectional medical record review involved patients aged≥18 years. Records of 1 280 hospitalized VH patients at 16 sites diagnosed with IHC who had received intravenous SAMe 1 000 mg or 2 000 mg q.d. for at least 7 days from January 1, 2006 to June 30, 2009, were screened and 905 records were randomly selected. Results The safety set (SS) included 834 patients and the full analysis set included 826 patients. TBil levels after 14 days injection treatment were available for 763 patients. TBil decreased≥ 50%versus baseline after 14 days treatment in 288 (37.7%) patients (95%CI 34.3%, 41.2%). Twenty-nine non-serious adverse events (non-SAEs) were reported in 19 (2.3%) patients, and 29 SAEs were reported in 10 patients (1.2%). All adverse events (AEs) were considered unrelated to the drug. Conclusions This retrospective study shows that intravenous SAMe administration in VH patients with IHC is associated with signiifcant reduction of TBil levels in more than 30%of patients 14 days after treatment initiation.

  20. A Retrospective, Multi-Center, Post-Marketing Observational Study to Evaluate the Effectiveness of Ademetionine 1,4-Butanedisulfonate Injection (Transmetil?) Treatment in Chinese Patients with Intrahepatic Cholestasis Caused by Viral Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Obejective Ademetionine 1,4-butanedisulfonate [S-adenosyl-L-methionine (SAMe)/Transmetil?, Abbott] has been available in China for more than 15 years, and it has been shown to reduce serum bilirubin and transaminase levels in patients with viral hepatitis (VH). However, no large-scale studies have focused on the impact of SAMe treatment regimen on reducing the serum total bilirubin (TBil) in VH patients with intrahepatic cholestasis (IHC). The main objective of this study was to evaluate the effectiveness of intravenous SAMe (Transmetil?) treatment in reducing the serum TBil by 50%. Methods This retrospective, multi-center, cross-sectional medical record review involved patients aged≥18 years. Records of 1 280 hospitalized VH patients at 16 sites diagnosed with IHC who had received intravenous SAMe 1 000 mg or 2 000 mg q.d. for at least 7 days from January 1, 2006 to June 30, 2009, were screened and 905 records were randomly selected. Results The safety set (SS) included 834 patients and the full analysis set included 826 patients. TBil levels after 14 days injection treatment were available for 763 patients. TBil decreased≥ 50%versus baseline after 14 days treatment in 288 (37.7%) patients (95%CI 34.3%, 41.2%). Twenty-nine non-serious adverse events (non-SAEs) were reported in 19 (2.3%) patients, and 29 SAEs were reported in 10 patients (1.2%). All adverse events (AEs) were considered unrelated to the drug. Conclusions This retrospective study shows that intravenous SAMe administration in VH patients with IHC is associated with signiifcant reduction of TBil levels in more than 30%of patients 14 days after treatment initiation.

  1. Identification of a Large SLC25A13 Deletion via Sophisticated Molecular Analyses Using Peripheral Blood Lymphocytes in an Infant with Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency (NICCD: A Clinical and Molecular Study

    Directory of Open Access Journals (Sweden)

    Qi-Qi Zheng

    2016-01-01

    Full Text Available Background. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD is a Mendelian disorder arising from biallelic SLC25A13 mutations, and SLC25A13 genetic analysis was indispensable for its definite diagnosis. However, conventional SLC25A13 analysis could not detect all mutations, especially obscure large insertions/deletions. This paper aimed to explore the obscure SLC25A13 mutation in an NICCD infant. Methods. Genomic DNA was extracted to screen for 4 high-frequency SLC25A13 mutations, and then all 18 exons and their flanking sequences were analyzed by Sanger sequencing. Subsequently, cDNA cloning, SNP analyses, and semiquantitative PCR were performed to identify the obscure mutation. Results. A maternally inherited mutation IVS16ins3kb was screened out, and then cDNA cloning unveiled paternally inherited alternative splicing variants (ASVs featuring exon 5 skipping. Ultimately, a large deletion c.329-1687_c.468+3865del5692bp, which has never been described in any other references, was identified via intensive study on the genomic DNA around exon 5 of SLC25A13 gene. Conclusions. An NICCD patient was definitely diagnosed as a compound heterozygote of IVS16ins3kb and c.329-1687_c.468+3865del5692bp. The large deletion enriched the SLC25A13 mutation spectrum, and its identification supported the concept that cDNA cloning analysis, along with other molecular tools such as semiquantitative PCR, could provide valuable clues, facilitating the identification of obscure SLC25A13 deletions.

  2. 表现为婴儿胆汁淤积的CFTR基因缺陷致囊性纤维化病一例并文献复习%Infantile cholestasis caused by CFTR mutation: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    李丽; 王能里; 龚敬宇; 王建设

    2016-01-01

    Objective To study the clinical presentation,biochemical features and genetic analysis of an infant with cholestasis related to the CFTR mutations.Method The clinical presentation,laboratory investigations and management of a case with infantile cholestasis caused by CFTR mutations were summarized and the relevant literature was reviewed.Result (1) The patient was a 5 months old boy with cholestasis which developed in neonatal period with delayed meconium exclusion.The laparoscopic exploration was performed to exclude biliary atresia because of acholic stool when he was two months old.Ursodeoxycholic acid (UDCA),cholestyramine and phenobarbital treatment was applied.The genetic analysis showed compound heterozygous mutations in CFTR.The liver function normalized when he was 11 months old.When he was 21 months old,he had normal appearance except mild splenomegaly.(2) Literatures review identified 25 infantile cholestatic cases related to cystic fibrosis (CF) diagnosed by sweat test or gene analysis.Delayed meconium passage was found in five,meconium ileus in six cases.The liver function tests characterized by the direct hyperbilirubinemia with elevated transaminase,glutamyltranspeptidase and alkaline phosphatase levels.Genetic analysis revealed eight homozygotes of delF508,four heterozygotes of delF508 and one compound heterozygotes of c.263T > G/ c.2089-2090ins in CFTR.Jaundice resolved in 20 patients,ten of them were prescribed oral ursodesoxycholic acid (15-20 mg/(kg· d)).Five patients died,none of them received oral UDCA.Two of them had persisted cholestatic until death.Among the other three dead,two died from respiratory failure and one from cardiopulmonary failure.Conclusion Cystic fibrosis should be considered in cholestatic infants with meconium ileus or delayed meconium passage.Genetic analysis could confirm the diagnosis.UDCA may be beneficial to improve the liver function.%目的 总结表现为婴儿胆汁淤积的CFTR基因缺陷致囊性纤维化

  3. 甲状腺功能亢进症伴严重药物性胆汁郁积性肝炎1例并文献复习%One case of hyperthyroidism with severe drug-induced cholestasis hepatitis and literature review

    Institute of Scientific and Technical Information of China (English)

    曹雯; 郑仁东; 陈国芳; 包薇萍; 刘超

    2014-01-01

    甲状腺功能亢进症(甲亢)本身可导致肝功能损害,而抗甲状腺药物亦可引起肝功能损伤.但出现严重药物性胆汁郁积性肝炎的病例比较少见,临床治疗较为困难.本院收治1例,在治疗甲亢的基础上,采用甲强龙静脉脉冲冲击联合口服强的松的方案,降低患者胆红素水平,使肝功能恢复正常,甲亢亦得以控制.%Hyperthyroidism can cause liver damage,while anti-thyroid drugs can also cause liver dysfunction.Severe case of drug-induced cholestasis hepatitis is rare,difficult to treat.Here we report a case with drug-induced cholestasis hepatitis.On the basis of the treatment of hyperthyroidism,intravenous methylprednisolone pulse therapy combined with oral prednisone was used to reduce bilirubin levels in patients,therefore the liver function of the patient returned back to normal,and the hyperthyroidism was controlled.

  4. Risk factors of parenteral nutrition associated cholestasis in preterm infant%早产儿胃肠外营养相关性胆汁淤积影响因素研究

    Institute of Scientific and Technical Information of China (English)

    杨慧; 王卫; 刘晓红

    2013-01-01

    目的 探讨早产儿胃肠外营养相关性胆汁淤积的影响因素.方法 对2008年10月至2011年5月在我院新生儿重症监护病房进行胃肠外营养持续14天以上的早产儿资料进行回顾性分析,按照是否发生胆汁淤积分为病例组和对照组,比较两组胃肠外营养时间、禁食时间、体重增长及三大营养素提供热卡等的差别.结果 研究期间共有102例早产儿应用胃肠外营养14天以上,病例组21例,对照组81例,胃肠外营养相关性胆汁淤积发生率20.6%.病例组禁食时间(天)长于对照组[(9.9±4.9)比(5.7±3.3)],氨基酸及脂肪乳提供热卡比率(%)高于对照组[(7.8±3.5)比(4.2±2.0),(17.8±8.2)比(10.5±5.4)],每天总热卡[kcal/(kg·d)]低于对照组[(109.1±35.3)比(128.8±27.6)],发生喂养困难的比例高于对照组(60.0%比33.3%),差异均有统计学意义(P<0.05).多因素分析结果显示,禁食时间长、氨基酸和脂肪乳提供热卡比率高是发生胆汁淤积的危险因素(OR值分别为4.758、6.128、3.756),经口喂养提供热卡比率高是保护性因素(OR值0.012),P均<0.05.结论 胃肠外营养相关性胆汁淤积的发生与氨基酸及脂肪乳提供热卡比率高、禁食时间长有关,经口喂养提供热卡高为保护因素.%Objective To determine risk factors of parenteral nutrition associated cholestasis ( PNAC ) in preterm infants. Methods This retrospective analysis was conductcd on hospitalization data of 102 preterm infants receiving parenteral nutrition ( PN ) for more than 14 days in N1CU. The patients were assigned into the PNAC ( 21 cases ) and the control non-PNAC ( 81 cases ) groups. The duration of time for which patients were restricted from oral feeding ( NPO ) and received parental nutrition; the patients'caloric intake from glucose, protein and intralipid; and the patients' weiglit gain were compared and subjected to statistical analyses. Results The incidence of PNAC occurrence was 20. 6% . Comparing to

  5. A case-control study on 121 cases of intrahepatic cholestasis of pregnancy%121例妊娠期肝内胆汁淤积症的病例对照分析

    Institute of Scientific and Technical Information of China (English)

    张东升

    2013-01-01

    Objective To analyze the impact of intrahepatic cholestasis of pregnancy (ICP) on adverse perinatal outcomes. Methods 121 cases of intrahepatic cholestasis of pregnancy women who delivered from January to September 2008 in Anhui Province maternal and child health care hospital were selected as case group,121 normal cases were matched as control group. Socio-demographic data,clinical diagnosis information and delivery information were recordsed. Differences of main adverse perinatal outcomes were compared by statistic analysis between the two groups. Results There were no significant differences in socio-demographic information between ICP group and control group(P>0.05). Also there were no significant difference of parity,fetal gender,postpartum hemorrhage,severe asphyxia between the two groups(P>0.05). The rate of remature rupture of membranes in ICP group(10.7%) was lower than that in control group(17.5%);the rate of caesarean delivery was 81.8% in ICP group,higher than that in control group (63.6%);amniotic fluid pollution rate of ICP group(31.4%) was higher than that in control group (15.7%) ;birth weight in ICP group(3 032.3±392.0)g were lower than that in control group(3 222.3±469.6)g; These differences were all of statistical significance (P 0.05 ). Conclusion After controlling the confounding factors,ICP may have adverse effect on perinatal outcomes including high rates of caesarean delivery,premature and amniotic fluid pollution. Higher level the cholic acid may reflect the severity of the desease.%  目的探讨妊娠期肝内胆汁淤积症对围产儿结局的影响。方法以2008年1~9月在我院住院分娩的121妊娠期肝内胆汁淤积产妇为研究对象,按照1︰1配对设定对照组,记录两组人口统计学特征、临床诊断,追踪分娩情况,分析两组间围产儿不良结局差异。结果 ICP组与对照组产妇的户籍、年龄、自评家庭经济状况、文化程度等人口统计学因素分布差

  6. 重症监护病房感染相关性淤积性黄疸患者的临床分析%The clinical analysis of severe sepsis induced cholestasis jaundice patients in intensive care unit

    Institute of Scientific and Technical Information of China (English)

    徐前程; 查磊; 刘小彬; 陈尚华

    2016-01-01

    Objective To investigate the epidemiological characteristics and prognosis assessment mortality risk factors of severe sepsis induced cholestasis jaundice (SSICJ) patients admitted into intensive care unit (ICU), and to strengthen acknowledge of SSICJ and guild clinical treatment. Methods The clinical data of 60 SSICJ patients were retrospectively analyzed with statistical description. All the patients admitted to the ICU of the Wuhu second people′s hospital affiliated to Wannan medical college from January 2011 to December 2013 were assigned to two groups (survival group and non-survival group) according to the survival outcome. Logistic regression analysis was employed to identify independent risk factors of the death of SSICJ during ICU stay. Results The respiratory system was the most common site of infection [42%(25/60)], followed by abdominal infection and blood stream infection 22%(13/60),12%(7/60) respectively. Fifty-two patients were positive in bacterial isolation and 73 strains were identified , Gram-negative bacteria was the most common pathogens [48%(35/73)], followed by Gram-positive bacteria [30%(22/73)] and fungi [22%(16/73)]. Nosocomial infections accounted for [48%(29/60)] of the enrolled patients. Overall ICU mortality of SSICJ patients was[35%(21/60)], with nosocomial infections and chronic disease infections, septic shock, the ICU mortality were increased to [41%(12/29)], [64%(9/14)], [77%(17/22)] respectively. The patient with continue increaseing cholestasis jaundice in non-survival group was more than survival group[0%(0/31) vs 86%(18/21), P<0.01], the AST was similar in the two groups[(82±21) U/L vs(89±27) U/L, P=0.30]. Logistic regression analysis showed that APACHEⅡscores[odds(OR)=2.34, 95%CI 1.20-5.81, P=0.032], coexist with septic shock(OR=4.43, 95%CI 1.76-7.38, P=0.049), pre-ICU therapy time(OR=1.56,95%CI 1.05-3.78, P=0.015) were the independent risk factors of ICU mortality. Conclusion SSICJ was a common cause of ICU admission

  7. Changes of blood lipid in intrahepatic cholestasis of pregnancy and its clinical significance%妊娠期肝内胆汁淤积症血脂变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    文春蓉; 刘敏利

    2015-01-01

    Objective To explore the changes of blood lipid in intrahepatic cholestasis of pregnancy (ICP) patients and its clinical significance. Methods Collected empty stomach serum of 49 ICP patients in third trimester of pregnancy (ICP group) and 50 healthy pregnant women (control group) who gave birth in this hospital from 2010 to 2011. Measured and compared their blood lipid parameter. Divided ICP group′s patients into normal blood lipid group and abnormal blood lipid group ,and observed their liver function change. Results (1) ICP group′s total cholesterol,triacylglycerol and low density lipoprotein were all higher than control group′s while the high density lipoprotein was lower,differences showing statistical significance(P<0.05). (2)Abnor-mal blood lipid group′s alanine aminotransferase,aspartic transaminase amino acids,total bilirubin and direct bilirubin were all higher than normal blood lipid group′s,while the albumin was lower,and the amniotic fluid pollution and newborn complication′s incidence rate were higher,differences showing statistical significance(P<0.05). Conclusion The abnormal blood lipid of ICP patients is different from physiologic change of blood lipid during gestation period. It reflects the severe state of the illness and should be ICP patients′important monitoring index.%目的:探讨妊娠期肝内胆汁淤积症(ICP)患者血脂变化及其临床意义。方法收集2010~2011年在该院分娩的49例妊娠晚期ICP患者(ICP组)和50例健康孕妇(对照组)的空腹血清,测定血脂指标并进行比较。将ICP组患者分为血脂正常组(15例)和血脂异常组(34例),观察两组患者肝功能变化。结果(1)ICP组患者总胆固醇、三酰甘油、低密度脂蛋白均高于对照组,高密度脂蛋白低于对照组,差异均有统计学意义(P<0.05);(2)血脂异常组患者丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、总胆红素及结合胆红素均

  8. Percutaneous transhepatic cholecystostomy: An effective treatment of cholestasis in early postoperative inflammatory ileus patients%经皮经肝胆囊穿刺术在术后早期炎性肠梗阻并发淤胆治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    何长生; 朱维铭; 李宁

    2012-01-01

    目的 禁食、全胃肠外营养(total parenteral nutrition,TPN)时间长及应用生长抑素治疗,引起少数术后早期炎性肠梗阻(early postoperative inflammatory ileus,EPII)患者出现淤胆症状.文中探讨经皮经肝胆囊穿刺术(percutaneous transhepatic cholecystostomy,PTC)在术后EPII并发淤胆患者中的应用价值.方法 回顾性分析15例腹部手术后EPII并发淤胆患者运用PTC的治疗效果.患者均行B超或腹部CT检查,常规进行禁食、胃肠减压、灌肠、TPN、生长抑素、小剂量糖皮质激素等综合治疗,运用PTC行胆汁外引流.结果 15例患者均非手术治愈,无穿刺并发症发生,平均住院时间为(32.5±5.7)d,TPN支持时间平均为(26.6±10.5)d,穿刺后至肛门排气为1~4d,平均时间为(2.3±0.9)d.11例患者谷丙转氨酶(GPT)、谷草转氨酶(GOT)、γ-谷氨酰转肽酶(γ-GT)、碱性磷酸酶(AKP)、总胆红素、直接胆红素水平升高,穿刺后GPT、GOT、γ-GT、AKP、总胆红素、直接胆红素水平较快恢复正常,淤胆症状消失.6例患者出现低热、右上腹不适症状,穿刺后体温恢复正常,右上腹不适症状缓解.结论 PTC运用安全有效,虽不能根本改变术后EPII的病理过程,但能明显改善术后患者因禁食而长期应用TPN导致的淤胆症状,改善肝功能,恢复胆汁流,促进肠蠕动,加速康复.%Objective One of the most important issues in a patient with suspected early postoperative inflammatory ileus is the risk of cholestasis resulting from fasting, total parenteral nutrition ( TPN ) and somatostatin, which can lead to stasis of biliary function and liver dysfunction. This paper is to determine the safety and effectiveness of percutaneous transhepatic cholecystostomy ( PTC ) in the treatment of cholestasis in early postoperative inflammatory ileus patients. Methods A retrospective study was made on the treatment of PTC on 15 early postoperative inflammatory ileus patients with cholestasis. Routine

  9. 肝内胆汁淤积症患者围生儿预后不良因素分析%Analysis of perinatal poor prognosis factor in patients with intrahepatic cholestasis of perinatal

    Institute of Scientific and Technical Information of China (English)

    刘娟; 陈雄; 汪宇平; 金玉珍; 吴颖

    2012-01-01

    目的:探讨影响肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)患者围生儿预后的相关因素.为临床采取恰当的分娩方式和选择适时的手术时机提供可靠依据.方法:随机抽取我院2009年1月-2012年4月发生胎儿窘迫50例与未发生胎儿窘迫的ICP患者50例瘙痒出现孕周、天冬氨酸转氨酶、总胆红素、血清总胆汁酸、脐血流、胎心监护、分娩方式、及新生儿吸入性肺炎、新生儿窒息(Apgar评分)、围生儿死亡率、早产率、小于胎龄儿发生率等进行对比分析,探讨影响ICP患者围生儿预后的因素.结果:发生胎儿窘迫的ICP患者脐血流(S/D值)异常升高及产前胎心监护NST评分、血清总胆汁酸水平、早产率明显高于未发生胎儿窘迫的ICP患者(P<0.05),但瘙痒出现的孕周及AL T、血清总胆红素值,两组间差异无统计学意义(P>0.05).前组新生儿吸入性肺炎、新生儿窒息、围生儿死亡率均较对照组高,其差异均有统计学意义(P<0.05);两组小于胎龄儿发生率无明显差异,无统计学意义(P>0.05).结论:脐血流S/D值及血清总胆汁酸、NST评分与ICP患者胎儿窘迫有关,致使新生儿早产率、吸入性肺炎、新生儿窒息、围生儿死亡率均升高,而瘙痒出现的孕周、AL T水平、血清总胆红素水平与之无关.妊娠期ICP严重影响围生儿的预后,应做到早期诊断、早期治疗,适时终止妊娠,降低ICP对围生儿的危害.%Objective:To study the factors influencing the perinatal prognosis in patients with intrahepatic cho-testasis of pregnancy (ICP) and to provide a reliable basis for taking appropriate mode of delivery and choosing timely moment of surgery. Methods: 50 ICP cases with fetal distress and 50 ICP cases without fetal distress were randomly selected in our hospital from January 2009 to April 2012. The comparative analysis about itching gestational age, aspartate aminotransferase, total

  10. 湖北地区 Citrin 缺陷导致的新生儿肝内胆汁淤积症临床研究%Clinical research of neonatal intrahepatic cholestasis caused by Citrin deficiency in Hubei Province

    Institute of Scientific and Technical Information of China (English)

    熊小丽; 鄢素琪; 丁艳; 周俪姗; 陈鹏; 赵东赤

    2015-01-01

    目的:探讨湖北地区 Citrin 缺陷导致的新生儿肝内胆汁淤积症(NICCD)的临床表现及实验室特点。方法收集2010年9月至2013年1月在武汉市儿童医院住院20例 NICCD 患儿未经治疗时的生化指标(肝功能、血脂、乳酸、血氨、总胆汁酸、甲胎蛋白)、凝血象、血氨基酸谱、酰基肉碱谱、尿有机酸谱及 SLC25A13基因分析,并随访1年。结果 NICCD 患儿实验室检查表现为高胆红素血症、肝酶升高、胆汁酸增高,高脂血症、高甲胎蛋白、高乳酸血症、高氨血症、低蛋白血症、低血糖、凝血机制障碍;多种氨基酸升高,以瓜氨酸升高为主;酰基肉碱中以长链酰基肉碱升高为主;尿4-羟基苯乙酸、4-羟基苯乳酸、4-羟基苯丙酮酸异常增高;SLC25A13基因分析共发现6个突变位点,其中 L477R,G639S 为新发突变位点,851del4、1638ins23、IVS6+5G ﹥A 为热点突变。20例患儿黄疸均在1岁内缓解。结论 NICCD 患儿多项临床实验指标异常,高脂血症在病程早期即已出现,L477R、G639S 为新发突变位点。%Objective To explore the clinical manifestations and the characteristics of neonatal intrahepatic cholestasis caused by Citrin deficiency(NICCD)in Hubei province. Methods The biochemical indicators including liver function,blood lipid,lactic acid,blood ammonia,total bile acid,alpha feto protein,coagulogram,blood amino spec-trum,acylcrnitine spectrum,urine organic acid and SLC25A13 gene analysis of 20 cases with NICCD,who came from Wuhan Children's Hospital,during September 2010 to January 2013,were collected before treatment,then followed up for 1 year. Results Laboratory results of NICCD patients showed high blood bilirubin,elevated liver enzymes and bile acid,hyperlipidemia,high alpha feto protein,high lactic acidosis,high ammonia,hypoalbuminemia,hypoglycemia,disor-der of blood coagulation mechanism,variety of amino acids increase,mainly citrulline

  11. Estado nutricional e absorção intestinal de ferro em crianças com doença hepática crônica com e sem colestase Nutritional status and intestinal iron absorption in children with chronic hepatic disease with and without cholestasis

    Directory of Open Access Journals (Sweden)

    Regina Helena Guedes da Motta Mattar

    2005-08-01

    Full Text Available OBJETIVO: Avaliar a ingestão alimentar, a ocorrência de desnutrição energético-protéica e de anemia e a absorção intestinal de ferro em crianças com doença hepática crônica. CASUÍSTICA E MÉTODOS: Foram estudados 25 pacientes com doença hepática crônica, sendo 15 com colestase e 11 sem colestase. A idade variou entre 6,5 meses e 12,1 anos. A absorção intestinal de ferro foi avaliada pela elevação do ferro sérico uma hora após a ingestão de 1 mg/kg de ferro elementar e pela resposta à ferroterapia oral. A absorção intestinal de ferro foi comparada com um grupo de crianças com anemia ferropriva. RESULTADOS: A ingestão média de energia e proteínas nos pacientes com doença hepática com colestase foi maior do que nos pacientes sem colestase. O déficit nutricional foi mais grave nos pacientes com colestase, predominando os déficits de estatura-idade e peso-idade. A anemia foi freqüente tanto nas crianças com doença hepática com colestase (11/14; 78,6% como nas sem colestase (7/11; 63,6%. Na doença hepática com colestase, observou-se menor (p OBJECTIVES: to evaluate food intake, occurrence of energy-protein malnutrition and anemia, and intestinal iron absorption in children with chronic liver disease. METHODS: The study included 25 children with chronic liver disease, 15 with cholestasis and 11 without cholestasis. The age varied between 6.5 months and 12.1 years. Intestinal iron absorption was evaluated by the increment of serum iron one hour after the ingestion of 1 mg/kg of elemental iron and by the response to oral iron therapy. Iron intestinal absorption was compared to a group with iron deficiency anemia (without liver disease. RESULTS: The mean intake of energy and protein in the cholestatic group was higher than in patients without cholestasis. The nutritional deficit was more severe in cholestatic patients, especially with regard to height-for-age and weight-for-age indices. Anemia was found in both

  12. 妊娠期糖尿病合并妊娠肝内胆汁淤积症对围产儿的影响%The effects to the perinatal outcome in gestational diabetes mellitus complicated with intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    李艳; 徐曦; 周淑; 刘毅; 高岚; 付利侠

    2011-01-01

    Objective To explore the effects on the perinatal outcome in gestational diabetes mellitus(GDM) complicated with intrahepatic cholestasis of pregnancy (ICP). Methods Collect the clinical datum of 1080 pregnant women of the last three year, dividing into three groups; Group GDM and ICP 180 ,Group GDM 426 and Group ICP 474,and analying the perinatal out come between group GDM and ICP and group GDM , between group GDM and ICP and group ICP. Results Hie rate of termina ting pregnancy less than 34 gestational weeks(9. 44% ) 、 the rate of neonatal asphyxia(7. 22% )、 the rate of amniotic fluid pol lution over than D (21. 11% )、the rate of small for gestational age (7. 22% ) of Group GDM and ICP was higher than group GDM and group ICP, And there is significantly difference (P <0.05) among these three groups . Conclusion The risk of adverse peri natal outcome was added in gestational diabetes mellitus complicated with intrahepatic cholestasis of pregnancy. Inorder to Impro ving the perinatal outcome , enhancing fetal monitoring and termination of pregnancy in suitable time is very important.%目的 探讨妊娠期糖尿病合并妊娠肝内胆汁淤积症对围产儿结局的影响.方法 回顾性分析我院2008年1月~2010年10月住院分娩的妊娠期糖尿病合并妊娠期肝内胆汁淤积症(GDM+ ICP组)孕妇180例临床资料,与同期住院的妊娠期糖尿病(GDM组)426例、妊娠期肝内胆汁淤积症(ICP组)474例孕妇所分娩围产儿的结局情况分别进行比较.结果 GDM+ ICP组34周前终止妊娠率、新生儿窒息率、Ⅱ度以上羊水粪染率、小于胎龄儿发生率显著高于其余两组(P<0.05).结论 妊娠期糖尿病合并妊娠肝内胆汁淤积症围产儿不良结局风险增加,应加强胎儿监护,适时终止妊娠,提高出生质量.

  13. The role of glutamine and C. C. K in preventing cholestasis during PN%谷氨酰胺、胆囊收缩素预防胃肠外营养期间胆汁瘀积的动物实验研究

    Institute of Scientific and Technical Information of China (English)

    王盛江; 刘立人; 慕海峰; 禹宏; 孙大强; 杨闯

    2000-01-01

    Objective Purpose: Study Glutarnine (GLN)/Cholecystokinin (CCK)'s action of preventing cholestasis during total parenteral nutrition (TPN) and detail action mechanism of GLN and CCK and relationship between each other. Methods Adopt Newzealand pure species white hares as TPN models. All hares were divided into four teams, in which 1st team was designated as TPN team, 2nd team as TPN + GLN team, 3rd team as TPN + CCK team, and 4th team as TPN + GLN + CCK team. Each team was divided into two halves in turn. One half were killed after four-week observation and the other half were killed after 8 weeks. Through blood biochemical examination, analysis of chole components, observation of macrostructure, scan of light and esectron microecopes, we observed if there were cholestasis, gallbladder constmctural alteration and its degree. Results Through blood monitoring, increases of GPT. AKP. cholehilirubin and cholesterol were observed in the first team as compared with the second to forth teams at the forth week and higher increases were found at the 8th week. In choletest,cholebilirubin and cholesterol were higher in the first and second teams than in the third and fourth ones at the 4th week and were higher instinctively in the first to third teams than in the forth team at the 8th week. Scan of light and electron microscopes demonstrated that cholepithelia became low-column shape. Dyeing was deepened. There was cytoedema and mitochondrial got swelling at the 4th week in the first and third teams. At the 8th week, there was tissue between lamina propria and muscle layer. Cyto-plasm became muddy, in which there were bigger fatty drops. There were vacuity in cytoreticulum. In the second and forth teams, we found normal cell density at the 4th week. At the 8th week, there was small alteration in the second team and normal density in the forth team. Conclusions It is true that cholestasis will take place during TPN and become serious with time prolonging. Integrality and

  14. Clinical analysis of fetal death cases in intrahepatic cholestasis of pregnancy%妊娠期肝内胆汁淤积症发生死胎的临床因素分析

    Institute of Scientific and Technical Information of China (English)

    贺晶; 陈璐; 梁琤

    2011-01-01

    Objective To investigate the clinical features,critical laboratory parameters,and fetal monitoring methods in intrahepatic cholestasis of pregnancy(ICP).Methods A retrospective analysis of 21 cases of ICP suffered with fetal death in Women's hospital.School of Medicine.Zhejiang University from January 1999 to December 2010 were discussed.Results(1)The average age of ICP patients suffered with fetal death were(30.2±4.6)years old.Among them,4 cases were older than 35 years,six cases were multipara.oneo of them suffered stillbirth 2 year before.Twenty cases were singleton pregnancies and 1 cage was twin pregnancy.(2)All 21 cases of fetal death occurred in the third trimester,12 cases occurred before 37 weeks,9 cases after 37 weeks.Nine cases were diagnosed by ultrasound in outpatient clinics,fetal heart beat disappeared in 9 patients after admission because of ICP, two disappeared after labor, one during anesthesia before emergent surgery. Perinatal mortality rate of ICP was 0. 148% (21/14 184), and fetal death occurred from 29 to 41 weeks with an average gestational age of ( 33.8 ± 4. 2 ) weeks, ( 3 ) Puritus occurred in all 21 cases while 11 of them had pruritus all over the body. Ten pregnant women felt the fetal movement decreased or disappeared before diagnosis of fetal death. The glycocholic acid levels increased in all of the 21 cases. Among them, glycocholic acid levels in 11 cases were (21.49 -64. 48) μmol/L, while in 10 cases were ≥64. 48 μmol/L Serum bile acid levels elevated in 16 cases which had been analyzed ( the other 5 cases had not been checked ), and the highest level reached 270 μmol/L Serum alanine aminotransferase and aspartate aminotransferase were increased in 14 cases. Seven cases had their total bilirubin >21 μmoL/L, and 12 cases had their direct bilirubin levels significantly elevated. Among the 21 cases of ICP, 15 cases were in severe status, while the other 6 cases were mild. (4) Nine patients had no antepartum surveillance since

  15. Expressions of SHP and CYP7A1 in pregnant rats with intrahepatic cholestasis%小异二聚体伴侣与胆固醇7a-羟化酶在肝内胆汁淤积症孕鼠中的表达

    Institute of Scientific and Technical Information of China (English)

    兰易; 刘建; 程浩; 邹姝丽; 甘晓玲

    2008-01-01

    Objectives To investigate the expressions of small heterodimer partner (SHP) and target gene cholesterol-7-hydroxylase (CYP7A1) in livers of rats with intrahepatic cholestasis of pregnancy (ICP), and to study the mechanism of ICP. Methods Thirty SD rats (pregnant for 15 days) were equally and randomly divided into two groups: an estradiol benzoate (EB) group and a normal saline (NS) group. Two ml blood was drawn from each rat before and on the 5th day after medicine administration to measure the levels of ALT, AST, ALP, TBA, TBIL, and DBIL. After delivery, the histopathological changes of the mother rat livers were studied. The mRNA and protein expressions of SHP and CYP7A1 in the livers were determined by RT-PCR and Western blot. Results (1) In the EB group, the serum levels of ALT, AST, ALE TBA, TBil, and DBil after EB administration increased significantly (P0.05); (2) Intrahepatic cholestasis appeared in the EB group, but not in the NS group; (3) The mRNA expressions of SHP and CYP7A1 were significantly higher in the EB group than in the NS group [(SHPmRNA: NS 0.365±0.0317 vs EB 0.4865±0.0237, P0.05).雌激素组孕鼠肝脏出现肝内胆汁淤积表现,对照组肝脏形态、结构正常.雌激素组和对照组SHP mRNA分别为0.4865±0.0237和0.3657±0.0317, CYP7A1 mRNA分别为0.4311±0.0157和0.3285±0.0123,差异均有统计学意义(P<0.01).雌激素组和对照组SHP蛋白表达分别为0.5033±0.0274和0.3762±0.0284, CYP7A1蛋白表达分别为0.4802±0.0217和0.3570±0.0175,差异均有统计学意义(P<0.01).结论 雌激素诱导的胆汁淤积促进肝脏SHP及其靶基因CYP7A1表达增加,导致胆汁酸合成进一步增加,从而引发胆汁淤积,这可能是妊娠期肝内胆汁淤积症发病机制之一.

  16. Protective effect of Zhizi Bopi decoction on α-naphthylisothiocyanate induced intrahepatic cholestasis in rats%栀子柏皮汤对α-萘异硫氰酸酯诱导的肝内胆汁淤积大鼠的保护作用

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    曹璐; 李俊; 黄成; 韩静文

    2013-01-01

    Objective To investigate the protective effects of Zhizi Bopi decoction on rats against a-naphthyliso-thiocyanaten ( ANIT )induced liver injury with cholestasis and analyzed the possible mechanism. Methods ANIT was used to mimick the drug-induced liver injuery. 48 h after the ANIT treatment, serum of total bilirubin ( TBIL ), alkaline phosphatase ( ALP ), alanine aminotransferase ( ALT ), aspartate aminotransferase ( AST ), 7-glutamyltranspeptidase ( GGT ), liver specimens of superoxide dismutase ( SOD ), malondialdehyde ( MDA ), gluta-thione ( GSH ), and glutathione peroxidase ( GSH-Px ) were measured. To further explore the molecular mechanisms , we measured the expression of the bile metabolism-related transporters: bile salt export pump ( BSEP ), sodi-um-taurocholate cotrans-porting polypeptide ( NTCP ) and the enzyme related to oxidative stress: cytochrome P4502E1 ( CYP2E1 ) in both mRNA and protein level. Results Zhizi Bopi decoction improved live history with reduced the serum levels of TBIL, ALP, ALT, AST, GGT. Furthermore, hepatic MDA activities and contents in liver tissue were significantly reduced, while SOD, GSH, GSH-Px activities, which had been suppressed by ANIT were significantly elevated in the groups pretreated with Zhizi Bopi decoction in a dose-dependent manmer. Additionally, Zhizi Bopi decoction was found to increase the expression of liver NTCP, and decrease the BSEP in ANIT-induced liver injury with cholestasis. CYP2E1 was decreased in accordance with the protein expression. Conclusion Zhizi Bopi decoction exerts protective effects against ANIT-induced liver injury. The mechanisms could be related to transshipment of bile metabolism-related transporters and anti-oxidative damage.%目的 探讨栀子柏皮汤对α-萘异硫氰酸酯(ANIT)诱导的肝内胆汁淤积大鼠的保护作用及可能机制.方法 实验组大鼠灌胃给予栀子柏皮汤7 d,第7天给药后4 h给ANIT造模.48 h后,测血清总胆红素(TBIL)含量、碱性磷酸

  17. S-腺苷蛋氨酸联合熊去氧胆酸治疗极低出生体质量患儿肠外营养相关性胆汁淤积症的疗效观察%Efficacy of S-adenosylmethionine and ursodeoxycholic acid on parenteral nutrition associated cholestasis in very low birth weight infants

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    何伟彬; 杨辉; 戴怡蘅

    2013-01-01

    目的 观察S-腺苷蛋氨酸联合熊去氧胆酸治疗极低出生体质量患儿肠外营养相关性胆汁淤积症的疗效.方法 研究对象为本院2008年1月-2012年10月出生的极低出生体质量患儿67例,出生后接受静脉营养(PN)并出现肠外营养相关性胆汁淤积症(PNAC),随机分为观察组36例,对照组31例.对照组在减少肠外营养基础上给予口服熊去氧胆酸10~30mg/(kg·d)治疗10d,观察组在对照组治疗基础上联合S-腺苷蛋氨酸30~50mg/(kg·d)治疗10d.治疗前后分别检测2组患儿血清谷丙转氨酶(ALT)、总胆红素(TBIL)、直接胆红素(DBIL)和总胆酸(TBA)的水平.结果 2组各观察指标ALT、TBIL、DBIL、TBA的水平均较治疗前下降,差异有统计学意义(P<0.01).观察组ALT、TBIL、DBIL、TBA的水平较对照组下降更明显(P<0.05).结论 S-腺苷蛋氨酸联合熊去氧胆酸治疗极低出生体质量患儿胆汁淤积症疗效更显著,安全性高,值得临床推广.%Objective To observe the efficacy of the S - adenosylmethionine and ursodeoxy-cholic acid on parenteral nutrition associated cholestasis in very low birth weight infants. Methods Sixty-seven very low birth weight infants received parenteral nutrition (PN) after born, and suffered from parenteral nutrition associated cholestasis (PN AC). They were randomly divided into observation group (n =36) and the control group (n = 31). In the control group, the patients received the reduced dose of parenteral nutrition, and were treated with ursodeoxycholic acid of dosage 10 - 30 mg/(kg·d) for 10 days. In the observation group, the patients received same treatment as those in the control group, and treated with S- adenosylmethionine of dosage 30~50 mg/(kg·d) for 10 days. Before and after treatment in two groups, we detected their serum levels of alanine amino-transferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA). Results Levels of ALT, TBIL, DBIL and TBA in

  18. Effects of FXR and CYP7A1 on metabolism of acid bile of pregnant rats with intra-hepatic cholestasis%FXR、CYP7A1在妊娠期肝内胆汁淤积症孕鼠胆汁酸代谢中的作用

    Institute of Scientific and Technical Information of China (English)

    兰易; 刘建; 邹姝丽; 程浩; 甘晓玲

    2008-01-01

    目的 分析法尼醇受体(FXR)及其靶基因胆固醇7α-羟化酶(CYP7A1)在妊娠期肝内胆汁淤积症(intrahe-patic cholestasis of pregnancy,ICP)孕鼠肝脏的表达情况,探讨FXR与CYP7AI在ICP发病机制中的作用.方法 用随机数字表法将30只孕15 d的SD大鼠分成2组:生理盐水(NS)组和苯甲酸雌二醇(estradiol benzoate,EB)组,每组15只.用药前和用药后第5天分别测定血清中ALT、AST、ALJP、TBA水平,同时观察肝脏形态学变化,并应用RT-PCR和Westernblot分别检测肝脏FXR、CYP7A1两者mRNA和蛋白的表达.结果 EB组用药后备血清生化指标比用药前显著升高(P0.05);EB组孕鼠肝脏出现肝内胆汁淤积表现,Ns组肝脏形态结构正常;EB组FXR和CYP7A1两者的mRNA和蛋白表达均显著高于Ns组(P<0.01).结论 EB诱导的ICP孕鼠肝脏FXR及CYP7A1表达均增加,说明存在胆汁酸合成自身反馈调节障碍,导致胆汁酸合成增加,这可能是ICP发病机制之一.

  19. Expression of Estrogen Receptor mRNA and Genes Related to Regulation of Bile acid Metabolism in Fetal Rat Liver of Pregnant Rats with Intrahepatic Cholestasis%雌激素受体及胆汁酸代谢相关基因在胆汁淤积孕鼠胎鼠肝脏中的表达

    Institute of Scientific and Technical Information of China (English)

    时青云; 赵晋; 林宇庚; 闫时; 周新; 林颖奇

    2011-01-01

    目的 探讨雌激素受体(estrogen receptor,ERα)与胆汁酸代谢相关基因胆固醇7α羟化酶(cholesterol 7α-hydroxylase,CYP7A1)、胆固醇27α羟化酶(cholesterol 27-hydroxylase,CYP27A1)、胆固醇12α羟化酶(cholesterol 12α-hydroxylase,CYP8B1)mRNA在妊娠期肝内胆汁淤积孕鼠胎鼠肝脏中的表达及其意义.方法 将60只清洁级SD孕鼠自孕第13天均分为2组:对照组孕鼠皮下注射精制植物油2.0 mL*kg-1*d-1;研究组孕鼠皮下注射17-α-乙炔雌二醇1.25 mg*kg-1*d-1.2组孕鼠分别于妊娠第13、17、21天断尾采母鼠血2 mL检测血清生物化学指标,于妊娠第21天处死.抽取母鼠、胎鼠血并提取母鼠、胎鼠肝脏组织.应用酶联免疫吸附试验检测2组孕鼠以及胎鼠血清中胆酸浓度;应用实时定量PCR技术检测各组胎鼠肝脏ERα、CYP7A1、CYP27A1、CYP8B1的mRNA表达量.结果 ①胆酸指标比较:在妊娠第17天时对照组、研究组母鼠胆汁酸浓度分别为(24.6±1.3)μmol/L、(58.7±3.2)μmol/L,研究组母鼠胆汁酸浓度明显高于对照组(t=2.462,P<0.05);在妊娠第21天时对照组、研究组母鼠胆汁酸浓度分别为(26.5±3.1)μmol/L、(66.4±2.7)μmol/L,研究组母鼠胆汁酸浓度与妊娠第17天时研究组以及对照组相比(F=5.43,P<0.05),差异有统计学意义.②胎鼠肝脏CYP7A1 mRNA、CYP27A1 mRNA、CYP8B1 mRNA表达:研究组中CYP7A1 mRNA(1.25±0.01)、CYP27A1 mRNA(2.05±0.03)、CYP8B1 mRNA明显高于对照组(0.35±0.02、0.75±0.03、0.85±0.02),P值均<0.05,差异有统计学意义.③胎鼠肝脏雌激素受体的表达:研究组中ERα mRNA(0.75±0.02)明显高于对照组ERα mRNA(0.45±0.01).结论 妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)孕鼠胎鼠肝细胞ER、CYP7A1、CYP27A1、CYP8B1的表达升高,胆汁酸的合成与代谢调节机制存在障碍,可能是导致ICP胎儿围生期死亡发生的原因之一.%Objective To study the expression of estrogen receptor(ER) and

  20. 进行性家族性肝内胆汁淤积非移植外科治疗荟萃分析%Treatment of progressive familial intrahepatic cholestasis with non-transplant surgery: a review of literature and meta-analysis

    Institute of Scientific and Technical Information of China (English)

    刘壵; 李龙; 侯文英; 王海斌

    2013-01-01

    Objective To review the outcome of the different choices of non-transplant surgical treatment for progress familial intrahepatic cholestasis (PFIC) by performing meta-analysis.Methods A systematic literature search of PubMed,Embase,Scopus and Chinese Biomedical Literature Database (CBM) was performed.All the articles regarding the outcome of non-transplant surgery in PFIC patients were recruited in this study.Results A total of 20 case series or case reports were included in this study.Of the 144 patients who underwent a non-transplant surgery,108 (75%) patients had favorable outcomes.Unfavorable outcomes were often associated with more advanced stage of liver fibrosis or cirrhosis.Conclusions Non-transplant surgical interventions in PFIC patients can effectively delay progression of liver cirrhosis.%目的 总结分析进行性家族性肝内胆汁淤积(PFIC)的非移植外科治疗的不同手术方式及其治疗现状.方法 检索PubMed、EMBASE、Scopus和中国生物医学文献数据库(CBM)非移植外科治疗PFIC的所有相关文献,提取临床资料,总结分析.结果 20项个案或病例系列报道纳入本研究,共144例患儿接受非移植外科治疗,其中108例(75%)预后良好.疾病进展,脏纤维化或硬化,往往提示预后不良.结论 从某种意义上讲,虽然本荟萃分析所纳入研究存在一定的不全面性和不一致性,但是非移植外科治疗确实能明显缓解PFIC患儿症状,遏制疾病进展.

  1. 妊娠期肝内胆汁淤积症的新生儿血清胱抑素c测定分析%Newborn Infants Suffering from Intrahepatic Cholestasis of Pregnancy (ICP) by Measuring the Content of Serum Cystatin C (CysC)

    Institute of Scientific and Technical Information of China (English)

    李作娅; 李伟; 夏梅梅; 任盛

    2012-01-01

    目的:通过对妊娠期肝内胆汁淤积症(ICP)的新生儿血清胱抑C(CysC)血尿素氮(BuN),血肌肝(scR)测定分析,探讨妊娠期肝内胆汁淤积症的新生儿肾功能变化.方法:对35例妊娠期肝内胆汁淤积症(ICP)的新生儿与正常对照组新生儿均于生后24小对内和第七天,分别测定血清胱抑素C(CysC)、血尿素氮(BuN)、血肌肝(scR)水平,并将两组测定数据进行对比分析.结果:妊娠期肝内胆汁淤积症(ICP)的新生儿组血清胱抑素C(CysC)与正常对照组的新生儿比较明显增高(p<0.05),而血清尿素氮( BUN)及肌肝SCR两组比较差异无统计学意义.一周后两组胱抑素C(CysC)、肌肝(BuN)、尿素氮( BUN)比较无差异(P>0.05).结论:妊娠期肝内胆汁淤积症ICP的新生儿有一过性肾损害,血清胱抑素C与血尿素氨、血肌酐比较,是早期诊断肾功能损害更灵敏的指标.%Objective: To explore changes in renal functions of newborn infants suffering from Intrahepatic Cholestasis of Pregnancy (ICP) by measuring the content of serum cystatin C (CysC), Urea nitrogen (BUN) and serum creatinine (SCr).Methods: The contents of serum cystatin C (CysC), Urea nitrogen (BUN) and serum creatinine (SCr) of 35 newborn children suffering from ICP were measured within 24 hours of birth and the seventh day of birth, respectively. As the control, the measuring were performed in the exactly the same way for regular new born children.Results: the children suffering from ICP showed obvious increase in CysC in contrast with the control (p0.05).Conclusion: transient kidney injuries exist in newborn infants suffering from ICP. Compared with BUN and SCr, CysC is a sensitive indicator for kidney injury early diagnosis.

  2. Identification and diagnosis of three novel mutations in SLC25A13 gene of neonatal intrahepatic cholestasis caused by citrin deficiency%Citrin缺陷导致的新生儿肝内胆汁淤积症SLC25A13基因三个新突变的识别及诊断

    Institute of Scientific and Technical Information of China (English)

    宋元宗; 盛建胜; 牛飼美晴; 胡務亮; 张春花; 小林圭子

    2008-01-01

    Objective Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD, OMIM 605814 ) is a novel autosomal recessive disease results from mutations in the gene SLC25A13 that encodes for citrin, a liver-type aspartate/glutamate cartier located in the mitochondrial inner membrane. Most of the Chinese NICCD patients diagnosed by genetic analysis had the sameSLC25A13 mutations as Japanese, however, in some cases, the known mutations were not detected. This research aimed to identify novel SLC25A13 mutations in Chinese NICCD patients and to explore the experimental conditions for their genetic diagnosis.Methods Genomic DNA was extracted from blood samples of 3 NICCD patients from Taiwan (P757), Guangdong (P1194) and Hebei (P1443) Province of China, respectively; and all the 18 exons and their flanking sequences of SLC25A13 gene were sequenced. Furthermore, the identified novel mutations were diagnosed by amplification with PCR, digestion with corresponding restriction endonuclease, and agarose gel electrophoresis.Results Three novel mutations identified in SLC25A13 gene of the 3 NICCD patients were an abnormal splicing IVS7-2A>G (P757), a missense A541D (c. 1622C > A, P1194) and a nonsense R319X (c. 955C > T, P1443). The PCR-RFLP procedures for their genetic diagnosis were also established, with specific fragments on electrophoresis after digestion of the PCR products with three different restriction endonucleases Msp Ⅰ, Hpy188Ⅰ and Taq Ⅰ, respectively.Conclusions The three novel mutations in SLC25A13 gene of Chinese NICCD patients were first identified, suggesting that SLC25A13 mutation distributed in Chinese population is somewhat different from that in Japanese. Moreover, the PCR-RFLP diagnostic procedures established in this research provide valuable tools not only for the genetic diagnosis of NICCD but also for further molecular epidemiologic investigations in Chinese population.Acknowledgement We are grateful to all research subjects and their family

  3. 雌激素受体α对胆汁酸转运相关基因的调控及其与孕鼠肝内胆汁淤积症发生的相关性%Regulation of estrogen receptor αon bile acid transporters related gene and its correlation with intrahepatic cholestasis in pregnant rats

    Institute of Scientific and Technical Information of China (English)

    宋昭逸; 王晶晶; 时青云

    2016-01-01

    Objective To investigate the regulation of estrogen receptor α( ERα) on bile acid transporters related gene ,such as farnesoid X receptor (FXR), sodium taurocholate co-transporting polypeptide (NTCP)and bile salt export pump (BSEP),to evaluate ERα’ s correlation with intrahepatic cholestasis in pregnant rats .Methods Forty SPF class pregnant Sprague-Dawley rats were selected and divided into four groups randomly with 10 in each.Since the 15th day of pregnancy , rats in control group were injected subcutaneously with refined vegetable oil 2.0 mL/kg· d, those in the low-dose, moderate-dose and high-dose groups received 17α-ethynylestradiol (EE) 1.0 mg/kg· d, 1.25 mg/kg· d, 1.5 mg/kg· d.All rats were sacrificed on the 21st day of pregnancy and maternal hepatic tissue were collected .The serum levels of biochemical indicators , protein and mRNA expressions of ERαFXR, NTCP, BSEP were examined .Results Biochemical:the serum levels of ALT , AST, TBS, BIL were significantly lower in the control group than that in the treatment groups ( P<0.05 ) .Protein and mRNA expression of ERα, FXR, NTCP, BSEP: compared with control group, low-dose, moderate-dose, high-dose group activated ERαsignificantly; FXR, NTCP, BSEP decreased in a dose-dependent manner , which were all significantly lower than that in control group ( P<0.05 ) .Conclusions Along with the rise of estrogen,the repression of ERαrise and FXR, NTCP, BSEP decrease, these findings suggest lower metabolism and transporting function of bile acid .We propose that this may contribute to development of the EE-induced intrahepatic cholestasis of pregnancy .%目的:探讨雌激素受体α( estrogen receptor α, ERα)对参与调节胆汁酸转运相关的基因,如法尼醇X受体(farnesoid X receptor, FXR)、钠离子-牛磺胆酸共转运蛋白(sodium taurocholate co-transprorting polypeptide,NTCP)、胆盐输出泵(bile salt export pump, BSEP)的调控作用及其对孕鼠肝内

  4. Protective effect of capillary artemisia polysaccharide for liver oxidative damage rats with intrahepatic cholestasis of pregnancy%茵陈多糖对妊娠胆汁淤积大鼠肝脏氧化损伤的保护作用研究

    Institute of Scientific and Technical Information of China (English)

    范丽梅; 徐立堃; 张兰; 胡春玲; 林常青; 李莉群

    2013-01-01

    目的 探讨茵陈多糖对妊娠胆汁淤积大鼠肝脏氧化损伤的保护作用.方法 采用随机数字表法将32只妊娠SD大鼠分为对照组、模型组、低剂量组及高剂量组,妊娠16周除对照组外均采用苯甲酸雌二醇注射法建立妊娠胆汁淤积大鼠模型,造模成功后低剂量组[50 mg/(kg·d)]及高剂量组[100mg/(kg·d)]分别给予茵陈多糖干预,1周后检测各组大鼠肝脏生化指标[血清谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)、直接胆红素(direct bilirubin,DBIL)及间接胆红素(indirect bilirubin,IBLI)]及氧化还原酶[超氧化物歧化酶(erythrocuprein,SOD)、丙二醛(malonaldehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GPx)、过氧化氢酶(catalase,CAT)]活力变化.结果茵陈多糖干预1周后,低剂量组及高剂量组血清ALT、AST、ALP、DBIL及IBLI水平明显低于模型组(P < 0.05),低剂量组及高剂量组间差异有统计学意义(P < 0.05).低剂量组及高剂量组肝组织匀浆MDA水平低于模型组(P < 0.05),SOD、GPx,、CAT平高于模型组(P < 0.05),低剂量组同高剂量组间差异有统计学意义(P < 0.05).结论 茵陈多糖能够减轻妊娠胆汁淤积大鼠肝脏氧化损伤,发挥对肝功能的保护作用.%Objective To investigate the protective effects of capillary artemisia polysaccharide on liver oxidative damage rats with intrahepatic cholestasis of pregnancy (ICP). Methods 32 SD rats were divided into the control group (CG), model group (MG), high-dose group (HG) and low-dose group (LG) with random digits table. Animal model of ICP were made with injecting estradiol benzoate in rats with 16 weeks of pregnancy except CG. Rats in HG [100 mg/ (kg·d)] and LG [(50 mg/(kg·d)) were interfered with artemisia capillaries polysaccharides. Biochemical indicators in rats liver (serum ALT, AST, ALP, DBIL and IBLI) and oxidordeuctase

  5. CYP1B1基因A119S多态性与妊娠期肝内胆汁淤积症风险关系的研究%Study on the relationship between gene polymorphism of CYP1B1 A119S and risk of intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    朱壮彦; 富晓敏; 穆雅琴; 赵富玺

    2013-01-01

    Objective: To explore the relationship between gene polymorphism of CYP1B1 A119S and the occurrence of intrahepat-io cholestasis of pregnancy (ICP) . Methods: Allele - specific polymerase chain reaction method (AS - PCR) was used to analyze gene polymorphism locus in exon 2 codon 119 (G -T) of CYP1B1 in 73 cases with endometrial cancer and 90 normal women. Three genotypes were defined, including homozygous wild type (G/G) , heterozygous variant (G/T) , and homozygous variant (T/T) . Results: The prevalence rates of CYP1 Bl A119S genotypes G/G, G/T, and T/T were 3. 8% , 39. 7% , and 16. 5% in ICP group, 64. 4% , 26. 7% , and 8. 9% in control group. The frequencies of CYP1B1 G and T alleles were 63. 7% and 36. 3% in ICP group, 77. 8% and 22. 2% in control group, respectively. There were statistically significant differences in distribution frequencies of polymorphism genotypes and alleles of CYP1B1 A119S between the two groups (P<0. 05) . Compared with G/G, the OR value of T/T was 2. 719 (1.007-7.341), the OR value of GT was 2. 190 (1. 096 -4. 375) , respectively. The risk of ICP in patients with T allele increased by 1. 995 times (1. 226 -3. 246) . Conclusion: The distributions of three gene polymorphism locus of CYP1B1 have a certain correlation with risk of ICP, mutant genotypes increase the risk of ICP.%目的:探讨CYP1BI基因A119S多态性与妊娠期肝内胆汁淤积症(ICP)发生危险性的关系.方法:用等位基因特异性PCR (AS-PCR)法,对73例妊娠期肝内胆汁淤积症患者和90例正常女性的CYP1B1 A119S多态位点进行检测分析,确定出多态性的3种基因型,即野生型G/G、杂合型G/T、突变型T/T.结果:CYP1B1基因A119S多态性G/G、G/T、T/T 3种基因型分布频率,ICP组分别为3.8%、39.7%和16.5%,对照组分别为64.4%、26.7%和8.9%;ICP组G、T等位基因频率为63.7%,36.3%,对照组为77.8%,22.2%.CYP1 B1 A119S多态性基因型及等位基因型在两组间分布频率

  6. 早期应用脂肪乳对极低出生体重儿胃肠外营养相关性胆汁淤积的影响%Effect of early fat emulsion usage on parenteral nutrition associated with cholestasis of very low birth weight infant

    Institute of Scientific and Technical Information of China (English)

    杨军; 李水霞

    2015-01-01

    objectiveTo study the effect of fat emulsion ociated in parenteral nutrition (PN) associated with cholestasis (PNAC) of very low birth weight infant (VLBWI) .MethodsTo study retrospectively the clinical data of 18 VLBWI PNAC (PNAC group,18 cases) and 36 without PNAC (non-PNAC group,36 cases) ,matched by stop taking food of time ,gestational age, birth weight and duration of PN , Meanwhile, the associated factors with PNAC were also analyzed in two groups.Results Within 2 weeks after birth fat emulsion calories, PNAC group was significantly higher than non PNAC,( 23.0±7.3)% vs(15.1±4.5)%, t= 3.815,p= 0.016, the difference was statistically significant. Two groups in the ratio of total calories, the ratio of amino acid calories,the ratio of sugar calories difference has no statistical significance (P> 0.05). PN in use process, the two groups in the fat emulsion, amino acid and sugar intake of total difference has no statistical significance (P > 0.05).ConclusionsThe occurrence of PNAC is associated with higher calorie ratio of fat emulsion intake during the first two weeks of PN support after birth in VLBWI.Further prospective randomized double blind controlled studies should be performed.%目的:探讨胃肠外营养(PN)中的脂肪乳对极低出生体重儿(VLBWI)胃肠外营养相关性胆汁淤积(PNAC)的影响。方法:回顾性分析2009年1月至2015年4月静脉营养(PN)超过14d的VLBWI中的PNAC病例和配对非PNAC病例临床资料(两组在胎龄、出生体重、PN持续时间和禁食时间相匹配),比较两组发生PNAC相关因素的差异。结果:PNAC组(18例)生后2周内脂肪乳热卡比明显高于非PNAC组(36例),为23.0±7.3%vs 15.1±4.5%,t=3.815,p=0.016,差异有统计学意义,而在总热卡比、氨基酸热卡比及糖热卡比差异无统计学意义(P>0.05)。两组在PN应用期间脂肪乳、氨基酸及糖的累计摄入量差异无统计学意义(P>0.05)。结论:极低出生体

  7. Comparison of different diagnostic methods in infants with Cholestasis

    Institute of Scientific and Technical Information of China (English)

    Seyed Mohsen Dehghani; Mahmood Haghighat; Mohammad Hadi Imanieh; Bita Geramizadeh

    2006-01-01

    AIM: To evaluate different methods in differentiating idiopathic neonatal hepatitis from biliary atresia.METHODS: Sixty-five infants with cholestatic jaundice and final diagnosis of idiopathic neonatal hepatitis and biliary atresia were studied prospectively from September 2003 to March 2006. A thorough history and physical examination were undertaken and the liver enzymes were examined. All cases underwent abdominal ultrasonography, hepatobiliary scintigraphy,and percutaneous liver biopsy. The accuracy, sensitivity,specificity and predictive values of these various methods were compared.RESULTS: There were 34 girls and 31 boys, among them 46 subjects had idiopathic neonatal hepatitis (age,61 ± 17 d) and 19 had biliary atresia (age, 64 ± 18 d).The mean age at onset of jaundice was significantly lower in cases of biliary atresia when compared to idiopathic neonatal hepatitis cases (9 ± 13 d vs 20 ± 21 d;P = 0.032). The diagnostic accuracy of different methods was as follows: liver biopsy, 96.9%; clinical evaluation,70.8%; ultrasonography, 69.2%; hepatobiliary scintigraphy, 58.5%; and liver enzymes, 50.8%.CONCLUSION: Our results indicate that clinical evaluation by an experienced pediatric hepatologist and a biopsy of the liver are considered as the most reliable methods to differentiate idiopathic neonatal hepatitis and biliary atresia.

  8. [Hepatic amyloidosis as cause of severe intrahepatic cholestasis].

    Science.gov (United States)

    Gavilán, J C; Bermúdez, F J; Márquez, A; Sánchez-Carrillo, J J; González-Santos, P

    2003-01-01

    The liver is frequently involved by amyloidosis, but hyperbilirubinemia and liver failure are uncommon features. A mild elevation of the serum alkaline phosphatase value and, less frequently, hepatomegaly are the most common findings. Usually the patients have no symptoms related with the liver involvement; the clinical manifestation and the long term prognosis depends on the renal and cardiac disease. We report an unusual clinical presentation of primary amyloidosis in a previously asymptomatic 65 years old woman who was admitted to the hospital because of ictericia and ascitis mimicking a drug induced acute hepatic failure.

  9. Is ursodeoxycholic acid effective for intrahepatic cholestasis of pregnancy?

    Directory of Open Access Journals (Sweden)

    Sebastián Sepúlveda Marín

    2016-04-01

    Full Text Available La colestasia intrahepática del embarazo es una condición propia de la gestación y se asocia a mayor morbilidad y mortalidad perinatal. Dentro de las alternativas terapéuticas se ha propuesto el uso del ácido ursodeoxicólico, sin embargo su beneficio sigue siendo controvertido. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen ocho estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de ácido ursodeoxicólico en la colestasia intrahepática del embarazo podría reducir el riesgo de prematurez y de necesidad de hospitalización del recién nacido en unidad de cuidado intensivo. También podría disminuir el prurito materno.

  10. Pancreatic adenocarcinoma in type 2 progressive familial intrahepatic cholestasis

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    Green Richard M

    2010-03-01

    Full Text Available Abstract Background BSEP disease results from mutations in ABCB11, which encodes the bile salt export pump (BSEP. BSEP disease is associated with an increased risk of hepatobiliary cancer. Case Presentation A 36 year old woman with BSEP disease developed pancreatic adenocarcinoma at age 36. She had been treated with a biliary diversion at age 18. A 1.7 × 1.3 cm mass was detected in the pancreas on abdominal CT scan. A 2 cm mass lesion was found at the neck and proximal body of the pancreas. Pathology demonstrated a grade 2-3 adenocarcinoma with invasion into the peripancreatic fat. Conclusions Clinicians should be aware of the possibility of pancreatic adenocarcinoma in patients with BSEP disease.

  11. 妊娠肝内胆汁淤积症患者血清 SOCS3含量检测及其与胎盘中过氧化反应、凋亡过程关系的研究%Detection of serum SOCS3 contents in patients with intrahepatic cholestasis of pregnancy and its correlation with peroxidation response and apoptosis process in placenta

    Institute of Scientific and Technical Information of China (English)

    曾学平; 谭三阳; 赵涛

    2016-01-01

    Objective To study the serum suppressor of cytokine signaling(SOCS)content of patients with intrahepatic cholestasis of pregnancy and analyze its correlation with peroxidation response index and apoptosis index in placenta tissue. Methods 50 cases of intrahepatic cholestasis of pregnancy treated and laboring in our hospital from June 2013 to August 2014 were enrolled as observation group;50 cases of healthy parturient women laboring during the same period were enrolled as control group. Serum was collected and SOCS - 3 content was detected;placen-ta tissue was collected and mRNA contents of survivin,Xiap,Bcl - 2,CCO,SDH,SOD,GSH - Px,CAT,HO - 1 and MDA were detected. Re-sults serum SOCS3 content of observation group was lower than that of control group. mRNA contents of survivin,Xiap,Bcl - 2,CCO and SDH in placenta of observation group were lower than those of control group and were positively correlated with SOCS - 3. SOD,GSH - Px,CAT and HO - 1 contents in placenta tissue of observation group were lower than those of control group and were positively correlated with SOCS - 3. MDA content was higher than that of control group and was negatively correlated with SOCS - 3. Conclusion Serum SOCS3 content of patients with in-trahepatic cholestasis of pregnancy abnormally decreases and may cause occurrence of the disease through participating in the regulation of peroxida-tion response and apoptosis process in placenta.%目的:研究妊娠肝内胆汁淤积症患者血清中细胞因子信号传导负调控因子( SOCS)的含量并分析其与胎盘组织中过氧化反应指标、凋亡指标的相关性。方法选择2013年6月至2014年8月就诊和分娩的妊娠肝内胆汁淤积症患者50例作为观察组,将同期分娩的健康产妇50例作为对照组,采集血清并检测 SOCS -3含量,采集胎盘组织并检测 Survivin、Xiap、Bcl -2、细胞色素 c 氧化酶(CCO)、琥珀酸脱氢酶(SDH)、超氧化物歧化酶(SOD)、谷

  12. 胆汁酸代谢主要调节核受体和相关基因在胆汁淤积孕鼠肝脏中的表达%Expression of FXR mRNA, PPAR alpha mRNA and bile acid metabolism related genes in intrahepatic cholestasis of pregnant rats

    Institute of Scientific and Technical Information of China (English)

    时青云; 林宇庚; 周新; 林颖奇; 闫时

    2010-01-01

    Objective To study the expressions of FXR, PPARα and Bile acid metabolism related genes in intrahepatic cholestasis of pregnant rats. Methods 60 clean SD pregnant rats were selected and divided randomly into three groups. Since the 13th day of pregnancy rats in control group were injected then were treated with fenofibrate for another four days untill the 21th day. All rats were killed at the 21th day and livers were collected for study. The levels of serum TBA were examined by ELISA. The mRNA expressions of PPAR α, FXR, CYP7A1, CYP27A1 and CYP8B1 were examined by real-time PCR. Results (1)The levels of TBA were significantly higher in no-treated group (68.7 ± 4.2) μmol/L and treated group (69.5 ± 3.8) μmol/L compared with that of control group (26.6 ± 2.3) μmol/L at the 17th day (P < 0.05) and no difference found between treated and no-treated groups (P > 0.05). The levels of TBA were higher in notreated group (69.4 ± 3.7) μmol/L and treated group (48.5 ± 4.8) μmol/L as compared to control group (27.1 ± 3.2) μmol/L at the 21th day (P < 0.05). The lever of TBA was significantly lower in Treated group compared with No-treated group (P < 0.05). (2) The mRNA expressions of CYP7A1, FXR, CYP27A1 and CYP8B1 increased in No-treated group (1.55 ± 0.03, 1.75 ± 0.02, 2.45 ± 0.01, 2.15 ± 0.01, respectively)and were all higher as compared to control group (0.75 ± 0.02, 1.25 ± 0.03, 0.65 ± 0.03, 1.50 ± 0.02,respectively) (P < 0.05). However, the mRNA expression of PPAR α decreased in No-treated group (0.85 ±0.02) compared with control group (1.45 ± 0.02) (P < 0.05). The mRNA expressions of CYP27A1, PPAR α and CYP8B1 increased in treated group (1.25 ± 0.01, 1.65 ± 0.05, 1.65 ± 0.02, respectively) and were all higher than that of control group (P < 0.05). Conclusion Abnormal expressions of CYP7A1, FXR, CYP27A1,CYP8B1 and PPARα may play a role in pathogenesis of estrogen-induced intrahepatic cholestasis. Activator of PPAR α may be used

  13. Effect of InsR/FoxO1 on the expression of POMC in the hypothalamus of intrahepatic cholestasis of pregnancy rats offspring%InsR/FoxO1信号通路对妊娠胆汁淤积症子代大鼠下丘脑中POMC表达的影响

    Institute of Scientific and Technical Information of China (English)

    闫时; 王晶晶; 宋昭逸; 时青云

    2015-01-01

    Objective:To study the effect of InsR/FoxO1 on the expression of POMC in the hypothalamus of the intrahepatic cholestasis of pregnancy rats offspring. Methods:40 clean SD pregnant rats were selected and divided into two groups at random,20 in every group. Since the 13th day of pregnancy,Control group was injected subcutaneously with refined vegetable oil 2 . 0 ml/( kg · d ) , ICP group was injected subcutaneously with the 17-α-ethynylestradio ( EE ) 1 . 0 mg/( kg · d ) . 20 Female 0 ffspring in both ICP group and control group were selected at random and feed to six months. At the 24 weeks of age,offspring underwent a glucose tolerance test. All rats were killed at the six months. The mRNA of InsR、FoxO1 and POMC in hypothala-mus were examined by real-time PCR and western blot. The expression of POMC in hypothalam-ic arcuate of 6 months offspring was also examined by immunohistochemistry. Result:The glu-cose values of female in ICP group were higher than that of control group offspring(P<0. 05).The mRNA expressions of InsR、FoxO1 and POMC in hypothalamus in ICP group offspring were different with control offspring at six months ( P<0 . 05 ) . The positive cells of POMC in hypotha-lamic arcuate in ICP group were little than that control group. Conclusion:Bile acid levers is higher in ICP group. The bad intrauterine environment may be a major contributor to change of InsR/FoxO1 and POMC decreased. ICP offspring showed a hunger state and then gained weight.%目的:探讨胰岛素受体(InsR)/胰岛素调节转录因子(FoxO1)信号通路对妊娠肝内胆汁淤积症出生后6 个月子代大鼠下丘脑中阿片-促黑素细胞皮质素原( POMC )表达的影响. 方法:40只清洁级SD孕鼠随机分为2组,每组20只. 孕第13天时,对照组孕鼠皮下注射精制植物油2. 0ml/(kg·d),ICP组孕鼠皮下注射17-α-乙炔雌二醇1. 0 mg/( kg·d) ,直至孕21天. 从ICP组和对照组出生子代中各随机选取雌性20只喂养至6月龄.

  14. Clinical analysis of risk factors of parenteral nutrition-associated cholestasis in very low birthweight infants%极低出生体质量儿胃肠外营养相关性胆汁淤积危险因素临床分析

    Institute of Scientific and Technical Information of China (English)

    杨军; 李水霞; 陈莉娜

    2015-01-01

    Objective To investigate the risk factors of parenteral nutrition-associated cholestasis (PNAC)in very low birth weight infants (VLBWI).Methods VLBWI who were accorded with inclusion and exclusion criteria of this study:treatment for parenteral nutrition (PN)for over 14 days in West China Second University Hospital of Sichuan University from May 2008 to May 2014 were chosen as study subjects.By retrospectively analyzed method,they were divided into PNAC group and non PNAC group according to whether suflered from PNAC or not.First of all,according to the clinical experience,the influence factors of PNAC were identified and carried on the single factor analysis,then comprehensively considered with statistically significant variables and professional knowledge,multiple factors unconditional logistic regression analysis method was used to further analyze the independent and risk factors of PNAC. Results ① A total of 1 72 cases of VLBWI were chosen as study subjects finally.According to whether suffered from PNAC or not,they were divided into PNAC group (n=29)and non PNAC group (n=143), and the incidence of PNAC was 1 6.9%.There were no significant differences between two groups among gender ratio,gestational age at delivery and mode of delivery,etc.(P > 0.05 ).② According to clinical experience,the single factor analysis results about 27 clinical observation items and 1 9 nutritional factors which may lead to PNAC showed that 8 clinical observation items and 5 nutritional factors were influence factors of PNAC,such as VLBWI,less than appropriate for gestational age (SGA),long fasting time and longer duration of PN,higher amino acid and fat emulsion calories,milk lower calories,higher neonatal infections,such as infectious pneumonia,sepsis,neonatal necrotizing enterocolitis (NEC)and septic shock rate,lower breastfeeding and oral probiotics rate,and all the differences were statistically significant (t/χ2 =3.306,3.306,1.790,1.231,3.1 93,2.81 5,2.5 1 9,4.61 5,3

  15. Cholestasis induced by total parenteral nutrition: effects of the addition of Taurine (Tauramin® on hepatic function parameters; possible synergistic action of structured lipids (SMOFlipid® Colestasis inducida por nutrición parenteral total: efecto de la adición de Taurina (Tauramin® sobre los parámetros de función hepática; posible acción sinérgica de lípidos estructurados (SMOFlipid®

    Directory of Open Access Journals (Sweden)

    J. González-Contreras

    2012-12-01

    Full Text Available Objective: Assess the hepatoprotective effect of Taurine (Tau in cases of hepatic cholestasis induced by Total Parenteral Nutrition (TPN. Methods: We describe a retrospective series of 54 patients who received TPN, in which cholestasis was detected at an (Intermediate point that separates the duration of TPN into 2 Phases. From this moment -Phase 2- on, and according to clinical criteria, some patients (Group A, n = 27 received amino acids with Tau (22.41 ± 3.57 mg/kg/day(Tauramin®, while the rest (Group B, n = 27 received the standard solution without Tau. The mean TPN durations were 39.2 ± 17.1 and 36.4 ± 18.1 days respectively, with the Intermediate points on days 19.56 ± 10.51 and 17.89 ± 11.14. They all received diets that were homogeneous in terms of kcal and macronutrients. In Phase 2, 21 patients from Group A received structured lipids (SMOFlipid®; while 20 from Group B received soy MCT/LCT [ Medium Chain Triglycerides/Long Chain Triglycerides ] (physical or structured mixture. In a retrospective study, differences could not be avoided. The analytical parameters from three periods (Initial, Intermediate, and Final were obtained from Nutridata® and Servolab®. We compared interperiod values using the Wilcoxon test SPSS® (p Objetivo: Evaluar el papel hepatoprotector de Taurina (Tau en situación de colestasis hepática inducida por Nutrición Parenteral Total (NPT. Métodos: Se describe una serie retrospectiva de 54 pacientes, que recibieron NPT, detectándose colestasis en un momento (Intermedio que separa en 2 Fases la duración de la NPT. A partir de este momento - Fase 2- y según criterios clínicos, unos -grupo A, n = 27- recibieron aminoácidos con Tau -22,41 ± 3,57 mg/kg/día (Tauramin®, mientras otros -grupo B, n = 27- recibieron solución estándar sin Tau. La duración media de NPT fue de 39,2 ± 17,1 y 36,4 ± 18,1 días respectivamente; con el punto Intermedio en día 19,56 ± 10,51 y 17,89 ± 11,14. Todos

  16. Interaction among peroxisome proliferators-activated receptor alpha, cytochrome P450 oxysterol 7α-hydroxylase and estrogen receptor and its association with intrahepatic cholestasis in pregnant rats%过氧化物酶增殖体激活受体α、氧固醇7α羟化酶及雌激素受体间调控关系及其与孕鼠肝内胆汁淤积发生的相关性

    Institute of Scientific and Technical Information of China (English)

    时青云; 林宇庚; 周新; 林颖奇; 闫时

    2010-01-01

    Objective To investigate the relationship between interaction of peroxisome proliferators-activated receptor alpha (PPARα), cytochrome P450 oxysterol 7α-hydroxylase (CYP7B1) and estrogen receptor (ER) and intrahepatic cholestasis in pregnant rats. Methods Eighty clean SD pregnant rats were selected and divided into four groups randomly with 20 in each. Since the 13th day of pregnancy,rats in the control group was injected subcutaneously with refined vegetable oil 2.0 ml · kg-1 · d -1 , those in the low-dose, moderate-dose and high-dose groups received 17-α-ethynylestradiol (EE) 1.0 mg · kg-1 · d-1,1.25 mg · kg-1 · d-1 and 1.5 mg · kg-1 · d-1, respectively. All rats were sacrificed at the 21at day of pregnancy and maternal hepatic tissues were collected. The serum levels of alanine aminotransferase(ALT), aspartate transaminase (AST), total bile acid (TBA) and bilirubin (BIL) were determined by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of PPARα, CYP7B1, Erα and Erβ in maternal rat livers were examined by real-time PCR. Results (1) Biochemical indicators: the serum levels of ALT,AST, TBA and BIL were significantly lower in the control group than in the rest 3 groups,respectively [ control group: (41.1 ± 2.8 ) U/L, (44.4 ± 3.6) U/L, (26.4 ± 5.6 ) μmol/L and( 2.8 ± 0.2)U/L;low-dose group: (48.2 ±3.4) U/L,(47.9 ±3.7) U/L,(36.4 ±4.2) μmol/L and (4.2 ±0.2) U/L;moderate-dose group: (70.4 ± 5.3 ) U/L, (68.4 ± 5.6) U/L, (64.3 ± 3.8 ) μmol/L and ( 6.2 ± 1.2)U/L; high-dose group: (72.4 ±7.6) U/L, (70.2 ±3.8) U/L, (72.4 ±7.8) μmol/L and (8.2 ±2.2)U/L, P 0.05 ). (3) mRNA expression of CYP7B1 and PPARα: the mRNA expression of CYP7B1 in pregnant rat livers increased from the low-dose group to the high-dose group, and were all higher than that of the control group ( low-dose group: 0.93 ± 0.01; moderate-dose group: 0.99 ±0.06; high-dose group: 1.22 ± 0.04; control group: 0.75 ± 0.02, P 0.05).(3)CYP7B1 mRNA及PPARα m

  17. Thymic cyst haemorrhages and transient cholestasis in a 4-week-old infant

    NARCIS (Netherlands)

    Koopman, LP; Plotz, FB; Meuzelaar, JJ; Knoester, H

    1998-01-01

    We report a 4-week-old boy with acute respiratory distress, due to massive haemorrhages in multiple thymic cysts. A right hemithymectomy was performed because of mechanical obstruction of the trachea by the cysts. The origin of the multilocular thymic cysts remained unclear. Most likely, these haemo

  18. Prevalence of Vitamin D Deficiency and Rickets in Children with Cholestasis in Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Eshagh Roze

    2012-07-01

    Full Text Available This study was aimed to determine prevalence of Vitamin D deficiency and rickets in children with cholestatic liver diseases. Forty eight children with established cholestatic liver disease who referred to gastrointestinal clinic of Children Medical Center (Tehran, Iran between April 2010 and March 2011 were enrolled in a cross-sectional study. Laboratory analysis including calcium, phosphate, albumin, total and direct bilirubin, aminotransferases, alkalinephosphatase (ALP, prothrombin time (PT, parathyroid hormone (PTH, total protein determined by routine laboratory techniques. Mean age of participants was 299.1 ± 676.8 days (range 2-3600 days whereas twenty one were female (43.8% and 27 (56.3% were male. Twenty two (45.8% had evidences of rickets in X-ray evaluation. Three children with rickets and two with normal X-ray had Vitamin D deficiency while ten in rickets group and 16 in normal group had Vitamin D insufficiency. The main underlying diseases were anatomical biliary atresia in cases with rickets and idiopathic in other group. Rickets and Vitamin D deficiency should be considered in chronic cholestatic children.

  19. A STUDY ON DETECTION OF SERUMFASTING TOTAL BILE ACID AND CHOLOYGLYCIN IN NEONATE FOR CHOLESTASIS

    Institute of Scientific and Technical Information of China (English)

    郭文; 吴明昌; 裴学义; 关德华; 徐洛

    1996-01-01

    Enzyme-linked colorimetric analysis and radioimmunossay were employed to detect serum fasting total bile acids(FBA) and choloyglyein (CG) respectively in eases of 32 neonatal hepatitis, 33 cases of neona-tal uneonjugated hyperbilirubinemia and 34 cases of breast milk jaundice(BMJ). FBA and CG in acute period of neonatal hepatitis were obviously elevated and decreased gradually in convalescent and recovered period. The difference was significant for each stage as compared with controls. Acute FBA correlated strongly with the course. Both neonatal unconjugated hyperbilirubinemia and BMJ differed significantlyfrom controls in FBA and CG. The results suggested that serum FBA and CGr were helpful in judging the course and state of neonatal hepatitis, and eholestasls might existed in neonatal unconjngated hyperbilirubinemia.

  20. Prolonged intrahepatic cholestasis and renal failure secondary to anabolic androgenic steroid-enriched dietary supplements.

    Science.gov (United States)

    Krishnan, Prashant V; Feng, Zhen-Zhou; Gordon, Stuart C

    2009-08-01

    The illegal enrichment of anabolic androgenic steroids in over-the-counter dietary supplements is well documented, but the health consequences have not been widely recognized. Three recent reports document cholestatic jaundice and nephropathy due to these compounds. We present 3 additional cases of anabolic androgenic steroid-enriched dietary supplement-induced hepatotoxicity and 1 case of renal failure, and we review the literature and the relevant features of this growing health concern. Recognition of this entity could obviate the need for invasive diagnostic testing and hospitalization and facilitate diagnosis and appropriate counseling.

  1. Down-regulation of OATP1B proteins correlates with hyperbilirubinemia in advanced cholestasis

    NARCIS (Netherlands)

    Sticova, E.; Lodererova, A.; Steeg, E. van de; Frankova, S.; Kollar, M.; Lanska, V.; Kotalova, R.; Dedic, T.; Schinkel, A.H.; Jirsa, M.

    2015-01-01

    Aim: Organic anion-transporting polypeptides OATP1B1 and OATP1B3 are sinusoidal membrane transporters mediating liver uptake of a wide range of substrates including conjugated and unconjugated bilirubin, xenobiotics and drugs. Absence of OATP1Bs in the liver causes Rotor syndrome. Our aim was to cor

  2. Prevalence of vitamin D deficiency and rickets in children with cholestasis in Iran.

    Science.gov (United States)

    Mohammadi, Bahram; Najafi, Mehri; Farahmand, Fateme; Motamed, Farzaneh; Ghajarzadeh, Mahsa; Mohammadi, Jamshid; Eshagh Roze, Mohammad

    2012-01-01

    This study was aimed to determine prevalence of vitamin D deficiency and rickets in children with cholestatic liver diseases. Forty eight children with established cholestatic liver disease who referred to gastrointestinal clinic of Children Medical Center (Tehran, Iran) between April 2010 and March 2011 were enrolled in a cross-sectional study. Laboratory analysis including calcium, phosphate, albumin, total and direct bilirubin, aminotransferases, alkalinephosphatase (ALP), prothrombin time (PT), parathyroid hormone (PTH), total protein determined by routine laboratory techniques. Mean age of participants was 299.1 ± 676.8 days (range 2-3600 days) whereas twenty one were female (43.8%) and 27 (56.3%) were male. Twenty two (45.8%) had evidences of rickets in X-ray evaluation. Three children with rickets and two with normal X-ray had vitamin D deficiency while ten in rickets group and 16 in normal group had vitamin D insufficiency. The main underlying diseases were anatomical biliary atresia in cases with rickets and idiopathic in other group. Rickets and vitamin D deficiency should be considered in chronic cholestatic children.

  3. Diagnosis of cholestasis%胆汁淤积的诊断

    Institute of Scientific and Technical Information of China (English)

    陶小红

    2008-01-01

    胆汁淤积这一名称首先由Popper和Schaffner在1970年提出,并定义为形态学上胆汁在肝小叶肝细胞、毛细胆管、库普弗细胞内贮积。当今对胆汁淤积的定义是肝细胞内胆汁生成障碍、胆管分泌或胆汁流动受损所引起的结果。根据其发生部位的差异分为肝内胆汁淤积和肝外胆汁淤积,肝外胆汁淤积最常见的原因是机械性阻塞;肝内胆汁淤积的原因则较为复杂,包括感染性、药物性、自身免疫性、妊娠性等,但有时两者可有交叉,如原发性硬化性胆管炎(PSC)可同时有肝外和肝内部分的病变。本文重点阐述肝内胆汁淤积的诊断。

  4. [Development of vibration-induced intrahepatic cholestasis in pilots and new ways of correcting these disorders].

    Science.gov (United States)

    Preobrazhenskiĭ, V N; Vasilenko, V V; Taianovskiĭ, V Iu

    1999-01-01

    Data of analysis of the role of vibration in the development of hepatobiliary pathology in helicopter pilots are reported. Vibration was found to drastically deteriorate colloid-osmotic qualities of the bile and increase the lithogenesis risk. Exposure to vibration over 10 and more years of the flying career may instigate cholelithiasis. Dynamic USI with functional testing for early diagnostics and correction with ursodeoxycholic acid (ursosan) of disorders in the colloid-osmotic properties of the bile and can be proposed as one of the methods to prevent cholelithiasis.

  5. Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diet

    NARCIS (Netherlands)

    M.T. Flowers; A.K. Groen; A.T. Oler; M.P. Keller; Y. Choi; K.L. Schueler; O.C. Richards; H. Lan; M. Miyazaki; F. Kuipers; C.M. Kendziorski; J.M. Ntambi; A.D. Attie

    2006-01-01

    Stearoyl-coenzyme A desaturase 1-deficient (SCD1(-/-)) mice have impaired MUFA synthesis. When maintained on a very low-fat (VLF) diet, SCD1(-/-) mice developed severe hypercholesterolemia, characterized by an increase in apolipoprotein B (apoB)-containing lipoproteins and the appearance of lipoprot

  6. Curcumin and hemopressin treatment attenuates cholestasis-induced liver fibrosis in rats: role of CB1 receptors.

    Science.gov (United States)

    El Swefy, Sahar; Hasan, Rehab A; Ibrahim, Amal; Mahmoud, Mona F

    2016-01-01

    Curcumin exerts hepatoprotective effects via poorly defined mechanisms. Recently, some studies suggested that this effect was mediated by antagonizing CB1 receptors in hepatic stellate cells. The current study aimed to investigate whether CB1 antagonist, hemopressin, could potentiate the hepatoprotective effect of curcumin, in comparison with silymarin in bile duct-ligated (BDL) rats. Curcumin and hemopressin each alone and in combination ameliorated biochemical and structural fibrotic injury, and downregulated cyclooxygenase-2 (COX-2) and both mRNA and protein levels of nuclear factor kappa B (NF-κB) in fibrotic liver. In contrast to the previous studies, curcumin alone did not affect the gene expression of cannabinoid receptors. However, the combination of hemopressin and curcumin reduced the expression of CB1 in fibrotic liver. Surprisingly, silymarin upregulated CB2 receptors and downregulated CB1 at mRNA level more than all the administered drugs. Both curcumin and hemopressin each alone decreased lipid peroxidation product, malondialdehyde (MDA), while the combination increased the reduced glutathione content. All the administered drugs increased the hepatic antiapoptotic marker, Bcl2. Our study suggests that hemopressin potentiates the hepatoprotective effect of curcumin on fibrotic liver. We identified a new mechanism of the hepatoprotective effect of silymarin via modulation of cannabinoid receptors in fibrotic liver.

  7. Effect of ATRA on Contents of liver Retinoids, Oxidative Stress and Hepatic Injury in Rat Model of Extrahepatic Cholestasis

    Institute of Scientific and Technical Information of China (English)

    JIANG Haiyan; DAN Zili; WANG Hui; LIN Jusheng

    2007-01-01

    The effects of all-trans-retinoic acid (ATRA) administration on the concentration of retinoids (RA and vitamin A) in liver, oxidative stress and the hepatic injury in a rat model of com-mon bile duct ligation (CBDL)-induced liver injury were investigated. Female rats were subjected to a sham (n=5) or CBDL (n=48). Two weeks after operation, rats undergoing CBDL were randomized to receive treatment with either ATRA at three different doses (0.1, 1.5, 7.5 mg/kg) dissolved in bean oil or only bean oil every day over a 4-week experimental period. Rats were killed and blood samples were collected from the heart for determination of the serum transaminase. The contents of retinoids in rat liver were detected by using HPLC. Malondialdehyde (MDA), glutathione (GSH) and superox-ide dismutase (SOD) levels in liver were determined by a spectrophotometric method according to the instruction of the kits. Liver pathologic changes were observed under the light microscopy and electron microscopy. The results showed that compared with sham-operated group, the levels of reti-noids in the liver tissue were significantly decreased in the CBDL group (P<0.01). ATRA (0.1 mg/kg) administration in CBDL rats partially restored the contents of retinoids (P<0.05). Liver RA and vita-min A contents in CBDL group were significantly increased after ATRA (1.5 and 7.5 mg/kg) sup-plementation as compared with sham-operated group (P<0.05). However, in ATRA-treated CBDL group, hepatic GSH level and SOD activity, depressed by CBDL, and hepatic MDA level, increased by CBDL were returned to those in sham-operated group (P<0.05). The histologic observation of liver tissues indicated that ATRA treatment notably alleviated hepatocellular swelling, steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER). Treatment with ATRA could reduce levels of serum transaminase as compared with sham-operated group, more greatly in 1.5 and 7.5 mg/kg ATRA-treated groups than in 0.1 mg/kg ATRA-treated group. It was concluded that ATRA treatment can recover MDA and GSH levels and SOD activity in CBDL rat liver through restoring RA and vitamin A contents, and eventually ameliorate liver injury.

  8. ANCA Associated Vasculitis and Renal Failure Related to Propylthiouracil and Hyperthyroidism Induced Cholestasis in the Same Case

    Directory of Open Access Journals (Sweden)

    Mehmet Tuncay

    2014-01-01

    Full Text Available Introduction. Liver involvement due to hyperthyroidism and also ANCA positive vasculitis related renal failure cases were reported separately several times before. However, to our knowledge, these two complications together in the same case had never been observed before. Case Presentation. The case of an ANCA positive 71-year-old Caucasian male with renal failure and lung involvement, subclinical hyperthyroidism, and intrahepatic cholestatic jaundice was presented in this paper. After exclusion of all of the other possibilities, cholestatic hepatitis was explained by subclinical hyperthyroidism; renal failure and lung involvement were interpreted as ANCA related vasculitis which might be a side effect of propylthiouracil use. Conclusion. The coexistence of these rare conditions in the same patient deserves emphasis and it is worth reporting. This case demonstrates that following the clinical course of the patient is essential after prescribing any medications to see whether any complication occurs or not. If the complications of this case were noticed earlier, it would be possible to treat and to prevent the permanent damages.

  9. Rescue of defective ATP8B1 trafficking by CFTR correctors as a therapeutic strategy for familial intrahepatic cholestasis

    DEFF Research Database (Denmark)

    van der Woerd, Wendy L; Wichers, Catharina G K; Vestergaard, Anna L;

    2016-01-01

    in cystic fibrosis transmembrane conductance regulator (CFTR), associated with cystic fibrosis, impair protein folding and trafficking. The aim of this study was to investigate whether compounds that rescue CFTR F508del trafficking are capable of improving p.I661T-ATP8B1 plasma membrane expression. METHODS...... functionality. Combination therapy of SAHA and compound C4 resulted in an additional improvement of ATP8B1 cell surface abundance. CONCLUSIONS: This study shows that several CFTR correctors can improve trafficking of p.I661T-ATP8B1 to the plasma membrane in vitro. Hence, these compounds may be suitable...... in other protein folding diseases. Using these compounds, we could indeed show improved trafficking to the (apical) plasma membrane of a mutated ATP8B1 protein, carrying the p.I661T missense mutation. This is the most frequently identified mutation in this rare cholestatic disorder. Importantly, ATP8B1...

  10. Cholestasis and regulation of genes related to drug metabolism and biliary transport in rat liver following treatment with cyclosporine A and sirolimus (Rapamycin)

    DEFF Research Database (Denmark)

    Bramow, S; Ott, P; Thomsen Nielsen, F;

    2001-01-01

    Cyclosporine A and sirolimus are used alone or in combination as immunosuppressants in organ transplantation. To elucidate hepatic side effects, we examined hepatic mRNA of proteins involved in biliary and hepatocellular transport of drugs, formation of glutathione (GSH) and drug metabolising cyt...

  11. The effects of ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy on maternal and fetal outcomes: a meta-analysis including non-randomized studies.

    Science.gov (United States)

    Grand'Maison, Sophie; Durand, Madeleine; Mahone, Michèle

    2014-07-01

    Objectif : Les avantages de l’utilisation d’acide ursodésoxycholique (AUDC) pour la prise en charge de la cholestase intrahépatique de la grossesse (CIG) demeurent incertains. Une analyse Cochrane de 2010 ayant porté sur des essais comparatifs randomisés n’a pas été en mesure de se prononcer pour ou contre l’utilisation d’AUDC pour la prise en charge de la CIG. Nous avons mené une méta-analyse de la littérature, en englobant tant les études non randomisées (ENR) que les ECR. Nous avions pour objectif de déterminer si les patientes ayant participé aux ENR étaient comparables à celles qui avaient participé aux ECR; nous avions également pour objectif de déterminer si l’inclusion des ENR pouvait renforcer les données probantes disponibles et orienter la pratique clinique quant à l’utilisation d’AUDC chez les femmes qui présentent une CIG. Sources de données : Nous avons mené des recherches dans Medline (Ovid), Embase (Ovid), EMB Reviews, Cinahl (Ebsco) et Web of Knowledge (Thomson Reuters) en vue d’en tirer les articles publiés entre 1966 et juin 2012. Sélection des études : Nous avons inclus tous les ECR admissibles ayant comparé l’AUDC à un placebo ou à d’autres traitements et toutes les ENR ayant comparé l’AUDC à tout autre traitement chez des femmes présentant une CIG. Synthèse des données : Nous avons inclus 11 ECR (n = 625 grossesses) et six ENR (n = 211 grossesses). Bien que les femmes ayant participé aux ECR et aux ENR aient été comparables, la qualité des études était plus faible dans le cas des ENR. De façon générale, les femmes traitées à l’AUDC ont connu une atténuation du prurit dans 73 % des ECR et dans 100 % des ENR disposant de données disponibles. Les épreuves de fonction hépatique ont présenté une amélioration dans 82 % des ECR et dans 100 % des ENR disposant de données disponibles. Bien que l’utilisation d’AUDC n’ait pas affecté le taux de césarienne, elle a été associée à une prématurité moindre, à une utilisation moindre des unités néonatales de soins intensifs (données disponibles pour seulement trois des 17 études) et à des tendances à l’augmentation du poids de naissance et à l’atténuation de la teinte méconiale du liquide amniotique. Aucune mortinaissance n’a été constatée dans le cadre de 356 grossesses ayant fait l’objet d’un traitement à l’AUDC et trois mortinaissances ont été constatées dans le cadre de 399 grossesses ayant fait l’objet d’un traitement au moyen d’un agent de comparaison. Conclusion : Le traitement à l’AUDC devrait être recommandé aux femmes qui présentent une CIG en vue d’atténuer les issues indésirables maternelles et fœtales.

  12. A homozygous nonsense mutation (c.214C->A) in the biliverdin reductase alpha gene (BLVRA) results in accumulation of biliverdin during episodes of cholestasis

    DEFF Research Database (Denmark)

    Nytofte, Nikolaj S; Serrano, Maria A; Monte, Maria J;

    2011-01-01

    Green jaundice is a rare finding usually associated with end-stage liver disease. OBJECTIVE The authors investigated two unrelated Inuit women from different geographical areas in Greenland who had episodes of green jaundice associated with biliary obstruction....

  13. Severe intrahepatic cholestasis and hemochromatosis secondary to hereditary spherocytosis%遗传性球形红细胞增多症合并重度肝内胆汁淤积和继发性血色病

    Institute of Scientific and Technical Information of China (English)

    赵彩彦; 王玮; 刘英辉; 王亚东; 周俊英

    2010-01-01

    @@ 一、病例资料 病例1:男性患者,23岁.主因眼黄16年,加重伴皮肤黄染1月余于2008年6月27日10:00入院.患者缘于16年前无明显诱因出现眼黄,无恶心、呕吐、腹胀、腹泻、于当地医院查肝功能异常,应用保肝药物1个月后停药.

  14. 妊娠期胆汁淤积症对新生儿中枢神经的影响%Affection of intrahepatic cholestasis of pregnancy (ICP) on neonatal central nervous system

    Institute of Scientific and Technical Information of China (English)

    刘静; 万俊; 蒋犁

    2004-01-01

    妊娠期肝内胆汁淤积症时在各种机制作用下母儿胆汁酸淤积,通过胆汁酸、胆红素的细胞毒作用,影响胎盘血流灌注、血液携氧能力、机体抗氧化防御系统引起胎儿窘迫、窒息致中枢神经系统缺氧损伤.神经细胞中钙稳态是保证其结构完整和功能正常的重要因素,烯醇化酶是缺氧缺血性脑损伤早期的标志酶.通过检测新生儿脐动脉血中的游离钙,烯醇化酶浓度来预测脑损伤及其严重程度,对早期干预具有十分重要的意义.

  15. 疱疹样脓疱病并发妊娠期肝内胆汁淤积症1例%A case of impetigo herpetiformis and gestational intrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    樊平申; 李淼; 高天文; 廖文俊; 陈必良

    2004-01-01

    报告1例疱疹样脓疱病并发妊娠期肝内胆汁淤积症.患者女,26岁.妊娠34-1周,躯干和四肢出现红斑、脓疱伴瘙痒和疼痛5个月,加重1个月,近期出现黄疸.入院时血清丙氨酸转氨酶、天冬氨酸转氨酶、血清胆红素和胆汁酸均升高,皮损组织病理改变符合疱疹样脓疱病.行剖宫产术,给予糖皮质激素、局部抗感染及对症支持等治疗后皮损痊愈.

  16. 妊娠期肝内胆汁淤积症致胎儿宫内窘迫的经验教训%Intrauterine Asphyxia due to Cholestasis in Pregnancy:Experience and lesson

    Institute of Scientific and Technical Information of China (English)

    马俊如

    2006-01-01

    妊娠期肝内胆汁淤积症(intrahepatic chol estasis of pregnancy,ICP)是妊娠期严重并发症之一,以妊娠中、晚期全身瘙痒、黄疸为特征,可导致早产、胎儿窘迫及胎儿死亡,因其早产率及围产儿死亡率高,近年因ICP导致围产儿死亡的医疗纠纷逐渐增多,给产科工作者带来一定的工作压力。现报告2例ICP致胎儿宫内窘迫并死亡的病例,结合文献资料,总结ICP处理过程中的经验教训。

  17. Clinical value of prenatal care with different methods on intrahepatic cholestasis of pregnancy%产前不同监测方法对ICP胎儿监测的临床意义

    Institute of Scientific and Technical Information of China (English)

    蒋惠玲; 王冬梅; 王志梅

    2008-01-01

    目的:探讨妊娠期肝内胆汁淤积症(ICP)的产前监测方法.方法:对我院同期的ICP患者与正常孕妇60例进行肝功能、S/D值(脐动脉收缩期最大血流速/舒张末期最低血流速)、Manning评分、无应激试验(NST)及羊水污染、Apgar 评分、胎儿体重进行对比分析;通过x2检验分析Manning评分各项监测指标中对ICP有意义的项目;利用多元回归分析的方法了解不同产前监测方法与ICP新生儿Apgar评分的关系.结果:ICP患者与正常孕妇在肝功能指标、S/D值、Manning评分及羊水污染率、Apgar评分间的差异有统计学意义;在Manning评分各项监测指标中对ICP的监测有意义的指标是胎动和肌张力;产前监测ICP患者的转氨酶及NST水平变化可预测ICP患者新生儿的Apgar评分,而胆红素、胆汁酸、甘胆酸、S/D值、Manning 评分的变化与ICP患者新生儿的Apgar评分的变化无相关性.结论:ICP患者Manning评分的监测指标中胎动和肌张力的变化对胎儿宫内情况有监测意义;在对ICP患者的各种产前监测方法中,转氨酶水平及NST评分的监测能够反应新生儿出生状态.

  18. Creation of Reversible Cholestatic Rat Model

    OpenAIRE

    2011-01-01

    Cholestasis is a clinical condition commonly encountered by both surgeons and gastroenterologists. Cholestasis can cause various physiological changes and affect the nutritional status and surgical outcomes. Study of the pathophysiological changes occurring in the liver and other organs is of importance. Various studies have been done in cholestatic rat models.

  19. Prognostic significance of cholestatic alcoholic hepatitis. VA Cooperative Study Group #119.

    Science.gov (United States)

    Nissenbaum, M; Chedid, A; Mendenhall, C; Gartside, P

    1990-07-01

    Tissue cholestasis is a histologic feature in some patients with alcoholic liver disease, but its significance is unknown. We studied prospectively the clinical, laboratory, and histologic findings of 306 chronic male alcoholics in whom liver tissue was available. Tissue cholestasis permitted identification of two groups: group I, absent or mild cholestasis (239 patients), and group II, moderate to severe cholestasis (67 patients). Statistical evaluation was performed by Student's t test and regression analyses. In patients with tissue cholestasis, 97% had elevated serum cholylglycine levels, while only 61% had significant jaundice (serum bilirubin greater than 5 mg/dl). In patients without tissue cholestasis, 66% had elevated serum cholylglycine and 13.5% jaundice. Highly significant statistical correlations (P less than 0.0001) were found between cholestasis and malnutrition, prothrombin time, AST, alkaline phosphatase, bilirubin, Maddrey's discriminant function, serum cholylglycine level, albumin, and histologic severity score. In group I, 54% survived 60 months versus 22% in group II (P less than 0.0001). Highly significant statistical correlations (P less than 0.0001) were noted between serum cholylglycine levels and the parameters enumerated earlier, but not with survival. We conclude that tissue cholestasis is a highly significant prognostic indicator of outcome in alcoholic hepatitis and is more consistently associated with bile salt retention than jaundice.

  20. Strain background modifies phenotypes in the ATP8B1-deficient mouse

    NARCIS (Netherlands)

    Shah, S.; Sanford, U.R.; Vargas, J.C.; Xu, H.; Groen, A.; Paulusma, C.C.; Grenert, J.P.; Pawlikowska, L.; Sen, S.; Oude Elferink, R.P.J.; Bull, L.N.

    2010-01-01

    BACKGROUND: Mutations in ATP8B1 (FIC1) underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis) to intermittent (benign recurrent intrahepatic cholestasis). The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficie

  1. Perbedaan Manifestasi Klinis dan Laboratorium Kolestasis Intrahepatal dengan Ekstrahepatal pada Bayi

    Directory of Open Access Journals (Sweden)

    Dwi Prasetyo

    2016-05-01

    Full Text Available Physiological jaundice found in infants and most symptoms are often mild. Jaundice symptoms usually disappear within 2 weeks after birth. In conjugated jaundice defects in intra-hepatic production, transmembran transport from bile, i.e. cholestasis intra hepatic (IH, or extra-hepatic (EH obstruction/cholestasis occur, resulting in bile barriers. This study was conducted to look at the differences in the clinical and laboratory manifestations of IH and EH cholestasis in infants. A cross-sectional study was performed on 72 infants with cholestasis who came to Dr. Hasan Sadikin General Hospital Bandung, during the period of January 2014–December 2015. Data analysis was performed with Pearson Chi-square test and Mann-Whitney. Subjects consisted of 43 (60% infant boys and 29 (40% infant girls, IH cholestasis were 61 (85% and EH cholestasis were 11 (15.3%. Significant differences in the clinical manifestations of acites with IH and EH cholestasis were found (p=0.047, whereas insignificant differences in venectation, hepatomegaly and splenomegaly were observed. On examination of stool color, no significant difference was found (p=0.936. The same was true for laboratory results of total bilirubin, direct bilirubin, serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase and gamma glutamyl transferase. In conclusion, we found differences in clinical manifestation of acites, while for other clinical manifestations and laboratory results no differences were found between IH and EH cholestasis.

  2. Aquaporins: Their role in cholestatic liver disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This review focuses on currant knowledge on hepato-cyte aquaporins (AQPs) and their significance in bile formation and cholestasis. Canalicular bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate wa-ter flow in response to the osmotic gradients created. During choleresis, hepatocytes rapidly increase their canalicular membrane water permeability by modulat-ing the abundance of AQP8. The question was raised as to whether the opposite process, i.e. a decreased canalicular AQP8 expression would contribute to the development of cholestasis. Studies in several experi-mental models of cholestasis, such as extrahepatic obstructive cholestasis, estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition, biophysical studies in canalicular plasma membranes revealed decreased water permeability as-sociated with AQP8 protein downregulation. The com-bined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water flow. Thus cholestasis may result from a mutual occurrence of impaired sol-ute transport and decreased water permeability.

  3. Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus

    Institute of Scientific and Technical Information of China (English)

    Maud Lemoine; Aurélie Revaux; Claire Francoz; Guillaume Ducarme; Sabine Brechignac; Emmanuel Jacquemin; Michèle Uzan; Nathalie Ganne-Carrié

    2008-01-01

    Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of HARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.C 2008 The WJG Press. All rights reserved.

  4. Effect of melatonin on myocardial oxidative stress induced by experimental obstructive jaundice Efecto de la melatonina en el estrés oxidativo del miocardio en un modelo experimental de obstrucción biliar

    Directory of Open Access Journals (Sweden)

    A. Cruz

    2009-07-01

    Full Text Available Objective: melatonin has been demonstrated to have active antioxidant properties in different tissues during experimental cholestasis. The aim of this research was to study myocardial oxidative stress on obstructive jaundice, and to analyze the effect of melatonin on myocardial oxidative lesions. Material and methods: we achieved cholestasis by ligature and sectioning of the main bile duct. Melatonin was administered intraperitoneally (500 µg/kg/day. We measured malondialdehyde (MDA, reduced glutathione (GSH, catalase (CAT, superoxide dismutase (SOD and glutathione peroxydase (GPx antioxidant enzyme levels in the heart tissue. Results: obstructive cholestasis increased MDA and decreased GSH as well as all antioxidant enzymes. Melatonin administration significantly decreased MDA values, and increased GSH and antioxidant enzymes on the icteric animal myocardium. Conclusions: melatonin treatment prevents oxidative stress in the cardiac tissue as induced by experimental cholestasis.

  5. Pathogenesis and medical therapy of primary sclerosing cholangitis. Any news?

    NARCIS (Netherlands)

    van den Berg, A; Jansen, PLM

    1999-01-01

    Primary sclerosing cholangitis is characterized by inflammation and fibrosis of the intra- and extrahepatic bile ducts. Medical therapy has focused on anticholestatic, antiinflammatory and immunosuppressive drugs. Although inflammation, fibrosis and cholestasis may all occur at the same time, inflam

  6. Dermatological Diseases Associated with Pregnancy

    DEFF Research Database (Denmark)

    Sävervall, Christine; Sand, Freja Lærke; Thomsen, Simon Francis

    2015-01-01

    Dermatoses unique to pregnancy are important to recognize for the clinician as they carry considerable morbidity for pregnant mothers and in some instances constitute a risk to the fetus. These diseases include pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis...

  7. Vanishing bile duct syndrome in human immunodeficiency virus: Nevirapine hepatotoxicity revisited

    Institute of Scientific and Technical Information of China (English)

    Rajan; Kochar; Moises; I; Nevah; Frank; J; Lukens; Michael; B; Fallon; Victor; I; Machicao

    2010-01-01

    Vanishing bile duct syndrome (VBDS) refers to a group of disorders characterized by prolonged cholestasis as a result of destruction and disappearance ofintrahepatic bile ducts. Multiple etiologies have been indentifi ed including infections, neoplastic disorders, autoimmune conditions and drugs. The natural history of this condition is variable and may involve resolution of cholestasis or progression with irreversible damage. VBDS is extremely rare in human immunodeficiency virus (HIV)-infected patients an...

  8. Relationship between parameters of lipid peroxidation during obstructive jaundice and after bile flow restoration.

    Science.gov (United States)

    Dudnik, L B; Tsupko, A N; Shupik, M A; Akhaladze, G G; Galperin, E I; Latonova, L V; Pantaz, E A; Alessenko, A V

    2008-01-01

    Restoration of bile flow after 9-day cholestasis in rat liver normalized the content of lipid peroxidation products. The removal of the cholestatic factor after 12-day cholestasis was not followed by recovery of these parameters. We showed that measurement of serum concentration of lipid peroxidation products in patients with cholelithiasis during the preoperative period holds promise for selection of the optimum time for surgical treatment and prediction of the risk of postoperative complications.

  9. Study on hepatotoxicity of aqueous extracts of Polygonum multiflorum in rats after 28-day oral administration: cholestasis-related mechanism%何首乌水提物大鼠连续灌胃给药28 d肝毒性研究——胆汁淤积相关机制探讨

    Institute of Scientific and Technical Information of China (English)

    王涛; 王佳颖; 周植星; 江振洲; 李妍妍; 张良; 张陆勇

    2015-01-01

    目的:考察何首乌水提物(AEPM)对大鼠肝脏中胆汁酸合成、代谢、转运相关分子影响,探讨何首乌肝毒性相关机制.方法:SD大鼠分别灌胃AEPM60,30 g·kg-1,每天1次,连续28 d.28 d后解剖取肝脏,分别采用荧光定量PCR和Westernblot检测肝脏MRP3,MRP2,BSEP,FXR,CYP7A1等分子的mRNA和蛋白表达水平.结果:与正常组相比,AEPM高剂量组雄性大鼠肝脏中MRP3和BSEP的mRNA表达均显著升高(P<0.05),而AEPM高、低剂量组肝脏FXR的mRNA表达均显著降低(P<0.05);AEPM高、低剂量组雌性大鼠肝脏MRP3,MRP2,BSEP,CYP7A1的mRNA表达均显著升高(P<0.05).Westernblot检测结果显示,AEPM高、低剂量给药组雄性和雌性大鼠肝脏中MRP3,MRP2,BSEP,FXR,CYP7A1蛋白表达水平与mRNA变化基本一致,但均未达统计学显著差异.结论:AEPM大鼠灌胃给药28 d对肝脏胆汁酸合成、转运、排泄相关蛋白的表达具有一定的影响,在mRNA表达水平既具有胆汁淤积分子特征,同时也可见促进胆汁酸排泄的分子特征.

  10. Changes of cholesterol 7alpha-hydroxylase,farnesoid X receptor,and small heterodimer partner expression in liver tissues of rats with obstructive cholestasis%阻塞性胆汁淤积大鼠肝脏胆固醇7α-羟化酶和核受体FXR、SHP表达变化

    Institute of Scientific and Technical Information of China (English)

    吴晓平; 柴进; 陈文生

    2009-01-01

    目的:通过建立梗阻性黄疸动物模型,观察胆固醇7α-羟化酶(cholesterol 7alpha-hydroxylase,CYP7A1)、类法尼醇X受体(farnesoid X receptor,FXR)及小异源二聚体伴侣受体(small heterodimer partner,SHP)的表达变化,并分析CYP7A1和FXR、SHP之问的关系.方法:采用胆总管结扎术制备大鼠梗阻性黄疸模型,分别于术后1、3、14 d麻醉后放血处死.取大鼠肝脏,抽提总RNA,采用实时定量RT-PCR检测CYP7A1 mRNA表达;提取肝细胞核蛋白,采用蛋白质印迹技术检测FXR和SHP蛋白表达.结果:与假手术对照组相比,梗阻性黄疸组大鼠肝细胞CYP7A1 mRNA表达明显增强,FXR和SHP蛋白表达同步降低,差异均有统计学意义(P<0.001,P<0.05).结论:CYP7A1表达增强可能与FXR、SHP表达减弱有关.

  11. 茵陈蒿汤对胆汁淤积性肝纤维化大鼠内质网应激PERK通路的影响%Experimental Study on Effects of Yinchenhao Tang (茵陈蒿汤) on Endoplasmic Reticulum Stress PERK Pathway in Cholestasis Liver Fibrosis Rats

    Institute of Scientific and Technical Information of China (English)

    李木松; 张贵贤; 魏媛媛; 刘震霞

    2016-01-01

    目的:观察茵陈蒿汤对胆汁淤积性肝纤维化大鼠PKR样内质网激酶(PERK)-真核生物翻译起始因子(eIF2α)-转录活性因子4(ATF4)的影响,探讨茵陈蒿汤抗胆汁淤积性肝纤维的作用机制.方法:将35只SD大鼠分为假手术组和造模组,采用胆总管结扎法复制胆汁淤积性肝纤维化大鼠模型,1W后将造模组动物分为模型组和中药组,中药组予以3.5 g/kg茵陈蒿汤灌胃,4W后处死动物.HE、Masson染色观察肝脏组织病理学变化;Western blot法检测各组大鼠肝脏PERK、eIF2α和ATF4蛋白表达的变化.结果:肝脏组织病理学变化显示模型组大鼠肝纤维化程度较假手术组明显增加(P<0.05),中药组大鼠肝纤维化程度较模型组减轻(P<0.05),但仍重于假手术组.Western blot结果显示,模型组肝脏PERK、eIF2α和ATF4蛋白的表达与假手术组相比显著升高(P<0.01),中药组较模型组PERK、eIF2α和ATF4蛋白表达明显降低(P<0.01).结论:抑制PERK、eIF2α和ATF4的活化,从而减少肝细胞凋亡,进而抑制内质网应激在胆汁淤积性肝纤维化中的促进作用,是茵陈蒿汤抗胆汁淤积性肝纤维化的作用机制之一.

  12. 妊娠肝内胆汁淤积症胎盘雌激素受体及血管舒缩因子的变化%The changes and sign ificance of the estrogen receptors on placenta and the levels of serum free estr iol,blood vessel endothelium factor in intrahepatic cholestasis of pregnancy.

    Institute of Scientific and Technical Information of China (English)

    王冬梅; 朱启英; 腊晓琳

    2002-01-01

    目的:探讨妊娠肝内胆汁淤积症(ICP )患者血清中一氧化氮(NO)、内皮素(ET)、游离雌三醇(E3)水平的变化和胎盘雌激素受体( ER)表达强度在ICP病理生理改变中的作用.方法:以ICP组30例为研究组 ,手术前30min取外周静脉血测定NO、ET及游离E3的含量,以年龄相近同期手术的30例正常孕妇作为对照组,产后从研究组和对照组中随机抽取20例的胎盘中央组织块用免疫组化法检测ER的表达强度.结果:ICP组的血清ET水平明显高于对照组(P<0.05),NO水平与对照组差异无显著性(P>0.05). ICP组血清游离E3水平显著高于对照组(P<0.01),胎盘ER阳性表达百分比显著高于对照组(P<0.05),血清中E3水平与胎盘组织中E R水平间呈正相关(r′s=0.598,P<0.01).结论:雌激素水平升高及胎盘中ER表达增强和ET水平的升高可能与ICP的发生、发展有关.

  13. CYP1B1基因多态性与妊娠期肝内胆汁淤积症易感性的关系%Association of Gene Polymorphisms of CYP1B1 with Intrahepatic Cholestasis of Pregnancy

    Institute of Scientific and Technical Information of China (English)

    王晓莉; 谭欣; 张力; 欧容清; 颜爱华; 陈强; 邹海

    2008-01-01

    目的 研究CYP1B1基因外显子2密码子119(G-T)和外显子3密码子432(C-G)多态性与妊娠期肝内胆汁淤积症(ICP)发病的关系.方法 分别应用等位基因特异性PCR(AS-PCR)技术和人工修饰双等位基因特异性引物扩增(diASA-AMP)法,对100例ICP患者和100例正常对照孕妇CYP1B1基因外显子2密码子119(G-T)和外显子3密码子432(C-G)多态性进行分析.结果 ①CYP1B1基因密码子119多态分析表明ICP组T等位基因频率高于对照组(P0.05).结论 CYP1B1基因外显子2密码子119多态性可能与成都地区ICP易感性有关.

  14. 妊娠期肝内胆汁淤积症总胆汁酸、雌三醇与新生儿Apgar评分的关系%Relationship between total bile acid and estriol of patients with intrahepatic cholestasis of pregnancy and neonatal Apgar score

    Institute of Scientific and Technical Information of China (English)

    蔡林燕

    2016-01-01

    目的 研究妊娠期肝内胆汁淤积症(ICP)总胆汁酸、雌三醇与新生儿APgar评分的关系.方法 收集2013年6月-2014年12月于该院就诊的ICP患者80例,所有患者均行肝功能生化指标及激素水平检测,对其新生儿均进行出生1 min时的APgar评价,应用单因素方差分析比较正常新生儿、中度窒息新生儿及重度窒息新生儿其母亲的血清胆汁酸和雌三醇情况的差异,采用多重线性回归分析患者血清胆汁酸和雌三醇与其产儿的新生儿Apgar评分的相关性.结果 不同级别Apgar评分的新生儿相对应母亲的血清胆汁酸和雌三醇差异较大,P<0.01,差异具有统计学意义;建立回归方程发现CIP患者血清胆汁酸和雌三醇的回归系数t检验的P值均<0.05,具有统计学意义,总胆汁酸、雌三醇的标准回归系数分别-12.047、-2.473,说明其与新生儿的Apgar评分具有负相关性,且对于新生儿的Apgar评分中总胆汁酸对其影响更大.结论 ICP患者血清胆汁酸和雌三醇与其新生儿的Apgar评分呈现负相关性,ICP患者进行血清胆汁酸和雌三醇的检测对新生儿窒息有一定的预警作用.

  15. Disseminated Langerhans Cell Histiocytosis Presenting as Cholestatic Jaundice

    Science.gov (United States)

    Loizides, Anthony M.; Sachdeva, Soumya; Paul, Premila

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a disorder associated with proliferation of Langerhans cells in various organs. LCH secondary to multisystem involvement can present in a variety of ways. Because of its infiltrative nature, LCH can involve the skin, lymph nodes, the lung or the liver. Jaundice in LCH is a manifestation of liver disease; biliary dilatation secondary to lithiasis or may be due to coexistent Niemann-Pick disease. However, a case of cholestasis has been very rarely described. Cholestasis may result from lymph nodes obstructing the porta hepatis. In this report, we describe a case of type II histiocytosis X with obstructive cholestasis and pulmonary involvement in the form of cysts without significant lymphadenopathy at the porta. PMID:25859497

  16. Early enteral fat supplementation with microlipid® and fish oil in the treatment of two premature infants with short bowel.

    Science.gov (United States)

    Yang, Qing; Welch, Cherrie D; Ayers, Kathleen; Turner, Charles; Pranikoff, Thomas

    2010-01-01

    The infusion of Intralipid® is a main risk factor for parenteral nutrition-associated cholestasis in infants with short bowel syndrome. Early provision of enteral fat to reduce the use of Intralipid while providing adequate fat for the growth of infants with short bowel has not been reported. We present 2 cases of premature infants with short bowel who received early supplementation of enteral Microlipid® and fish oil. This approach allowed us to discontinue Intralipid shortly after initiating feedings. The infants tolerated Microlipid/fish oil well without adverse reactions, had appropriate weight gain and ostomy output. They underwent bowel reanastomosis 3 weeks after enteral feeding began, and were discharged on full oral feedings. In case 1, the infant did not develop parenteral nutrition-associated cholestasis; in case 2, cholestasis had developed before initiating feeds, but was not aggravated by enteral fat and was improving prior to discharge.

  17. [Evaluation of plasma PIVKA-II as a new marker for hepatocellular carcinoma].

    Science.gov (United States)

    Tada, H; Kagawa, K; Hikita, H; Takeuchi, T; Ohta, Y; Fukui, S; Shintani, H; Deguchi, T; Okanoue, T; Takino, T

    1989-04-01

    We have measured the plasma PIVKA-II levels in 188 cases of various liver disease with HCC and malignant diseases in other organs by an EIA, using a monoclonal antibody (E-1023 kit, Eisai), and also have measured the plasma vitamin K levels in cases of HCC and cholestasis by an HPLC. Plasma PIVKA-II was detected in many cases of HCC (67%, 35 of 52 cases) and cholestasis (60%, 6 of 10 cases). In contrast, the positivities of PIVKA-II in the other diseases including benign liver diseases were very low. Combination assays of PIVKA-II and vitamin K revealed that PIVKA-II correlates with vitamin K in cholestasis but not in HCC, suggesting that PIVKA-II in HCC does not depend on a systemic deficiency of vitamin K. From these results, it was concluded that PIVKA-II is a reliable marker which can reflect the clinical course of HCC.

  18. Fatal Bile Duct Necrosis: A Rare Complication of Transcatheter Arterial Chemoembolization in a Patient with Endocrine Hepatic Metastasis

    Directory of Open Access Journals (Sweden)

    Anne-Laure Pelletier

    2008-11-01

    Full Text Available We report the first case of fatal bile duct necrosis following transcatheter arterial chemoembolization (TACE in a 58-year-old woman. The patient underwent two TACEs to treat hepatic metastases from an ileal endocrine tumor. Persistent cholestasis occurred after the second procedure, leading to the diagnosis of bile duct necrosis confirmed by liver biopsy. The patient died of liver failure with encephalopathy six months after the second TACE. Even though this complication is very rare, physicians should consider this diagnosis in patients who develop chronic, marked cholestasis following a TACE procedure.

  19. A letter on ABCB4 from Iceland: On the highway to liver disease.

    Science.gov (United States)

    Lammert, F; Hochrath, K

    2015-12-01

    Large-scale whole-genome sequencing of the Icelandic population identified an association between several mutations of ABCB4 encoding the hepatobiliary phosphatiylcholine floppase with liver diseases and function in the general population. Whereas rare mutations of this transporter were known to cause progressive familial intrahepatic cholestasis, the genome-wide association studies in Iceland find the common ABCB4 variant c.711A>T to be a general risk factor for elevated aminotransferases and higher impact variants to be potential determinants of early-onset gallstone disease, cholestasis of pregnancy, liver cirrhosis, and hepatobiliary cancer.

  20. Asymptomatic leukemic-cell infiltration of the pancreas: US findings.

    Science.gov (United States)

    Collado, Laura; Dardanelli, Esteban; Sierre, Sergio; Moguillansky, Silvia; Lipsich, José

    2011-06-01

    Pancreatic infiltration of leukemic cells is a very rare manifestation at the onset of acute lymphoblastic leukemia (ALL) in childhood. Pancreatic enlargement in this situation is unusual and pancreatic involvement is often associated with biliary obstruction, cholestasis and pancreatitis. We report a 3-month-old girl who presented with asymptomatic leukemic infiltration of the pancreas, demonstrated by US with heterogeneous pancreatic enlargement associated with multiple hypoechogenic lesions, without cholestasis. Although these manifestations are rare, ALL should be considered a cause of pancreatic enlargement.

  1. ESPGHAN Committee on Nutrition Position Paper. Intravenous lipid emulsions and risk of hepatotoxicity in infants and children

    DEFF Research Database (Denmark)

    Hojsak, Iva; Colomb, Virginie; Braegger, Christian

    2016-01-01

    be performed. Available studies found that the use of multicomponent fish oil (FO) containing ILE compared to pure soya bean oil (SO) ILE reduced liver enzymes and bilirubin levels in non-cholestatic children on long-term PN and one other RCT found that FO based ILE reversed cholestasis in a proportion...

  2. Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice

    DEFF Research Database (Denmark)

    McNeilly, Alison D; Macfarlane, David P; O'Flaherty, Emmett

    2010-01-01

    Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5beta-reductase....

  3. Unusual causes of intrahepatic cholestatic liver disease

    Institute of Scientific and Technical Information of China (English)

    Elias E Mazokopakis; John A Papadakis; Diamantis P Kofteridis

    2007-01-01

    We report five cases with unusual causes of intrahepatic cholestasis,including consumption of Teucrium polium (family Lamiaceae) in the form of tea,Stauffer's syndrome,treatment with tamoxifen citrate for breast cancer,infection with Coxiella Burnetii (acute Q fever),and infection with Brucella melitensis (acute brucellosis).

  4. Kupffer cell depletion with liposomal clodronate prevents suppression of Ntcp expression in endotoxin-treated rats

    NARCIS (Netherlands)

    Sturm, E; Havinga, R; Baller, JFW; Wolters, H; van Rooijen, N; Kamps, JAAM; Verkade, HJ; Karpen, SJ; Kuipers, F

    2005-01-01

    Background/Aims: In sepsis-associated cholestasis, expression of many genes involved in bile acid transport, including Ntcp, is suppressed by cytokines. Kupffer cells (KC) are an important source of cytokines in sepsis. To assess the consequences of KC depletion on hepatic Ntcp expression in endotox

  5. Obstetric dermatoses

    DEFF Research Database (Denmark)

    Hjortø, Sofie; Skov, Lone; Lykke, Jacob Alexander

    2014-01-01

    The specific dermatoses of pregnancy are rare and consist of pemphigoid gestationis (PG), intrahepatic cholestasis of pregnancy (ICP), polymorphic eruption of pregnancy and atopic eruption of pregnancy. The dermatoses are characterized by pruritus, and they are important to recognize since PG and...

  6. Low-fat, high calorie parenteral nutrition (PN), reverses liver affection in long term PN dependent infants

    DEFF Research Database (Denmark)

    Jakobsen, Marianne Skytte; Hørby Jørgensen, Marianne; Husby, Steffen

    2015-01-01

    INTRODUCTION: Parenteral nutrition-associated cholestasis (PNAC) is a complication of long-term parenteral nutrition (PN). Removal of lipids may reverse PNAC but compromises the energy to ensure infant growth. The purpose of this study was to test whether a low-fat, high-carbohydrate PN regimen...

  7. Vitamin K deficiency bleeding in cholestatic infants with alpha-1-antitrypsin deficiency.

    NARCIS (Netherlands)

    Hasselt, P.M. van; Kok, K.F.; Vorselaars, A.D.; Vlerken, L. van; Nieuwenhuys, E.; Koning, T.J. de; Vries, R.A. de; Houwen, R.H.J.

    2009-01-01

    OBJECTIVE: Exclusively breastfed infants with unrecognised cholestatic jaundice are at high risk of a vitamin K deficiency (VKD) bleeding. It is presently unknown whether (the size of) this risk depends on the degree of cholestasis. Since alpha-1-antitrypsin deficiency (A1AD) induces a variable degr

  8. Prevention of vitamin K deficiency bleeding in breastfed infants: lessons from the Dutch and Danish biliary atresia registries.

    NARCIS (Netherlands)

    Hasselt, PM van; Koning, TJ de; Kvist, N.; Vries, E. De; Lundin, C.R.; Berger, R.; Kimpen, J.L.; Houwen, R.H.; Jorgensen, M.H.; Verkade, H.J.; Aronsen, D.C.; Kindermann, A.; Kneepkens, C.M.; Heurn, L.W.E. van; Neucker, A.M.; Langen, Z.J. de; Peeters, P.M.; Madern, G.C.; Escher, J.H.; Zee, D.C. van der; Rieu, P.N.M.A.; Tolboom, J.J.M.

    2008-01-01

    OBJECTIVE: Newborns routinely receive vitamin K to prevent vitamin K deficiency bleeding. The efficacy of oral vitamin K administration may be compromised in infants with unrecognized cholestasis. We aimed to compare the risk of vitamin K deficiency bleeding under different prophylactic regimens in

  9. Prevention of vitamin K deficiency bleeding in breastfed infants : Lessons from the Dutch and Danish biliary atresia registries

    NARCIS (Netherlands)

    van Hasselt, Peter M.; de Koning, Tom J.; Kvist, Nina; de Vries, Elsemieke; Lundin, Christina Rydahl; Berger, Ruud; Kimpen, Jan L. L.; Houwen, Roderick H. J.; Jorgensen, Marianne Horby; Verkade, Henkjan J.

    2008-01-01

    OBJECTIVE. Newborns routinely receive vitamin K to prevent vitamin K deficiency bleeding. The efficacy of oral vitamin K administration may be compromised in infants with unrecognized cholestasis. We aimed to compare the risk of vitamin K deficiency bleeding under different propylactic regimens in i

  10. Vitamin K deficiency bleeding in cholestatic infants with alpha-1-antitrypsin deficiency

    NARCIS (Netherlands)

    van Hasselt, P. M.; Kok, K.; Vorselaars, A. D. M.; van Vlerken, L.; Nieuwenhuys, E.; de Koning, T. J.; de Vries, Rindert; Houwen, R. H. J.

    2009-01-01

    Objective: Exclusively breastfed infants with unrecognised cholestatic jaundice are at high risk of a vitamin K deficiency (VKD) bleeding. It is presently unknown whether (the size of) this risk depends on the degree of cholestasis. Since alpha-l-antitrypsin deficiency (A1AD) induces a variable degr

  11. Regulation of organic anion transport in the liver

    NARCIS (Netherlands)

    Roelofsen, H; Jansen, PLM

    1997-01-01

    In several liver diseases the biliary transport is disturbed, resulting in, for example, jaundice and cholestasis. Many of these symptoms can be attributed to altered regulation of hepatic transporters. Organic anion transport, mediated by the canalicular multispecific organic anion transporter (cmo

  12. Delayed immune recovery following sequential orthotopic liver transplantation and haploidentical stem cell transplantation in erythropoietic protoporphyria

    NARCIS (Netherlands)

    Smiers, Frans J.; Van de Vijver, Els; Delsing, Bas J. P.; Lankester, Arjan C.; Ball, Lynne M.; Rings, Edmund H. H. M.; van Rheenen, Patrick F.; Bredius, Robbert G. M.

    2010-01-01

    A nine-yr-old boy with EPP suffered from severe skin burns and liver failure caused by progressive cholestasis and fibrosis. OLT was performed without major complications. Four months following liver transplantation he underwent parental haploidentical HSCT. The myeloablative conditioning regimen wa

  13. Disease: H00624 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available familial cholestasis found in aboriginal children from northwestern Quebec. It has reported that a missense ...:1443-9 (2002) PMID:11045837 Drouin E, Russo P, Tuchweber B, Mitchell G, Rasquin-Weber A North American Indian cirrhosis in children

  14. In silico identification and in vitro validation of potential cholestatic compounds through 3D ligand-based pharmacophore modeling of BSEP inhibitors

    NARCIS (Netherlands)

    Ritschel, T.; Hermans, S.M.; Schreurs, M.J.; Heuvel, J.J.M.W. van den; Koenderink, J.B.; Greupink, R.; Russel, F.G.

    2014-01-01

    Drug-induced cholestasis is a frequently observed side effect of drugs and is often caused by an unexpected interaction with the bile salt export pump (BSEP/ABCB11). BSEP is the key membrane transporter responsible for the transport of bile acids from hepatocytes into bile. Here, we developed a phar

  15. Prolonged Cholestatic Jaundice Associated With Flurbiprofen.

    Science.gov (United States)

    Dogan, Serkan; Celikbilek, Mehmet; Demirkan, Kutay; Yilmaz, Semih; Deniz, Kemal; Gursoy, Sebnem; Yucesoy, Mehmet

    2014-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia.

  16. Severe liver dysfunction in an infant with cystic fibrosis masquerading as metabolic liver disease

    Directory of Open Access Journals (Sweden)

    K P Srikanth

    2016-01-01

    Full Text Available We present a rare presentation of cystic fibrosis with neonatal cholestasis. Histological features of mucoviscidosis were present in liver involving the biliary tract, intestinal mucosa, pancreas, and lung. Besides, there was a rare association with autosomal dominant type of polycystic renal disease.

  17. Hepatitis in growth promotor treated cows

    NARCIS (Netherlands)

    Groot, M.J.

    2002-01-01

    Adult female beef cattle found positive for stanozolol in the urine were investigated for liver pathology. In all the animals toxic hepatitis was found, including cholestasis, periportal fibrosis and inflammation, focal necrosis and blood filled lacunae. As no clinical data of the cows were availabl

  18. An Unusual Presentation of Liver Failure in a Patient with Primary Gastrointestinal Hodgkin's Lymphoma

    Directory of Open Access Journals (Sweden)

    Gabrielle B. Rocque

    2011-01-01

    Full Text Available Introduction. Hodgkin's lymphoma (HL presenting either with primary bowel involvement or with cholestasis is unusual. The combination of primary gastrointestinal HL presenting with cholestasis and ductopenia has not been previously described. Case Report. We present a case of primary gastrointestinal HL with evidence of liver involvement, but also with prominent ductopenia on liver biopsy and associated intrahepatic cholestasis. A 50-year-old man with a history of Crohn's disease presented with a bowel obstruction, for which he underwent a small bowel resection. Histology revealed HL. His course was complicated by cholestatic liver failure. A subsequent liver biopsy revealed both focal involvement by lymphoma and ductopenia, resembling vanishing bile duct syndrome (VBDS. He was treated with chemotherapy with improvement in his cholestasis, but he eventually succumbed due to further complications of his disease and treatment toxicities. Conclusion. This case of primary gastrointestinal HL associated with ductopenia does not meet classic criteria for VBDS, but the clinical presentation and pathology are suggestive of a VBDS-like paraneoplastic process. Therapies for HL in the setting of cholestatic liver failure require special consideration, but some reports of durable remissions and recovery of liver function have been reported.

  19. Endotoxin detoxification by alkaline phosphatase in cholestatic livers

    NARCIS (Netherlands)

    Poelstra, K; Bakker, WW; Hardonk, MJ; Meijer, DKF; Wisse, E; Knook, DL; Balabaud, C

    1997-01-01

    Increased expression of alkaline phosphatase (AP) in the liver is a hallmark of cholestasis but the pathophysiological role of this is not clear. We argue that deprotonation of carboxyl groups at the active site of the enzyme may be a prerequisite for optimal AP activity. Such a creation of negative

  20. Vitamin E added to intralipid and enriched in omegaven protects against PNALD in TPN-fed preterm pigs

    Science.gov (United States)

    Prolonged parenteral nutrition (PN) may lead to cholestasis and parenteral nutrition associated liver disease (PNALD). The etiology of PNALD is unknown, but plant phytosterols in soybean oil emulsions (e.g., Intralipid) have been suggested to negatively impact bile acid homeostasis (BAH) by antagoni...

  1. Jaundice

    Science.gov (United States)

    ... PA: Elsevier Mosby; 2014:chap 28. Read More Autoimmune hepatitis Bile Bile duct stricture Biliary atresia Bilirubin blood test Cholestasis Delta agent (Hepatitis D) Dubin-Johnson syndrome Gallstones Gilbert disease Hemolytic anemia Hepatitis A Hepatitis B Hepatitis C Malaria Newborn ...

  2. Autoimmune Cholangitis: A Variant Syndrome of Autoimmune Hepatitis

    OpenAIRE

    Brij Sharma; Sujeet Raina; Rajesh Sharma

    2014-01-01

    Autoimmune cholangitis (AIC) or autoimmune cholangiopathy is a chronic inflammation of liver and a variant syndrome of autoimmune hepatitis (AIH). We present a case of an adult female who had biochemical features of cholestasis and transaminasemia but aminotransferases were not in the hepatitis range and had histological evidence of bile duct injury which was subsequently diagnosed as autoimmune cholangitis.

  3. Antiviral therapy effects upon hepatitis C cholestatic syndrome.

    Science.gov (United States)

    Vere, C C; Gofiţă, Eliza; Forţofoiu, C; Streba, Letiţia Adela Maria; Genunche, Amelia

    2007-01-01

    Cholestasis includes, as a syndrome, all clinical and biological manifestations caused by the deficient or simply absent biliar secretion or caused by the obstruction of the biliary ducts. The hepatic cholestasis from the chronic hepatitis C (HC VHC) is a result of the altered interlobular biliary canalicules, caused by the modified cellular transport mechanisms and it is associated with a medium to severe degree of fibrosis. The aim of this study was to evaluate the efficiency of antiviral therapy in HC VHC patients. The study included a number of 37 HC VHC patients admitted at the Medical Department no. 1 of the Emergency County Hospital of Craiova; they were treated with Pegasys, 180 microg/week and Copegus, 1000 or 1200 mg/day, taking in consideration their weight, for 48 weeks and they were monitored for 24 weeks after the treatment. The following parameters were analyzed: direct bilirubine, total cholesterol, alkaline phosphatase, gamma-glutamiltranspeptidase and leucin-aminopeptidase. Under treatment, the clinical status caused by the cholestasis (pruritus, icteric syndrome, hemoragipary syndrome) was improved in six of the given cases (16.22%). Before therapy, the hepatic cholestasis was present in 20 patients (54.05%), and after treatment in 14 patients (37.83%). During therapy, the average values for all the monitored parameters decreased: direct bilirubine (0.38 +/- 0.18 mg/dl vs. 0.34 +/- 0.24 mg/dl, p = 0.0867), total cholesterol (198.53 md/dl vs. 183.16 mg/dl, p = 0.0808), alkaline phosphatase (236.99 +/- 79.09 iu/l vs. 227.82 +/- 87.59 iu/l, p = 0.0845), gamma-glutamiltranspeptidase (47 +/- 32.89 iu/l vs. 43.91 +/- 29.66 iu/l, p = 0.1509), and leucin-aminopeptidase (32.33 +/- 13.22 iu/l vs. 28.95 +/- 14.22 iu/l, p = 0.0038). Under antiviral treatment there was noticed an improvement of the cholestasis clinical status in a small number of cases. Antiviral therapy favorably influenced the liver cholestasis associated in patients with chronic hepatitis

  4. Alterations of biliary biochemical constituents and cytokines in infantile hepatitis syndrome

    Institute of Scientific and Technical Information of China (English)

    Yan Ding; Lei Zhao; Hong Mei; Zhi-Hua Huang; Shu-Ling Zhang

    2006-01-01

    AIM: To investigate the biliary biochemical constituents and cytokines in infantile hepatitis syndrome (IHS).METHODS: From 42 IHS subjects and 21 controls,serum and biliary biochemical constituents, including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GT), total bile acid (TBA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) both in bile and serum,were assayed. The subjects with IHS were divided into a cholestasis group (n = 21) and a hepatitis group (n = 21).RESULTS: In the cholestasis group, serum TBIL, DBIL,ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01); and also the biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control, whereas biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the cholestasis group, serum IL-6 and TNF-α levels were lower than those in bile (P < 0.01). In the hepatitis group, serum DBTL, ALT, γ-GT, TBA, IL-6 and TNF-αlevels were higher than those in the control (P < 0.01or 140.57 ± 70.32 vs 79.06 ± 35.25, P < 0.05), while biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control (P < 0.01), and biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the hepatitis group, serum IL-6 and TNF-α levels were also lower than those in bile (P <0.01). Serum TBIL, DBIL, γ-GT, IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitis group, while biliary IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitis group. Biliary IL-6 and TNF-α were found to be more significantly increased than serum IL-6 and TNF-α in IHS (P < 0.01). The biliary IL-6 and TNF-α levels were positively correlated with serum DBIL, TBA and γ-GT levels in IHS subjects.CONCLUSION: Biliary biochemical constituents alter in coincidence with pathological changes in

  5. The use of Yes-associated protein expression in the diagnosis of persistent neonatal cholestatic liver disease.

    Science.gov (United States)

    Gurda, Grzegorz T; Zhu, Qingfeng; Bai, Haibo; Pan, Duojia; Schwarz, Kathleen B; Anders, Robert A

    2014-05-01

    Although physiologic jaundice of neonates is common, persistent neonatal cholestasis is life-threatening and has multiple etiologies. Among these etiologies, biliary atresia (BA) requires rapid diagnosis and treatment. In diagnosing BA, the surgical pathologist must recognize subtle histologic changes, often with only a small core liver biopsy. To aid in the differential diagnosis of neonatal cholestasis, we investigated Yes-associated protein (YAP), a regulator of organ size and bile duct development. We examined whether a YAP immunostain can highlight emerging hepatobiliary epithelium in BA (n = 28) versus other causes of persistent cholestasis (non-BA; n = 15) and thus serve as a useful diagnostic marker in persistent neonatal jaundice. We show significantly (P < .01) more high-grade (<2) fibrosis and ductular proliferation among BA versus non-BA cases. Likewise, there was significantly more high-grade (2-3/3) cytoplasmic and nuclear YAP staining in BA (97% and 89%) versus non-BA (20% and 13%). High-grade nuclear YAP staining was both sensitive (88%) and specific (87%) for the diagnosis of BA. In contrast to neonatal cholestasis, the differences in YAP localization in cholestatic/obstructed versus nonobstructed adult livers were not significant. Lastly, we found that pharmacologic inhibition of the YAP complex in both cholangiocyte and cholangiocarcinoma cell lines blocked compensatory bile duct proliferation, an early marker of BA that requires nuclear YAP expression, in a time- and dose-dependent manner. In summary, we show that YAP expression modulates both bile duct proliferation and liver damage/fibrosis while acting as a sensitive and specific marker in the differential diagnosis of persistent neonatal cholestasis.

  6. Pathogenesis and Management of Pruritus in PBC and PSC.

    Science.gov (United States)

    Kremer, Andreas E; Namer, Barbara; Bolier, Ruth; Fischer, Michael J; Oude Elferink, Ronald P; Beuers, Ulrich

    2015-01-01

    Pruritus is a preeminent symptom in patients with chronic cholestatic liver disorders such as primary biliary cirrhosis and primary sclerosing cholangitis. More than two-thirds of these patients experience itching during the course of their disease. This symptom is also frequently observed in patients with other causes of cholestasis such as cholangiocarcinoma, inherited forms of cholestasis and intrahepatic cholestasis of pregnancy, but may accompany almost any other liver disease. The pathogenesis of pruritus of cholestasis remains largely elusive. Increased concentrations of bile salts, histamine, serotonin, progesterone metabolites and endogenous opioids have been controversially discussed as potential pruritogens. However, for these molecules, neither a correlation with itch intensity nor a causative link could be established. The G protein-coupled receptor for bile salts, TGR5, has been shown to be expressed in dorsal root ganglia and give rise to itch in rodents, albeit upon stimuli with suprapathological concentrations of bile salts. The potent neuronal activator lysophosphatidic acid (LPA) and its forming enzyme, autotaxin (ATX), could be identified in the serum of patients with cholestatic pruritus. ATX activity correlated with itch severity and effectiveness of several anti-pruritic therapeutic interventions in cholestatic patients. Thus, the ATX-LPA-axis may represent a key element in the pathogenesis of this agonizing symptom. Treatment options for pruritus of cholestasis remain limited to a few evidence-based and several experimental medical and interventional therapies. The current guideline-based recommendations include the anion exchange resins colestyramine, the pregnane X receptor-agonist and enzyme inducer rifampicin, the μ-opioid antagonist naltrexone, and the selective serotonin reuptake inhibitors sertraline. Still, a considerable part of patients is unresponsive to these drugs and requires experimental approaches including phototherapy

  7. Detection of atypical bile acids in disease states and their identification by gas chromatography-mass spectrometry-computer techniques

    Energy Technology Data Exchange (ETDEWEB)

    Szczepanik-Van Leeuwen, P. A.; Stellaard, F.

    1978-01-01

    The study of the bile acid constituents of serum, bile, urine, and stool of patients exhibiting liver disease has increased in importance with the availability of newer methods for their detection and identification. A cogent question for study has been whether specific bile acids are toxic and thus are the cause of liver disease, or whether they accumulate as a result of disease-induced alteration in metabolism. Examining a wide variety of clinical samples, we have observed that many patients with diagnosed cholestasis show the presence of atypical bile acids due to metabolic aberrations in either the side chain or in the steroid ring. Because cholestasis represents a spectrum of diseases with differing metabolic and/or anatomic defects and because our studies cover a variety of cholestatic states, we have sought to establish a correlation between the presence of these atypical bile acids and the disease state. The complexity of the bile acid mixtures to be examined requires that gas chromatographic-mass spectrometric-computer techniques be used to provide a reliable analysis. It is believed that atypical bile acids can be readily identified by GC/CI mass spectrometry with great sensitivity. It is also believed that such bile acid analysis may prove useful to the study and diagnosis of liver disease. Present data suggest that the identification of atypical bile acids in biological samples may enable differentiation between different types of intrahepatic cholestasis. Such analyses may prove useful to distinguish specific diseases, such as Byler's disease (and Byler's-like cholestasis) from other types of cholestasis and may distinguish diseases involving mitochondrial defects. Finally, the presence of atypical bile acids may indicate, by the particular compounds formed, where and what kind of damage occurs in a disease and may ultimately establish if these atypical bile acids are a cause or effect of the liver damage.

  8. Biochemical Characterization of P4-ATPase Mutations Associated with Intrahepatic Cholestatic Disease

    DEFF Research Database (Denmark)

    Gantzel, Rasmus; Vestergaard, Anna Lindeløv; Mikkelsen, Stine;

    The cholestatic disorders progressive familial intrahepatic cholestasis type 1 (PFIC1, also referred to as Byler’s disease) and benign recurrent intrahepatic cholestasis type 1 (BRIC1) are caused by mutation of the P4-ATPase ATP8B1. The substrate of ATP8B1 is very likely to be phosphatidylserine...... families have been investigated, and more than 50 distinct disease mutations have been identified, with roughly half being missense mutations. In this project we try to answer the question whether PFIC1 mutations are generally more disturbing than BRIC1 mutations with respect to expression, structural...... stability and function. We investigate the mutations in our well functioning system of ATP8A2, being expressed in mammalian HEK293T cells, affinity-purified, and reconstituted in lipid vesicles. Well-known mutations from both groups of patients have been selected for study. I91P in ATP8A2 (L127P in ATP8B1...

  9. Primary Biliary Cirrhosis in A Patient with Turner Syndrome

    Directory of Open Access Journals (Sweden)

    Piotr Milkiewicz

    2005-01-01

    Full Text Available An increased prevalence of X chromosome monosomy has recently been demonstrated in patients with primary biliary cirrhosis (PBC. Chronic cholestasis of unknown etiology is a common clinical feature in patients with Turner syndrome who reach the fourth and fifth decades of life. A 37-year-old patient with Turner syndrome who presented with clinical and biochemical features of chronic cholestasis is described. Subsequent investigations confirmed the diagnosis of PBC. The patient did not respond to the medical treatment and was referred for liver transplant assessment. The present case may support the importance of X chromosome genes in the development of genetic predisposition to PBC, and emphasizes the necessity for a systematic study of the prevalence of PBC in patients with Turner syndrome.

  10. Biochemical characterization of P4-ATPase mutations associated with Intrahepatic Cholestatic Disease

    DEFF Research Database (Denmark)

    Gantzel, Rasmus; Vestergaard, Anna Lindeløv; Mikkelsen, Stine

    Progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis type 1 (BRIC1) are caused by mutation of the P4-ATPase ATP8B1 that flips phospholipid from the exoplasmic leaflet to the cytoplasmic leaflet of canalicular membranes. It is hypothesized...... that PFIC1 mutations are the most disturbing with respect to expression, structural stability and/or function. Although recent data indicates that the specific phospholipid substrate of ATP8B1 is phosphatidylcholine (PC) [1] whereas ATP8A2 flips phosphatidylserine (PS) and phosphatidylethanolamine (PE......), there may be several mechanistic similarities between ATP8B1 and ATP8A2, and here we investigate known disease mutations using our well-functioning methodology for expression, affinity purification and assay of the partial reactions of ATP8A2. Mutations I91P (L127P in ATP8B1) and L308F (I344F) are located...

  11. Plasmapheresis and corticosteroid treatment for persistent jaundice after successful drainage of common bile duct stones by endoscopic retrograde cholangiography

    Institute of Scientific and Technical Information of China (English)

    Ulku Saritas; Bunyamin Aydin; Yucel Ustundag

    2007-01-01

    Prolonged cholestasis is a very rare complication of endoscopic retrograde cholangiography (ERC). Only few cases with this complication are reported in the English literature. We report persisting cholestatic jaundice in a 73-year old man after successful therapeutic ERC for choledocholithiasis. Serologic tests for viral and autoimmune hepatitis were all negative. A second-look ERC was normal also. He denied any medication except for prophylaxis given intravenous 1 g ceftriaxon prior to the ERC procedure.After an unsuccessful trial with ursodeoxycholic acid and cholestyramine for 2 wk, this case was efficiently treated with corticosteroids and plasmapheresis. His cholestatic enzymes became normal and intense pruritis quickly resolved after this treatment which lasted during his follow-up period. We discussed the possible mechanisms and treatment alternatives of intrahepatic cholestasis associated with the ERC procedure.

  12. [Postoperative medical icterus].

    Science.gov (United States)

    Cerf, M

    1978-06-01

    The onset of jaundice following a surgical operation sometimes raises difficult problems. It is rarely due to hemolysis, infective hepatitis or decomposated cirrhosis of the liver. One should seek as a routine hepatitis due to halotane. However the most frequent cause is "benign postoperative cholestasis". This variety of jaundice presents in the form of an icterus due to conjugated bilirubine with often a large increase in alkaline phosphatase levels. The ocurse is variable. Almost always due to severe surgical or septic trauma, accompanied by shock and/or anoxia, it raises difficult diagnostic problems. The clinical and physiopathological aspects of benign postoperative cholestasis are recalled. One should remember, above all, that this is not an autonomous clinical entity but the sign of local or general complications which should be sought carefully.

  13. [Experimental results after acute and chronic ligation of bile duct (author's transl)].

    Science.gov (United States)

    Kirchner, R; Hartung, H; Trendelenburg, C

    1980-08-01

    The bile duct was ligated in 14 bastard dogs. Bilirubine, alcaline phosphatase, GOT, GPT, GLDH, and gamma GT were measured pre- and postoperatively. On the 8th postoperative day stenosis of the choledochus was eliminated using a patch plasty for dilatation in 7 dogs, whereas the occlusion remained in the other 7 dogs. Laboratory and histological results were characteristic for cholestasis 8 days after occlusion; these changes disappeared within 4 weeks after patch plastic surgery. In the controls these parameters normalized as well within 8 weeks, in spite of the persisting occlusion. These results show, that pathological changes after short term cholestasis are fully reversible; they demonstrate as well, that there are compensatory mechanisms operating in dogs with permanent occlusion of the bile duct.

  14. The Pitfalls of Febrile Jaundice. A Case Report

    Directory of Open Access Journals (Sweden)

    Obreja Maria

    2016-04-01

    Full Text Available Jaundice in sepsis is usually caused by cholestasis, and its onset can precede other manifestations of the infection. Inflammation-induced cholestasis is a common complication in patients with an extrahepatic infection or those with inflammatory processes. We describe the case of a 47 years old female who presented with low back pain and paravertebral muscular contracture. She subsequently developed a cholestatic syndrome with clinical manifestations such as jaundice, followed by fever and sepsis with multiple organ dysfunction. Initially labeled as biliary sepsis, the diagnosis was crucially reoriented as the blood cultures were positive for Streptococcus pyogenes and the magnetic resonance imaging (MRI findings suggested spondylodiscitis as well as a paravertebral abscess.

  15. Tamoxifen-associated vasculitis in a breast cancer patient

    Directory of Open Access Journals (Sweden)

    Vargas-Viveros Pablo

    2007-01-01

    Full Text Available Abstract Background Estrogen plays a critical role in breast cancer. Thereafter, endocrine therapy is a standard of care in patients with breast carcinoma, expressing ER or PR. Case presentation Herein we report the case of a 53-year old patient, who developed cholestasis and vasculitis during the treatment with tamoxifen. This toxicity was reversable after the removal of the drug. Thereafter she continued adjuvant treatment for breast carcinoma with anastrazole. Since tamoxifen has been widely indicated for patients with breast carcinoma, we did a literature review, looking for other cases with this type of toxicity. Conclusion This case is the third with vasculitis informed in the literature, but the first one that additionally developed cholestasis and arthritis. Although it is rare, we discuss the indication of this drug in the actual era, where aromatase inhibitors offer a better security profile.

  16. Vitamin A-induced cholestatic hepatitis: a case report

    DEFF Research Database (Denmark)

    Becker, P.; Maurer, B.; Schirrmacher, P.

    2007-01-01

    showed an acute toxic liver injury with focal parenchymal necrosis, sinusoidal lesions, inflammatory infiltrate (round cells, macrophages), and activation and proliferation of stellate cells. The hepatic vitamin A concentration was found to be significantly elevated. There were no signs of intrahepatic......We report a case of intrahepatic cholestasis due to chronic vitamin A supplementation. A 70-year-old woman was admitted to the hospital for jaundice and reduced nutritional and general status with a 2-month history of increasing cholestasis. Some years previously she had suffered from breast...... and ovarian cancer with subsequent surgery and chemotherapy. Chemotherapy was terminated one month before elevated serum transaminase activities and cholestatic serum markers were noted. Following the chemotherapy, supportive care included weekly vitamin A injections (100,000 IU per injection). Liver biopsy...

  17. Bupivacaine drug-induced liver injury: a case series and brief review of the literature.

    Science.gov (United States)

    Chintamaneni, Preethi; Stevenson, Heather L; Malik, Shahid M

    2016-08-01

    Bupivacaine is an established and efficacious anesthetic that has become increasingly popular in postoperative pain management. However, there is limited literature regarding the potential for bupivacaine-induced delayed liver toxicity. Describe cholestasis as a potential adverse reaction of bupivacaine infusion into a surgical wound. Retrospective review of patients' medical records. We report the cases of 3 patients with new onset of cholestatic injury after receiving bupivacaine infusion for postoperative herniorrhaphy pain management. All patients had negative serologic workups for other causes of liver injury. All patients achieved eventual resolution of their liver injury. Bupivacaine-induced liver injury should be on the differential of individuals presenting with jaundice and cholestasis within a month of infusion via a surgically placed catheter of this commonly used anesthetic.

  18. The dermatoses of pregnancy

    Directory of Open Access Journals (Sweden)

    Sachdeva Silonie

    2008-01-01

    Full Text Available The skin changes in pregnancy can be either physiological (hormonal, changes in pre-existing skin diseases or development of new pregnancy specific dermatoses. Pregnancy-specific skin dermatoses include an ill-defined heterogeneous group of pruritic skin eruptions which are seen only in pregnancy. These include atopic eruption of pregnancy, polymorphic eruption of pregnancy, pemphigoid gestationis and intrahepatic cholestasis of pregnancy. Atopic eruption of pregnancy is the most common of these disorders. Most skin eruptions resolve postpartum and require only symptomatic treatment. Antepartum surveillance is recommended for patients with pemphigoid gestationis and intrahepatic cholestasis of pregnancy as they carry fetal risk. This article deals with the classification, clinical features and treatment of the specific dermatoses of pregnancy.

  19. Reversal of intestinal failure-associated liver disease (IFALD)

    DEFF Research Database (Denmark)

    Hvas, Christian; Kodjabashia, Kamelia; Nixon, Emma

    2016-01-01

    Patients with intestinal failure (IF) and home parenteral nutrition commonly develop abnormal liver function tests. The presentations of IF-associated liver disease (IFALD) range from mild cholestasis or steatosis to cirrhosis and decompensated liver disease. We describe the reversal of IFALD....... Multidisciplinary treatment in a tertiary IF referral centre included aggressive sepsis management, discontinuation of hepatotoxic medications and a reduction of parenteral nutrition dependency through optimisation of enteral nutrition via distal enteral tube feeding. Upon this, liver function tests normalised....

  20. Systems Level Analysis and Identification of Pathways and Networks Associated with Liver Fibrosis

    Science.gov (United States)

    2014-11-07

    liver cholestasis, liver steatosis, and myocardial infarction . More recently, the concept of adverse outcome pathways (AOPs) has been proposed as a novel...and control of fibrosis is accurate diagnosis or early indicators of damage. The gold standard for diagnosing fibrosis is currently via liver biopsy...identify sensitive, specific, and non-invasive biomarkers of liver fibrosis. Identification of such biomarkers will improve diagnosis and allow better

  1. Proteomics Investigations of Drug-Induced Hepatotoxicity in HepG2 Cells

    OpenAIRE

    Van Summeren, Anke; Renes, Johan; Bouwman, Freek G.; Noben, Jean-Paul; van Delft, Joost H. M.; Kleinjans, Jos C.S.; Mariman, Edwin C. M.

    2011-01-01

    Unexpected hepatotoxicity is one of the major reasons of drugs failing in clinical trials. This emphasizes the need for new screening methods that address toxicological hazards early in the drug discovery process. Here, proteomics techniques were used to gain further insight into the mechanistic processes of the hepatotoxic compounds. Drug-induced hepatotoxicity is mainly divided in hepatic steatosis, cholestasis, or necrosis. For each class, a compound was selected, respectively amiodarone, ...

  2. PXR antagonists and implication in drug metabolism

    OpenAIRE

    Mani, Sridhar; Dou, Wei; Redinbo, Matthew R.

    2013-01-01

    Adopted orphan nuclear receptor (NR), pregnane X receptor (PXR), plays a central role in the regulation of xeno- and endobiotic metabolism. Since the discovery of the functional role of PXR in 1998, there is evolving evidence for the role of PXR agonists in abrogating metabolic pathophysiology (e.g., cholestasis, hypercholesterolemia, and inflammation). However, more recently, it is clear that PXR is also an important mediator of adverse xeno- (e.g., enhances acetaminophen toxicity) and endob...

  3. An emerging, recognizable facial phenotype in association with mutations in GLI-similar 3 ( GLIS3 )

    OpenAIRE

    Dimitri, P.; Franco, E; Habeb, A. M.; Gurbuz, F.; Moussa, K.; Taha, D.; Wales, J.K.H.; Hogue, J.; Slavotinek, A.; Shetty, A; M. Balasubramanian

    2016-01-01

    Neonatal diabetes and hypothyroidism (NDH) syndrome was first described in 2003 in a consanguineous Saudi Arabian family where two out of four siblings were reported to have presented with proportionate IUGR, neonatal non-autoimmune diabetes mellitus, severe congenital hypothyroidism, cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterised by enlarged kidneys and multiple small cysts with deficient cortico-med...

  4. Dubin-Johnson syndrome presenting after acute viral hepatitis.

    Science.gov (United States)

    Lahmi, Farhad; Roshani, Mohammad; Khosravi, Katayoun; Azizi, Morteza; Mohebbi, Seyed Reza; Zali, Mohammad Reza

    2011-01-01

    Elevated serum level of bilirubin is a common manifestation which is occurred in several diseases. Hyperbilirubinemia can manifest either conjugated or unconjugated. Conjugated or direct hyperbilirubinemia usually are caused by hepatocellular diseases or cholestatic liver diseases. Merely conjugated hyperbilirubinemia is the main manifestation of two congenital syndromes, including Dubin-Johnson and rotor syndrome; however it can be seen in some patients with recurrent benign intrahepatic cholestasis. This article reports a patient with Dubin- Johuson syndrome as a benign and rare condition.

  5. ДИСЛИПИДЕМИЯ И АССОЦИИРОВАНЫЕ МЕТАБОЛИЧЕСКИЕ ЗАБОЛЕВАНИЯ

    Directory of Open Access Journals (Sweden)

    О. Ш. Ойноткинова

    2011-01-01

    Full Text Available This article presents the pathogenesis of dyslipidemia and associated metabolic disorders with the position of lipid metabolism. The role of natural mechanism of cholesterol homeostasis changing was showed, functional disorders of the enterohepatic circulation of bile acids and intrahepatic cholestasis due to violation of the reticuloendothelial system, entailing disruption of a specific target organ, on the one hand, and the development of atherosclerosis with ischemic syndromes — on the other, were demonstrated. Diagnostic and treatment algorithm is presented.

  6. Transcriptome Analysis of the Effects of Gomisin A on the Recovery of Carbon Tetrachloride-Induced Damage in Rat Liver

    OpenAIRE

    Choi, Young Mi; Choi, In Soo; Lee, Sang Mong; Hwang, Dae Youn; Choi, Young Whan; Park, Young Hoon

    2011-01-01

    Gomisin A possesses a hepatic function-facilitating property in liver-injured rats. Its preventive action on carbon tetrachloride-induced cholestasis is due to maintenance of the function of the bile acids-independent fraction. To investigate alterations in gene expression after gomisin A treatment on injured rat liver, DNA microarray analyses were performed on a Rat 44K 4-Plex Gene Expression platform with duplicated reactions after gomisin A treatment. We identified 255 up-regulated and 230...

  7. Evaluation of the use of laparoscopic-guided cholecystocholangiography and liver biopsy in definitive diagnosis of neonatal cholestatic jaundice

    Directory of Open Access Journals (Sweden)

    Khalid Shreef

    2016-01-01

    Full Text Available Background: Once it is established that a jaundiced infant has direct hyperbilirubinemia, the principal diagnostic concern is to differentiate hepatocellular from obstructive cholestasis. Traditional tests such as ultrasonography, percutaneous liver biopsy and technetium 99 m hepatobiliary iminodiacetic acid (HIDA scan are often not sufficiently discriminating. Definitive exclusion of biliary atresia (BA in the infant with cholestatic jaundice usually requires mini-laparotomy and intra-operative cholangiography. This approach has many drawbacks because those sick infants are subjected to a time-consuming procedure with the probability of negative surgical exploration. Aim of the Study: The aim of this study was to determine the feasibility of laparoscopic-guided cholecystocholangiography (LGCC and its accuracy and safety in the diagnosis of BA and thus preventing unnecessary laparotomy in infants whose cholestasis is caused by diseases other than BA. Patients and Methods: Twelve cholestatic infants with direct hyperbilirubinemia subjected to LGCC (age, 7–98 days; mean, 56 days after ultrasound scan and (99 mTc HIDA scan and percutaneous liver biopsy failed to provide the definitive diagnosis. Results: One patient had completely absent gall bladder (GB so the laparoscopic procedure was terminated and laparotomy was done (Kasai operation. Four patients had small size GB; they underwent LGCC that showed patent common bile duct with atresia of common hepatic duct, so laparotomy and Kasai operation was performed. Seven patients had well-developed GB, LGCC revealed patent biliary tree, so laparoscopic liver biopsies were taken for histopathology. Five of those patients had neonatal hepatitis, and two had cholestasis as a complication of prolonged TPN. No perioperative complications or mortalities were recorded. Conclusion: When the diagnosis neonatal cholestasis remains elusive after traditional investigations, LGCC is an accurate and simple method

  8. Down Syndrome with Patent Ductus Venosus and Hepato-Biliary-Pancreatic Abnormalities.

    Science.gov (United States)

    Yamaguchi, Hiroshi; Kosugiyama, Kiyotaka; Honda, Shohei; Tadao, Okada; Taketomi, Akinobu; Iwata, Seido

    2016-01-01

    The association between Down syndrome and congenital portosystemic shunts, most commonly caused by patent ductus venosus, remains relatively unknown. The authors present a girl with Down syndrome with patent ductus venosus, pancreaticobiliary maljunction and paucity of interlobular bile ducts, presenting with neonatal cholestasis and transient abnormal myeloproliferative disorder. To the best of authors' knowledge, no report of the concurrent presence of the above in Down syndrome has been published.

  9. Disorder of homeostasis and blood aggregation in patients with obstructive jaundice of non-neoplastic ethiology

    OpenAIRE

    Kashaeva, M.

    2011-01-01

    Indicators of homeostasis have been studied in 457 patients with obstructive jaundice. 232 of them had cholestasis for 10 days and 225 for 3-6 week. Indicators have been studied before and after the membrane, antioxidant and antiplatelet therapy in 140 patients. Increase in viscosity, erythrocyte aggregation, decrease of their deformability, blood coagulation potential and increase of fibrinolytic activity of blood have been observed in patients with obstructive jaundice on the background of ...

  10. Dermatoses Específicas da Gravidez

    OpenAIRE

    2013-01-01

    During pregnancy immunological, metabolic, hormonal and vascular changes occur, and can cause specific skin diseases. The specific dermatoses of pregnancy have undergone numerous changes in nomenclature and classification, partly due to advances in the knowledge of the pathogenesis of these skin diseases. Currently the following diseases are considered specific dermatoses of pregnancy: pemphigoid gestations, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy and atopic e...

  11. Acute fatty liver of pregnancy

    OpenAIRE

    Ko, Hin Hin; Yoshida, Eric

    2006-01-01

    Acute fatty liver of pregnancy (AFLP) is a rare, potentially fatal complication that occurs in the third trimester or early postpartum period. Although the exact pathogenesis is unknown, this disease has been linked to an abnormality in fetal fatty acid metabolism. Early diagnosis of AFLP sometimes can be difficult because it shares features with other common conditions such as pre-eclampsia, viral hepatitis and cholestasis of pregnancy. However, a careful history and physical examination, in...

  12. Nonicteric liver damage with a gamma-glutamyl transpeptidase level of 5,609 units/l in a renal-transplant recipient receiving azathioprine.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1984-12-01

    Full Text Available A 26-year-old male with renal allograft, who received immunosuppressive treatment with azathioprine, presented marked elevations of serum biliary tract enzymes, such as gamma-glutamyl transpeptidase (5,609 units/l and alkaline phosphatase (60.5 Bessey-Lowry units, 14 months after transplantation. Two months later the patient became icteric; he died of respiratory failure 19 months after the renal allograft. Postmortem examination revealed intrahepatic cholestasis with minimal inflammatory cell infiltration, indicating drug hepatotoxicity.

  13. Diagnostic and therapeutic approach to cholestatic liver disease Abordaje diagnóstico y terapéutico del síndrome colestásico

    OpenAIRE

    T. Pérez Fernández; P. López Serrano; E. Tomás; Mª L. Gutiérrez; J. L. Lledó; G. Cacho; C. Santander; C. M. Fernández Rodríguez

    2004-01-01

    When cholestatic liver disease is present, liver ultrasound should be performed to ascertain if cholestasis is extrahepatic or intrahepatiic. If bile ducts appear dilated and the probability of interventional treatment is high, endoscopic retrograde cholagio-pancreatography (ERCP) or trans-hepatic cholangiography (THC) should be the next step. If the probability of interventional therapeutics is low, cholangio-MRI should be performed. Once bile duct dilation and space occupying lesions are ex...

  14. Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat.

    Science.gov (United States)

    Quinn, Matthew; Ueno, Yoshiyuki; Pae, Hae Yong; Huang, Li; Frampton, Gabriel; Galindo, Cheryl; Francis, Heather; Horvat, Darijana; McMillin, Matthew; Demorrow, Sharon

    2012-01-01

    Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitary-adrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown. We evaluated 1) HPA axis activity in various rat models of cholestasis and 2) effects of HPA axis modulation on cholangiocyte proliferation. Expression of regulatory molecules of the HPA axis was determined after BDL, partial BDL, and α-naphthylisothiocyanate (ANIT) intoxication. The HPA axis was suppressed by inhibition of hypothalamic corticotropin-releasing hormone (CRH) expression by central administration of CRH-specific Vivo-morpholinos or by adrenalectomy. After BDL, the HPA axis was reactivated by 1) central administration of CRH, 2) systemic ACTH treatment, or 3) treatment with cortisol or corticosterone for 7 days postsurgery. There was decreased expression of 1) hypothalamic CRH, 2) pituitary ACTH, and 3) key glucocorticoid synthesis enzymes in the adrenal glands. Serum corticosterone and cortisol remained low after BDL (but not partial BDL) compared with sham surgery and after 2 wk of ANIT feeding. Experimental suppression of the HPA axis increased cholangiocyte proliferation, shown by increased cytokeratin-19- and proliferating cell nuclear antigen-positive cholangiocytes. Conversely, restoration of HPA axis activity inhibited BDL-induced cholangiocyte proliferation. Suppression of the HPA axis is an early event following BDL and induces cholangiocyte proliferation. Knowledge of the role of the HPA axis during cholestasis may lead to development of innovative treatment paradigms for chronic liver disease.

  15. Sclerosing cholangitis following severe trauma: Description of a remarkable disease entity with emphasis on possible pathophysiologic mechanisms

    Institute of Scientific and Technical Information of China (English)

    Johannes Benninger; Rainer Grobholz; Yurdaguel Oeztuerk; Christoph H. Antoni; Eckhart G. Hahn; Manfred V. Singer; Richard Strauss

    2005-01-01

    AIM: Persistent cholestasis is a rare complication of severe trauma or infections, Little is known about the possible pathomechanisms and the clinical course,METHODS: Secondary sclerosing cholangitis was diagnosed in five patients with persistent jaundice after severe trauma (one burn injury, three accidents, one power current injury). Medical charts were retrospectively reviewed with regard to possible trigger mechanisms for cholestasis, and the clinical course was recorded.RESULTS: Diagnosis of secondary sclerosing cholangitis was based in all patients on the primary sclerosing cholangitis (PSC)-like destruction of the intrahepatic bile ducts at cholangiography after exclusion of PSC. In four patients, arterial hypotension with subsequent ischemia may have caused the bile duct damage, whereas in the case of power current injury direct thermal damage was assumed to be the trigger mechanism. The course of secondary liver fibrosis was rapidly progressive and proceeded to liver cirrhosis in all four patients with a follow-up >2 years. Therapeutic possibilities were limited.CONCLUSION: Posttraumatic sclerosing cholangitis is a rare but rapidly progressive disease, probably caused by ischemia of the intrahepatic bile ducts via the peribiliary capillary plexus due to arterial hypotension. Gastroenterologists should be aware of this disease in patients with persistent cholestasis after severe trauma.

  16. Isolated Liver Hilar Infiltration by IgG4 Inflammation Mimicking Cholangiocarcinoma

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    Laurent Bochatay

    2016-10-01

    Full Text Available IgG4-related disease represents a heterogeneous group of disease characterized by infiltration of various tissues by IgG4 plasmocytes. In case of liver infiltration, this condition classically mimics primary sclerosing cholangitis or multifocal cholangiocarcinoma due to inflammation that preferentially affects the intra- and extrahepatic bile duct. Diagnostic criteria have recently been reviewed in order to better define the disease and help physicians make the diagnosis. Herein, we present the case of a patient who died after liver surgery for suspected cholangiocarcinoma that finally turned out to be IgG4-associated liver disease, a condition being out of current consensual criteria. The patient presented with progressive cholestasis identified by MR cholangiography as an isolated hilar mass responsible for dilatation of the left and right intrahepatic bile duct suspicious for a Klatskin tumor. The IgG4 blood level was normal as was biliary cytology. The patient underwent right portal embolization followed by right extended hepatectomy. Pathologic examination found no tumor but intense fibrosclerotic infiltration with a marked inflammatory infiltrate characterized by IgG4-positive plasmocytes. Despite immunosuppressive treatment, cholestasis was never controlled and successive biopsies of the remaining liver showed progressive cholestasis, liver infiltrate and no bile duct regeneration. The patient finally presented an upper gastrointestinal hemorrhage leading to death 4 months after hepatectomy and appropriate immunosuppressive therapy.

  17. Naproxen-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Sharif Ali; Jason D Pimentel; Chan Ma

    2011-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the-counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractablepruritusthatdevelopedshortlyaftertakingnaproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS:  Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.

  18. Identification of Bile Duct Paucity in Alagille Syndrome: Using CK7 and EMA Immunohistochemistry as a Reliable Panel for Accurate Diagnosis.

    Science.gov (United States)

    Herman, Haley K; Abramowsky, Carlos R; Caltharp, Shelley; Metry, Diana; Cundiff, Caitlin A; Romero, Rene; Gillespie, Scott E; Shehata, Bahig M

    2016-01-01

    Bile duct paucity is the absence or marked reduction in the number of interlobular bile ducts (ILBD) within portal tracts. Its syndromic variant, Alagille syndrome (ALGS), is a multisystem disorder with effects on the liver, cardiovascular system, skeleton, face, and eyes. It is inherited as an autosomal dominant trait due to defects in NOTCH signaling pathway. ALGS is characterized by vanishing ILBD with subsequent chronic obstructive cholestasis in approximately 89% of cases. Cholestasis stimulates formation of new bile ductules through a process of neoductular reaction, making it difficult to evaluate the presence or absence of ILBD. Therefore, finding a method to differentiate clearly between ILBD and the ductular proliferation is essential for accurate diagnosis. A database search identified 28 patients with confirmed diagnosis of ALGS between 1992 and 2014. Additionally, 7 controls were used. A panel of two immunostains, cytokeratin 7 (CK7) and epithelial membrane antigen (EMA), was performed. CK7 highlighted the bile duct epithelium of ILBD and ductular proliferation, while EMA stained only the brush border of ILBD. In our ALGS group, the ratio of EMA-positive ILBD to identified portal tracts was 12.6% (range, 0%-41%). However, this same ratio was 95.0% (range, 90%-100%) among control cases (P EMA, to differentiate ILBD from ductular proliferation in patients with cholestasis. With this panel, identification of bile duct paucity can be achieved. Additional studies, including molecular confirmation and clinical correlation, would provide a definitive diagnosis of ALGS.

  19. Medical treatment of cholestatic liver diseases: From pathobiology to pharmacological targets

    Institute of Scientific and Technical Information of China (English)

    Gustav Paumgartner

    2006-01-01

    Bile secretion is dependent on the coordinated functions of a number of hepatobiliary transport systems.Cholestasis may be caused by an impairment of bile secretion, an obstruction of bile flow or a combination of the two. The common consequence of all forms of cholestasis is retention of bile acids and other potentially toxic compounds in the hepatocytes leading to apoptosis or necrosis of hepatocytes and eventually to chronic cholestatic liver disease. In certain cholestatic disorders there is also leakage of bile acids into the peribiliary space causing portal inflammation and fibrosis. The following pharmacological targets for treatment of intrahepatic cholestasis can be identified: stimulation of orthograde biliary secretion and retrograde secretion of bile acids and other toxic cholephils into the systemic circulation for excretion via the kidneys to reduce their retention in the hepatocytes; stimulation of the metabolism of hydrophobic bile acids and other toxic compounds to more hydrophilic, less toxic metabolites;protection of injured cholangiocytes against toxic effects of bile; inhibition of apoptosis caused by elevated levels of cytotoxic bile acids; inhibition of fibrosis caused by leakage of bile acids into the peribiliary space. The clinical results of ursodeoxcholic acid therapy of primary biliary cirrhosis may be regarded as the first success of this strategy.

  20. Subdural hemorrhage: A unique case involving secondary vitamin K deficiency bleeding due to biliary atresia.

    Science.gov (United States)

    Miyao, Masashi; Abiru, Hitoshi; Ozeki, Munetaka; Kotani, Hirokazu; Tsuruyama, Tatsuaki; Kobayashi, Naho; Omae, Tadaki; Osamura, Toshio; Tamaki, Keiji

    2012-09-10

    Extrahepatic biliary atresia (EHBA) is a rare disease characterized by progressive and obliterative cholangiopathy in infants and is one of the major causes of secondary vitamin K deficiency bleeding (VKDB) due to cholestasis-induced fat malabsorption. Breast feeding increases the tendency of bleeding in EHBA patients because breast milk contains low amounts of vitamin K. A 2-month-old female infant unexpectedly died, with symptoms of vomiting and jaundice prior to death. She had been born by uncomplicated vaginal delivery and exhibited normal growth and development with breastfeeding. There was no history of trauma. She received vitamin K prophylaxis orally. In an emergency hospital, a CT scan showed a right intracranial hematoma and mass effect with midline shift to the left. In the postmortem examination, severe atresia was observed in the whole extrahepatic bile duct. Histologically, cholestasis, periductal fibrosis, and distorted bile ductules were noted. The gallbladder was not identified. A subdural hematoma and cerebellar tonsillar herniation were found; however, no traumatic injury in any part of the body was observed. Together, these findings suggest that the subdural hemorrhage was caused by secondary vitamin K deficiency resulting from a combination of cholestasis-induced fat malabsorption and breastfeeding. Subdural hemorrhage by secondary VKDB sometimes occurs even when vitamin K prophylaxis is continued. This case demonstrated that intrinsic factors, such as secondary VKDB (e.g., EHBA, neonatal hepatitis, chronic diarrhea), should also be considered in infant autopsy cases presenting with subdural hemorrhage.

  1. Creation of Reversible Cholestatic Rat Model

    Science.gov (United States)

    Subhas, Gokulakkrishna

    2011-01-01

    Cholestasis is a clinical condition commonly encountered by both surgeons and gastroenterologists. Cholestasis can cause various physiological changes and affect the nutritional status and surgical outcomes. Study of the pathophysiological changes occurring in the liver and other organs is of importance. Various studies have been done in cholestatic rat models. We used a reversible cholestatic rat model in our recent study looking at the role of methylprednisolone in the ischemia reperfusion injury. Various techniques for creation of a reversible cholestatic model have been described. Creation of a reversible cholestatic rat model can be challenging in view of the smaller size and unique hepatopancreatobiliary anatomy in rats. This video article demonstrates the creation of a reversible cholestatic model. This model can be used in various studies, such as looking at the changes in nutritional, physiological, pathological, histological and immunological changes in the gastrointestinal tract. This model can also be used to see the effects of cholestasis and various therapeutic interventions on major hepatic surgeries. PMID:21633335

  2. Congenital Cholestatic Syndromes: What Happens When Children Grow Up?

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    Simon C Ling

    2007-01-01

    Full Text Available Although advances in the management of children with congenital cholestasis have enabled many to survive into adulthood with their native livers, even the most common of these conditions remains rare in adult hepatology practice. Among four congenital cholestatic syndromes (biliary atresia, Alagille syndrome, Caroli disease and congenital hepatic fibrosis, and progressive familial intrahepatic cholestasis, the published data on outcomes of the syndromes into adulthood suggest that a spectrum of severity of liver disease can be expected, from cirrhosis (almost universal in adults with biliary atresia who have not required liver transplantation to mild and subclinical (eg, in the previously undiagnosed affected parent of an infant with Alagille syndrome. Complications associated with portal hypertension and nutritional deficiencies are common, and other associated features of the cholestatic syndrome may require appropriate attention, such as congenital heart disease in Alagille syndrome. Indications for liver transplantation include synthetic failure, progressive encephalopathy, intractable pruritus, recurrent biliary sepsis and recurrent complications of portal hypertension. Improved understanding of biliary physiology will hopefully translate into improved therapy for children and adults with cholestasis.

  3. [CLINICAL CASE OF COMBINATION OF PRIMARY SCLEROSING CHOLANGITIS WITH NONSPECIFIC ULCERATIVE COLITIS IN TWINS MONOZYGOTIC].

    Science.gov (United States)

    Gubergrits, N B; Belyayeva, N V; Klochkov, A Ye; Fomenko, P G; Lukashevich, G M

    2015-01-01

    The article presents discussion of basic hypotheses of pathogenesis of primary sclerosing cholangitis (PSC): genetically conditioned pathology, autoimmune pathology, result of inflammatory reaction in bile ducts, cholangiopathy. The authors presents a clinical case of monozygotic twins with association of PSC and nonspecific ulcerative colitis (NUC). The first twin had a severe course of PSC and mild course of NUC; he died due to bacterial complications of cholangitis. The second twin--patient B--had an opposite situation: severe course of NUC, while PSC was suspected only after determination of cholestasis biochemical markers. As soon as cholestasis was revealed, patients B was treated with Ursofalk and Budenofalk (2001). He received Salofalk as a remedy of basic therapy for NUC. Repeated liver biopsy (2005) showed no progression of PSC, but there were present minimal biochemical signs of cholestasis. So, it is necessary to investigate the first degree relatives of patients with PSC. The timely administered treatment in some cases gives the possibility of the control of the disease course.

  4. Effect of chemotherapy on autoimmune hepatitis in thymoma:a case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Nesrine Mejri; Imen Chabchoub; Ines Gargouri; Imtinen Belaid; Faten Ezairi; Sihem Hmissa; Slim Ben Ahmed

    2013-01-01

    Autoimmune hepatitis (AIH) has rarely been described as an autoimmune paraneoplastic syndrome of thymoma. This case is the seventh case of AIH revealed by cholestasis few years after the diagnosis of thymoma and the first case treated with chemotherapy alone. We report in this paper a new approach to this rare severe condition. A 29 year-old man presented with chest pain and dyspnea with a history of thymoma surgically removed 4 years ago. CT scan showed the recurrence of an anterior mediastinal mass. Biology showed elevated liver enzymes and profound cholestasis. No sign of viral or toxic hepatitis or bile duct abnormalities were observed. Autoimmune antibodies, except for the anti-nuclear antibody, were negative. Liver biopsy showed active chronic AIH. The patient was diagnosed with recurrent thymoma with AIH and underwent 6 cycles of chemotherapy. A complete response on thymoma and cholestasis was obtained after 10 months of follow-up. Steroids and immunosuppressors are the standard treatment for AIH. The effect of chemotherapy as a specific treatment of this paraneoplastic syndrome needs to be considered.

  5. Isolated Liver Hilar Infiltration by IgG4 Inflammation Mimicking Cholangiocarcinoma

    Science.gov (United States)

    Bochatay, Laurent; Majno, Pietro; Giostra, Emiliano; Frossard, Jean Louis

    2016-01-01

    IgG4-related disease represents a heterogeneous group of disease characterized by infiltration of various tissues by IgG4 plasmocytes. In case of liver infiltration, this condition classically mimics primary sclerosing cholangitis or multifocal cholangiocarcinoma due to inflammation that preferentially affects the intra- and extrahepatic bile duct. Diagnostic criteria have recently been reviewed in order to better define the disease and help physicians make the diagnosis. Herein, we present the case of a patient who died after liver surgery for suspected cholangiocarcinoma that finally turned out to be IgG4-associated liver disease, a condition being out of current consensual criteria. The patient presented with progressive cholestasis identified by MR cholangiography as an isolated hilar mass responsible for dilatation of the left and right intrahepatic bile duct suspicious for a Klatskin tumor. The IgG4 blood level was normal as was biliary cytology. The patient underwent right portal embolization followed by right extended hepatectomy. Pathologic examination found no tumor but intense fibrosclerotic infiltration with a marked inflammatory infiltrate characterized by IgG4-positive plasmocytes. Despite immunosuppressive treatment, cholestasis was never controlled and successive biopsies of the remaining liver showed progressive cholestasis, liver infiltrate and no bile duct regeneration. The patient finally presented an upper gastrointestinal hemorrhage leading to death 4 months after hepatectomy and appropriate immunosuppressive therapy. PMID:27843427

  6. Oxidative stress influence on renal dysfunction in patients with obstructive jaundice: A case and control prospective study

    Directory of Open Access Journals (Sweden)

    David Martínez-Cecilia

    2016-08-01

    Full Text Available Background: Obstructive Jaundice (OJ is associated with a significant risk of developing acute renal failure (ARF. The involvement of oxidative stress in the development of cholestasis has been demonstrated in different experimental models. However, its role in the morbidity of human cholestasis is far to be elucidated. The aim of the study was the evaluation of oxidative stress markers in blood from patients with OJ and its relation to complications and benign/malignant evolution of cholestasis. Methods: A prospective cross-sectional study of 105 patients with OJ and 34 control subjects were included. Several markers of liver function and oxidative stress, such as lipoperoxides (LPO, as well as reduced glutathione (GSH, catalase (CAT, superoxide dismutase (SOD and glutathione peroxidase (GSH-Px activities were assessed. Results: The patients with OJ showed a marked increase in plasma levels of LPO, SOD and GSH, while GSH-Px levels were decreased. The increase in lipid peroxidation products and the depletion of SOD activity in blood were also related to renal dysfunction. The highest level of LPO was associated with malignant etiology of the disease. The logistic regression analysis showed that the age of the patient and the levels of LPO in blood were predictors of renal dysfunction in OJ patients. Conclusions: This study demonstrates a correlation between oxidative stress and renal dysfunction patients with OJ.

  7. {sup 99m}Tc sestamibi imaging. Can it be a useful substitute for hepatobiliary scintigraphy in infantile jaundice?

    Energy Technology Data Exchange (ETDEWEB)

    Sadeghi, R.; Kakhki, V.R.D.; Zakavi, R. [Mashhad Univ. of Medical Sciences (Iran). Nuclear Medicine Dept.; Kianifar, H.R. [Mashhad Univ. of Medical Sciences (Iran). Paediatric Dept.; Ansari, K. [Tehran Univ. of Medical Sciences (Iran). Nuclear Medicine Dept.

    2009-07-01

    Hepatobiliary scintigraphy is an integral part in the diagnostic work-up of the neonatal cholestasis syndrome. However, less than optimal specificity is its major disadvantage. Differentiation between biliary atresia and neonatal hepatitis is nearly impossible in some cases with poor hepatocellular function. {sup 99m}Tc sestamibi (MIBI) is a cationic lipophilic agent which is a substrate of P-glycoprotein. This glycoprotein is normally expressed in biliary canalicular surfaces of hepatocytes. This property provides a hepatic excretory mechanism which is different from bilirubin excretion. In this study we evaluated the value of {sup 99m}Tc MIBI in differential diagnosis of neonatal cholestasis. 20 infants with a mean age of 2.41 months (range, 0.1-5 months) were included in the study. Ten infants turned out to have extrahepatic biliary atresia and the other ten had neonatal hepatitis. Hepatobiliary (with {sup 99m}Tc BrIDA) and {sup 99m}Tc MIBI scintigraphy were performed for all the patients. {sup 99m}Tc MIBI scintigraphy has shown bowel activity in all patients, including the patients with biliary atresia. Hepatobiliary scintigraphy revealed bowel activity only in five patients with neonatal hepatitis. Bowel visualization with {sup 99m}Tc MIBI may be seen in patients with biliary atresia and {sup 99m}Tc MIBI has limited value in differential diagnosis of neonatal cholestasis. (orig.)

  8. Huqi San-Evoked Rat Colonic Anion Secretion through Increasing CFTR Expression

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    Xiaowei Xue

    2015-01-01

    Full Text Available Huqi San (HQS is a Chinese herbal preparation of eight medicinal herbs that promote diuresis, detoxification, blood circulation, and cholestasis. Defects in transporter expression and function can cause cholestasis and jaundice. However, the mechanism of the cholestasis underlying HQS effects, especially on the gastrointestinal tract ion secretion, has not been elucidated. Real-time RT-PCR and Western blotting were used to study the expression and localization of cystic fibrosis transmembrane conductance regulator (CFTR and α-ENaC in rat alimentary tract, and then the effect of HQS on the ion transport in rat distal colon mucosa was investigated using the short-circuit current (ISC technique. The results showed that pretreatment with HQS significantly enhanced mRNA transcripts and protein content of CFTR in liver and distal colon but not α-ENaC in alimentary organs. HQS increases ISC and decreases the transepithelial resistance. Pretreatment with epithelial Na+ channel blocker did not affect the ISC responses elicited by HQS, but removal of extracellular Cl− or pretreatment with Cl− channel or Na+-K+-2Cl− cotransporter blocker inhibited HQS-elicited ISC responses. These findings demonstrated that HQS, RA, and RP can stimulate Cl− secretion in the distal colon by increasing the mRNA transcripts and protein content of CFTR in liver and distal colon.

  9. Diagnostic and therapeutic approach to cholestatic liver disease Abordaje diagnóstico y terapéutico del síndrome colestásico

    Directory of Open Access Journals (Sweden)

    T. Pérez Fernández

    2004-01-01

    Full Text Available When cholestatic liver disease is present, liver ultrasound should be performed to ascertain if cholestasis is extrahepatic or intrahepatiic. If bile ducts appear dilated and the probability of interventional treatment is high, endoscopic retrograde cholagio-pancreatography (ERCP or trans-hepatic cholangiography (THC should be the next step. If the probability of interventional therapeutics is low, cholangio-MRI should be performed. Once bile duct dilation and space occupying lesions are excluded, a work up for intrahepatic cholestasis should be started. Some especific clinical situations may be helpful in the diagnostic strategy. If cholestasis occurs in the elderly, drug-induced cholestatic disease should be suspected, whereas if it occurs in young people with risk factors, cholestatic viral hepatitis is the most likely diagnosis. During the first trimester of pregnancy cholestasis may occur in hiperemesis gravidorum, and in the third trimester of gestation cholestasis of pregnancy should be suspected. A familial history of recurrent cholestasis points to benign recurrent intrahepatic cholestasis. The occurrence of intrahepatic cholestasis in a mid-dle-aged woman is a frequent presentation of primary biliary cirrhosis, whereas primary sclerosing cholangitis should be suspected in young males with inflammatory bowel disease. The presence of vascular spider nevi, ascites, and a history of alcohol abuse should point to alcoholic hepatitis. Neonatal cholestasis syndromes include CMV, toxoplasma and rubinfections or metabolic defects such as cystic fibrosis, α1-antitripsin deficiency, bile acid synthesis defects, or biliary atresia. The treatment of cholestasis should include a management of complications such as pruritus, osteopenia and correction of fat soluble vitamin deficiencies. When hepatocellular failure or portal hypertension-related complications occur, liver transplantation should be considered.Ante la presencia de colestasis, se debe

  10. Effects of structural injure in the bile bacterial contamination after balloon transduodenal sphincteroplasty (papillary dilation in dogs

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    Zavadinack Netto Martin

    2006-01-01

    Full Text Available PURPOSE: To evaluate, in dogs, the biliary sphincter subjected to dilation by hydrostatic balloon by the point of view of structural alterations of the papilla and the biochemestry and bacterial contamination of the bile. METHODS: Twenty dogs were submitted to laparotomy, duodenotomy, and enlargement of the major duodenal papilla- GA(n=10 - with balloon of 8mm inflated with pressure of 0,5atm, during 2 minutes or to the sham procedure - GB(n=10. Blood samples collected on times t(0day, t(7days and t(28days were subjected to dosages of alkaline phosphatase (ALP and gamma-glutamyltransferase (GGT for cholestasis evaluation. The collected material from the gall bladder at the same times were registered and numbered to be submitted to culture in BHI, blood agar (rich, non-selective element and Mac Conkey (selective element for Gram-negative bacillus. On the 28th day three fragments of the papilla were tranversally cut by the choledoc axis 3mm from the duodenal papilla and the cuts, stained with hematoxylin-eosin and Masson's tricome, were evaluated according to their inflammatory reaction. RESULTS: The GGT and ALP averages on the three periods in the groups A and B did not show significant differences, not being characterizes the cholestasis. The bacterian contamination was significantly higher in GA (2,19 than in GB (1,96; the contamination was lower in the initial time compared with 7 and 28 days (t0cholestasis. The morphologic lesions are more intense in the late phase, not associated with an eventual papilla esthenosis.

  11. Cholesterol metabolism in cholestatic liver disease and liver transplantation:From molecular mechanisms to clinical implications

    Institute of Scientific and Technical Information of China (English)

    Katriina; Nemes; Fredrik; ?berg; Helena; Gylling; Helena; Isoniemi

    2016-01-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.

  12. ATP8B1 gene expression is driven by a housekeeping-like promoter independent of bile acids and farnesoid X receptor.

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    Dita Cebecauerová

    Full Text Available BACKGROUND: Mutations in ATP8B1 gene were identified as a cause of low γ-glutamyltranspeptidase cholestasis with variable phenotype, ranging from Progressive Familial Intrahepatic Cholestasis to Benign Recurrent Intrahepatic Cholestasis. However, only the coding region of ATP8B1 has been described. The aim of this research was to explore the regulatory regions, promoter and 5'untranslated region, of the ATP8B1 gene. METHODOLOGY/PRINCIPAL FINDINGS: 5'Rapid Amplification of cDNA Ends using human liver and intestinal tissue was performed to identify the presence of 5' untranslated exons. Expression levels of ATP8B1 transcripts were determined by quantitative reverse-transcription PCR and compared with the non-variable part of ATP8B1. Three putative promoters were examined in vitro using a reporter gene assay and the main promoter was stimulated with chenodeoxycholic acid. Four novel untranslated exons located up to 71 kb upstream of the previously published exon 1 and twelve different splicing variants were found both in the liver and the intestine. Multiple transcription start sites were identified within exon -3 and the proximal promoter upstream of this transcription start site cluster was proven to be an essential regulatory element responsible for 70% of total ATP8B1 transcriptional activity. In vitro analysis demonstrated that the main promoter drives constitutive ATP8B1 gene expression independent of bile acids. CONCLUSIONS/SIGNIFICANCE: The structure of the ATP8B1 gene is complex and the previously published transcription start site is not significant. The basal expression of ATP8B1 is driven by a housekeeping-like promoter located 71 kb upstream of the first protein coding exon.

  13. Investigation of Homocystein Plasma Level in Cholestatic Rat and Its Effect on Nitric Oxide Secretion in Liver

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    N. Mirazi

    2005-04-01

    Full Text Available Homocystein (Hcy,one of the thio-amino acid is known as a risk factor in some cardiovascular diseases with releasing O2 radical . It has also been reported that; there is oxidative stress effects of Hcy in cholestasis. The aim of this study is to determine plasma Hcy alteration and nitric oxide (NO in liver and its effects on pathologic disfunction.In this study , 150 Spraque – Dawley male rats with 200 ± 20g body weight were used in the experiments and they were randomly divided in three control, SHAM and bile duct ligation (BDL groups (n= 10-12 . In 7th,14th,21st and 28th days cholestasis was observed in BDL group,the animal were anesthetized with ether and then blood samples were taken from heart directly and analysed for cystein , methionine by HPLC and HPLC-UV. Two hours before blood sampling , 40 and 100 mg/kg methionine were injected (I.P .All data are expressed as mean  SEM. Statistical evaluation of data performed by SPSS soft ware using analysis of variance (ANOVA followed by post hoc test. P-values less than 0.05 were considered statistically significant .The results suggest that billirubin and hepatic enzymes were significantly elevated in BDL rats compared with SHAM and controls (P<0.05. Homocystein concentration was significantly rised in 14th day in BDL group (P<0.05. The plasma cystein and methionine level were significantly elevated in BDL rats compared with SHAM and control groups ( p = 0.01 . Plasma nitrate / nitrite ratio were significantly increased in BDL rats compared with SHAM and control rats (P<0.05. With these data we suppose that some of the systemic oxidative stresses in BDL rat model of cholestasis contributes possibly through NO-dependent mechanisms disorders.

  14. EGFR participates downstream of ERα in estradiol-17β-D-glucuronide-induced impairment of Abcc2 function in isolated rat hepatocyte couplets.

    Science.gov (United States)

    Barosso, Ismael R; Zucchetti, Andrés E; Miszczuk, Gisel S; Boaglio, Andrea C; Taborda, Diego R; Roma, Marcelo G; Crocenzi, Fernando A; Sánchez Pozzi, Enrique J

    2016-04-01

    Estradiol-17β-D-glucuronide (E17G) induces acute endocytic internalization of canalicular transporters, including multidrug resistance-associated protein 2 (Abcc2) in rat, generating cholestasis. Several proteins organized in at least two different signaling pathways are involved in E17G cholestasis: one pathway involves estrogen receptor alpha (ERα), Ca(2+)-dependent protein kinase C and p38-mitogen activated protein kinase, and the other pathway involves GPR30, PKA, phosphoinositide 3-kinase/AKT and extracellular signal-related kinase 1/2. EGF receptor (EGFR) can potentially participate in both pathways since it interacts with GPR30 and ERα. Hence, the aim of this study was to analyze the potential role of this receptor and its downstream effectors, members of the Src family kinases in E17G-induced cholestasis. In vitro, EGFR inhibition by Tyrphostin (Tyr), Cl-387785 or its knockdown with siRNA strongly prevented E17G-induced impairment of Abcc2 function and localization. Activation of EGFR was necessary but not sufficient to impair the canalicular transporter function, whereas the simultaneous activation of EGFR and GPR30 could impair Abcc2 transport. The protection of Tyr was not additive to that produced by the ERα inhibitor ICI neither with that produced by Src kinase inhibitors, suggesting that EGFR shared the signaling pathway of ERα and Src. Further analysis of ERα, EGFR and Src activations induced by E17G, demonstrated that ERα activation precedes that of EGFR and EGFR activation precedes that of Src. In conclusion, activation of EGFR is a key factor in the alteration of canalicular transporter function and localization induced by E17G and it occurs before that of Src and after that of ERα.

  15. Extrahepatic bile duct atresia from the pathologist’s perspective: pathological features and differential diagnosis

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    Peter Van Eyken

    2014-06-01

    Full Text Available Extrahepatic biliary atresia (EHBA refers to stenosis or atresia of the extrahepatic biliary tree. It accounts for 25-30% of cases of neonatal cholestasis. If left untreated, EHBA progresses to biliary cirrhosis and is universally fatal within the first 2 years of life. Early diagnosis is crucial since surgical treatment (Kasai procedure is the only treatment option. Histopathologic examination of liver biopsy specimens is a key element in the diagnostic work-up of infants with suspected EHBA. Pathologic diagnosis aims at excluding non-surgically correctable causes of neonatal cholestasis thereby leading to surgical exploration for confirmation of the diagnosis. All published data indicate that pathologists can diagnose EHBA with high sensitivity, high specificity and reasonable interobserver agreement. The most useful histologic features in the diagnosis of EHBA are portal tract changes including ductular proliferation and bile plugs in ducts and ductules. These lesions are not pathognomonic but can be seen in extrahepatic obstruction of any cause. Total parenteral nutrition (TPN-associated cholestasis and alpha1-antitrypsin (A1AT deficiency cannot be differentiated from EHBA without access to clinical data and may lead to false-positive diagnosis. False-negative interpretation may be caused by early age at diagnosis or by small/indequate specimens. The pathologist also plays a role in the examination of the resected fibrotic segment and of explant specimens. Histopathology can yield prognostic information, being also an indispensable tool in research for the possible pathogenesis of this disease. A well-coordinated, multidisciplinary approach is required in the assessment of suspected cases of EHBA.  Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in

  16. Unusual duodenal perforation following endoscopic retrograde cholangiopancreatography

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    Martin Kobborg

    2011-02-01

    Full Text Available Perforation is a known but rare complication to Endoscopic retrograde cholangiopancreatography (ERCP with endoscopic sphincterotomy (ES. Most of the perforations are located in the periampullary area due to ES. This report presents an unusual perforation in the third part of the duodenum following ES. The patient an eigthy-sixt-year-old man underwent ERCP with ES. The patient had Magnetic Resonance Cholangio-pancreatography (MRCP and Computerized Tomography (CT verified cholelithiasis and intra- and extrahepatic cholestasis. The perforation was not found under the ERCP procedure but was clinically revealed when the patient developed pneumoscrotum after the procedure. A CT-scan with oral contrast later confirmed the duodenal perforation.

  17. TGFβ1, TNFα, and insulin signaling crosstalk in regulation of the rat cholesterol 7α-hydroxylase gene expression*

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    Li, Tiangang; Ma, Huiyan; Chiang, John Y. L.

    2008-01-01

    The TGFβ1/Smad pathway plays a critical role in cholestasis and liver fibrosis. Previous studies show that TGFβ1, TNFα, and insulin inhibit cholesterol 7α-hydroxylase (CYP7A1) gene transcription and bile acid synthesis in human hepatocytes. In this study, we investigated insulin, TGFβ1, and TNFα regulation of rat Cyp7a1 gene transcription. In contrast to inhibition of human CYP7A1 gene transcription, TGFβ1 stimulates rat Cyp7a1 reporter activity. Smad3, FoxO1, and HNF4α synergistically stimul...

  18. LONG-TERM CONSEQUENCES OF HEPATITIS A IN CHILDREN

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    V. F. Uchaikin

    2014-01-01

    Full Text Available Various embodiments of lingering forms of hepatitis A, for the aggravation still cause differential diagnostic difficulties and mistakes. Continuing to the present heavy and cholestasis form of hepatitis A in children, fulminant form of adolescents, adults and pregnant women let to suggest this issue to be relevance. The task of vaccine prevention of hepatitis A in the National Immunization ScheduleRussiakeeping up to be relevance and perspective. Numerous studies have shown that the French vaccine AVAXIM 80 showed good immunogenicity and safety vaccinate in children.

  19. Ursodeoxycholic acid treatment of vanishing bile duct syndromes

    Institute of Scientific and Technical Information of China (English)

    Thomas Pusl; Ulrich Beuers

    2006-01-01

    Vanishing bile duct syndromes (VBDS) are characterized by progressive loss of small intrahepatic ducts caused by a variety of different diseases leading to chronic cholestasis, cirrhosis, and premature death from liver failure. The majority of adult patients with VBDS suffer from primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA), a hydrophilic dihydroxy bile acid, is the only drug currently approved for the treatment of patients with PBC, and anticholestatic effects have been reported for several other cholestatic syndromes. Several potential mechanisms of action of UDCA have been proposed including stimulation of hepatobiliary secretion, inhibition of apoptosis and protection of cholangiocytes against toxic effects of hydrophobic bile acids.

  20. The Reliability of Highly Elevated CA 19-9 Levels

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    B. R. Osswald

    1993-01-01

    Full Text Available CA 19-9 is used as a tumour marker of the upper gastrointestinal tract. However, extremely elevated CA 19-9 levels are found also in patients with benign diseases. Cholestasis was present in 97.1 % of patients with high elevated CA 19-9, independent of their primary disease. 50% of patients with non-malignant diseases and increased CA 19-9 levels showed liver cirrhosis, cholecystitis, pancreatitis and/or hepatitis. In 8.8% no explanation was found for the extremely high CA 19-9 level. The results provide evidence of different factors influencing the CA 19-9 level.

  1. 新生儿胃肠外营养相关性胆汁淤积的危险因素

    Institute of Scientific and Technical Information of China (English)

    李卉; 冯琪

    2005-01-01

    随着围产医学的发展,早产儿、低出生体重儿的存活率不断提高,胃肠外营养(parenteral nutrition, PN)的应用越来越普遍,相应的新生儿胃肠外营养相关性胆汁淤积(parenteral nutrition associated cholestasis, PNAC)这一常见的并发症也越来越多地引起围产医学界的重视.

  2. Liver Involvement with Acute Myeloid Leukemia

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    Emily Mathews

    2008-03-01

    Full Text Available Liver involvement with acute myeloid leukemia (AML is rarely reported. The majority of published cases suggest a cholestatic picture and obstructive jaundice at presentation. On the contrary, our patient presented with transaminitis without cholestasis. Elevated liver function tests persisted in our patient despite cholecystectomy; however, they normalized with chemotherapy administration, suggesting that AML was the causative effect of the hepatitis-like picture. Our review of the literature revealed that most reported cases of AML with liver involvement had short-lived remissions and an overall ominous prognosis. In our opinion, patients who have liver involvement with AML should be offered alternative investigational therapies with a low hepatic toxicity profile.

  3. Diagnosis in bile acid-CoA: Amino acid N-acyltransferase deficiency

    Institute of Scientific and Technical Information of China (English)

    Nedim Had(z)i(c); Laura N Bull; Peter T Clayton; AS Knisely

    2012-01-01

    Cholate-CoA ligase (CCL) and bile acid-CoA:amino acid N-acyltransferase (BAAT) sequentially mediate bile-acid amidation.Defects can cause intrahepatic cholestasis.Distinction has required gene sequencing.We assessed potential clinical utility of immunostaining of liver for CCL and BAAT.Using commercially available antibodies against BAAT and CCL,we immunostained liver from an infant with jaundice,deficiency of amidated bile acids,and transcription-terminating mutation in BAAT.CCL was normally expressed.BAAT expression was not detected.Immunostaining may facilitate diagnosis in bileacid amidation defects.

  4. Etiology of the obstructive pattern in hepatobiliary imaging

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    Hughes, K.S.; Marrangoni, A.G.; Turbiner, E.

    1984-04-01

    The records of all patients undergoing hepatobiliary imaging with technetion radioisotopes at our hospital from January 1980 to March 1983 were reviewed and 29 scans met the criteria for a pattern consistent with complete biliary tract obstruction. Biliary tract obstruction (due to choledocholithiasis, primary or secondary carcinoma involving the common bile duct, and pancreatitis) was documented in 24 of these patients. However, the remaining five patients had a patent common bile duct, and the etiologic factor was intrahepatic cholestasis secondary to sepsis in four and peritonitis in one. A classification of altered biliary dynamics in hepatobiliary imaging, which is based on the classification of jaundice, is proposed.

  5. Vanishing bile duct and Stevens-Johnson syndrome associated with ciprofloxacin treated with tacrolimus

    Institute of Scientific and Technical Information of China (English)

    Gokhan Okan; Serpil Yaylaci; Onder Peker; Sabahattin Kaymakoglu; Murat Saruc

    2008-01-01

    Stevens-Johnson syndrome (SJS) is a serious and potentially life-threatening disease. Vanishing bile duct syndrome (VBDS) is a rare cause of progressive cholestasis. Both syndromes are mostly related with drugs. We report a case of a patient withciprofloxacin-induced SJS and acute onset of VBDS,and reviewed the related literature. It is the first case of ciprofloxacin-induced VBDS successfully treatedwith tacrolimus. This case reminds physicians of the importance of drug reactions, their severity, techniques for diagnosis and methods of management.

  6. Successful treatment of parenteral nutrition-associated liver disease in an adult by use of a fish oil-based lipid source.

    Science.gov (United States)

    Venecourt-Jackson, Esra; Hill, Simon J; Walmsley, Russell S

    2013-01-01

    Liver disease occurs in 15% to 40% of adults on long-term parenteral nutrition, with steatosis being more common than cholestasis in the adult population. This problem has been well reported in the pediatric population, but we describe the case of a man who became profoundly jaundiced after being on parenteral nutrition for 3 y and responded rapidly to a change in lipid source from soybean and olive oil-based emulsion (ClinOleic) to a fish oil-based lipid emulsion (Omegaven).

  7. Chinese Expert Consensus for the Diagnosis and Treatment of Cholestatic Liver Disease

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Cholestatic liver disease (CLD) is a common problem in clinical practice with the main manifestation being cholestasis.Recently,there has been a steady increase in knowledge associated with the diagnosis and treatment of CLD.Therefore,the experts in China were organized by the editorial board of Chinese Journal of Experimental and Clinical Infectious Diseases (Electronic Edition),Chinese Journal of Liver Diseases (Electronic Edition) and Infection International (Electronic Edition) to collect and analyze relevant research,ultimately resulting in the development of this work (Chinese Expert consensus for the diagnosis and treatment of CLDs,also abbreviated as consensus).

  8. Green teeth are a late complication of prolonged conjugated hyperbilirubinemia in extremely low birth weight infants.

    Science.gov (United States)

    Battineni, Sireesha; Clarke, Paul

    2012-01-01

    Eruption of green, discolored teeth affecting the primary dentition has been described in association with congenital viral infection, sepsis, hemolytic jaundice, and cholestasis. The purpose of this paper was to present the cases of 3 extremely low birth weight preterm infants who were noted to have green teeth at the corrected ages of 10 to 12 months. All had a history of prolonged conjugated hyperbilirubinemia during their time in neonatal intensive care. For infants with prolonged conjugated hyperbilirubinemia, extreme preterm birth and/or extremely low birth weight may be additional risk factors predisposing to the eruption of green teeth in later infancy.

  9. Elevated copper impairs hepatic nuclear receptor function in Wilson's disease.

    Science.gov (United States)

    Wooton-Kee, Clavia Ruth; Jain, Ajay K; Wagner, Martin; Grusak, Michael A; Finegold, Milton J; Lutsenko, Svetlana; Moore, David D

    2015-09-01

    Wilson's disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b⁻/⁻ mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the nuclear receptors FXR, RXR, HNF4α, and LRH-1 to promoter response elements and decreased mRNA expression of nuclear receptor target genes in Atp7b⁻/⁻ mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired nuclear receptor activity. Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels.

  10. Repeated Oral Administration of Oleanolic Acid Produces Cholestatic Liver Injury in Mice

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    Yasha Xu

    2013-03-01

    Full Text Available Oleanolic acid (OA is a triterpenoid and a fantastic molecule with many beneficial effects. However, high-doses and long-term use can produce adverse effects. This study aimed to characterize the hepatotoxic potential of OA. Mice were given OA at doses of 100–3,000 µmol/kg (45–1,350 mg/kg, po for 10 days, and the hepatotoxicity was determined by serum biochemistry, histopathology, and toxicity-related gene expression via real-time RT-PCR. Animal body weight loss was evident at OA doses of 1,000 µmol/kg and above. Serum alanine aminotransferase activities were increased in a dose-dependent manner, indicative of hepatotoxicity. Serum total bilirubin concentrations were increased, indicative of cholestasis. OA administration produced dose-dependent pathological lesions to the liver, including inflammation, hepatocellular apoptosis, necrosis, and feathery degeneration indicative of cholestasis. These lesions were evident at OA doses of 500 µmol/kg and above. Real-time RT-PCR revealed that OA produced dose-dependent increases in acute phase proteins (MT-1, Ho-1, Nrf2 and Nqo1, decreases in bile acid synthesis genes (Cyp7a1 and Cyp8b1, and decreases in liver bile acid transporters (Ntcp, Bsep, Oatp1a1, Oatp1b2, and Ostβ. Thus, the clinical use of OA and OA-type triterpenoids should balance the beneficial effects and toxicity potentials.

  11. Successful orthotopic liver transplantation in an adult patient with sickle cell disease and review of the literature

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    Morey Blinder

    2013-05-01

    Full Text Available Sickle cell disease can lead to hepatic complications ranging from acute hepatic crises to chronic liver disease including intrahepatic cholestasis, and iron overload. Although uncommon, intrahepatic cholestasis may be severe and medical treatment of this complication is often ineffective. We report a case of a 37 year-old male patient with sickle cell anemia, who developed liver failure and underwent successful orthotopic liver transplantation. Both pre and post-operatively, he was maintained on red cell transfusions. He remains stable with improved liver function 42 months post transplant. The role for orthotopic liver transplantation is not well defined in patients with sickle cell disease, and the experience remains limited. Although considerable challenges of post-transplant graft complications remain, orthotopic liver transplantation should be considered as a treatment option for sickle cell disease patients with end-stage liver disease who have progressed despite conventional medical therapy. An extended period of red cell transfusion support may lessen the post-operative complications.

  12. Endoscopic sphincterotomy in patients with stenosis of ampulla of Vater: Three-year follow-up of exocrine pancreatic function and clinical symptoms

    Institute of Scientific and Technical Information of China (English)

    Nils Ewald; Axel Michael Marzeion; Reinhard Georg Bretzel; Hans Ulrich Kloer; Philip Daniel Hardt

    2007-01-01

    AIM: To investigate retrospectively the long-term effect of endoscopic sphincterotomy (ES) including exocrine pancreatic function in patients with stenosis of ampulla of Vater.METHODS: After diagnostic endoscopic retrograde cholangiopancreatography (ERCP) and ES because of stenosis of the ampulla of Vater (SOD Type I), follow-up examinations were performed in 60 patients (mean follow-up time 37.7 mo). Patients were asked about clinical signs and symptoms at present and before intervention using a standard questionnaire. Before and after ES exocrine pancreatic function was assessed by determination of immunoreactive fecal elastase 1. Serum enzymes indicating cholestasis as well as serum lipase and amylase were measured.RESULTS: Eighty percent of patients reported an improvement in their general condition after ES. The fecal elastase 1 concentrations (FEC) in all patients increased significantly after ES. This effect was even more marked in patients with pathologically low concentrations (< 200 ng/g) of fecal elastase prior to ES. The levels of serum lipase and amylase as well as serum alcaline phosphatase (AP) and gamma-glutamyltranspeptidase (GGT) decreased significantly after ES.CONCLUSION: The results of this study demonstrate that patients with stenosis of the ampulla of Vater can be successfully treated with endoscopic sphincterotomy. The positive effect is not only indicated by sustained improvement of clinical symptoms and cholestasis but also by improvement of exocrine pancreatic function.

  13. Long-Term Therapy of a Patient with Summerskill-Walshe-Tygstrup Syndrome by Applying Prometheus® Liver Dialysis: A Case Report

    Directory of Open Access Journals (Sweden)

    Mikolaj Walensi

    2012-08-01

    Full Text Available Summerskill-Walshe-Tygstrup syndrome is a rare benign chronic liver disease characterized by recurring cholestasis with jaundice and severe pruritus. Due to insufficient conservative treatment, liver dialysis by Prometheus® was applied to a 45-year-old female patient with resistant pruritus. Initially, other possible liver diseases were excluded and the patient was treated symptomatically since the diagnosis of Summerskill-Walshe-Tygstrup was stated in 1998. As conservative and endoscopic methods progressively failed to relieve the patient’s suffering, Prometheus® liver dialysis was performed regularly since 2006 at 3-month intervals and successfully led to a decrease in the patient’s symptoms. Cholestatic liver enzymes and also serum bile acids could be lowered significantly from an average of 22.5 ± 2.7 to 7.3 ± 1.7 µmol/l. Consequently, Prometheus® liver dialysis may be a beneficial option for patients with benign recurrent intrahepatic cholestasis suffering from therapy-resistant symptoms and may be used as well as other extracorporeal liver support devices which have already been reported to improve cholestatic pruritus.

  14. [The use of ultrasonography for diagnosing the cause of colic in cows. A review].

    Science.gov (United States)

    Braun, U; Nuss, K; Knubben-Schweizer, G; Gerspach, C

    2011-01-01

    Ultrasonography is a very useful technique for diagnosing the cause of colic in cows. It allows visualisation of abnormal reticular contour and occasionally of abnormal contractility in cows with reticuloperitonitis. In right-displaced abomasum, the dilated abomasum can be detected between the right abdominal wall and the liver. Fluid ingesta are seen ventrally and a gas cap of varying size dorsally. Dilated loops of small intestines that are almost always static are the main diagnostic criterion for ileus of the small intestine, but the cause of the ileus can only rarely be determined. Cholestasis can almost always be diagnosed by imaging a dilated biliary system. With obstruction at the level of the hepatic portal, only the intrahepatic biliary ducts are dilated, while a dilatation of the entire biliary tract, including the gallbladder, occurs in the case of an obstruction near the duodenal papilla. Urinary tract diseases cause colic in cows when concrement or inflammatory products become lodged in a ureter. The importance of ultrasonography in the diagnosis of diseases causing colic in cows varies. For example, with colic attributable to ileus of the small intestines, cholestasis or urinary tract disease, ultrasonography is a very useful diagnostic tool. On the other hand, for diagnosis of left or right displacement of the abomasum or caecal dilatation, ultrasonography is generally not required, but it is helpful in difficult cases to confirm or rule out a tentative diagnosis and to avoid an unnecessary exploratory laparotomy.

  15. The Sea Lamprey as an Etiological Model for Biliary Atresia

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    Yu-Wen Chung-Davidson

    2015-01-01

    Full Text Available Biliary atresia (BA is a progressive, inflammatory, and fibrosclerosing cholangiopathy in infants that results in obstruction of both extrahepatic and intrahepatic bile ducts. It is the most common cause for pediatric liver transplantation. In contrast, the sea lamprey undergoes developmental BA with transient cholestasis and fibrosis during metamorphosis, but emerges as a fecund adult with steatohepatitis and fibrosis in the liver. In this paper, we present new histological evidence and compare the sea lamprey to existing animal models to highlight the advantages and possible limitations of using the sea lamprey to study the etiology and compensatory mechanisms of BA and other liver diseases. Understanding the signaling factors and genetic networks underlying lamprey BA can provide insights into BA etiology and possible targets to prevent biliary degeneration and to clear fibrosis. In addition, information from lamprey BA can be used to develop adjunct treatments for patients awaiting or receiving surgical treatments. Furthermore, the cholestatic adult lamprey has unique adaptive mechanisms that can be used to explore potential treatments for cholestasis and nonalcoholic steatohepatitis (NASH.

  16. Bile composition in Alagille Syndrome and PFIC patients having Partial External Biliary Diversion

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    Thompson Richard J

    2008-10-01

    Full Text Available Abstract Background Partial External Biliary Diversion (PEBD is a surgical intervention to treat children with Progressive Familial Intrahepatic Cholestasis (PFIC and Alagille syndrome (AGS. PEBD can reduce disease progression, and examining the alterations in biliary lipid composition may be a prognostic factor for outcome. Methods Biliary lipid composition and the clinical course of AGS and PFIC patients were examined before and after PEBD. Results Pre-PEBD bile from AGS patients had greater chenodeoxycholic/cholic acid (CDCA/CA, bile salt, cholesterol and phospholipid concentrations than PFIC patients. AGS patients, and PFIC patients with familial intrahepatic cholestasis 1 (FIC1 genotype, responded better to PEBD than PFIC patients with bile salt export protein (BSEP genotype. After successful PEBD, AGS patients have higher biliary lipid concentrations than PFIC patients and PEBD also increases biliary phospholipid concentrations in FIC1 patients. Conclusion Both AGS and FIC1 patients can benefit from PEBD, and preserved biliary phospholipid concentrations may be associated with better outcomes post-PEBD.

  17. Protective effects of curcumin against oxidative stress parameters and DNA damage in the livers and kidneys of rats with biliary obstruction.

    Science.gov (United States)

    Tokaç, Mehmet; Taner, Gökçe; Aydın, Sevtap; Ozkardeş, Alper Bilal; Dündar, Halit Ziya; Taşlıpınar, Mine Yavuz; Arıkök, Ata Türker; Kılıç, Mehmet; Başaran, Arif Ahmet; Basaran, Nursen

    2013-11-01

    Curcumin, a most active antioxidant compound, has been suggested to have potential beneficial effects against most metabolic and psychological disorders, including cholestasis. In the present study, the effects of curcumin against oxidative stress and DNA damage induced by bile duct ligation (BDL) in Wistar albino rats for 14 days were investigated. The rats were divided into three following groups: Sham group, the BDL group and the BDL+curcumin group. A daily dose of 50mg/kg curcumin was given to the BDL+curcumin group intragastrically for 14 days. The biomarkers of hepatocellular damage were decreased in the BDL+curcumin group compared to the BDL group, indicating that curcumin recovered the liver functions. DNA damage as assessed by the alkaline comet assay was also found to be low in the BDL+curcumin group. Curcumin significantly reduced malondialdehyde and nitric oxide levels, and enchanced reduced glutathione levels and catalase, superoxide dismutase, and glutathione S-transferase enzymes activities in the livers and kidneys of BDL group. Curcumin treatment in BDL group was found to decrease tumor necrosis factor-alpha levels in the livers of rats. These results suggest that curcumin might have protective effects on the cholestasis-induced injuries in the liver and kidney tissues of rats.

  18. Ultrasound-guided percutaneous cholecysto-cholangiography for the exclusion of biliary atresia in infants

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kyung Min; Ryeom, Hun Kyu; Choe, Byung Ho; Kim, Kap Cheol; Kim, Jong Yeol; Lee, Jong Min; Kim, Hye Jeong; Lee, Hee Jung [Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2006-08-15

    The aim of this study is to determine the feasibility and effectiveness of performing an ultrasound-guided percutaneous cholecysto-cholangiogram (PCC) for excluding biliary atresia as the cause of neonatal jaundice. Between Oct. 2003 and Feb. 2005, six ultrasound-guided PCC procedures were performed to five jaundiced infants (4 females and 1 male; mean age: 60 days old) for whom possibility of biliary atresia could not be ruled out by the DISIDA scan as the cause of their neonatal jaundice. Gallbladder puncture was performed under ultrasound guidance with a 23-gauge needle. Contrast material injection during fluoroscopic examination was performed after dilatation of the gallbladder lumen with normal saline under ultrasound guidance. The criteria used for excluding biliary atresia were complete visualization of the extrahepatic biliary trees and/or contrast excretion into the duodenum. The complications and final diagnosis was assessed according to the clinical and laboratory findings. The procedures were successful in all the patients without any complication. Biliary atresia could be ruled out in all the patients. The final diagnosis was neonatal cytomegalovirus hepatitis in two patients, total parenteral nutrition-associated cholestasis in two patients, and combined cytomegalovirus hepatitis and total parenteral nutrition-associated cholestasis in one patient. Ultrasound-guided PCC is a feasible and effective method for the early definitive exclusion of biliary atresia as the cause of neonatal jaundice. By the technique of injecting normal saline before contrast injection, PCC can be done even in a totally collapsed or very small gallbladder.

  19. Evaluation of liver enzyme levels in workers exposed to vinyl chloride vapors in a petrochemical complex: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Dolati Mandana

    2007-08-01

    Full Text Available Abstract Background Polyvinyl chloride is used in production and manufacturing of many essential tools (e.g. plastic pipes, photography films, etc.. Its production is impossible without the use of vinyl chloride monomer (VCM, which can cause liver damage in long-term. In this study we intend to assess the effects of mild to moderate long term exposure to VCM on liver and to assess the importance of liver enzyme measurements as a screening tool. Methods In this study, liver enzyme levels of 52 workers were compared to 48 control workers using the T-test. The cases all worked in a PVC production unit in a petrochemical complex and the controls were randomly selected from office personnel of the same complex. A questionnaire was also filled in about information such as age, weight, work history, etc. in both groups. Results Mean comparisons for ALP and GGT using T-test showed statistically significant differences between the two groups. For AST, ALT and bilirubin (total, direct the mean was higher in the case group but this difference was not statistically significant. Discussion This study showed that mild exposure to VCM can cause mild liver cholestasis. So, using cholestasis assessment tests such as ALP and GGT should be considered in periodic assessment of liver function in PVC producing units.

  20. Concept on the pathogenesis and treatment of primary biliary cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Vasiliy Ivanovich Reshetnyak

    2006-01-01

    Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic, progressive destruction of small intrahepatic bile ducts with portal inflammation and ultimately fibrosis, leading to liver failure in the absence of treatment. Little is known about the etiology of PBC. PBC is characterized by anti-mitochondrial antibodies and destruction of intrahepatic bile ducts. The serologic hallmark of PBC is the presence of auto-antibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex (PDC). Current theories on the pathogenesis of PBC favor the hypothesis that the disease develops as a result of an inappropriate immune response following stimulation by an environmental or infectious agent. Some reports suggest that xenobiotics and viral infections may induce PBC. The pathogenetic mechanism is believed to be caused by a defect in immunologic tolerance, resulting in the activation and expansion of self-antigen specific T and B lymphocyte clones and the production of circulating autoantibodies in addition to a myriad of cytokines and other inflammatory mediators.This leads to ductulopenia and persistent cholestasis, by developing end-stage hepatic-cell failure. In this review are given our own and literary data about mechanisms of development of intrahepatic cholestasis and possible ways of its correction.

  1. Long-term therapy of a patient with summerskill-walshe-tygstrup syndrome by applying prometheus® liver dialysis: a case report.

    Science.gov (United States)

    Walensi, Mikolaj; Canbay, Ali; Witzke, Oliver; Gerken, Guido; Kahraman, Alisan

    2012-05-01

    Summerskill-Walshe-Tygstrup syndrome is a rare benign chronic liver disease characterized by recurring cholestasis with jaundice and severe pruritus. Due to insufficient conservative treatment, liver dialysis by Prometheus(®) was applied to a 45-year-old female patient with resistant pruritus. Initially, other possible liver diseases were excluded and the patient was treated symptomatically since the diagnosis of Summerskill-Walshe-Tygstrup was stated in 1998. As conservative and endoscopic methods progressively failed to relieve the patient's suffering, Prometheus(®) liver dialysis was performed regularly since 2006 at 3-month intervals and successfully led to a decrease in the patient's symptoms. Cholestatic liver enzymes and also serum bile acids could be lowered significantly from an average of 22.5 ± 2.7 to 7.3 ± 1.7 µmol/l. Consequently, Prometheus(®) liver dialysis may be a beneficial option for patients with benign recurrent intrahepatic cholestasis suffering from therapy-resistant symptoms and may be used as well as other extracorporeal liver support devices which have already been reported to improve cholestatic pruritus.

  2. Tanshinone IIA exerts protective effects in a LCA-induced cholestatic liver model associated with participation of pregnane X receptor.

    Science.gov (United States)

    Zhang, Xianxie; Ma, Zengchun; Liang, Qiande; Tang, Xianglin; Hu, Donghua; Liu, Canglong; Tan, Hongling; Xiao, Chengrong; Zhang, Boli; Wang, Yuguang; Gao, Yue

    2015-04-22

    Tanshinone IIA (Tan IIA) is one of the main natural active ingredients purified from Salvia miltiorrhiza radix, which has long been used in clinical practice in China to treat diseases including liver fibrosis, Alzheimer׳s disease, and cardiovascular diseases. Tan IIA has hepatoprotective properties, and is an efficacious PXR agonist. Our study was designed to observe the function and mechanism of the hepatoprotective properties of Tan IIA. HepG2 cells were used to investigate the vitrol effects of Tan IIA on PXR and CYP3A4. Gut-formed LCA is hepatotoxic, and has been implicated in the pathogenesis of cholestatic diseases. To further investigate the hepatoprotective mechanisms of Tan IIA against LCA-induced cholestasis in vivo, we choose the normal mice and siRNA-treated mice. The in vitro study demonstrated that the effect of Tan IIA on CYP3A4 was mediated by transactivation of PXR in a dose- and time-dependent manner. The in vivo experiments using PXR siRNA revealed that Tan IIA could protect against LCA-induced hepatotoxicity and cholestasis in a dose-dependent manner. These effects were partially caused by the upregulation of PXR, as well as Cyp3a11, Cyp3a13, and Mdr1, which are the enzymes responsible for LCA metabolism. This is the first report showing that the hepatoprotective effects of Tan IIA are partly mediated by PXR.

  3. 体质性高胆红素血症及其分子诊断%Hereditary hyperbilirubinemia and its molecular diagnosis

    Institute of Scientific and Technical Information of China (English)

    周艳; 揭盛华

    2011-01-01

    体质性高胆红素血症是由常染色体遗传变异引起某些酶代谢缺陷所致的胆红素代谢异常,包括Gilbert综合征(gilbert syndrome,GS)、Crigler-Najjar综合征(crigler-Najjar syndrome,CNS)、Lucey-driscoll综合征(luceydriscoll syndrome,LDS)、Dubin-Johnson综合征(dubin-johnson syndrome,DJS)、Rotor综合征(rotor syndrome,RS)及进行性家族性肝内胆汁淤积症(progressive familial intrahepatic cholestasis,PFIC)-.本文就几种体质性高胆红素血症的分子基础及检测方法作一综述.%Hereditary hyperbilirubinemia is caused by genetic defects in the enzymes that control bili-rubin metabolism. It includes Gilbert syndrome (GS), Crigler-Najjar syndrome (CNS), Lucey-Driscoll syndrome (LDS), Dubin-Johnson syndrome (DJS), Rotor syndrome (RS) and progressive familial intrahepatic cholestasis (PFIC). This literature review covers the molecular basis of and laboratory detection methods for hereditary hyperbilirubinemia.

  4. Acute renal failure in obstructive diseases of the extrahepatic biliary ducts.

    Science.gov (United States)

    Acalovschi, I; Chirileanu, T

    1984-01-01

    A series of 46 patients with obstructive disease of the bile ducts complicated by acute renal failure (ARF) is presented. The patients exhibited obstructive jaundice with prevalence of conjugated bilirubine. In 80% of the cases biliary obstruction was associated with cholangitis. Disturbances of the liver function (from mild cholestasis to biliary cirrhosis) were also present. The renal damage was due to biliary disorders and was either present on admission (33 cases) or developed postoperatively (13 cases). Most of the patients presented nonoliguric ARF as well as poor perfusion resulting from decreased circulating blood volume (dehydration and electrolyte loss). Among the criteria used to determine the type of ARF, the urinary/plasma creatinine ratio less than 10 and urinary/plasma osmolarity ratio less than 1.1 were the most valuable. Management of ARF by dialysis alone was not satisfactory. Attention is called to the surgical treatment of the biliary disorder as being essential to prognosis. Patients not treated by radical surgery died in proportion of 87 to 100%. From the rest of 18 patients in whom the operation provided an adequate biliary drainage, in 15 the renal function was restored and 12 survived. Better prognosis in these patients was dependent not only on the ability to cure the cholestasis and infection, but on the early surgical treatment. The ultimate prognosis depends on the improvement of the liver function.

  5. Dexamethasone pretreatment attenuates lung and kidney injury in cholestatic rats induced by hepatic ischemia/reperfusion.

    Science.gov (United States)

    Zhou, Liangyi; Yao, Xiangqing; Chen, Yanling

    2012-02-01

    Hepatic ischemia followed by reperfusion (IR) results in mild to severe organ injury, in which tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) seem to be involved. Thus, we aim to assess the influence of hepatic ischemia/reperfusion injury on remote organs in addition to cholestasis and consider the possible efficacy of steroid pretreatment in reducing the injury. A common bile duct ligation model was done on 24 male Sprague-Dawley rats. After 7 days, the rats were divided randomly into control group, IR group, and dexamethasone (DEX) group. The IR group showed significant increases in serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels compared with the control and DEX groups. By ELISA techniques, higher levels of TNF-α and IL-1β in lung and kidney tissues were measured in the IR group than in the control and DEX groups, these were verified by immunohistochemistry. The lung histology of the IR group rats showed neutrophil infiltration, interstitial edema, and alveolar wall thickening. Kidney histology of the IR group rats showed vacuolization of the proximal tubular epithelial cells and tubular dilatation with granular eosinophilic casts. Better morphological aspects were observed in the DEX-pretreated animals. Minimal lesions were observed in the control. The results suggest that hepatic ischemia/reperfusion injury in cholestatic rats induced lung and kidney injuries. Pretreatment with dexamethasone reduced the IR-induced injury in addition to cholestasis.

  6. Clinical and morphological variants of hepatitis onset with congenital cytomegalovirus and hepatitis C infection

    Directory of Open Access Journals (Sweden)

    R. A. Ushakova

    2013-01-01

    Full Text Available We present comparative analysis of clinical – morphological data from infants with congenital cytomegalovirus and hepatitis C infection. 97 patients with hepatitis underwent a standard set of clinical and laboratory tests. ELISA and PCR were used to verify infectious agents. Informed consent to perform a liver biopsy was obtained from the parents of 28 children. immunohistochemical test of the liver samples managed to identify markers of cytomegalovirus (protein pp65 and p52 and hepatitis C (helicase NS3. The hepatitis C virus was detected in 41 patients: 3a genotype – 68.3%, 1b –31.7% respectively. Congenital hepatitis C onset presents itself as mild and atypical and causes chronic hepatitis with the 1st degree fibrosis. Cytomegalovirus replication markers were found in 56 children. The most common manifestations of hepatitis associated with cytomegalovirus infection are prolonged jaundice, cholestasis, gepatolienalny syndrome, early onset of the disease with increased transaminase levels and dominance in AST. Structural changes of the liver are characterized by the presence of inflammatory infiltration, cholestasis with duktulopenia, lobular structure damage. Congenital cytomegalovirus-related hepatitis is likely to result in liver cirrhosis and is associated with poor prognosis.

  7. Cytokines and Liver Diseases

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    Herbert Tilg

    2001-01-01

    Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

  8. Novel insight into mechanisms of cholestatic liver injury

    Institute of Scientific and Technical Information of China (English)

    Benjamin L Woolbright; Hartmut Jaeschke

    2012-01-01

    Cholestasis results in a buildup of bile acids in serum and in hepatocytes.Early studies into the mechanisms of cholestatic liver injury strongly implicated bile acidinduced apoptosis as the major cause of hepatocellular injury.Recent work has focused both on the role of bile acids in cell signaling as well as the role of sterile inflammation in the pathophysiology.Advances in modern analytical methodology have allowed for more accurate measuring of bile acid concentrations in serum,liver,and bile to very low levels of detection.Interestingly,toxic bile acid levels are seemingly far lower than previously hypothesized.The initial hypothesis has been based largely upon the exposure of μmol/L concentrations of toxic bile acids and bile salts to primary hepatocytes in cell culture,the possibility that in vivo bile acid concentrations may be far lower than the observed in vitro toxicity has far reaching implications in the mechanism of injury.This review will focus on both how different bile acids and different bile acid concentrations can affect hepatocytes during cholestasis,and additionally provide insight into how these data support recent hypotheses that cholestatic liver injury may not occur through direct bile acid-induced apoptosis,but may involve largely inflammatory cell-mediated liver cell necrosis.

  9. Elevated copper impairs hepatic nuclear receptor function in Wilson’s disease

    Science.gov (United States)

    Wooton-Kee, Clavia Ruth; Jain, Ajay K.; Wagner, Martin; Grusak, Michael A.; Finegold, Milton J.; Lutsenko, Svetlana; Moore, David D.

    2015-01-01

    Wilson’s disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b–/– mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the nuclear receptors FXR, RXR, HNF4α, and LRH-1 to promoter response elements and decreased mRNA expression of nuclear receptor target genes in Atp7b–/– mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired nuclear receptor activity. Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels. PMID:26241054

  10. Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells

    Science.gov (United States)

    Imagawa, Kazuo; Takayama, Kazuo; Isoyama, Shigemi; Tanikawa, Ken; Shinkai, Masato; Harada, Kazuo; Tachibana, Masashi; Sakurai, Fuminori; Noguchi, Emiko; Hirata, Kazumasa; Kage, Masayoshi; Kawabata, Kenji; Sumazaki, Ryo; Mizuguchi, Hiroyuki

    2017-01-01

    Bile salt export pump (BSEP) plays an important role in hepatic secretion of bile acids and its deficiency results in severe cholestasis and liver failure. Mutation of the ABCB11 gene encoding BSEP induces BSEP deficiency and progressive familial intrahepatic cholestasis type 2 (PFIC2). Because liver transplantation remains standard treatment for PFIC2, the development of a novel therapeutic option is desired. However, a well reproducible model, which is essential for the new drug development for PFIC2, has not been established. Therefore, we attempted to establish a PFIC2 model by using iPSC technology. Human iPSCs were generated from patients with BSEP-deficiency (BD-iPSC), and were differentiated into hepatocyte-like cells (HLCs). In the BD-iPSC derived HLCs (BD-HLCs), BSEP was not expressed on the cell surface and the biliary excretion capacity was significantly impaired. We also identified a novel mutation in the 5′-untranslated region of the ABCB11 gene that led to aberrant RNA splicing in BD-HLCs. Furthermore, to evaluate the drug efficacy, BD-HLCs were treated with 4-phenylbutyrate (4PBA). The membrane BSEP expression level and the biliary excretion capacity in BD-HLCs were rescued by 4PBA treatment. In summary, we succeeded in establishing a PFIC2 model, which may be useful for its pathophysiological analysis and drug development. PMID:28150711

  11. Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells.

    Science.gov (United States)

    Imagawa, Kazuo; Takayama, Kazuo; Isoyama, Shigemi; Tanikawa, Ken; Shinkai, Masato; Harada, Kazuo; Tachibana, Masashi; Sakurai, Fuminori; Noguchi, Emiko; Hirata, Kazumasa; Kage, Masayoshi; Kawabata, Kenji; Sumazaki, Ryo; Mizuguchi, Hiroyuki

    2017-02-02

    Bile salt export pump (BSEP) plays an important role in hepatic secretion of bile acids and its deficiency results in severe cholestasis and liver failure. Mutation of the ABCB11 gene encoding BSEP induces BSEP deficiency and progressive familial intrahepatic cholestasis type 2 (PFIC2). Because liver transplantation remains standard treatment for PFIC2, the development of a novel therapeutic option is desired. However, a well reproducible model, which is essential for the new drug development for PFIC2, has not been established. Therefore, we attempted to establish a PFIC2 model by using iPSC technology. Human iPSCs were generated from patients with BSEP-deficiency (BD-iPSC), and were differentiated into hepatocyte-like cells (HLCs). In the BD-iPSC derived HLCs (BD-HLCs), BSEP was not expressed on the cell surface and the biliary excretion capacity was significantly impaired. We also identified a novel mutation in the 5'-untranslated region of the ABCB11 gene that led to aberrant RNA splicing in BD-HLCs. Furthermore, to evaluate the drug efficacy, BD-HLCs were treated with 4-phenylbutyrate (4PBA). The membrane BSEP expression level and the biliary excretion capacity in BD-HLCs were rescued by 4PBA treatment. In summary, we succeeded in establishing a PFIC2 model, which may be useful for its pathophysiological analysis and drug development.

  12. Endoscopic management of biliary fascioliasis: a case report

    Directory of Open Access Journals (Sweden)

    Kasnazani Kalandar A

    2010-03-01

    Full Text Available Abstract Introduction Fasciola hepatica, an endemic parasite common in Iraq and its neighboring countries, is a very rare cause of cholestasis worldwide. Humans can become definitive hosts of this parasite through their ingestion of a contaminated water plant, for example, contaminated watercress. Symptoms of cholestasis may appear suddenly and, in some cases, are preceded by long periods of fever, eosinophilia, and vague gastrointestinal symptoms. Here we report the case of a woman with a sudden onset of symptoms of cholangitis. Her infection was proved by endoscopic retrograde cholangiography to be due to Fasciola hepatica infestation. Case presentation A 38-year-old Kurdish woman from the northern region of Iraq presented with fever, right upper quadrant abdominal pain, and jaundice. An examination of the patient revealed elevated total serum bilirubin and liver enzymes. An ultrasonography also showed a dilatation of her common bile duct. During endoscopic retrograde cholangiopancreatography, a filling defect was identified in her common bile duct. After sphincterotomy and balloon extraction, one live Fasiola hepatica was extracted and physically removed. Conclusion Fasciola hepatica should be a part of the differential diagnosis of common bile duct obstruction. When endoscopic retrograde cholangiopancreatography is available, the disease can be easily diagnosed and treated.

  13. Evaluation Of Gonadotropin And Testosterone Hormons In Adult Male Cholestatic Rats

    Directory of Open Access Journals (Sweden)

    Nasiri E

    2003-11-01

    Full Text Available Obstructive cholestasis is associated with overproduction of endogenous opioids (EOP, nitric oxide (NO, and cytokins in the blood streams. Therefore we investigated the relationship between obstructive cholestasis and function of germ cells in adult male rats."nMaterial and Methods: To study this, we used three groups of animals: No-surgery, Sham-surgery, and surgical ligation of the bile duct. After 3 weeks all animal were killed by ether, serum concentrations of FSH, LH and testosterone were determined by Radioimmunoassay, apoptosis was evaluated by DNA fragmentation detected by in situ terminal deoxynucloetidyl Transfrase-mediated dUTP nike end labeling (TUNEL."nResults: The mean of FSH level in cholestatic, control and sham groups were 13.22+ 1.038, 18.14+ 1.276, and 16.92+ 1.072 ng/ml, respectively. The mean of LH level in cholestatic, control and sham groups were 0.83 + 0.21, 2.058 ± 0.26, and 1.84 + 0.17 ng/ml, respectively. In addition, the mean of testosterone level in cholestatic, control and sham groups were 1.52 ± 0.16, 2.41 ± 0.18, and 2.31 + 0.14 ng/ml, respectively. The results of this study were indicated that serum FSH, LH and testosterone were significantly lower in cholestatic than control and sham groups (p=0.0195, P= 0.0029, and P=0.0023, respectively. However there was no significant difference in apoptotic index between all of groups (P=0.195. The apoptotic index in cholestatic, control and sham rats were 9.897± 1.374, 7.086 + 0.91, and 7.729 + 1.101, respectively. "nConclusion: These findings have been shown which as obstructive cholestasis was decreased the levels of serum gonadotropins and testosterone but it has no significant effector testicular germinal cells apoptosis."n"n"n"n 

  14. [Animal experiments with 99mTc-diethyl-HIDA in acute complete bile duct occlusion (author's transl)].

    Science.gov (United States)

    Bähre, M; Biersack, H J; Breuel, H P; Degen, H; Busch, F; Grouls, V; Lindstaedt, H; Thelen, M

    1979-10-01

    In order to establish whether a complete obstructive jaundice can abolish the accumulation of diethyl-HIDA (EHIDA) in the liver parenchyma, the common bile duct was ligated in 14 mongrel dogs. Before as well as at regular intervals after ligature of the common bile duct, a sequence scintigraphy was performed with 2 mCi 99mTc-EHIDA. For evaluation, time-activity curves (Tmax, T1/2), and analogue scintigrams as well as laboratory parameters were used for assessment. Up to seven weeks after ligation of the common bile duct, there was a marked accumulation of EHIDA in the liver parenchyma. The relative liver uptake (liver/background ratio) fell from 8.9 to 2.7, whereas conversely the cholestasis indicators aP and bilirubine rose markedly. Tmax did not show any significant alterations, whereas T1/2 was prolonged from about one week after ligation. Because of the duct ligation, there was no excretion of activity into the intestines. Immediately after ligation of the common bile duct, the gallbladder was shown up as a "hot" area in which the majority of the applied activity appeared from about one hour p.i. Begining with the fifth to the seventh day after ligation, the gallbladder was seen as a "cold" area in the liver paraenchyma. Bilirubine and aP were raised by about 50 times the initial value. With longer lasting cholestasis, the scintigram no longer altered whereas bilirubine and aP rose further. Histological examination after ligation for more than five weeks showed slight alterations as a whole. Gamma-GT and in particular GPT were likewise slightly raised compared to bilirubine and aP. The conclusion was drawn from this that the good accumulation of EHIDA in the liver parenchyma which is to be observed without exception even in cholestasis lasting for several weeks could be explained by a relatively slight hepatocellular damage. Only when there is a consecutive parenchymal damage in extrahepatic jaundice, accumulation of EHIDA in the liver can be abolished.

  15. Fulminant Wilson's Disease Managed with Plasmapheresis as a Bridge to Liver Transplant.

    Science.gov (United States)

    Hilal, Talal; Morehead, R Scott

    2014-01-01

    New-onset jaundice can be a manifestation of multiple pathologic processes including hemolysis, parenchymal liver disease, and cholestasis; the differential diagnosis is broad and requires a systematic approach. We report a case of a patient who presented with jaundice after starting minocycline for the treatment of acne vulgaris and rapidly developed fulminant liver failure found to be due to Wilson's disease. She also manifested severe Coomb's negative hemolytic anemia and renal failure secondary to hepatorenal syndrome. As a bridge to liver transplant, she was successfully treated with plasmapheresis to decrease serum copper in addition to hemodialysis for acidosis and hyperkalemia. She was able to receive a liver and made a full recovery. The case highlights the use of plasmapheresis as an adjunctive treatment modality in cases of fulminant liver failure due to Wilson's disease.

  16. Reversion of severe hepatopulmonary syndrome in a non cirrhotic patient after corticosteroid treatment for granulomatous hepatitis: A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Nikolaos Tzovaras; Aggelos Stefos; Sarah P Georgiadou; Nikolaos Gatselis; Georgia Papadamou; Eirini Rigopoulou; Maria Ioannou; Ioannis Skoularigis; Georgios N Dalekos

    2006-01-01

    Hepatopulmonary syndrome (HPS) is defined as a clinical triad including liver disease, abnormal pulmonary gas exchange and evidence of intrapulmonary vascular dilatations. We report a 61-year-old male presented with fatigue, long-lasting fever, loss of weight, signs of portal hypertension, hepatosplenomegaly, cholestasis and progressive dyspnoea over the last year. Clinical, laboratory and histological findings confirmed the diagnosis of granulomatous hepatitis. HPS due to hepatic granulomainduced portal hypertension was proved to be the cause of severe hypoxemia of the patient as confirmed by contrast-enhanced echocardiography. Reversion of HPS after corticosteroid therapy was confirmed by a new contrastenhanced echocardiography along with the normalization of cholestatic enzymes and improvement of the patient's conditions. This is the first case of complete reversion of HPS in a non-cirrhotic patient with hepatic granuloma,indicating that intrapulmonary shunt in liver diseases is a functional phenomenon and HPS can be developed even in miscellaneous liver involvement as in this case.

  17. Scrub typhus hepatitis confirmed by immunohistochemical staining

    Institute of Scientific and Technical Information of China (English)

    Jong-Hoon Chung; Sung-Chul Lim; Na-Ra Yun; Sung-Heui Shin; Choon-Mee Kim; Dong-Min Kim

    2012-01-01

    Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi (O.tsutsugamushi).We report herein the case of a woman who presented with fever and elevated serum levels of liver enzymes and who was definitively diagnosed with scrub typhus by histopathological examination of liver biopsy specimens,serological tests and nested polymerase chain reaction.Immunohistochemical staining using a monoclonal anti-O.tsutsugamushi antibody showed focally scattered positive immunoreactions in the cytoplasm of some hepatocytes.This case suggests that scrub typhus hepatitis causes mild focal inflammation due to direct liver damage without causing piecemeal necrosis or interface hepatitis.Thus,scrub typhus hepatitis differs from acute viral hepatitis secondary to liver damage due to host immune responses,which causes severe Iobular disarray with diffuse hepatocytic degeneration,necrosis and apoptosis as well as findings indicative of hepatic cholestasis,such as hepatic bile plugs or brown pigmentation of hepatocytes.

  18. Life-threatening intracranial bleeding in a newborn with congenital cytomegalovirus infection: late-onset neonatal hemorrhagic disease.

    Science.gov (United States)

    Dallar, Yildiz; Tiras, Ulku; Catakli, Tulin; Gulal, Gonul; Sayar, Yavuz; Selvar, Beray; Alioglu, Bulent

    2011-02-01

    The authors present a case of a 36-day-old infant with intracranial and intramuscular hemorrhage due to vitamin K deficiency bleeding, who received intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent with vitamin K deficiency abnormality. Serological analyses showed that cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The infant was treated successfully with intravenous ganciclovir and blood products. This case suggests that it is imperative to meticulously investigate the etiology in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver disease caused by congenital cytomegalovirus infection should be in mind in term infants who presented with late-onset hemorrhagic disease.

  19. Alpha1-antitrypsin deficiency with fatal intracranial hemorrhage in a newborn.

    Science.gov (United States)

    Israels, S J; Gilfix, B M

    1999-01-01

    A 4-week-old boy had a fatal intracranial hemorrhage resulting from vitamin K deficiency. The infant had received no vitamin K prophylaxis and was exclusively breastfed. At autopsy, examination of the liver showed cholestasis and fibrosis. DNA was isolated from a blood spot on a Gutherie sample card obtained from the infant for routine metabolic screening. This DNA was used for alpha1-antitrypsin genotyping studies. Genotyping studies identified homozygosity for the point mutation 9989G-->A, confirming a diagnosis of alpha1-antitrypsin deficiency (ZZ phenotype), and resulted in appropriate screening of siblings born after this child's death. Alpha1-antitrypsin deficiency should be considered in the differential diagnosis of infants with late hemorrhagic disease of the newborn. Use of blood from the metabolic screening card as a source of DNA allowed confirmation of this diagnosis after the infant's death.

  20. Severe iron overload and hyporegenerative anemia in a case with rhesus hemolytic disease: therapeutic approach to rare complications

    Directory of Open Access Journals (Sweden)

    Fatih Demircioğlu

    2010-09-01

    Full Text Available A 33 weeks’ gestation, a baby with rhesus hemolytic disease (RHD, who had received intrauterine transfusions twice, developed cholestatic hepatic disease and late hyporegenerative anemia. Her serum ferritin and bilirubin levels increased to 8842 ng/ml and 17.9 mg/dl, respectively. Liver biopsy showed cholestasis and severe iron overload. Treatment with recombinant erythropoietin (rHuEPO decreased the transfusion need, and intravenous deferoxamine resulted in a marked decreased in serum ferritin levels and normalization of liver function. In patients who have undergone intrauterine transfusions due to RHD, hyperferritinemia and late hyporegenerative anemia should be kept in mind. Chelation therapy in cases with symptomatic hyperferritinemia and rHuEPO treatment in cases with severe hyporegenerative anemia should be considered.

  1. Zschokkella icterica sp. nov. (Myxozoa, Myxosporea), a pathogen of wild rabbitfish Siganus luridus (Ruppell, 1829) from the Red Sea.

    Science.gov (United States)

    Diamant, A; Paperna, H

    1992-02-21

    Zschokkella icterica sp. nov. is described from the liver and gall bladder of wild rabbitfish Siganus luridus from the Red Sea. This coelozoic myxosporean produces large (300 × 400 μm) Plasmodia that inhabit the hepatic bile ducts. The species is disporoblastic and pansporoblast forming. Small plasmodia are found in the gall bladder. Spores average 9.9 urn in length, 5.8 μm in width and 3.5 um in thickness, and the polar filament has 3-4 coils. It is suggested that the hepatic bile ducts are the primary target organ, their blockage by the parasite producing cholestasis and duct breakdown. In severe infections, invasion of the liver parenchyma by the parasite occurred. In these cases, the infection was often associated with massive hepatic necrosis, ascites and jaundice.

  2. The Src family kinases: distinct functions of c-Src, Yes, and Fyn in the liver.

    Science.gov (United States)

    Reinehr, Roland; Sommerfeld, Annika; Häussinger, Dieter

    2013-04-01

    The Src family kinases Yes, Fyn, and c-Src play a pivotal role in regulating diverse liver functions such as bile flow, proteolysis, apoptosis, and proliferation and are regulated by anisoosmotic cell volume changes, death receptor ligands, and bile acids. For example, cell swelling leads to an integrin-sensed and focal adhesion kinase-mediated activation of c-Src-triggering choleresis, proteolysis inhibition, regulatory volume decrease via p38MAPK and proliferation via the activation of the epidermal growth factor receptor and extracellular regulated kinases 1 and 2. In contrast, hepatocyte shrinkage generates an almost instantaneous oxidative stress response that triggers the activation of c-Jun N-terminal kinase and the Src family kinases Fyn and Yes. Whereas Fyn activation mediates cholestasis, Yes triggers CD95 activation and apoptosis. This review will discuss the role of Src family kinases in the regulation of liver function with emphasis on their role in osmo-signaling and bile acid signaling.

  3. Liver Hydatid Cyst and Acute Cholangitis: a Case Report.

    Science.gov (United States)

    Nemati Honar, Behzad; Hayatollah, Gholamhossein; Nikshoar, Mohammadreza; Forootan, Mojgan; Feizi, Ali Mohammad

    2016-04-01

    Amongst the cause of cystic hepatic disease, hydatid cyst is common in the Asia, South America, and Africa. The definitive therapy for hepatic hydatid disease is surgical resection. Rupture of the hydatid cyst into the biliary tree can lead to serious cholangitis. In this report, a 22-year-old man is presented with the signs and symptoms of obstructive jaundice and cholangitis. Ultrasonography reported dilated common bile duct (CBD) with sludge and stones, a hydatid cyst adjacent to the gall bladder and mild thickening of gallbladder wall without a stone. MRCP revealed dilated CBD with a cyst in segment fifth of liver. Due to signs and symptoms of obstructive jaundice in addition to lab data and imaging modalities, the ruptured hydatid cyst into a biliary tree was considered, and surgical intervention was performed to extract daughter vesicles from the CBD. Post intervention, signs and symptoms and cholestasis enzymes were subsided.

  4. [Chronic active hepatitis: clinical, biochemical, and histopathologic correlation].

    Science.gov (United States)

    Subauste, M C

    1989-01-01

    A retrospective study over 26 female patients with chronic active hepatitis was made. The mean age was 39 years old, the mean length of illness of 8 months; 5 patients had positive markers for hepatitis B. Patients were selected with the grade of histological activity: 8 patients had a mild form from disease (2A) and 16 with a severe one (2B). The predominant group was 2B. Severe inflammatory infiltration was the hallmark and multiobulillar necrosis, bridging, eosinophils and hiperplasia of kuppfer cells were found only in this group. Clinical features range from hepatic manifestations to systemic ones. Chronic active hepatitis may present with cholestasis, but the latter is not always related with the grade of activity. Group 2B had elevated aminotransferases and a low concentration for protrobine.

  5. Idiopathic cholangiopathy in a biliary cast syndrome necessitating liver transplantation following head trauma.

    Science.gov (United States)

    Byrne, Michael F; Chong, Hon I; O'Donovan, Deidre; Sheehan, Katherine M; Leader, Mary B; Kay, Elaine; McCormick, P Aiden; Broe, Patrick; Murray, Frank E; McCormack, Aiden

    2003-04-01

    The development of total biliary casts is very unusual, especially in patients who have not undergone liver transplantation. The aetiology of these casts is uncertain but several factors are believed to play a role, including periods of fasting, haemolysis, cholangitis and recent surgery. Resultant bile stasis and/or gallbladder hypocontractility promote sludge and subsequent stone formation. Here we present the case of a previously well 66-year-old woman who developed a total biliary cast several weeks after being involved in a road traffic accident during which she sustained head injuries but no obvious liver insult. This cast was removed at laparotomy but the patient had resultant diffuse biliary tree abnormalities and persistent cholestasis and subsequently required a liver transplant. The possible aetiologies of biliary cast formation and subsequently cholangiopathy necessitating transplantation in this patient are described.

  6. Primary sclerosing cholangitis and pregnancy

    Directory of Open Access Journals (Sweden)

    Casper Q. Kammeijer

    2011-08-01

    Full Text Available Primary sclerosing cholangitis is a progressive disease, and coincidentally in pregnancy it is rare. It is characterized by progressive inflammation and destruction of bile ducts finally resulting in liver failure. A rare case of primary sclerosing cholangitis in pregnancy is presented. The course of the pregnancy was marked by threatened preterm delivery and exacerbation of cholestasis. She was successfully treated with ursodeoxycholic acid (UDCA. Although, primary sclerosing cholangitis has both maternal and fetal effects on pregnancy, the overall outcome is favorable. Only few cases have been reported using high dose ursodeoxycholic acid for primary sclerosing cholangitis in pregnancy, it often improves pruritus but has no protection against stillbirth. Data on the safety to the fetus or neonate and long-term outcome are scarce.

  7. An autopsy case showing massive fibrinoid necrosis of the portal tracts of the liver with cholangiographic findings similar to those of primary sclerosing cholangitis

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Hano; Ichiro Takagi; Keisuke Nagatsuma; Tomoe Lu; Chenxi Meng; Satoru Chiba

    2007-01-01

    An 81-year-old Japanese man with jaundice was strongly suspected clinically of having primary sclerosing cholangitis based on clinical examinations and later died of hepatic failure. The entire course of the disease lasted about 10 mo. The autopsy revealed extensive fibrinoid necrosis in the liver, kidney, spleen, pancreas,lung, lymph nodes, and pleura. Particularly extensive fibrinoid necrosis in the portal tracts of the liver induced severe stenoses of the intrahepatic bile ducts, resulting in cholestasis in association with prominent liver injury.There were no findings indicating primary sclerosing cholangitis. The hepatic lesions in this case did not coincide with any known disease including collagen diseases. To clarify the cause of irregular stenoses of the intrahepatic biliary trees on cholangiographic findings, we postulate that some form of immunological derangement might be involved in pathogenesis of fibrinoid necrosis.However, the true etiology remains unknown.

  8. Glucocorticosteroids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Giljaca, Vanja; Poropat, Goran; Stimac, Davor

    2010-01-01

    Primary sclerosing cholangitis is a chronic cholestatic disease of intrahepatic and extrahepatic biliary ducts, characterised by chronic periductal inflammation and sclerosis of the ducts, which results in segmental stenoses of bile ducts, cholestasis, fibrosis, and ultimately, liver cirrhosis....... Patients with primary sclerosing cholangitis are at higher risk of cholangiocarcinoma as well as of colonic neoplasia, since primary sclerosing cholangitis is associated with inflammatory bowel disease in more than 80% of the patients. Several therapeutic modalities have been proposed for primary...... sclerosing cholangitis, like ursodeoxycholic acid, glucocorticosteroids, and immunomodulatory agents, but none has been successful in reversing the process of the disease. To date, liver transplantation is the only definite therapeutic solution for patients with advanced primary sclerosing cholangitis...

  9. Biliary Cast Formation with Sclerosing Cholangitis in Critically Ill Patient: Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, O Nyoung; Park, Chang Keun [Daegu Fatima Hospital, Daegu (Korea, Republic of); Cho, Seung Hyun [Kyungpook National University, School of Medicine, Daegu (Korea, Republic of); Mun, Sung Hee [Catholic University of Daegu, School of Medicine, Daegu (Korea, Republic of)

    2012-06-15

    Sclerosing cholangitis in critically ill patients (SC-CIP) is a rare condition that is not familiar to many radiologists. In addition, the associated imaging findings have not been described in the radiological literature. We report a case of biliary cast formation with SC-CIP and describe the radiological findings of CT, magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiography (ERC). A diagnosis of SC-CIP should be considered in intensive care unit (ICU) patients with persistent cholestasis during or after a primary illness. The typical CT, MRCP and ERC findings include new biliary casts in the intrahepatic duct with multiple irregular strictures, dilatations, and relative sparing of the common bile duct.

  10. Effect of living donor liver transplantation on outcome of children with inherited liver disease and hepatocellular carcinoma.

    Science.gov (United States)

    Ozçay, Figen; Canan, Oğuz; Bilezikçi, Banu; Torgay, Adnan; Karakayali, Hamdi; Haberal, Mehmet

    2006-01-01

    We described six children with heritable liver disease and hepatocellular carcinoma treated with living-related liver transplantation. Underlying liver diseases were type-1 tyrosinemia (three patients), progressive familial intrahepatic cholestasis type II (two patients), and Wilson's disease (one patient). Two of the tumors were found incidentally during liver transplantation. Number of nodules was 12, 15, 3, 2, and 1 (in two patients). Three patients were treated with chemotherapy before the procedure. Chemotherapy was not given to any patient after liver transplantation. The mean follow-up was 17.7 +/- 6 months (range: 7-24). All patients are tumor recurrence free. Both graft and patient survival rates are 100% at a median of 18.5 months follow-up. Physicians in charge of treating children with heritable liver disease should screen them periodically for the development of hepatocellular carcinoma. Liver transplantation may offer these children better survival rates.

  11. BONE TURNOVER AND MINERAL DENSITY OF THE LUMBAR VERTEBRAE IN WOMEN WITH PRIMARY BILIARY CIRRHOSIS BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    I. A. Pronchenko

    2013-01-01

    Full Text Available Aim. To elucidate the role of cholestasis and menopausal status in the development of osteoporosis in women with primary biliary cirrhosis (PBC before and after orthotopic liver transplantation (OLT. Methods and re- sults. There were fulfilled 74 estimations of biochemical markers of bone metabolism, estrogen (E2, parathy- roid hormone (PTH endogenous secretion so as mineral content of lumbar vertebras in 21 women with PBC (10 women before and 17 in different terms after OLT. Bone turnover disturbances were characterized by delay of bone formation associated with hyperbilirubinaemia before OLT while increased bone turnover following OLT. Bone resorption markers correlated inversely with E2 in postmenopausal women and positively with PTH in premenopausal women. Conclusion. Bone wastes degree depended on hard and duration of disease before OLT so as menopausal status after OLT. In postmenopausal women bone wastes were associated with degree of endogenous E2 decreasing, increased bone turnover, and graft dysfunction. 

  12. Fibrosing cholestatic hepatitis following cytotoxic chemotherapy for small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jaime Ceballos-Viro; José M López-Picazo; José L Pérez-Gracia; Jesús J Sola; Gregorio Aisa; Ignacio Gil-Bazo

    2009-01-01

    Fibrosing cholestatic hepatitis (FCH) is a variant of viral hepatitis reported in hepatitis B virus or hepatitis C virus infected liver, renal or bone transplantation recipients and in leukemia and lymphoma patients after conventional cytotoxic chemotherapy. FCH constitutes a well-described form of fulminant hepatitis having extensive fibrosis and severe cholestasis as its most characteristic pathological findings. Here, we report a case of a 49-year-old patient diagnosed with small-cell lung cancer who developed this condition following conventional chemotherapy-induced immunosuppression. This is the first reported case in the literature of FCH after conventional chemotherapy for a solid tumor. In addition to a detailed report of the case, a physiopathological examination of this potentially life-threatening condition and its treatment options are discussed.

  13. Hemophagocytic Lymphohistiocytosis, an Unclear Nosologic Entity: Case Report of an Adult Man with Rising of Amylase and Lipase and Spinal Cord Infiltration

    Science.gov (United States)

    Perrone, Antonio; Agosti, Pasquale; Boccuti, Viera; Campobasso, Anna; Sabbà, Carlo

    2017-01-01

    Here we present the case of a 57-years old patient affected by hemophagocytic lymphohistiocytosis (HLH), a rare disease characterized by an uncontrolled immune activation, resulting in clinical and biochemical manifestations of extreme inflammation. In a previous hospitalization, the patient showed fever, hepato-splenomegaly, pancytopenia, hyperferrtitinemia, lymphadenopathy and cholestasis. No diagnosis was done, however, he totally recovered after splenectomy. Eight months later, he relapsed, showing also hypofibrinogenemia, hypertriglyceridemia, hemophagocytic signs in bone marrow, cholestatic jaundice, high LDH and high PT-INR. Interestingly, he presented increased levels of amylase and lipase in absence of radiologic signs of pancreatitis. He was treated with Dexamethasone and Cyclosporine according to HLH-2004 guidelines. The clinical and biochemical manifestations disappeared in a few weeks, but he was newly hospitalized for lower limbs hypotonia caused by a hemophagocytic lesion of the cauda equina and lumbar cord. The death occurred in a few days, despite the immunosuppressive treatment. PMID:28286628

  14. Selective screening of 650 high risk Iranian patients for detection of inborn error of metabolism

    Directory of Open Access Journals (Sweden)

    Narges Pishva

    2015-02-01

    Full Text Available Objective: Although metabolic diseases individually are rare ,but overall have an incidence of 1/2000 and can cause devastating and irreversible effect if not diagnosed early and treated promptly. selective screening is an acceptable method for detection of these multi presentation diseases. Method: using panel neonatal screening for detection of metabolic diseases in 650 high risk Iranian patients in Fars province. The following clinical features were used as inclusion criteria for investigation of the patients. Lethargy, poor feeding ,persistent vomiting, cholestasis, intractable seizure ,decreased level of consciousness ,persistent hypoglycemia, unexplained acid base disturbance and unexplained neonatal death. Result: Organic acidemia with 40 cases (42% was the most frequent disorder diagnosed in our high risk populations, followed by disorder of galactose metabolism(30%, 15 patient had classic galactosemia(GALT

  15. Hemophagocytic Lymphohistiocytosis, an Unclear Nosologic Entity: Case Report of an Adult Man with Rising of Amylase and Lipase and Spinal Cord Infiltration.

    Science.gov (United States)

    Sangineto, Moris; Perrone, Antonio; Agosti, Pasquale; Boccuti, Viera; Campobasso, Anna; Sabbà, Carlo

    2017-02-23

    Here we present the case of a 57-years old patient affected by hemophagocytic lymphohistiocytosis (HLH), a rare disease characterized by an uncontrolled immune activation, resulting in clinical and biochemical manifestations of extreme inflammation. In a previous hospitalization, the patient showed fever, hepato-splenomegaly, pancytopenia, hyperferrtitinemia, lymphadenopathy and cholestasis. No diagnosis was done, however, he totally recovered after splenectomy. Eight months later, he relapsed, showing also hypofibrinogenemia, hypertriglyceridemia, hemophagocytic signs in bone marrow, cholestatic jaundice, high LDH and high PT-INR. Interestingly, he presented increased levels of amylase and lipase in absence of radiologic signs of pancreatitis. He was treated with Dexamethasone and Cyclosporine according to HLH-2004 guidelines. The clinical and biochemical manifestations disappeared in a few weeks, but he was newly hospitalized for lower limbs hypotonia caused by a hemophagocytic lesion of the cauda equina and lumbar cord. The death occurred in a few days, despite the immunosuppressive treatment.

  16. TAK1: Another mesh in the NF-κB - JNK controlled network causing hepatocellular carcinoma.

    Science.gov (United States)

    Greten, Florian R

    2011-09-01

    The MAP3-kinase TGF-beta-activated kinase 1 (TAK1) critically modulates innate and adaptive immune responses and connects cytokine stimulation with activation of inflammatory signaling pathways. Here, we report that conditional ablation of TAK1 in liver parenchymal cells (hepatocytes and cholangiocytes) causes hepatocyte dysplasia and early-onset of hepatocarcinogenesis, coinciding with biliary ductopenia and cholestasis. TAK1-mediated cancer suppression is exerted through activating NF-kappaB in response to tumor necrosis factor (TNF) and through preventing Caspase-3-dependent hepatocyte and cholangiocyte apoptosis. Moreover, TAK1 suppresses a procarcinogenic and pronecrotic pathway, which depends on NF-kappaB-independent functions of the I kappaB-kinase (IKK)-subunit NF-kappaB essential modulator (NEMO). Therefore, TAK1 serves as a gatekeeper for a protumorigenic, NF-kappaB-independent function of NEMO in parenchymal liver cells.

  17. 新生儿胃肠外营养相关性胆汁淤积症临床分析

    Institute of Scientific and Technical Information of China (English)

    李向红

    2004-01-01

    @@ 胃肠外营养(parenteral nutrition,PN)的出现使许多胃肠功能衰竭的患儿得以存活.随着胃肠外营养技术的提高,其代谢和感染并发症日渐减少,而与其相关的肝胆功能的损害日益受到重视.胃肠外营养相关性胆汁淤积症(parenteral nutrition associated cholestasis,PNAC)是新生儿期长期PN的最常见并发症,部分可发展为肝功能衰竭而死亡[1].本文就我科1999~2003年10例新生儿PNAC进行临床分析.

  18. Role of farnesoid X receptor and bile acids in alcoholic liver disease

    Directory of Open Access Journals (Sweden)

    Sharon Manley

    2015-03-01

    Full Text Available Alcoholic liver disease (ALD is one of the major causes of liver morbidity and mortality worldwide. Chronic alcohol consumption leads to development of liver pathogenesis encompassing steatosis, inflammation, fibrosis, cirrhosis, and in extreme cases, hepatocellular carcinoma. Moreover, ALD may also associate with cholestasis. Emerging evidence now suggests that farnesoid X receptor (FXR and bile acids also play important roles in ALD. In this review, we discuss the effects of alcohol consumption on FXR, bile acids and gut microbiome as well as their impacts on ALD. Moreover, we summarize the findings on FXR, FoxO3a (forkhead box-containing protein class O3a and PPARα (peroxisome proliferator-activated receptor alpha in regulation of autophagy-related gene transcription program and liver injury in response to alcohol exposure.

  19. Relationship between serum heat—stable alkaline phosphatase level and p[regnancy

    Institute of Scientific and Technical Information of China (English)

    CaoGuo-Xian; DingMei-Juan; 等

    1998-01-01

    Serum heat-stable alkaline phosphatase(HSAP) level in 649 cases of normal pregnancy and 164 cases of high-risk pregnancy is measured by raioimmunoassay (RIA).The results indicate that the HSAP level in normal prenancy increased proportionally with gestation weeks(r=0.9843).In 33 cases of pregnancy induced hypertension and 21 cases of intrauterine fetal growth retardation,the HSAP level is significantly low.In 7 cases of neonatal asphyxia and 26 cases of ftal distress,the HSAP level in the mother's serum is also low.In 53 cases of intrahepatic cholestasis of pregnancy,the HSAP level in similar to those of normal pregnancy,This study illustrates that HSAP RIA can play an important role in the evaluation of placental function and fetal prognosis for cases of high-risk pregancy.

  20. Heavy flow autochtonic case of hepatitis E in elderly men

    Directory of Open Access Journals (Sweden)

    S. V. Baramzina

    2016-01-01

    Full Text Available The article presents an analysis of the first clinical cases of acute hepatitis E autochtonic on the territory of the Kirov region. HEV-infection was diagnosed in 76 year old male, not to travel outside the region and the country for a long time, eat a lot of fresh fruit. A feature of the disease in non-endemic region was: severe course of hepatitis E in the elderly, with the development of clinic of acute liver failure and encephalopathy, the presence of the expressed syndrome cytolysis, cholestasis, hepatic-cell failure.Timely treatment of a patient for medical care, the lack of severe somatic diseases, chronic liver disease and adequate pathogenetic therapy helped to keep the patient’s life. In deciphering undifferentiated acute hepatitis in the elderly should be included in the scheme of examination and determination HEV RNA, a/HEV IgM and G.

  1. Outcome and management of antenatal patients with jaundice in tertiary care centre of eastern India: a retrospective study

    Directory of Open Access Journals (Sweden)

    Kalpana Singh

    2015-09-01

    Methods: A retrospective study done at IMS, BHU in obstetrics and gynecology department among pregnant patients with jaundice admitted in obstetric wards and labour room in six months duration. Results: Among total 1960 admissions, 78 (3.97% patients presented with jaundice. Out of all admissions 27 (1.37% were HBSAg, 8 (0.40% HEV, 7 (0.35% HCV, 6 (0.30% of HBSAg and HEV co-infection, cholestasis with pregnancy 20 (1% and 10 (0.51% patients with pre-eclamptic liver disease with HELLP. Conclusions: Jaundice in pregnancy may be lethal to mother and fetus. As the course of disease is also rapid and in short period it may affect the fetus in utero also, early detection and prompt management of these cases should be done. [Int J Res Med Sci 2015; 3(9.000: 2402-2404

  2. Influence of the Gut Microflora and of Biliary Constituents on Morphological Changes in the Small Intestine in Obstructive Jaundice

    Directory of Open Access Journals (Sweden)

    M. Saeed Quraishy

    1996-01-01

    Full Text Available Increased amounts of intestinal endotoxin are absorbed in obstructive jaundice. The precise mechanism is not known but the increased absorption may arise from alterations in the luminal contents, in the intestinal flora, in the gut wall or in interactions between all three. To examine the effects of the intestinal flora we have compared the morphological changes in the small intestine in obstructive jaundice in germ free and conventional rats while the effects of bile constituents have been examined by addition of bile constituents to the diet of bile duct ligated rats. Changes in the intestine were examined, histologically, by enzyme histochemistry, and by transmission and scanning electron microscopy. The results showed no differences in response between germ free and conventional rats. Feeding of diets containing bile salts exacerbated the lesion. Feeding of diets containing cholesterol, however, reduced the degree of intestinal changes produced by cholestasis and completely antagonised the increase in damage caused by feeding of bile salts.

  3. Late vitamin K deficiency bleeding leading to a diagnosis of cystic fibrosis: a case report.

    Science.gov (United States)

    Ngo, B; Van Pelt, K; Labarque, V; Van De Casseye, W; Penders, J

    2011-01-01

    Vitamin K deficiency bleeding (VKDB) in infants still occurs despite worldwide use of prophylaxis. Clinical manifestations can be dramatic with over 50% of patients presenting with intracranial haemorrhage and a mortality rate of 20% in late vitamin K deficiency bleeding. Special attention should be given to infants with a high risk profile (preterm, breast feeding, cholestasis, malabsorption). A tentative diagnosis can be made observing quick normalisation of some easy-to-perform haemostatic parameters (PT, aPTT) after administration of vitamin K. Nowadays, VKDB can still be the first clinical sign of diseases causing malabsorption of fat-soluble vitamins. In this case report, VKDB led to the diagnosis of cystic fibrosis, the most common fatal autosomal recessive disease among Caucasian people.

  4. Clinical findings, dental treatment, and improvement in quality of life for a child with Rothmund-Thomson syndrome.

    Science.gov (United States)

    De Oliveira, Katharina Morant Holanda; Silva, Raquel Assed Bezerra; Carvalho, Fabricio Kitazono; Silva, Lea Assed Bezerra; Nelson-Filho, Paulo; Queiroz, Alexandra Mussolino

    2016-01-01

    The purpose of this study was to report the clinical findings, dental treatment, and improvement in quality of life for a child with Rothmund-Thomson syndrome. The patient had alopecia, delayed speech, low weight and height, cholestasis, and iron deficiency anemia. Furthermore, there were carious lesions and darkened spots on all primary molars. Microdontia of a premolar was observed at the radiographic examination. The patient and family had no commitment to her oral health and dental treatment at first appointments. Oral hygiene instructions, composite restorations, endodontic treatments, teeth extractions, and stainless steel crown installations were performed. The patient was followed up for 7 years through the present due to other possible future clinical findings associated with the syndrome. An improvement in social aspects was observed after removal of toothache and improved esthetics. Such patients need continuous periodic services, which contributes to improving the quality of life in both buccal and general aspects.

  5. Diagnostic challenges of Wilson's disease presenting as acute pancreatitis, cholangitis, and jaundice.

    Science.gov (United States)

    Nussinson, Elchanan; Shahbari, Azmi; Shibli, Fahmi; Chervinsky, Elena; Trougouboff, Philippe; Markel, Arie

    2013-11-27

    Wilson's disease is a rare disorder of copper transport in hepatic cells, and may present as cholestatic liver disease; pancreatitis and cholangitis are rarely associated with Wilsons's disease. Moreover, cases of Wilson's disease presenting as pigmented gallstone pancreatitis have not been reported in the literature. In the present report, we describe a case of a 37-year-old man who was admitted with jaundice and abdominal pain. The patient was diagnosed with acute pancreatitis, cholangitis, and obstructive jaundice caused by pigmented gallstones that were detected during retrograde cholangiopancreatography. However, because of his long-term jaundice and the presence of pigmented gallstones, the patient underwent further evaluation for Wilson's disease, which was subsequently confirmed. This patient's unique presentation exemplifies the overlap in the clinical and laboratory parameters of Wilson's disease and cholestasis, and the difficulties associated with their differentiation. It suggests that Wilson's disease should be considered in patients with pancreatitis, cholangitis, and severe protracted jaundice caused by pigmented gallstones.

  6. Clinical findings, dental treatment, and improvement in quality of life for a child with Rothmund-Thomson syndrome

    Directory of Open Access Journals (Sweden)

    Katharina Morant Holanda De Oliveira

    2016-01-01

    Full Text Available The purpose of this study was to report the clinical findings, dental treatment, and improvement in quality of life for a child with Rothmund-Thomson syndrome. The patient had alopecia, delayed speech, low weight and height, cholestasis, and iron deficiency anemia. Furthermore, there were carious lesions and darkened spots on all primary molars. Microdontia of a premolar was observed at the radiographic examination. The patient and family had no commitment to her oral health and dental treatment at first appointments. Oral hygiene instructions, composite restorations, endodontic treatments, teeth extractions, and stainless steel crown installations were performed. The patient was followed up for 7 years through the present due to other possible future clinical findings associated with the syndrome. An improvement in social aspects was observed after removal of toothache and improved esthetics. Such patients need continuous periodic services, which contributes to improving the quality of life in both buccal and general aspects.

  7. Intestinal Hypoganglionosis Leading to Intestinal Failure and the Compassionate Use of Omegaven™

    Science.gov (United States)

    Karjoo, Sara; Danielson, Paul; Wilsey, Michael; Shakeel, Fauzia

    2017-01-01

    Intestinal hypoganglionosis is a rare innervation disorder that provides numerous nutritional, medical and surgical challenges. In this case report, we present a case of a newborn with intestinal hypoganglionosis leading to intestinal failure and intestinal failure-associated liver disease who responded to Omegaven™, a fat emulsion comprised of omega-3 fatty acids. Omegaven™ has been shown to be beneficial in the management of cholestatic liver injury. Clinical success with Omegaven™ was seen in this patient with a clear decrease in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and complete resolution of cholestasis with a direct bilirubin of zero within two weeks of initiation of Omegaven™. No current guidelines for the diagnosis and management of hypoganglionosis are available. We recommend a multidisciplinary approach and the use of novel therapies such as fat emulsions composed of omega-3 fatty acids for improved patient outcomes. Appropriate compassionate use protocols should be obtained from the Food and Drug Administration prior to initiation of Omegaven™.

  8. Selective screening of 650 high risk Iranian patients for detection of inborn error of metabolism

    Directory of Open Access Journals (Sweden)

    Narges Pishva

    2015-02-01

    Full Text Available Objective: Although metabolic diseases individually are rare ,but overall have an incidence of 1/2000 and can cause devastating and irreversible effect if not diagnosed early and treated promptly. selective screening is an acceptable method for detection of these multi presentation diseases.Method: using panel neonatal screening for detection of metabolic diseases in 650 high risk Iranian patients in Fars province. The following clinical features were used as inclusion criteria for investigation of the patients.Lethargy, poor feeding ,persistent vomiting, cholestasis, intractable seizure ,decreased level of consciousness ,persistent hypoglycemia, unexplained acid base disturbance and unexplained neonatal death.Result: Organic acidemia with 40 cases (42% was the most frequent disorder diagnosed in our high risk populations, followed by disorder of galactose metabolism(30%, 15 patient had classic galactosemia(GALT

  9. Oral Vancomycin Therapy in a Child with Primary Sclerosing Cholangitis and Severe Ulcerative Colitis

    Science.gov (United States)

    Buness, Cynthia; Miloh, Tamir

    2016-01-01

    Primary sclerosing cholangitis (PSC), a rare progressive liver disease characterized by cholestasis and bile duct fibrosis, has no accepted, effective therapy known to delay or arrest its progression. We report a 15 year old female patient diagnosed with PSC and moderate chronic active ulcerative colitis (UC) who achieved normalization of her liver enzymes and bile ducts, and resolution of her UC symptoms with colonic mucosal healing, after treatment with a single drug therapy of the antibiotic oral vancomycin. We postulate that the oral vancomycin may be acting both as an antibiotic by altering the intestinal microbiome and as an immunomodulator. Oral vancomycin may be a promising treatment for PSC that needs to be further studied in randomized trials. PMID:27738604

  10. Characterization of animal models for primary sclerosing cholangitis (PSC).

    Science.gov (United States)

    Fickert, Peter; Pollheimer, Marion J; Beuers, Ulrich; Lackner, Carolin; Hirschfield, Gideon; Housset, Chantal; Keitel, Verena; Schramm, Christoph; Marschall, Hanns-Ulrich; Karlsen, Tom H; Melum, Espen; Kaser, Arthur; Eksteen, Bertus; Strazzabosco, Mario; Manns, Michael; Trauner, Michael

    2014-06-01

    Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies. Currently there is no consensus on how to evaluate and characterize potential PSC models, which makes direct comparison of experimental results and effective exchange of study material between research groups difficult. The International Primary Sclerosing Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a position paper proposing standard requirements for the study of animal models of PSC.

  11. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management.

    Science.gov (United States)

    Eaton, John E; Talwalkar, Jayant A; Lazaridis, Konstantinos N; Gores, Gregory J; Lindor, Keith D

    2013-09-01

    Primary sclerosing cholangitis (PSC), first described in the mid-1850s, is a complex liver disease that is heterogeneous in its presentation. PSC is characterized by chronic cholestasis associated with chronic inflammation of the biliary epithelium, resulting in multifocal bile duct strictures that can affect the entire biliary tree. Chronic inflammation leads to fibrosis involving the hepatic parenchyma and biliary tree, which can lead to cirrhosis and malignancy. The etiology of PSC is not fully understood, which in part explains the lack of effective medical therapy for this condition. However, we have begun to better understand the molecular pathogenesis of PSC. The recognition of specific clinical subtypes and their pattern of progression could improve phenotypic and genotypic classification of the disease. We review our current understanding of this enigmatic disorder and discuss important topics for future studies.

  12. Regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis

    Science.gov (United States)

    Banushi, Blerida; Forneris, Federico; Straatman-Iwanowska, Anna; Strange, Adam; Lyne, Anne-Marie; Rogerson, Clare; Burden, Jemima J.; Heywood, Wendy E.; Hanley, Joanna; Doykov, Ivan; Straatman, Kornelis R.; Smith, Holly; Bem, Danai; Kriston-Vizi, Janos; Ariceta, Gema; Risteli, Maija; Wang, Chunguang; Ardill, Rosalyn E.; Zaniew, Marcin; Latka-Grot, Julita; Waddington, Simon N.; Howe, S. J.; Ferraro, Francesco; Gjinovci, Asllan; Lawrence, Scott; Marsh, Mark; Girolami, Mark; Bozec, Laurent; Mills, Kevin; Gissen, Paul

    2016-01-01

    Post-translational modifications are necessary for collagen precursor molecules (procollagens) to acquire final shape and function. However, the mechanism and contribution of collagen modifications that occur outside the endoplasmic reticulum and Golgi are not understood. We discovered that VIPAR, with its partner proteins, regulate sorting of lysyl hydroxylase 3 (LH3, also known as PLOD3) into newly identified post-Golgi collagen IV carriers and that VIPAR-dependent sorting is essential for modification of lysines in multiple collagen types. Identification of structural and functional collagen abnormalities in cells and tissues from patients and murine models of the autosomal recessive multisystem disorder Arthrogryposis, Renal dysfunction and Cholestasis syndrome caused by VIPAR and VPS33B deficiencies confirmed our findings. Thus, regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis and for the development and function of multiple organs and tissues. PMID:27435297

  13. Alagille syndrome: clinical perspectives

    Directory of Open Access Journals (Sweden)

    Saleh M

    2016-06-01

    Full Text Available Maha Saleh,1 Binita M Kamath,2 David Chitayat1,3 1Division of Clinical and Metabolic Genetics, 2Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children, 3Department of Obstetrics and Gynecology, Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada Abstract: Alagille syndrome is an autosomal dominant, complex multisystem disorder characterized by the presence of three out of five major clinical criteria: cholestasis with bile duct paucity on liver biopsy, congenital cardiac defects (with particular involvement of the pulmonary arteries, posterior embryotoxon in the eye, characteristic facial features, and butterfly vertebrae. Renal and vascular abnormalities can also occur. Inter- and intrafamilial variabilities in the clinical manifestations are common. We reviewed the clinical features and management as well as the molecular basis of Alagille syndrome. Keywords: Alagille syndrome, ALGS, genetics, liver 

  14. Role of nutrition in liver transplantation for end-stage chronic liver disease.

    Science.gov (United States)

    Stickel, Felix; Inderbitzin, Daniel; Candinas, Daniel

    2008-01-01

    Patients with end-stage liver disease often reveal significant protein-energy malnutrition, which may deteriorate after listing for transplantation. Since malnutrition affects post-transplant survival, precise assessment must be an integral part of pre- and post-surgical management. While there is wide agreement that aggressive treatment of nutritional deficiencies is required, strong scientific evidence supporting nutritional therapy is sparse. In practice, oral nutritional supplements are preferred over parenteral nutrition, but enteral tube feeding may be necessary to maintain adequate calorie intake. Protein restriction should be avoided and administration of branched-chain amino acids may help yield a sufficient protein supply. Specific problems such as micronutrient deficiency, fluid balance, cholestasis, encephalopathy, and comorbid conditions need attention in order to optimize patient outcome.

  15. Suppression of BSEP and MRP2 in mouse liver by miroestrol and deoxymiroestrol isolated from Pueraria candollei.

    Science.gov (United States)

    Udomsuk, Latiporn; Juengwatanatrakul, Thaweesak; Putalun, Waraporn; Jarukamjorn, Kanokwan

    2012-11-15

    Miroestrol and deoxymiroestrol are highly active phytoestrogens isolated from the tuberous root of Pueraria candollei var. mirifica (Leguminosae). Modulatory effects of miroestrol and deoxymiroestrol on the mRNAs of BSEP and MRP2 genes involved in bile salt transportation, in C57BL/6 mice were investigated. In contrast to estradiol, miroestrol and deoxymiroestrol suppressed the expression of BSEP and MRP2 mRNA in both male and female mice. The results suggest for the first time that the use of miroestrol and deoxymiroestrol-containing products as alternative medicines or health supplements should be concerned according to their effects on key genes that regulate the bile salt export pump, which could result in the risk of hepatotoxicity and intrahepatic cholestasis.

  16. Mycophenolate mofetil for drug-induced vanishing bile duct syndrome

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Amoxicillin/clavulanate is associated with liver injury,mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment,but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.

  17. Clinical characteristics of caroli's disease

    Institute of Scientific and Technical Information of China (English)

    Ozlem Yonem; Yusuf Bayraktar

    2007-01-01

    Caroli's disease is a rare congenital condition characterized by non-obstructive saccular or fusiform dilatation of larger intrahepatic bile ducts. Cholangitis,liver cirrhosis, and cholangiocarcinoma are its potential complications. The diagnosis of Caroli's disease depends on demonstrating that the cystic lesions are in continuity with the biliary tree which can be showed by ultrasonography, computerized tomography, endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography or magnetic resonance cholangiopancreatography. Treatment of Caroli's disease relies on the location of the biliary abnormalities. While localized forms confined to one lobe can be treated with surgery, liver transplantation is the only effective modality for diffuse forms. Although a rare disorder;Caroli's disease should always be considered in the differential diagnosis of chronic cholestasis of unknown cause.

  18. 新生儿胆汁淤积症

    Institute of Scientific and Technical Information of China (English)

    施诚仁

    2001-01-01

    @@ 新生儿胆汁淤积症(neonatal cholestasis)是指新生儿因某种原因导致正常胆汁流减少,伴有直接胆红素增高而引起临床上以黄疸为主要表现的一种征候群.Iglesias(1999)把这种现象归为“婴儿不正常胆流”,即三“B”征(Bad Baby Bile).新生儿内科最多见的病因是肝炎和近期广泛应用的肠外静脉高营养的合并症,外科疾病则是先天性胆道闭锁.本文着重介绍新生儿胆汁淤积症的处理.

  19. Common bile duct schwannoma: A case report and review of literature

    Institute of Scientific and Technical Information of China (English)

    Luigi Fenoglio; Rodolfo Brizio; Felice Borghi; Sara Severini; Paola Cena; Elena Migliore; Christian Bracco; Fulvio Pomero; Sergio Panzone; Giovan Battista Cavallero; Alberto Silvestri

    2007-01-01

    Schwannoma is a myelin sheath tumor complicated with neurofibroma, neurofibromatosis and neurogenic sarcoma. Peripheral nerve sheath tumors represent 2%-6% of gastrointestinal tract stromal tumors (GIST),but there are deficient data about location of neurogenic tumors in the biliary system and only nine cases of schwannoma of the extrahepatic biliary tract have been reported. These tumors are clinically non-specific. They are usually symptomatic by compressing the close or adjacent structures when being retroperitoneal, and their preoperative diagnosis is extremely difficult. This paper reviews the literature data and describes a case of schwannoma of the common bile duct associated with cholestasis in a healthy young woman, diagnosed and treated in our department. This case is of interest on account of the complexity of its diagnosis and the atypical macroscopic growth pattern of the tumor.

  20. Portal hypertension due to portal venous thrombosis: Etiology, clinical outcomes

    Institute of Scientific and Technical Information of China (English)

    Ozgur Harmanci; Yusuf Bayraktar

    2007-01-01

    The thrombophilia in adult life has major implications in the hepatic vessels. The resulting portal vein thrombosis has various outcomes and complications. Esophageal varices, portal gastropathy, ascites, severe hypersplenism and liver failure needing liver transplantation are known well. The newly formed collateral venous circulation showing itself as pseudocholangicarcinoma sign and its possible clinical reflection as cholestasis are also known from a long time. The management strategies for these complications of portal vein thrombosis are not different from their counterpart which is cirrhotic portal hypertension, but the prognosis is unquestionably better in former cases. In this review we present and discuss the portal vein thrombosis, etiology and the resulting clinical pictures. There are controversial issues in nomenclature,management (including anticoagulation problems), follow up strategies and liver transplantation. In the light of the current knowledge, we discuss some controversial issues in literature and present our experience and our proposals about this group of patients.

  1. Melatonin prevents brain oxidative stress induced by obstructive jaundice in rats.

    Science.gov (United States)

    Cruz, Adolfo; Túnez, Isaac; Martínez, Rubén; Muñoz-Castañeda, Juan Rafael; Ramírez, Luz María; Recio, Marta; Ochoa, Luís; Arjona, Alvaro; Montilla, Pedro; Muntané, Jordi; Padillo, Francisco J

    2007-12-01

    The aim of the study was to analyze the impact of melatonin on brain oxidative stress in experimental biliary obstruction. Cholestasis was done by a double ligature and section of the extrahepatic biliary duct. Melatonin was injected intraperitoneally (500 microg/kg/day). Malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) contents were determined in the brain tissue. Biliary obstruction raised MDA and reduced GSH contents in the cortex, cerebellum, and hypothalamus areas. Moreover, the scavenger enzyme activity significantly dropped in all areas of the brain. Melatonin drastically reduced MDA concentration and enhanced GSH concentration, as well as all antioxidant enzyme activity in all brain areas obtained from the bile duct-ligated animals. In conclusion, the treatment with melatonin decreased lipid peroxidation and recovered the antioxidant status in the brain from cholestatic animals.

  2. Hepatic failure caused by plasma cell infiltration in multiple Myeloma

    Institute of Scientific and Technical Information of China (English)

    Fadi E Rahhal; Robert R Schade; Asha Nayak; Teresa A Coleman

    2009-01-01

    Although plasma cell infiltration is not rare in autopsy of patients with multiple myeloma (MM), it is very rarely detected in living patients. This is because MM rarely causes significant liver dysfunction that requires further evaluation. A 49-year-old man presented with acute renal failure and was diagnosed with kappa light chain MM stage ?B. Thalidomide and dexamethasone were initiated. The patient developed a continuous increase in bilirubin that led to severe cholestasis. A liver biopsy revealed plasma cell infiltration. He then rapidly progressed to liver failure and died. Treatment options are limited in MM with significant liver dysfunction.Despite new drug therapies in MM, those patients with rapidly progressive liver failure appear to have a dismal outcome.

  3. Adenosine kinase deficiency with neurodevelopemental delay and recurrent hepatic dysfunction: A case report

    Science.gov (United States)

    Shakiba, Marjan; Mahjoub, Fatemeh; Fazilaty, Hassan; Rezagholizadeh, Fereshteh; Shakiba, Arghavan; Ziadlou, Maryam; Gahl, William A.; Behnam, Babak

    2016-01-01

    Hypermethioninemia may be benign, present as a nonspecific sign of nongenetic conditions such as liver failure and prematurity, or a severe, progressive inborn error of metabolism. Genetic causes of hypermethioninemia include mitochondrial depletion syndromes caused by mutations in the MPV17 and DGUOK genes and deficiencies of cystathionine β-synthase, methionine adenosyltransferase types I and III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase, citrin, fumarylacetoacetate hydrolase, and adenosine kinase. Here we present a 3-year old girl with a history of poor feeding, irritability, respiratory infections, cholestasis, congenital heart disease, neurodevelopmental delay, hypotonia, sparse hair, facial dysmorphisms, liver dysfunction, severe hypermethioninemia and mild homocystinemia. Genetic analysis of the adenosine kinase (ADK) gene revealed a previously unreported variant (c.479–480 GA>TG) resulting in a stop codon (p.E160X) in ADK. A methionine-restricted diet normalized the liver function test results and improved her hypotonia. PMID:27500280

  4. Clinical findings, dental treatment, and improvement in quality of life for a child with Rothmund-Thomson syndrome

    Science.gov (United States)

    De Oliveira, Katharina Morant Holanda; Silva, Raquel Assed Bezerra; Carvalho, Fabricio Kitazono; Silva, Lea Assed Bezerra; Nelson-Filho, Paulo; Queiroz, Alexandra Mussolino

    2016-01-01

    The purpose of this study was to report the clinical findings, dental treatment, and improvement in quality of life for a child with Rothmund-Thomson syndrome. The patient had alopecia, delayed speech, low weight and height, cholestasis, and iron deficiency anemia. Furthermore, there were carious lesions and darkened spots on all primary molars. Microdontia of a premolar was observed at the radiographic examination. The patient and family had no commitment to her oral health and dental treatment at first appointments. Oral hygiene instructions, composite restorations, endodontic treatments, teeth extractions, and stainless steel crown installations were performed. The patient was followed up for 7 years through the present due to other possible future clinical findings associated with the syndrome. An improvement in social aspects was observed after removal of toothache and improved esthetics. Such patients need continuous periodic services, which contributes to improving the quality of life in both buccal and general aspects. PMID:27307676

  5. The adverse outcome pathway concept: a pragmatic tool in toxicology.

    Science.gov (United States)

    Vinken, Mathieu

    2013-10-04

    Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies.

  6. Imaging of Drug-induced Complications in the Gastrointestinal System.

    Science.gov (United States)

    McGettigan, Melissa J; Menias, Christine O; Gao, Zhenqiang J; Mellnick, Vincent M; Hara, Amy K

    2016-01-01

    Drug-induced injury commonly affects the gastrointestinal and hepatobiliary systems because of the mechanisms of absorption and metabolism. In pill esophagitis, injury is frequently related to direct contact with the esophageal mucosa, resulting in small superficial ulcers in the mid esophagus. Nonsteroidal anti-inflammatory drugs can lead to gastrointestinal tract ulcers and small bowel mucosal diaphragms (thin weblike strictures). Injury to the pancreatic and hepatobiliary systems can manifest as pancreatitis, acute or chronic hepatitis, cholestasis, or steatosis and steatohepatitis (which may progress to cirrhosis). Various drugs may also insult the hepatic vasculature, resulting in Budd-Chiari and sinusoidal obstructive syndromes. Focal lesions such as hepatic adenomas may develop after use of oral contraceptives or anabolic steroids. Ultrasonography, computed tomography, and magnetic resonance imaging can aid in diagnosis of drug-induced injuries and often are necessary to exclude other causes.

  7. Fulminant Wilson’s Disease Managed with Plasmapheresis as a Bridge to Liver Transplant

    Directory of Open Access Journals (Sweden)

    Talal Hilal

    2014-01-01

    Full Text Available New-onset jaundice can be a manifestation of multiple pathologic processes including hemolysis, parenchymal liver disease, and cholestasis; the differential diagnosis is broad and requires a systematic approach. We report a case of a patient who presented with jaundice after starting minocycline for the treatment of acne vulgaris and rapidly developed fulminant liver failure found to be due to Wilson’s disease. She also manifested severe Coomb’s negative hemolytic anemia and renal failure secondary to hepatorenal syndrome. As a bridge to liver transplant, she was successfully treated with plasmapheresis to decrease serum copper in addition to hemodialysis for acidosis and hyperkalemia. She was able to receive a liver and made a full recovery. The case highlights the use of plasmapheresis as an adjunctive treatment modality in cases of fulminant liver failure due to Wilson’s disease.

  8. Activity of gammaglutamiltransferase in addicts of Dnipropetrovsk province

    Directory of Open Access Journals (Sweden)

    E. B. Motorya

    2012-07-01

    Full Text Available Change of GGT activity is studied in patients using alcohol and narcotic substances. 2878 residents of the Dnipropetrovsk province are examined. The increase of GGT activity is marked in 528 cases (18.3 %. It may be caused by increasing synthesis as a result of activating enzymes which ensure this process. The activation may be initiated by alcohol and medicines, by the damage of cellular membranes under the action of toxic agents, under ischemia and infection-induced liver injury, and by the detachment of enzymes from cellular membranes affected by detergent bile acids under the cholestasis. Ordinary values for major part of examined patients (81.7 % may be explained by only episodic taking alcohol and narcotic drugs, which was not affect the liver parenchyma, and also by effective treatment normalized the enzyme’s activity.

  9. [The noninvasive evaluation of degree of expression of fibrosis of liver and significance of polymorphism of gene of hyaluronic acid under chronic hepatitis C].

    Science.gov (United States)

    Bulatova, I A; Schekotova, A P; Krivtsov, A V; Schekotov, V V; Pavlov, A I

    2015-03-01

    The study was carries out to evaluate degree of expression of fibrosis, reparation processes in liver and value of polymorphism of gene of hyaluronic acid HASI (rs11084111) in progression of affection of liver in patients with chronic hepatitis C. The sampling included 100 patients with chronic hepatitis C. The control group included 83 healthy donors. The blood serum was tested to detect concentration of hyaluronic acid and alpha-fetoprotein. The stage of liver fibrosis (F) was evaluated by using ultrasound fibroflexography The polymorphism of gene (rs11084111) was analysed by polymerase chain reaction technique. In the group of patients with F1 the average concentration of hyaluronic acid in blood serum in 1.8 times surpassed this indicator in group with F0. The concentration of hyaluronic acid was almost 2 times higher under F3 as compared with F1-F2. This indicator permitted differentiating F3 and F4 which followed by activation of cytolysis and cholestasis in F1 and F3 and by increasing of level of alpha-fetoprotein at stages F1 and F4. The study detected no statistically significant difference between rates of genotypes and alleles of gene HASI (rs11084111) in groups of healthy patients and patients with chronic hepatitis C. The direct relationships are established between hyaluronic acid and markers of cytolysis, cholestasis, alpha-fetoprotein (p = 0.001), viral load (p = 0.003) liver elasticity index according fibroflexography data (p hyaluronic acid permits to stratify minimal expressed fibrosis and also the transition of disease to the stage of cirrhosis.

  10. Long-term outcome of endoscopic metallic stenting for benign biliary stenosis associated with chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Taketo Yamaguchi; Takeshi Ishihara; Katsutoshi Seza; Akihiko Nakagawa; Kentarou Sudo; Katsuyuki Tawada; Teruo Kouzu; Hiromitsu Saisho

    2006-01-01

    AIM: Endoscopic metal stenting (EMS) offers good results in short to medium term follow-up for bile duct stenosis associated with chronic pancreatitis (CP);however, longer follow-up is needed to determine if EMS has the potential to become the treatment of first choice.METHODS: EMS was performed in eight patients with severe common bile duct stenosis due to CR After the resolution of cholestasis by endoscopic naso-biliary drainage three patients were subjected to EMS while,the other five underwent EMS following plastic tube stenting. The patients were followed up for more than5 years through periodical laboratory tests and imaging techniques.RESULTS: EMS was successfully performed in all the patients. Two patients died due to causes unrelated to the procedure: one with an acute myocardial infarction and the other with maxillary carcinoma at 2.8 and 5.5years after EMS, respectively. One patient died with cholangitis because of EMS clogging 3.6 years after EMS.None of these three patients had showed symptoms of cholestasis during the follow-up period. Two patients developed choledocholithiasis and two suffered from duodenal ulcers due to dislodgement of the stent between 4.8 and 7.3 years after stenting; however, they were successfully treated endoscopically. Thus, five of eight patients are alive at present after a mean follow-up period of 7.4 years.CONCLUSION: EMS is evidently one of the very promising treatment options for bile duct stenosis associated with CP, provided the patients are closely followed up; thus setting a system for their prompt management on emergency is desirable.

  11. microRNA-222 modulates liver fibrosis in a murine model of biliary atresia

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Wen-jun; Dong, Rui; Chen, Gong, E-mail: chengongzlp@hotmail.com; Zheng, Shan

    2014-03-28

    Highlights: • The RRV infected group showed cholestasis, retardation and extrahepatic biliary atresia. • miR-222 was highly expressed, and PPP2R2A was inhibited in the murine biliary atresia model. • miR-222 profoundly modulated the process of fibrosis in the murine biliary atresia model. • miR-222 might represent a potential target for improving biliary atresia prognosis. - Abstract: microRNA-222 (miR-222) has been shown to initiate the activation of hepatic stellate cells, which plays an important role in the pathogenesis of liver fibrosis. The aim of our study was to evaluate the role of miR-22 in a mouse model of biliary atresia (BA) induced by Rhesus Rotavirus (RRV) infection. New-born Balb/c mice were randomized into control and RRV infected groups. The extrahepatic bile ducts were evaluated. The experimental group was divided into BA group and negative group based on histology. The expression of miR-222, protein phosphatase 2 regulatory subunit B alpha (PPP2R2A), proliferating cell nuclear antigen (PCNA) and phospho-Akt were detected. We found that the experimental group showed signs of cholestasis, retardation and extrahepatic biliary atresia. No abnormalities were found in the control group. In the BA group, miR-222, PCNA and Akt were highly expressed, and PPP2R2A expression was significantly inhibited. Our findings suggest that miR-222 profoundly modulated the process of fibrosis in the murine BA model, which might represent a potential target for improving BA prognosis.

  12. Mutation detection in cholestatic patients using microarray resequencing of ATP8B1 and ABCB11 [v2; ref status: indexed, http://f1000r.es/yv

    Directory of Open Access Journals (Sweden)

    Kirsten E McKay

    2013-03-01

    Full Text Available Background: Neonatal cholestasis is a common presentation of childhood liver diseases and can be a feature of various conditions including disorders of bile acid biogenesis and transport, various inborn errors of metabolism and perinatal infections. Some inherited metabolic diseases can be easily screened using biochemical assays, however many can only be accurately diagnosed by DNA sequencing. Fluorescent capillary Sanger sequencing (FS is the gold standard method used by clinical laboratories for genetic diagnosis of many inherited conditions; however, it does have limitations. Recently microarray resequencing (MR has been introduced into research and clinical practice as an alternative method for genetic diagnosis of heterogeneous conditions. In this report we compared the accuracy of mutation detection for MR with FS in a group of patients with ‘low-normal’ gamma glutamyl transpeptidase (gGT cholestasis without known molecular diagnoses. Methods: 29 patient DNA samples were tested for mutations in the ATP8B1 and ABCB11 genes using both FS and MR. Other known causes of “low gGT cholestasis” such as ARC syndrome and bile acid biosynthesis disorders were excluded. Results: Mutations were identified in 13/29 samples. In 3/29 samples FS and MR gave discordant results: MR had a false positive rate of 3.4% and a false negative rate of 7%. Conclusions: The major advantage of MR over FS is that multiple genes can be screened in one experiment, allowing rapid and cost-effective diagnoses.  However, we have demonstrated that MR technology is limited in sensitivity. We therefore recommend that MR be used as an initial evaluation, with FS deployed when genetic and clinical or histopathological findings are discordant.

  13. Serum alkaline phosphatase isoenzymes in laboratory beagle dogs detected by polyacrylamide-gel disk electrophoresis.

    Science.gov (United States)

    Hatayama, Kazuhisa; Nishihara, Yoshito; Kimura, Sayaka; Goto, Ken; Nakamura, Daichi; Wakita, Atsushi; Urasoko, Yoshinaka

    2011-10-01

    Serum alkaline phosphatase (ALP) activity is frequently measured in toxicity studies. Itoh et al. (2002) reported that a commercially available polyacrylamide-gel (PAG) disk electrophoresis kit used in humans (AlkPhor System, Jokoh Co., Ltd., Tokyo, Japan) for identifying serum ALP isoenzymes was useful for veterinary clinicopathological diagnosis in mongrel dogs. In the present study, based on the report of Itoh et al. (2002), we tried to expand the application range of this kit to laboratory beagle dogs which are commonly used in toxicity studies. In order to identify the origin of each ALP isoenzyme, tissue ALP extracts from the liver, bone and small intestine and serum samples were treated with neuraminidase, anti-small intestinal ALP antibody, ALP inhibitor levamisole and/or wheat germ agglutinin (WGA). The main serum ALP isoenzymes in 5-month-old intact beagle dogs were bone-derived (bone and atypical ALP: corresponding to human variant bone ALP) and they tended to decrease with age. However, liver-derived ALP isoenzyme greatly increased in the serum of cholestasis model dogs. The cholestasis model dogs also had a large molecular ALP detected in the resolving gel. This ALP could be originated from intestinal ALP or corticosteroid-induced ALP (CALP), because the activity remained even after levamisole inhibition. CALP was observed in intact laboratory beagle dogs with individual differences. These results suggest that the present method is a useful tool for detecting serum ALP isoenzymes in laboratory beagle dogs and concomitant levamisole inhibition with another gel is applicable for the evaluation of organ toxicity.

  14. A nested case-control study of maternal-neonatal transmission of hepatitis B virus in a Chinese population

    Institute of Scientific and Technical Information of China (English)

    Li-Zhang Chen; Wen-Qi Zhou; Shu-Shan Zhao; Zhi-Yu Liu; Shi-Wu Wen

    2011-01-01

    AIM: To examine the determinants of maternal-neo?natal transmission of hepatitis B virus (HBV).METHODS: A nested case-control study was conducted in Changsha, Hunan, People's Republic of China from January 1, 2005 to September 31, 2006. To avoid po?tential maternal blood contamination, we collected vein blood of newborns immediately after birth and before initial hepatitis B vaccination to determine the HBV in?fection status of the newborn. For each HBsAg-positive infant, one HBsAg-negative infant born to an HBsAg-positive mother was matched by hospital at birth (same), gender (same), and date of birth (within 1 mo). A face-to-face interview was conducted to collect clinical and epidemiological data. Conditional logistic regression analysis was used to estimate the independent effects of various determinants on maternal-neonatal transmis?sion of HBV.RESULTS: A total of 141 HBsAg-positive infants and 141 individually matched HBsAg-negative infants were included in the final analysis. Maternal first-degree family history of HBV infection, intrahepatic cholesta-sis, and premature rupture of membranes were risk factors for perinatal transmission of HBV, whereas sys?tematic treatment and HBV immunoglobulin injections for mothers with HBV infection were protective factors for maternal-neonatal transmission of HBV, after ad?justment for potential confounding factors.CONCLUSION: For HBsAg-positive mothers, system?atic treatment, HBV immunoglobulin administration, and controlling intrahepatic cholestasis and pregnancy complications may reduce the incidence of perinatal transmission of HBV.

  15. Cholestatic jaundice, acute kidney injury and acute pancreatitis secondary to the recreational use of methandrostenolone: a case report

    Directory of Open Access Journals (Sweden)

    Kwan Peter

    2011-04-01

    Full Text Available Abstract Introduction Over the last few years the use of anabolic steroids has become increasingly common amongst amateur athletes and for aesthetic purposes. As a result, the adverse events related to their use are being seen more frequently. Methandrostenolone is an anabolic steroid which is widely available and has been used for both performance enhancement and aesthetic purposes. This drug has also been reported to cause cholestasis of the intra-hepatic bile ducts resulting in elevated aminotransferases, hyperbilirubinemia and clinical jaundice. However, to the best of our knowledge this agent has not been previously reported to cause pancreatitis or acute kidney injury. Case presentation In this paper, we report the case of a 50-year-old man of Indian descent who presented with a six week history of diffuse abdominal pain, anorexia and weight loss following an eight week cycle of methandrostenolone use. At initial presentation, his lipase level was 785 U/L, bilirubin was 922 μmol/L and creatinine was 200 U/L while his aspartate aminotransferase and alanine aminotransferase levels were only mildly elevated at 61 U/L and 56 U/L respectively. His lipase peaked on day nine at >3000 U/L whilst his creatinine level was 299 U/L. Imaging was consistent with acute pancreatitis while a liver biopsy was consistent with intra-hepatic cholestasis and a kidney biopsy revealed evidence of acute tubular necrosis. Conclusion Both acute pancreatitis and acute kidney injury have rarely been reported with anabolic steroid use and they have not been previously reported to occur in the same patient. This case demonstrates some potentially new and serious adverse consequences occurring with the use of anabolic steroids, of which physicians need to be aware.

  16. Diagnosis of alpha-1-antitrypsin deficiency by DNA analysis of children with liver disease

    Directory of Open Access Journals (Sweden)

    De TOMMASO Adriana Maria Alves

    2001-01-01

    Full Text Available Background - Alpha-1-antitrypsin deficiency is a genetic disorder which is transmitted in a co-dominant, autosomal form. Alpha-1-antitrypsin deficiency affects mainly the lungs and the liver leading, in the latter case, to neonatal cholestasis, chronic hepatitis or cirrhosis. A precise diagnosis of Alpha-1-antitrypsin deficiency may be obtained by biochemical or molecular analysis. Objective - The purpose of this study was to use DNA analysis to examine the presence of an alpha-1-antitrypsin deficiency in 12 children suspected of having this deficiency and who showed laboratory and clinical characteristics of the disease. Patients and Methods - Twelve patients, aged 3 months to 19 years, who had serum alpha-1-antitrypsin levels lower than normal and/or had hepatic disease of undefined etiology were studied. The mutant alleles S and Z of the alpha-1-antitrypsin gene were investigated in the 12 children. Alpha-1-antitrypsin gene organization was analyzed by amplification of genoma through the polymerase chain reaction and digestion with the restriction enzymes Xmnl (S allele and Taq 1 (Z allele. Results - Seven of the 12 patients had chronic liver disease of undefined etiology and the other five patients had low serum levels of alpha-1-antitrypsin as well as a diagnosis of neonatal cholestasis and/or chronic liver disease of undefined etiology. Five of the 12 patients were homozygous for the Z allele (ZZ and two had the S allele with another allele (*S different from Z. Conclusion - These results show that alpha-1-antitrypsin deficiency is relatively frequent in children with chronic hepatic disease of undefined etiology and/or low alpha-1-antitrypsin levels (41.6%. A correct diagnosis is important for effective clinical follow-up and for genetic counseling.

  17. Peripheral and spinal 5-HT receptors participate in cholestatic itch and antinociception induced by bile duct ligation in rats

    Science.gov (United States)

    Tian, Bin; Wang, Xue-Long; Huang, Ya; Chen, Li-Hua; Cheng, Ruo-Xiao; Zhou, Feng-Ming; Guo, Ran; Li, Jun-Cheng; Liu, Tong

    2016-01-01

    Although 5-HT has been implicated in cholestatic itch and antinociception, two common phenomena in patients with cholestatic disease, the roles of 5-HT receptor subtypes are unclear. Herein, we investigated the roles of 5-HT receptors in itch and antinociception associated with cholestasis, which was induced by common bile duct ligation (BDL) in rats. 5-HT-induced enhanced scratching and antinociception to mechanical and heat stimuli were demonstrated in BDL rats. 5-HT level in the skin and spinal cord was significantly increased in BDL rats. Quantitative RT-PCR analysis showed 5-HT1B, 5-HT1D, 5-HT2A, 5-HT3A, 5-HT5B, 5-HT6, and 5-HT7 were up-regulated in peripheral nervous system and 5-HT1A, 5-HT1F, 5-HT2B, and 5-HT3A were down-regulated in the spinal cord of BDL rats. Intradermal 5-HT2, 5-HT3, and 5-HT7 receptor agonists induced scratching in BDL rats, whereas 5-HT3 agonist did not induce scratching in sham rats. 5-HT1A, 5-HT2, 5-HT3, and 5-HT7 agonists or antagonists suppressed itch in BDL rats. 5-HT1A agonist attenuated, but 5-HT1A antagonist enhanced antinociception in BDL rats. 5-HT2 and 5-HT3 agonists or antagonists attenuated antinociception in BDL rats. Our data suggested peripheral and central 5-HT system dynamically participated in itch and antinociception under cholestasis condition and targeting 5-HT receptors may be an effective treatment for cholestatic itch. PMID:27824106

  18. Contiguous ABCD1 DXS1357E deletion syndrome: report of an autopsy case.

    Science.gov (United States)

    Iwasa, Mitsuaki; Yamagata, Takanori; Mizuguchi, Masashi; Itoh, Masayuki; Matsumoto, Ayumi; Hironaka, Mitsugu; Honda, Ayako; Momoi, Mariko Y; Shimozawa, Nobuyuki

    2013-06-01

    Contiguous ABCD1 DXS1357E deletion syndrome (CADDS) is a contiguous deletion syndrome involving the ABCD1 and DXS1357E/BAP31 genes on Xq28. Although ABCD1 is responsible for X-linked adrenoleukodystrophy (X-ALD), its phenotype differs from that of CADDS, which manifests with many features of Zellweger syndrome (ZS), including severe growth and developmental retardation, liver dysfunction, cholestasis and early infantile death. We report here the fourth case of CADDS, in which a boy had dysmorphic features, including a flat orbital edge, hypoplastic nose, micrognathia, inguinal hernia, micropenis, cryptorchidism and club feet, all of which are shared by ZS. The patient achieved no developmental milestones and died of pneumonia at 8 months. Biochemical studies demonstrated abnormal metabolism of very long chain fatty acids, which was higher than that seen in X-ALD. Immunocytochemistry and Western blot showed the absence of ALD protein (ALDP) despite the presence of other peroxisomal proteins. Pathological studies disclosed a small brain with hypomyelination and secondary hypoxic-ischemic changes. Neuronal heterotopia in the white matter and leptomeningeal glioneuronal heterotopia indicated a neuronal migration disorder. The liver showed fibrosis and cholestasis. The thymus and adrenal glands were hypoplastic. Array comparative genomic hybridization (CGH) analysis suggested that the deletion was a genomic rearrangement in the 90-kb span starting in DXS1357E/BACP31 exon 4 and included ABCD1, PLXNB3, SRPK3, IDH3G and SSR4, ending in PDZD4 exon 8. Thus, the absence of ALDP, when combined with defects in the B-cell antigen receptor associated protein 31 (BAP31) and other factors, severely affects VLCFA metabolism on peroxisomal functions and produces ZS-like pathology.

  19. EU framework 6 project: predictive toxicology (PredTox)--overview and outcome.

    Science.gov (United States)

    Suter, Laura; Schroeder, Susanne; Meyer, Kirstin; Gautier, Jean-Charles; Amberg, Alexander; Wendt, Maria; Gmuender, Hans; Mally, Angela; Boitier, Eric; Ellinger-Ziegelbauer, Heidrun; Matheis, Katja; Pfannkuch, Friedlieb

    2011-04-15

    In this publication, we report the outcome of the integrated EU Framework 6 PROJECT: Predictive Toxicology (PredTox), including methodological aspects and overall conclusions. Specific details including data analysis and interpretation are reported in separate articles in this issue. The project, partly funded by the EU, was carried out by a consortium of 15 pharmaceutical companies, 2 SMEs, and 3 universities. The effects of 16 test compounds were characterized using conventional toxicological parameters and "omics" technologies. The three major observed toxicities, liver hypertrophy, bile duct necrosis and/or cholestasis, and kidney proximal tubular damage were analyzed in detail. The combined approach of "omics" and conventional toxicology proved a useful tool for mechanistic investigations and the identification of putative biomarkers. In our hands and in combination with histopathological assessment, target organ transcriptomics was the most prolific approach for the generation of mechanistic hypotheses. Proteomics approaches were relatively time-consuming and required careful standardization. NMR-based metabolomics detected metabolite changes accompanying histopathological findings, providing limited additional mechanistic information. Conversely, targeted metabolite profiling with LC/GC-MS was very useful for the investigation of bile duct necrosis/cholestasis. In general, both proteomics and metabolomics were supportive of other findings. Thus, the outcome of this program indicates that "omics" technologies can help toxicologists to make better informed decisions during exploratory toxicological studies. The data support that hypothesis on mode of action and discovery of putative biomarkers are tangible outcomes of integrated "omics" analysis. Qualification of biomarkers remains challenging, in particular in terms of identification, mechanistic anchoring, appropriate specificity, and sensitivity.

  20. Parenteral nutrition-associated liver disease in adult and pediatric patients.

    Science.gov (United States)

    Kumpf, Vanessa J

    2006-06-01

    There are essentially 3 types of hepatobiliary disorders associated with parenteral nutrition (PN) therapy: steatosis, cholestasis, and gallbladder sludge/stones. Reported prevalence rates of PN-associated liver disease (PNALD) vary greatly, and there are distinct differences between adult and pediatric patients. Various etiologic factors have been evaluated for significance in contributing to PNALD, including enteral feeding history, septic events, bacterial overgrowth, length of intestinal resection, and prematurity/low birth weight. Etiologic factors specifically related to the PN formulation or nutrient intake have also been evaluated, including excessive calorie intake, dextrose-to-lipid ratio, amino acid dose, taurine deficiency, IV fat emulsion (IVFE) dose, carnitine deficiency, choline deficiency, and continuous vs cyclic infusion. Minor increases in serum aminotransferase concentrations are relatively common in patients receiving PN therapy and generally require no intervention. The primary indicator of cholestasis is a serum conjugated bilirubin >2 mg/dL. When a patient receiving PN develops liver complications, it is necessary to rule out all treatable causes and minimize other risk factors. All potential hepatotoxic medications and herbal supplements should be eliminated. Modifications to the PN regimen that may be helpful include reduction of calories, reduction of IVFE dose to <1 g/kg/d, supplementation of taurine in the infant, and use of cyclic infusion. Initiation of even small amounts of enteral nutrition and use of ursodiol may be beneficial in stimulating bile flow. In the long-term PN patient with severe and progressive liver disease, intestinal or liver transplantation may be the only remaining treatment option.

  1. Dynamic localization of hepatocellular transporters in health and disease

    Institute of Scientific and Technical Information of China (English)

    Marcelo G Roma; Fernando A Crocenzi; Aldo D Mottino

    2008-01-01

    Vesicle-based trafficking of hepatocellular transporters involves delivery of the newly-synthesized carriers from the rough endoplasmic reticulum to either the plasma membrane domain or to an endosomal, submembrane compartment, followed by exocytic targeting to the plasma membrane. Once delivered to the plasma membrane, the transporters usually undergo recycling between the plasma membrane and the endosomal compartment, which usually serves as a reservoir of pre-existing transporters available on demand. The balance between exocytic targeting and endocytic internalization from/to this recycling compartment is therefore a chief determinant of the overall capability of the liver epithelium to secrete bile and to detoxify endo and xenobiotics. Hence, it is a highly regulated process. Impaired regulation of this balance may lead to abnormal localization of these transporters, which results in bile secretory failure due to endocytic internalization of key transporters involved in bile formation. This occurs in several experimental models of hepatocellular cholestasis, and in most human cholestatic liver diseases. This review describes the molecular bases involved in the biology of the dynamic localization of hepatocellular transporters and its regulation, with a focus on the involvement of signaling pathways in this process. Their alterations in different experimental models of cholestasis and in human cholestatic liver disease are reviewed. In addition, the causes explaining the pathological condition (e.g. disorganization of actin or actin-transporter linkers) and the mediators involved (e.g. activation of cholestatic signaling transduction pathways) are also discussed. Finally, several experimental therapeutic approaches based upon the administration of compounds known to stimulate exocytic insertion of canalicular transporters (e.g. cAMP, tauroursodeoxycholate) are described.

  2. Strain background modifies phenotypes in the ATP8B1-deficient mouse.

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    Sohela Shah

    Full Text Available BACKGROUND: Mutations in ATP8B1 (FIC1 underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis to intermittent (benign recurrent intrahepatic cholestasis. The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficiency. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of genetic background on phenotypes of ATP8B1-deficient and wild-type mice, using C57Bl/6 (B6, 129, and (B6-129 F1 strain backgrounds. B6 background resulted in greater abnormalities in ATP8B1-deficient mice than did 129 and/or F1 background. ATP8B1-deficient pups of B6 background gained less weight. In adult ATP8B1-deficient mice at baseline, those of B6 background had lower serum cholesterol levels, higher serum alkaline phosphatase levels, and larger livers. After challenge with cholate-supplemented diet, these mice exhibited higher serum alkaline phosphatase and bilirubin levels, greater weight loss and larger livers. ATP8B1-deficient phenotypes in mice of F1 and 129 backgrounds are usually similar, suggesting that susceptibility to manifestations of ATP8B1 deficiency may be recessive. We also detected differences in hepatobiliary phenotypes between wild-type mice of differing strains. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the ATP8B1-deficient mouse in a B6 background may be a better model of human ATP8B1 deficiency and highlight the importance of informed background strain selection for mouse models of liver disease.

  3. Síndrome de Alagille: Presentación de un caso Alagilles syndrome: report of a case

    Directory of Open Access Journals (Sweden)

    Fernando Alberto Gutiérrez Mendoza

    1999-02-01

    Full Text Available Se presenta el caso de un paciente con diagnóstico de síndrome de Alagille, quien consultó por colestasis crónica iniciada en el período neonatal y cuyo diagnóstico se estableció a los cinco meses de edad. El paciente tuvo como manifestaciones mayores del síndrome, además de la colestasis, la facies característica, vértebras en mariposa y soplo cardíaco. Como manifestación menor, retardo del crecimiento. El estudio histológico demostró disminución de los conductos biliares interlobulares. El paciente evolucionó con colestasis persistente e hipertensión porta; falleció a la edad de cuatro años por insuficiencia hepática. El estudio postmortem del hígado demostró cirrosis sin cambios neoplásicos. A patient with chronic cholestasis beginning during his neonatal period is reported. Diagnosis was made at the age of five months. In adition, the patient had the characteristic facies, failure of anterior vertebral arch fusion (butterfly vertebrae, and cardiac murmur, as major clinical manifestations of the syndrome; also he had growth retardation, a minor clinical manifestation. Histologic features revealed paucity of interlobular biliar ducts. Cholestasis persisted and the patient began to have portal hypertension and died at the age of four years with hepatic failure. Postmortem studies showed a hepatic cirrhosis without neoplasic changes.

  4. Portal Vein Embolization Before Liver Resection: A Systematic Review

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    Lienden, K. P. van, E-mail: k.p.vanlienden@amc.uva.nl [Academic Medical Center, Department of Radiology (Netherlands); Esschert, J. W. van den; Graaf, W. de [Academic Medical Center, Department of Surgery (Netherlands); Bipat, S.; Lameris, J. S. [Academic Medical Center, Department of Radiology (Netherlands); Gulik, T. M. van [Academic Medical Center, Department of Surgery (Netherlands); Delden, O. M. van [Academic Medical Center, Department of Radiology (Netherlands)

    2013-02-15

    This is a review of literature on the indications, technique, and outcome of portal vein embolization (PVE). A systematic literature search on outcome of PVE from 1990 to 2011 was performed in Medline, Cochrane, and Embase databases. Forty-four articles were selected, including 1,791 patients with a mean age of 61 {+-} 4.1 years. Overall technical success rate was 99.3 %. The mean hypertrophy rate of the FRL after PVE was 37.9 {+-} 0.1 %. In 70 patients (3.9 %), surgery was not performed because of failure of PVE (clinical success rate 96.1 %). In 51 patients (2.8 %), the hypertrophy response was insufficient to perform liver resection. In the other 17 cases, 12 did not technically succeed (0.7 %) and 7 caused a complication leading to unresectability (0.4 %). In 6.1 %, resection was cancelled because of local tumor progression after PVE. Major complications were seen in 2.5 %, and the mortality rate was 0.1 %. A head-to-head comparison shows a negative effect of liver cirrhosis on hypertrophy response. The use of n-butyl cyanoacrylate seems to have a greater effect on hypertrophy, but the difference with other embolization materials did not reach statistical significance. No difference in regeneration is seen in patients with cholestasis or chemotherapy. Preoperative PVE has a high technical and clinical success rate. Liver cirrhosis has a negative effect on regeneration, but cholestasis and chemotherapy do not seem to have an influence on the hypertrophy response. The use of n-butyl cyanoacrylate may result in a greater hypertrophy response compared with other embolization materials used.

  5. Analysis outcomes and complications of twin pregnancy by in vitro fertilization-embryotransfer and intracytoplasmic sperm injection%体外受精-胚胎移植与单精子卵胞浆内注射受孕双胎妊娠并发症及结局的比较

    Institute of Scientific and Technical Information of China (English)

    谢涛; 郑剑兰; 张小琼; 付景丽; 赵本华

    2013-01-01

    Objective:To investigate the outcomes and complications of twin pregnancy by in vitro fertilization-embryotransfer (IVF-ET) and intracytoplasmic sperm injection (ICSI).Methods:A retrospective study was carried out to measure premature rupture of membrane,placental abruption,pregnancy-induced hypertension,intrahepatic cholestasis of pregnancy and abortion,437 twin pregnant women who achieved pregnancy by IVF-ET or ICSI in our hospital from February,2004 to May,2011 had participated the study.Results:Incidences of premature rupture of membrane and placental abruption in IVF-ET group were significant higher than in ICSI group (x2 =5.93,6.01 ; P < 0.05) ; Ratios of pregnancy-induced hypertension and intrahepatic cholestasis of pregnancy between IVF-ET and ICSI group were no significant differences (x2 =2.68,1.37 ; P > 0.05) ; Ratio of abortion in IVF-ET group was significant higher than that in ICSI group (x2 =5.09; P < 0.05).Conclusion:The risk of twin pregnancy by IVF-ET is higher than by ICSI,IVF-ET and ICSI maybe are not the main cause of pregnancy-induced hypertension and intrahepatic cholestasis of pregnancy.%目的 比较体外受精-胚胎移植(IVF-ET)与单精子卵胞浆内注射(ICSI)受孕双胎妊娠围生期并发症及结局.方法 回顾性分析我院2004年2月~ 2011年5月437例IVF-ET、ICSI受孕双胎的并发症(如胎膜早破、胎盘早剥、妊娠期高血压疾病、妊娠期肝内胆汁淤积症)及妊娠结局(流产发生率).结果 IVF-ET受孕双胎组胎膜早破及胎盘早剥发生率高于ICSI受孕双胎组(x2=5.93,6.01;P<0.05);IVF-ET受孕双胎组与ICSI受孕双胎组妊娠期高血压疾病、妊娠期肝内胆汁淤积症发生率无统计学差异(x2=2.68,1.37; P>0.05); IVF-ET受孕双胎组较ICSI受孕双胎组流产率高,差异有统计学差异(x2 =5.09; P<0.05).结论 IVF-ET较ICSI受孕双胎妊娠风险较高,IVF-ET与ICSI本身可能不是导致妊娠期高血压疾病、妊娠期肝内胆汁淤积症的因素.

  6. Progress in diagnosis and therapy of extrahepatic manifestations of cholestatic liver diseases%胆汁淤积性肝病肝外并发症诊治研究进展

    Institute of Scientific and Technical Information of China (English)

    陆伦根

    2016-01-01

    胆汁淤积肝外并发症主要有瘙痒、疲劳和代谢性骨病,其分子机制目前尚未完全明确,针对发病机制拟定的治疗方案可暂时缓解症状,但疗效有限,阐明发病机制有助于找到更恰当的治疗手段.瘙痒可能由胆汁淤积的某些物质在体内蓄积影响神经传导导致,现行推荐考来烯胺等药物治疗和血液净化手段可明显缓解胆汁淤积性瘙痒.疲劳可能由中枢神经系统功能异常导致,目前尚无特异性治疗方法.代谢性骨病又称为肝性骨营养不良,常表现为骨质减少和骨质疏松症,纠正可导致骨质丢失的不良因素有利于缓解代谢性骨病,推荐二膦酸盐治疗胆汁淤积性骨质疏松.患者出现难以忍受的瘙痒和骨质疏松导致频繁骨折时宜进行肝移植评估.%Extra-hepatic complications of cholestasis mainly include pruritus,fatigue and metabolic bone diseases,and their molecular mechanisms have not yet been fully identified so far.Though therapeutic regimens targeted at the pathogenesis alleviate the symptoms temporarily,the therapeutic effects are limited,and therefore expounding the pathogenesis will help find more appropriate therapeutic approaches.Pruritus may be caused by nerve conduction block resulting from accumulation of some substances in the accumulated bile,existing recommended methods like drug therapy with cholestyramine and blood purification can markedly alleviate cholestasis-induced pruritus.Fatigue may be a consequence of the central nervous system disorders,and there is currently no specific therapy.Metabolic bone diseases (MBD),also known as hepatic osteodystrophy,are often manifested by osteopenia and osteoporosis,and correcting bad factors responsible for bone loss will help relieve MBD.Bisphosphonate is recommended for treatment of cholestasis-induced osteoporosis.In the event that a patient experiences intolerable pruritus and frequent fractures resulting from osteoporosis,assessment for

  7. Percutaneous transpapillary extraction of biliary calculus for symptomatic choledocholithiasis after unsuccessfully endoscopic treatment; Perkutane transpapillaere Gallensteinextraktion bei symptomatischer Choledocholithiasis nach frustranem endoskopischen Behandlungsversuch

    Energy Technology Data Exchange (ETDEWEB)

    Zorger, N.; Manke, C.; Lenhart, M.; Voelk, M.; Link, J.; Feuerbach, S. [Klinikum der Univ. Regensburg (Germany). Inst. fuer Roentgendiagnostik

    2001-02-01

    Purpose: Evaluation of a percutaneous transhepatic treatment of symptomatic choledocholithiasis in bile ducts that cannot be reached with the endoscope. Methods: From January 1996 to August 2000 a transhepatic extraction of biliary calculus was performed in four patients. Endoscopic retrograde cholangiography (ERC) was not successful in any of the cases. Clinical symptoms were icterus in four cases, additional cholangitis or colics in two cases. First, a ballon dilation of the papilla was performed by a percutaneous transhepatic approach. For removal of bile duct stones, occlusion catheters and Dormia baskets were used. Technical success was defined as complete removal of bile duct stones. Clinical success was defined as normalization of cholestasis and inflammation parameters. In the follow-up an ultrasound examination was performed and blood samples were taken for control of cholestasis parameters. Results: In all four cases treatment was technically and clinically successful. For complete removal of biliary calculus a second intervention was necessary in two cases. In each case an internal to external drainage was left over a mean of 7 days (3 - 13 days). In the mean follow-up of 30.5 months (6 - 50 months) all patients had persistent relief of symptoms. No further interventions were necessary. No complications were present. Conclusion: Percutaneous transpapillary extraction of biliary calculus is an effective alternative to surgery in patients with bile ducts, that cannot be reached with the endoscope. (orig.) [German] Ziel: Untersuchung der perkutanen transhepatischen Therapie der symptomatischen Choledocholithiasis bei endoskopisch nicht sondierbarem Gallengangssystem. Methoden: Von Januar 1996 bis August 2000 wurde bei 4 Patienten eine transhepatische Gallengangsstein-Entfernung durchgefuehrt. Die Endoskopisch Retrograde Cholangiographie (ERC) war in allen Faellen aufgrund einer vorangegangenen Magenresektion (B II) technisch nicht erfolgreich gewesen. In 4

  8. Organic anion transporting polypeptide 1a1 null mice are sensitive to cholestatic liver injury.

    Science.gov (United States)

    Zhang, Youcai; Csanaky, Iván L; Cheng, Xingguo; Lehman-McKeeman, Lois D; Klaassen, Curtis D

    2012-06-01

    Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in livers of mice and is thought to transport bile acids (BAs) from blood into liver. Because Oatp1a1 expression is markedly decreased in mice after bile duct ligation (BDL). We hypothesized that Oatp1a1-null mice would be protected against liver injury during BDL-induced cholestasis due largely to reduced hepatic uptake of BAs. To evaluate this hypothesis, BDL surgeries were performed in both male wild-type (WT) and Oatp1a1-null mice. At 24 h after BDL, Oatp1a1-null mice showed higher serum alanine aminotransferase levels and more severe liver injury than WT mice, and all Oatp1a1-null mice died within 4 days after BDL, whereas all WT mice survived. At 24 h after BDL, surprisingly Oatp1a1-null mice had higher total BA concentrations in livers than WT mice, suggesting that loss of Oatp1a1 did not prevent BA accumulation in the liver. In addition, secondary BAs dramatically increased in serum of Oatp1a1-null BDL mice but not in WT BDL mice. Oatp1a1-null BDL mice had similar basolateral BA uptake (Na(+)-taurocholate cotransporting polypeptide and Oatp1b2) and BA-efflux (multidrug resistance-associated protein [Mrp]-3, Mrp4, and organic solute transporter α/β) transporters, as well as BA-synthetic enzyme (Cyp7a1) in livers as WT BDL mice. Hepatic expression of small heterodimer partner Cyp3a11, Cyp4a14, and Nqo1, which are target genes of farnesoid X receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and NF-E2-related factor 2, respectively, were increased in WT BDL mice but not in Oatp1a1-null BDL mice. These results demonstrate that loss of Oatp1a1 function exacerbates cholestatic liver injury in mice and suggest that Oatp1a1 plays a unique role in liver adaptive responses to obstructive cholestasis.

  9. 早期微量喂养对新生儿肺透明膜病临床康复的影响%Effect of early micro feeding on the clinical rehabilitation of hyaline membrane disease

    Institute of Scientific and Technical Information of China (English)

    程书卿

    2015-01-01

    Objective: To investigate the effect of early micro feeding on the clinical rehabilitation of hyaline membrane disease(HMD).Methods:158 patients with HMD were treated.They were randomly divided into the observation group and the control group with 79 cases in each group.Patients in the observation group received the early minimal feeding treatment,while the control group adopted conventional feeding treatment.The clinical effect of two groups children were observed and compared. Results:The up to full enteral nutrition and recovery birth weight time,blood bilirubin peak,complicated with intrahepatic cholestasis,hospitalization days of the observation group were significantly better than those of the control group(P<0.05). Conclusion:Early trace feeding is helpful to HMD better transition to full enteral feeding,improve the children's weight effectively, reduce the incidence of cholestasis,improve the therapeutic effect.%目的:探讨早期微量喂养对新生儿肺透明膜病(HMD)临床康复的影响。方法:收治HMD患儿158例,随机分为观察组和对照组,各79例,观察组接受早期微量喂养治疗,对照组采取常规喂养治疗方式。观察比较两组患儿临床治疗效果。结果:观察组患儿达全量胃肠道营养时间、恢复出生体重时间、血胆红素峰值、并发胆汁淤积、住院天数等指标均显著优于对照组(P<0.05)。结论:早期微量喂养有利于HMD患儿更好地过渡到全量胃肠道喂养,能有效提高患儿体重,降低胆汁淤积发生率,提高治疗效果。

  10. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

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    Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa [Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba 292-0818 (Japan); Adam, Klaus-Peter; Alexander, Danny C.; Lawton, Kay A.; Milburn, Michael V.; Ryals, John A.; Wulff, Jacob E. [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States); Guo, Lining, E-mail: lguo@metabolon.com [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States)

    2013-04-01

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

  11. Aktivitas Antifibrotik Ekstrak Buah Delima Terstandar 40% Ellagic Acid pada Tikus Putih (Rattus norvegicus sebagai Hewan Model (ANTIFIBROTIC ACTIVITY OF POMEGRANATE FRUIT EXTRACT STANDARDIZED 40% ELLAGIC ACID ON RATS (RATTUS NORVEGICUS AS ANIMAL MODEL

    Directory of Open Access Journals (Sweden)

    Wiwik Misaco Yuniarti

    2014-08-01

    Full Text Available The number of patients with chronic liver disease (fibrosis or cirrhosis of the liver is increasing fromtime to time. However, until now there is no therapy that really effective to overcome that disease. Therapyfor liver fibrosis typically use substance that have antioxidant activity, anti-inflammatory or anti fibrotic.Various efforts always done to find alternative therapies for liver fibrosis. One of them is the use ofpotential plants that suspected having such activity. Various parts of pomegranate have been shown tohave various activities that beneficial for health. This study was conducted to determine the effect ofpomegranate fruit extract standardized 40% ellagic acid on the improvement degree of liver fibrosis causedby cholestasis by measuring of serum alkaline phosphatase levels (ALP and gamma-glutamyl transferase(GGT, as a specific indicator of liver damage becaused of cholestasis. The research was conducted by using32 male rats, wistar strain, 2.5 month old, weighing between 150-200 grams. Animal models of liver fibrosis obtained by using BDL technique. Subjects were divided into a control group (P0 = without BDLand giving of pomegranate extract and treatment groups (P1 = BDL with administration of CMC, P2 =BDL with ellagic acid 90% and P3 = BDL with pomegranate fruit extract standardized 40% ellagic acid.CMC, extract (150 mg / kg BW / PO and ellagic acid (60 mg / kg BW / PO administered for 21 consecutivedays in the same volume. At the end of 21 days periods, biochemical evaluation was performed to measureserum levels of GGT and ALP. The result indicated that administration of pomegranate fruit extract ( P3significantly reduced GGT ( 10.5±9.2 mg/dl and ALP level ( 509.0±4.2 mg/dl close to normal level of GGTand ALP ( P0, GGT : 2.8 ± 1.4; ALP : 449.0±62.3 (p<0.05. The level of GGT and ALP in P3 group were lowercompared to the group ellagic acid (P2, GGT=48.5±4.8 and ALP = 691.0± 29.7 and group which only begiven CMC (P1, GGT

  12. Protective effect of low dose of melatonin against cholestatic oxidative stress after common bile duct ligation in rats

    Institute of Scientific and Technical Information of China (English)

    Mukaddes Esrefoglu; Mehmet Gül; Memet Hanifi Emre; Alaattin Polat; Mukadder Ayse Selimoglu

    2005-01-01

    AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second,to evaluate the role of nitric oxide (NO), a free oxygen radical, in oxidative injury.METHODS: Thirty-two Sprague-Dawley rats were assigned to four groups: sham operation (SO), BDL, BDL+melatonin,and BDL+vehicle. Cholestasis was achieved by double ligature of the common bile duct. Melatonin was injected intraperitoneally 500 μg/(kg.d) for 8 d. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA),and reduced GSH. Total nitrite (NOx) concentrations were determined in hepatic homogenates. Histopathological examination was performed using a histological scoring system.RESULTS: The histopathological changes including portal inflammation, necrosis, apoptosis, focal inflammation and fibrosis were severe in the BDL and BDL+vehicle groups. There were numerous large areas of coagulation necrosis. Histological Activity Index scores of these groups were significantly higher than that of the SO group. Treatment with melatonin reduced these alterations significantly. The degree of necro-infiammation and fibrosis showed significant difference between the BDL and BDL+melatonin groups. BDL was accompanied by a significant increase in MDA and NOx, and a significant decrease in GSH levels. Mean±SE values of MDA, GSH and NOx levels of SO group were 147.47±6.69, 0.88±0.33 μmol/g and 180.70±6.58 nm/g, respectively. The values of BDL group were 200.14±21.30, 0.65±0.02 μmol/g, and 400.46±48.89 nm/g, respectively, whereas the values of BDL+melatonin group were 115.93±6.8, 0.74±0.02 μmol/g,and 290.38±32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NOx levels.CONCLUSION: We have concluded that oxidative stress is associated with the pathogenesis of cholestatic liver damage and NO

  13. Pharmacokinetic analysis of 14C-ursodiol in newborn infants using accelerator mass spectrometry.

    Science.gov (United States)

    Gordi, Toufigh; Baillie, Rebecca; Vuong, Le T; Abidi, Saira; Dueker, Stephen; Vasquez, Herbert; Pegis, Priscilla; Hopper, Andrew O; Power, Gordon G; Blood, Arlin B

    2014-09-01

    Pharmacokinetic studies in the neonatal population are often limited by the small volume of blood that can be collected. The high sensitivity of (14) C-accelerator mass spectrometry (AMS) enables pharmacokinetic studies to be conducted with greatly reduced sample volumes. We demonstrated the utility of AMS in infants by studying the plasma pharmacokinetic behavior of nanogram doses of (14) C-ursodiol administered as a non-perturbing microdose or as a microtracer with therapeutic doses of non-labeled ursodiol in infants. Five non-cholestatic infants were administered 3 consecutive oral microdoses of (14) C-ursodiol: 8 ng (1.0 nCi), 26 ng (3.3 nCi), and 80 ng (10 nCi) 48 hours apart. Three additional infants with cholestasis were administered a single 80 ng (10.0 nCi) oral dose of (14) C-ursodiol together with a therapeutic dose of 40 mg/kg of non-labeled ursodiol. A pharmacokinetic model describing ursodiol concentrations was developed using nonlinear mixed-effects modeling. The pharmacokinetics of ursodiol in this pilot study were best described by a two-compartment model with first-order elimination. This study demonstrates the feasibility and utility of microdose and microtrace methodology in pediatric research.

  14. Molecular cytotoxic mechanisms of chlorpromazine in isolated rat hepatocytes.

    Science.gov (United States)

    MacAllister, Stephanie L; Young, Cheryl; Guzdek, Anna; Zhidkov, Nickholas; O'Brien, Peter J

    2013-01-01

    Chlorpromazine (CPZ), a member of the largest class of first-generation antipsychotic agents, is known to cause hepatotoxicity in the form of cholestasis and hepatocellular necrosis in some patients. The mechanism of CPZ hepatotoxicity is unclear, but is thought to result from reactive metabolite formation. The goal of this research was to assess potential cytotoxic mechanisms of CPZ using the accelerated cytotoxicity mechanism screening (ACMS) technique with freshly isolated rat hepatocytes. This study identified CPZ cytotoxicity and inhibition of mitochondrial membrane potential (MMP) to be concentration-dependent. Furthermore, inhibition of cytochrome P450s (CYPs), including CYP2D1 and 1A2, delayed CPZ cytotoxicity, suggesting a role for CYP activation of CPZ to a toxic metabolite(s) in this model. Metabolism studies also demonstrated glucuronide and glutathione (GSH) requirement for CPZ detoxification in hepatocytes. Inactivating the 2-electron reduction pathway, NAD(P)H quinone oxidoreductase (NQO1), caused a significant increase in hepatocyte susceptibility to CPZ, indicating quinoneimine contribution to CPZ cytotoxicity. Nontoxic concentrations of peroxidase/H(2)O(2) (inflammatory model) increased cytotoxicity in CPZ-treated hepatocytes and caused additional mitochondrial toxicity. Inflammation further depleted GSH and increased oxidized glutathione (GSSG) levels. Results suggest activation of CPZ to reactive metabolites by 2 pathways in hepatocytes: (i) a CYP-catalyzed quinoneimine pathway, and (ii) a peroxidase-catalyzed oxidation of CPZ to CPZ radicals.

  15. The Interstitial Lymphatic Peritoneal Mesothelium Axis in Portal Hypertensive Ascites: When in Danger, Go Back to the Sea

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    M. A. Aller

    2010-01-01

    Full Text Available Portal hypertension induces a splanchnic and systemic low-grade inflammatory response that could induce the expression of three phenotypes, named ischemia-reperfusion, leukocytic, and angiogenic phenotypes.During the splanchnic expression of these phenotypes, interstitial edema, increased lymph flow, and lymphangiogenesis are produced in the gastrointestinal tract. Associated liver disease increases intestinal bacterial translocation, splanchnic lymph flow, and induces ascites and hepatorenal syndrome. Extrahepatic cholestasis in the rat allows to study the worsening of the portal hypertensive syndrome when associated with chronic liver disease. The splanchnic interstitium, the mesenteric lymphatics, and the peritoneal mesothelium seem to create an inflammatory pathway that could have a key pathophysiological relevance in the production of the portal hypertension syndrome complications. The hypothetical comparison between the ascitic and the amniotic fluids allows for translational investigation. From a phylogenetic point of view, the ancestral mechanisms for amniotic fluid production were essential for animal survival out of the aquatic environment. However, their hypothetical appearance in the cirrhotic patient is considered pathological since ultimately they lead to ascites development. But, the adult human being would take advantage of the potential beneficial effects of this “amniotic-like fluid” to manage the interstitial fluids without adverse effects when chronic liver disease aggravates.

  16. Clinical and pathological study on the hyperbaric oxygenation treatment ofchronic hepatitis

    Institute of Scientific and Technical Information of China (English)

    Wei Zhao; Wei Liu

    2000-01-01

    AIM To study the effect and alteration of hepatic blood flow as well as ultrastructure of hepatic tissue inchronic cholestatic hepatitis after hypebaric oxygenation (HBO).METHODS Using the hepatic rheometer and Doppler B-mode ultrasound equipment, the contractive waveof hepatic blood flow and blood flow of portal vein were tested; the biochemistry, immunohistochemistryand ultrastructure of hepatic tissue were determined and served as the evaluating indexes.RESULTS After the HBO treatment, the contractive wave of hepatic blood-flow in 76% patients and bloodof right portal vein in 70% patients were increased, the improvement of serum ALT and BILI was 88.9%and 93.3% respectively. In addition, the swelling mitochondria, cholestasis of hepatic cells and capillariesreduced obviously; Kupffer's cells decreased. There was significant difference (t=2.85, P<0.05) beforeand after HBO treatment.CONCLUSION It is suggested that the HBO could increase the blood flow of portal vein and arteries,improve the hepatic function, cholestatsis and inflammation.

  17. Current role of transient elastography in the management of chronic hepatitis B patients

    Science.gov (United States)

    2017-01-01

    Liver fibrosis is an important prognostic factor for chronic hepatitis B (CHB), and accurate evaluation of the stage of liver fibrosis is crucial in establishing management strategies. While liver biopsy is still considered the gold standard for staging liver fibrosis or cirrhosis, transient elastography (TE), a noninvasive means of assessing liver fibrosis, has come to play an increasing role in this process. After extensive validation, TE is now regarded as a reliable surrogate maker for grading the severity of liver fibrosis in CHB patients. It can detect the extent of fibrosis in a patient and can also be used to evaluate longitudinal changes in liver fibrosis over time with or without interventional management, such as antiviral therapy. However, several confounders hinder the effective assessment of liver fibrosis using TE, such as extensive liver necroinflammation, hepatic congestion, and cholestasis. TE has limited use in obese patients or patients with ascites. Although TE has several limitations, due to its accessibility and safety, it is a valuable tool for the initial evaluation and follow-up in patients with CHB. PMID:27956732

  18. Establishment of a Novel Simplified Surgical Model of Acute Liver Failure in the Cynomolgus Monkey

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    Lei Cai

    2016-01-01

    Full Text Available Models using large animals that are suitable for studying artificial liver support system (ALSS are urgently needed. Presently available acute liver failure (ALF models mainly involve pigs or dogs. Establishment of current surgical ALF models (hepatectomy/devascularization requires either very good surgical skills or multistep processes—even multiple stages of surgery. Therefore, it is necessary to develop a simplified surgical method. Here we report a novel simplified surgical ALF model using cynomolgus monkeys. Six monkeys underwent portal-right renal venous shunt combined with common bile duct ligation and transection (PRRS + CBDLT. Postoperatively, the monkeys had progressively increased listlessness, loss of appetite, and obvious jaundice. Blood biochemistry levels (Amm, ALT, AST, TBiL, DBiL, ALP, LDH, CK, and Cr and prothrombin time (PT were significantly increased (all P<0.01 and albumin (ALB was markedly reduced (P<0.01 compared with baseline values. Histological examination of liver specimens on postoperative day 10 revealed cholestasis and inflammation. PRRS + CBDLT produced ALF that closely correlated with clinical situations. Compared with other surgical or drug ALF models, ours was simplified and animals were hemodynamically stable. This model could provide a good platform for further research on ALSS, especially regarding their detoxification functions.

  19. Plasma fatty acids in premature infants with hyperbilirubinemia: before-and-after nutrition support with fish oil emulsion.

    Science.gov (United States)

    Klein, Catherine J; Havranek, Thomas G; Revenis, Mary E; Hassanali, Zahra; Scavo, Louis M

    2013-02-01

    Infants who are dependent on parenteral nutrition (PN) sometimes develop PN-associated cholestasis (PNAC). A compassionate use protocol, approved by the U.S. Food and Drug Administration and the institutional review board, guided enrollment of hospitalized infants with PNAC (3 weeks). Plasma concentrations of essential fatty acids were monitored before and after a soybean-based PN lipid, infused at 3 g/kg body weight/d, was replaced by an experimental fish oil-based intravenous fat emulsion (FO-IVFE) at 1.0 g/kg/d. All participants were born premature (n = 10; 20% male). At enrollment, infants were (mean ± SD) 86.5 ± 53.5 days of life and weighed 2.24 ± 0.87 kg; direct bilirubin was 5.5 ± 1.3 mg/dL. After treatment, blood concentrations significantly increased from baseline (P effects were observed attributable to FO-IVFE. Discontinuation of FO-IVFE was typically due to infants (body weight 3.76 ± 1.68 kg) transitioning to enteral feeding rather than for resolution of hyperbilirubinemia (direct bilirubin 7.9 ± 4.8 mg/dL). These exploratory results suggest that FO-IVFE raises circulating ω-3 fatty acids in premature infants without development of ω-6 deficiency in the 8.3 ± 5.8-week time frame of this study.

  20. The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood

    Science.gov (United States)

    Campos Silva, Soraya Luiza; Marques de Miranda, Débora; Ferreira, Alexandre Rodrigues

    2016-01-01

    Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients. PMID:27882046

  1. Hepatocyte and Sertoli Cell Aquaporins, Recent Advances and Research Trends

    Science.gov (United States)

    Bernardino, Raquel L.; Marinelli, Raul A.; Maggio, Anna; Gena, Patrizia; Cataldo, Ilaria; Alves, Marco G.; Svelto, Maria; Oliveira, Pedro F.; Calamita, Giuseppe

    2016-01-01

    Aquaporins (AQPs) are proteinaceous channels widespread in nature where they allow facilitated permeation of water and uncharged through cellular membranes. AQPs play a number of important roles in both health and disease. This review focuses on the most recent advances and research trends regarding the expression and modulation, as well as physiological and pathophysiological functions of AQPs in hepatocytes and Sertoli cells (SCs). Besides their involvement in bile formation, hepatocyte AQPs are involved in maintaining energy balance acting in hepatic gluconeogenesis and lipid metabolism, and in critical processes such as ammonia detoxification and mitochondrial output of hydrogen peroxide. Roles are played in clinical disorders including fatty liver disease, diabetes, obesity, cholestasis, hepatic cirrhosis and hepatocarcinoma. In the seminiferous tubules, particularly in SCs, AQPs are also widely expressed and seem to be implicated in the various stages of spermatogenesis. Like in hepatocytes, AQPs may be involved in maintaining energy homeostasis in these cells and have a major role in the metabolic cooperation established in the testicular tissue. Altogether, this information represents the mainstay of current and future investigation in an expanding field. PMID:27409609

  2. A shift in paradigm towards human biology-based systems for cholestatic-liver diseases.

    Science.gov (United States)

    Noor, Fozia

    2015-12-01

    Cholestatic-liver diseases (CLDs) arise from diverse causes ranging from genetic factors to drug-induced cholestasis. The so-called diseases of civilization (obesity, diabetes, metabolic disorders, non-alcoholic liver disease, cardiovascular diseases, etc.) are intricately implicated in liver and gall bladder diseases. Although CLDs have been extensively studied, there seem to be important gaps in the understanding of human disease. Despite the fact that many animal models exist and substantial clinical data are available, translation of this knowledge towards therapy has been disappointingly limited. Recent advances in liver cell culture such as in vivo-like 3D cultivation of human primary hepatic cells, human induced pluripotent stem cell-derived hepatocytes; and cutting-edge analytical techniques such as 'omics' technologies and high-content screenings could play a decisive role in deeper mechanistic understanding of CLDs. This Topical Review proposes a roadmap to human biology-based research using omics technologies providing quantitative information on mechanisms in an adverse outcome/disease pathway framework. With modern sensitive tools, a shift in paradigm in human disease research seems timely and even inevitable to overcome species barriers in translation.

  3. Clinical features and management of primary biliary cirrhosis

    Science.gov (United States)

    Crosignani, Andrea; Battezzati, Pier Maria; Invernizzi, Pietro; Selmi, Carlo; Prina, Elena; Podda, Mauro

    2008-01-01

    Primary biliary cirrhosis (PBC), which is characterized by progressive destruction of intrahepatic bile ducts, is not a rare disease since both prevalence and incidence are increasing during the last years mainly due to the improvement of case finding strategies. The prognosis of the disease has improved due to both the recognition of earlier and indolent cases, and to the wide use of ursodeoxycholic acid (UDCA). New indicators of prognosis are available that will be useful especially for the growing number of patients with less severe disease. Most patients are asymptomatic at presentation. Pruritus may represent the most distressing symptom and, when UDCA is ineffective, cholestyramine represents the mainstay of treatment. Complications of long-standing cholestasis may be clinically relevant only in very advanced stages. Available data on the effects of UDCA on clinically relevant end points clearly indicate that the drug is able to slow but not to halt the progression of the disease while, in advanced stages, the only therapeutic option remains liver transplantation. PMID:18528929

  4. Clinical features and management of primary biliary cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Andrea Crosignani; Pier Maria Battezzati; Pietro Invernizzi; Carlo Selmi; Elena Prina; Mauro Podda

    2008-01-01

    Primary biliary cirrhosis (PBC),which is characterised by progressive destruction of intrahepatic bile ducts,is not a rare disease since both prevalence and incidence are increasing during the last years mainly due to the improvement of case finding strategies.The prognosis of the disease has improved due to both the recognition of earlier and indolent cases,and to the wide use of ursodeoxycholic acid (UDCA).New indicators of prognosis are available that will be useful especially for the growing number of patients with less severe disease.Most patients are asymptomatic at presentation.Pruritus may represent the most distressing symptom and,when UDCA is ineffective,cholestyramine represents the mainstay of treatment.Complications of long-standing cholestasis may be clinically relevant only in very advanced stages.Available data on the effects of UDCA on clinically relevant end points clearly indicate that the drug is able to slow but not to halt the progression of the disease while,in advanced stages,the only therapeutic option remains liver transplantation.

  5. Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

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    Mikael Bjursell

    Full Text Available Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1, the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

  6. Circadian dysregulation disrupts bile acid homeostasis.

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    Ke Ma

    Full Text Available BACKGROUND: Bile acids are potentially toxic compounds and their levels of hepatic production, uptake and export are tightly regulated by many inputs, including circadian rhythm. We tested the impact of disrupting the peripheral circadian clock on integral steps of bile acid homeostasis. METHODOLOGY/PRINCIPAL FINDINGS: Both restricted feeding, which phase shifts peripheral clocks, and genetic ablation in Per1(-/-/Per2(-/- (PERDKO mice disrupted normal bile acid control and resulted in hepatic cholestasis. Restricted feeding caused a dramatic, transient elevation in hepatic bile acid levels that was associated with activation of the xenobiotic receptors CAR and PXR and elevated serum aspartate aminotransferase (AST, indicative of liver damage. In the PERDKO mice, serum bile acid levels were elevated and the circadian expression of key bile acid synthesis and transport genes, including Cyp7A1 and NTCP, was lost. This was associated with blunted expression of a primary clock output, the transcription factor DBP, which transactivates the promoters of both genes. CONCLUSIONS/SIGNIFICANCE: We conclude that disruption of the circadian clock results in dysregulation of bile acid homeostasis that mimics cholestatic disease.

  7. Freshwater Clam Extract Ameliorates Triglyceride and Cholesterol Metabolism through the Expression of Genes Involved in Hepatic Lipogenesis and Cholesterol Degradation in Rats

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    Thomas Laurent

    2013-01-01

    Full Text Available The freshwater clam (Corbicula spp. is a popular edible bivalve and has been used as a folk remedy for liver disease in Asia. As a Chinese traditional medicine, it is said that freshwater clam ameliorates alcoholic intoxication and cholestasis. In this study, to estimate the practical benefit of freshwater clam extract (FCE, we compared the effects of FCE and soy protein isolate (SPI on triglyceride and cholesterol metabolism in rats. FCE and SPI lowered serum cholesterol, and FCE tended to reduce serum triglycerides. FCE enhanced fecal sterol excretion and hepatic mRNA levels of CYP7A1 and ABCG5 more substantially than SPI; however, both diets reduced hepatic cholesterol. Both of the diets similarly suppressed liver lipids improved Δ9-desaturated fatty acid profile, and FCE was associated with a reduction in FAS and SCD1 mRNA levels. Hepatic transcriptome analysis revealed that inhibition of lipogenesis-related gene expression may contribute to downregulation of hepatic triglycerides by FCE. FCE would have better potential benefits for preventing metabolic disorders, through greater improvement of metabolism of triglycerides and cholesterol, likely through a mechanism similar to SPI.

  8. Involvement of SIK3 in glucose and lipid homeostasis in mice.

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    Tatsuya Uebi

    Full Text Available Salt-inducible kinase 3 (SIK3, an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3(-/- mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3(-/- mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3(-/- mice. Lipid metabolism disorders in Sik3(-/- mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice.

  9. The Diagnostic Value of Endoscopic Balloon Catheter Usage for Detecting Early-Stage Primary Sclerosing Cholangitis in Endoscopic Retrograde Cholangiopancreatography:A Case Report

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    Burhan Ozdil

    2010-02-01

    Full Text Available A 34-year-old woman was admitted to our clinic with abdominal pain, jaundice and pruritus. Endoscopic retrograde cholangiopancreatography was performed for cholestasis. Endoscopic retrograde cholangiopancreatography (ERCP was judged as normal, after a standard ERCP cannula was used for the cholangiogram. However, marked canalicular irregularities were identified in cholangiography when pressurized contrast agent was administrated via balloon catheter. This cholangiographic view was thought to reveal an early-stage alteration of sclerosing cholangitis. Primary sclerosing cholangitis (PSC is a chronic cholestatic liver disease characterized by destruction and fibrosis of the bile ducts. The diagnosis of PSC is based on typical cholangiographic findings, supported by nonspecific clinical signs and symptoms, cholestatic liver biochemical tests, and liver biopsy. Cholangiography is considered to be the gold standard for the diagnosis of PSC. The diagnosis is easy when diffuse multifocal biliary strictures, the hallmarks of the disease, resulting in a ‘beaded’ appearance on ERCP is detected. However, it may reveal a normal image in an early stage of the disease when bile duct changings are not prominent. We think that balloon catheter ERCP appears to facilitate the diagnosis of early-stage primary sclerosing cholangitis.

  10. Histological and immunohistochemical features in fatal acute fulminant hepatitis E

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    Vinita Agrawal

    2012-01-01

    Full Text Available Background: Hepatitis E is being increasingly recognized as an emerging infection in developed countries. Data on histological findings and nature of inflammatory cell infiltrate in liver in this disease are quite sparse. Aims: This study was planned to study the histological features and the type of inflammatory infiltrate in liver biopsies of patients with acute fulminant hepatitis E. Materials and Methods: We retrieved postmortem liver biopsies of 11 Indian patients with fulminant hepatitis E, and compared these with biopsies from seven patients with fulminant hepatitis B. Results : Biopsies from acute fulminant hepatitis E showed varying degrees of hepatocyte necrosis, mixed portal and lobular inflammation, accompanied by bile ductular proliferation, lymphocytic cholangitis, Kupffer cell prominence, cholestasis, apoptotic bodies, pseudo-rosette formation, steatosis, and presence of plasma cells in portal tracts. Interface hepatitis was more frequent in acute hepatitis B than in acute hepatitis E (100% vs 20%; P<0.05. These findings differ from those reported in cases with autochthonous hepatitis E in Europe. On immunohistochemistry, lymphocyte infiltrate consisted predominantly of CD3 + T cells in both hepatitis E and hepatitis B; these cells contained a predominant cytotoxic (CD8 + cell subpopulation in 81.8% of cases with hepatitis E and in 50% of cases with hepatitis B. Conclusion: Our findings suggest that histological changes in HEV infection may vary with geographical location because of prevalent HEV genotypes, and that CD8 + lymphocytes play a role in HEV-induced liver injury.

  11. Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis

    Institute of Scientific and Technical Information of China (English)

    Takehiro Kato; Atsumasa Komori; Sung-Kwan Bae; Kiyoshi Migita; Masahiro Ito; Yasuhide Motoyoshi; Seigo Abiru; Hiromi Ishibashi

    2012-01-01

    Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis, except epidemic schistosomiasis. Among them, primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues, giving rise to systemic amyloidosis, due to a progressive and unresolved inflammatory process, and its possible association with inflammatory bowel diseases. Nevertheless, only one such case has been reported in the literature to date. We report a 69-yearold Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis, without any evidence of other inflammatory disorders. As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4, the presence of IgG4+ plasma cells was examined systemically, resulting in unexpected documentation of Congo-red-positive amyloid deposits, but not IgG4+ plasma cells, in the liver, stomach and salivary glands. Elevated serum IgG4 is the hallmark of IgG4-related disease, including IgG4-associated cholangitis, but it has also been demonstrated in certain patients with PSC. Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.

  12. Histopathological changes in the livers and kidneys of fish in Sariyar Reservoir, Turkey.

    Science.gov (United States)

    Ayas, Zafer; Ekmekci, Guler; Ozmen, Murat; Yerli, Sedat V

    2007-03-01

    In this study, a total of 180 fish specimens (wels: Silurus glanis-60; common carp: Cyprinus carpio-60; bleak: Alburnus escherichii-60) of ages between one and two were caught at three different stations in Sariyar Reservoir. The histological changes in the livers and kidneys of three different species of fish were detected microscopically and evaluated with quantitative analyses. Also, organochlorine pesticide residues (OCP) have also been determined in the water and sediment samples and in the adipose tissues of fish caught in these stations. Results show that the reservoir was polluted by different kinds of OCP compounds and these chemicals have accumulated in the fish tissues. As a result of these analyses, histopathological changes were observed in the livers and kidneys of fish specimens, such as mononuclear cell infiltration, congestion and nuclear picnosis. Also intra-cytoplasmic cholestasis in their livers and tubular degenerations in the kidneys were observed. The incidences of the histopathological changes in wels and carps were found to be higher than bleak. Furthermore, histopathological changes in fish samples caught from Usakbuku were much more than the samples caught from other stations (Sariyar and Nallihan Bird Paradise Stations). In this study the possible reasons of histopathological changes were evaluated with respect to different fish species and localities and also the findings were evaluated in relation to OCP contamination.

  13. Taurolithocholate impairs bile canalicular motility and canalicular bile secretion in isolated rat hepatocyte couplets

    Institute of Scientific and Technical Information of China (English)

    Norihito Watanabe; Tatehiro Kagawa; Sei-ichiro Kojima; Shinji Takashimizu; Naruhiko Nagata; Yasuhiro Nishizaki; Tetsuya Mine

    2006-01-01

    AIM: To investigate the effects of taurolithocholate (TLC)on the canalicular motility in isolated rat hepatocyte couplets (IRHC).METHODS: TLC was added to IRHC at concentrations of 10 and 50 μmol/L, respectively. In each group, five time-lapse movies containing 3 representative bile canaliculi were taken under phase-contrast microscopy for 12 h. The number of bile canalicular contractions and the intervals between consecutive canalicular contractions were calculated. Furthermore, the effects of TLC on IRHC were examined by transmission electron microscopy.RESULTS: The bile canalicular contractions were spontaneous and forceful in the controls. Active vesicular movement was observed in the pericanalicular region. Immediately after the addition of TLC, the bile canaliculi were deformed, and canalicular bile was incorporated into the vacuoles. The canaliculi were gradually dilated, and canalicular contractions were markedly inhibited by TLC. The vesicular movements became extremely slow in the pericanalicular region. The number of canalicular contractions significantly decreased in the TLC-treated groups, as compared with that in the controls. The time intervals were prolonged, as the TLC dosage increased,indicating that bile secretion into the canaliculi was impaired with TLC. Transmission electron microscopy revealed the lamellar transformation of the canalicular membranes in IRHC treated with TLC.CONCLUSION: TLC impairs both the bile canalicular contractions and the canalicular bile secretion, possibly by acting directly on the canalicular membranes in TLCinduced cholestasis.

  14. Decompensated liver cirrhosis and neural regulation of mesenteric vascular tone in rats: role of sympathetic, nitrergic and sensory innervations

    Science.gov (United States)

    Sastre, Esther; Caracuel, Laura; Prieto, Isabel; Llévenes, Pablo; Aller, M. Ángeles; Arias, Jaime; Balfagón, Gloria; Blanco-Rivero, Javier

    2016-01-01

    We evaluated the possible alterations produced by liver cholestasis (LC), a model of decompensated liver cirrhosis in sympathetic, sensory and nitrergic nerve function in rat superior mesenteric arteries (SMA). The vasoconstrictor response to electrical field stimulation (EFS) was greater in LC animals. Alpha-adrenoceptor antagonist phentolamine and P2 purinoceptor antagonist suramin decreased this response in LC animals more than in control animals. Both non-specific nitric oxide synthase (NOS) L-NAME and calcitonin gene related peptide (CGRP) (8-37) increased the vasoconstrictor response to EFS more strongly in LC than in control segments. Vasomotor responses to noradrenaline (NA) or CGRP were greater in LC segments, while NO analogue DEA-NO induced a similar vasodilation in both experimental groups. The release of NA was not modified, while those of ATP, nitrite and CGRP were increased in segments from LC. Alpha 1 adrenoceptor, Rho kinase (ROCK) 1 and 2 and total myosin phosphatase (MYPT) expressions were not modified, while alpha 2B adrenoceptor, nNOS expression and nNOS and MYPT phosphorylation were increased by LC. Together, these alterations might counteract the increased splanchnic vasodilation observed in the last phases of decompensated liver cirrhosis. PMID:27484028

  15. Acute Acalculous Cholecystitis: A Rare Presentation of Primary Epstein-Barr Virus Infection in Adults—Case Report and Review of the Literature

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    Zuhal Yesilbag

    2017-01-01

    Full Text Available Primary Epstein-Barr virus (EBV infection is almost always a self-limited disease characterized by sore throat, fever, and lymphadenopathy. Hepatic involvement is usually characterized by mild elevations of aminotransferases and resolves spontaneously. Although isolated gallbladder wall thickness has been reported in these patients, acute acalculous cholecystitis is an atypical presentation of primary EBV infection. We presented a young women admitted with a 10-day history of fever, nausea, malaise who had jaundice and right upper quadrant tenderness on the physical examination. Based on diagnostic laboratory tests and abdominal ultrasonographic findings, cholestasis and acute acalculous cholecystitis were diagnosed. Serology performed for EBV revealed the acute EBV infection. Symptoms and clinical course gradually improved with the conservative therapy, and at the 1-month follow-up laboratory findings were normal. We reviewed 16 adult cases with EBV-associated AAC in the literature. Classic symptoms of EBV infection were not predominant and all cases experienced gastrointestinal symptoms. Only one patient underwent surgery and all other patients recovered with conservative therapy. The development of AAC should be kept in mind in patients with cholestatic hepatitis due to EBV infection to avoid unnecessary surgical therapy and overuse of antibiotics.

  16. Acute Acalculous Cholecystitis: A Rare Presentation of Primary Epstein-Barr Virus Infection in Adults—Case Report and Review of the Literature

    Science.gov (United States)

    Karadeniz, Asli; Kaya, Fatih Oner

    2017-01-01

    Primary Epstein-Barr virus (EBV) infection is almost always a self-limited disease characterized by sore throat, fever, and lymphadenopathy. Hepatic involvement is usually characterized by mild elevations of aminotransferases and resolves spontaneously. Although isolated gallbladder wall thickness has been reported in these patients, acute acalculous cholecystitis is an atypical presentation of primary EBV infection. We presented a young women admitted with a 10-day history of fever, nausea, malaise who had jaundice and right upper quadrant tenderness on the physical examination. Based on diagnostic laboratory tests and abdominal ultrasonographic findings, cholestasis and acute acalculous cholecystitis were diagnosed. Serology performed for EBV revealed the acute EBV infection. Symptoms and clinical course gradually improved with the conservative therapy, and at the 1-month follow-up laboratory findings were normal. We reviewed 16 adult cases with EBV-associated AAC in the literature. Classic symptoms of EBV infection were not predominant and all cases experienced gastrointestinal symptoms. Only one patient underwent surgery and all other patients recovered with conservative therapy. The development of AAC should be kept in mind in patients with cholestatic hepatitis due to EBV infection to avoid unnecessary surgical therapy and overuse of antibiotics. PMID:28194287

  17. Targeted inhibition of the FGF19-FGFR4 pathway in hepatocellular carcinoma; translational safety considerations.

    Science.gov (United States)

    Mellor, Howard R

    2014-07-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death and new therapies are urgently required to treat this disease. Recent data suggest that the FGF19-FGFR4 axis may be a key driver in certain forms of HCC, making the pathway an interesting, emerging molecular target for potential therapeutic intervention. A complication is that, outside of malignant disease, FGFR4 plays an important physiological role in the regulation of hepatic bile acid (BA) synthesis. FGF19 signalling via FGFR4 suppresses de novo BA production in the liver, tightly maintaining hepatic and systemic levels of these detergent-like molecules at a physiological threshold and preventing pathological complications of raised BA levels, such as cholestatic liver injury and bile acid diarrhoea. In some cases of HCC, the malignant disease causes bile duct obstruction, preventing BA secretion from the liver and resulting in cholestasis. Here, the role of FGFR4 signalling in both HCC and BA homoeostasis is discussed. The potential effects of therapeutic FGF19-FGFR4 inhibition on human hepatobiliary/gastrointestinal physiology are considered along with the potential safety implications of FGF19-FGFR4 blockade in patients with HCC.

  18. A nontumorigenic variant of FGF19 treats cholestatic liver diseases.

    Science.gov (United States)

    Luo, Jian; Ko, Brian; Elliott, Michael; Zhou, Mei; Lindhout, Darrin A; Phung, Van; To, Carmen; Learned, R Marc; Tian, Hui; DePaoli, Alex M; Ling, Lei

    2014-07-30

    Hepatic accumulation of bile acids is central to the pathogenesis of cholestatic liver diseases. Endocrine hormone fibroblast growth factor 19 (FGF19) may reduce hepatic bile acid levels through modulation of bile acid synthesis and prevent subsequent liver damage. However, FGF19 has also been implicated in hepatocellular carcinogenesis, and consequently, the potential risk from prolonged exposure to supraphysiological levels of the hormone represents a major hurdle for developing an FGF19-based therapy. We describe a nontumorigenic FGF19 variant, M70, which regulates bile acid metabolism and, through inhibition of bile acid synthesis and reduction of excess hepatic bile acid accumulation, protects mice from liver injury induced by either extrahepatic or intrahepatic cholestasis. Administration of M70 in healthy human volunteers potently reduces serum levels of 7α-hydroxy-4-cholesten-3-one, a surrogate marker for the hepatic activity of cholesterol 7α-hydroxylase (CYP7A1), the enzyme responsible for catalyzing the first and rate-limiting step in the classical bile acid synthetic pathway. This study provides direct evidence for the regulation of bile acid metabolism by FGF19 pathway in humans. On the basis of these results, the development of nontumorigenic FGF19 variants capable of modulating CYP7A1 expression represents an effective approach for the prevention and treatment of cholestatic liver diseases as well as potentially for other disorders associated with bile acid dysregulation.

  19. Pregnancy Dermatoses%妊娠期特异性皮肤病

    Institute of Scientific and Technical Information of China (English)

    敖俊红; 杨蓉娅

    2011-01-01

    The nomcnclature and nosologic classification of pregnancy dermatoses are still confusing,around which the dispute had been existing for a long time.According to the new classification system.the diseases were classified into five classes.which known as pemphigoid gestationis,intrahepatic cholestasis of pregnancy, impetigo herpetiformis, polymorphic eruption of pregnancy and papular dermatoses of pregnancy(prurigo of pregnancy.pruritic folliculitis of pregnancy and atopic eruption of pregnancy).The review focused on the advances in the following issues about pregnancy dermatoses:classification, characterization of clinical manifestations, diagnosis and management, prognosis and impacts on fetals.%妊娠期特异性皮肤病的命名及分类一直存在争议,最新的分类将其分为妊娠性类天疱疮、妊娠肝内胆汁淤积、疱疹样脓疱病、妊娠性多形疹、妊娠丘疹性皮肤病(包括妊娠痒疹、妊娠瘙痒性毛囊炎及妊娠特应性皮肤病)五类.本文主要介绍妊娠期特异性皮肤病的分类、临床特点、诊断和鉴别诊断、治疗、预后及对胎儿的影响等方面的研究进展.

  20. Prognostic value of hedgehog signal component expressions in hepatoblastoma patients

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    Li Ying-Cun

    2010-11-01

    Full Text Available Abstract Objective Activation of hedgehog (Hh pathway has been implicated in the development of human malignancies. Hh as well as related downstream target genes has been extensively studied in many kinds of malignant tumours for clinical diagnostic or prognostic utilities. This study aimed at investigating whether Hh molecules provides a molecular marker of hepatoblastoma malignancy. Methods We obtained tissue sections from 32 patients with hepatoblastoma as well as cholestasis and normal control. Immunohistochemical analysis were performed to determine Hh signal components in human hepatoblastoma. The prognostic significance of single expression of Hh signal components were evaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis for statistical analysis. Results Expression of Hh signal components showed an increase in hepatoblastoma compared with chole stasis and normal tissues. There was a positive correlation between Smo or Gli1 expression and tumor clinicopathological features, such as histological type, tumor grade, tumor size and clinical stage. Both Smo or Gli1 protein high expression was significantly associated with poor prognosis by univariate analyses and multivariate analyses. Conclusions Abnormal Hh signaling activation plays important roles in the malignant potential of hepatoblastoma. Gli1 expression is an independent prognostic marker.

  1. Early Hepatic Dysfunction in a Large Animal Model of Nonhypotensive Sepsis

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    Stephen Sullivan

    1991-01-01

    Full Text Available Sepsis was induced in 12 sheep by cecal devascularization and perforation. Intravenous crystalloid was administered to maintain th e pulmonary capillary wedge pressure at preseptic levels. By 24 h there was a significant drop in albumin and alkaline phosphatase with increases in aspartate aminotransferase (AST, lactate dehydrogenase and bilirubin. By 48 h the alkaline phosphatase had returned to presepsis levels, the bilirubin continued to rise, the AST and lactate dehydrogenase had plateaued while the alhumin remained low. These biochemical alterations were confirmed by examining data from 25 sheer used in similar sepsis experiments. These data revealed that marked elevations in AST were associated with a higher central venous pressure and worse renal impairment, but there was no relationship with any other hemodynamic parameter, PO2, pH or serum lactate. Histologically these biochemical alterations were associated with extensive microvesicular fatty change at 24 h and centrilobular necrosis at 48 h. Electron microscopy revealed mitochondrial degeneration, hyperplasia of the smooth endoplasmic reticulum and intracellular cholestasis.

  2. Hepatite de Lábrea em Salvador, BA?: (Apresentação de um possível caso Labrea hepatitis in Salvador, BA?: (Report of a possible case

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    Zilton A. Andrade

    1983-12-01

    Full Text Available Um menino de quatro anos de idade, natural e residente em Salvador, Bahia, apresentou uma doença febril, de curso rápido com febre, icterícia, dores abdominais, agitação psicomotora, coma e morte no 7º dia do internamento. Histologicamente o fígado exibiu extensa necrose lítica e de coagulação dos hepatócitos, além de degeneração gordurosa aguda ("células em mórula", infiltração mononuclear e colestase, um quadro considerado tipico da hepatite de Lábrea. A existência de tal caso levanta o problema da ocorrência de hepatite de Lábrea fora da Região Amazônica ou aquele de falta de especificidade do quadro histopatológico considerado como típico da referida condição.A case of a four-year-old boy from Salvador, Bahia, Brazil, with a probable Labrea hepatitis is reported. He ran a rapid course of fever, jaundice, abdominal pain, agitation, coma and death. Histologically, the liver presented widespread hepatic cell lytic and coagulative necrosis, acute fatty changes, mononuclear cell infiltration and cholestasis. The study of the case raises the question whether Lábrea hepatitis can occur outside the Amazonian region, or else its clinico-pathological features lack specificity.

  3. Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement.

    Science.gov (United States)

    Nakanuma, Yasuni; Zen, Yoh; Harada, Kenichi; Sasaki, Motoko; Nonomura, Akitaka; Uehara, Takeshi; Sano, Kenji; Kondo, Fukuo; Fukusato, Toshio; Tsuneyama, Koichi; Ito, Masahiro; Wakasa, Kenichi; Nomoto, Minoru; Minato, Hiroshi; Haga, Hironori; Kage, Masayoshi; Yano, Hirohisa; Haratake, Joji; Aishima, Shinichi; Masuda, Tomoyuki; Aoyama, Hajime; Miyakawa-Hayashino, Aya; Matsumoto, Toshiharu; Sanefuji, Hayato; Ojima, Hidenori; Chen, Tse-Ching; Yu, Eunsil; Kim, Ji-Hun; Park, Young Nyun; Tsui, Wilson

    2010-03-01

    Recently the authors proposed a new staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histological heterogeneity. Herein is proposed a convenient version of this system. Scores for fibrosis, bile duct loss, and chronic cholestasis were combined for staging: stage 1, total score of 0; stage 2, score 1-3; stage 3, score 4-6; and stage 4, score 7-9. Cholangitis activity (CA) and hepatitis activity (HA) were graded as CA0-3, and HA0-3, respectively. Analysis of interobserver agreement was then conducted. Digital images of 62 needle liver biopsy specimens of PBC were recorded as virtual slides on DVDs that were sent to 28 pathologists, including five located overseas. All participants were able to apply this version in all 62 cases. For staging, kappa was 0.385 (fair agreement) and the concordance rate was 63.9%. For necroinflammatory activity, the kappa and concordance rate were 0.110 (slight agreement) and 36.9% for CA, and 0.197 (slight agreement) and 47% for HA, respectively. In conclusion, this new staging and grading system for PBC seems to be more convenient and practical than those used at present, but more instruction and guidance are recommended for the grading of necroinflammatory activity in practice.

  4. After 3 years of starvation: duodenum swallowed remaining stomach.

    Science.gov (United States)

    Hillenbrand, Andreas; Waidner, Uta; Henne-Bruns, Doris; Maria Wolf, Anna; Buttenschoen, Klaus

    2009-05-01

    A 42-year-old morbidly obese patient (BMI 44.1 kg/m(2)) was admitted to our emergency room with upper abdominal pain, nausea, and cholestasis. Nine years ago, a vertical banded gastroplasty had been performed (former BMI 53.5 kg/m(2)) with a subsequent weight loss to BMI 33.0 kg/m(2). After regaining weight up to a BMI of 47.6 kg/m(2), 5 years ago a conversion to a gastric bypass was realized. A computed tomography of the abdomen showed an invagination of the remaining stomach into the duodenum causing obstruction of the orifice of common bile duct. The patient underwent an open desinvagination of the intussusception and resection of the remaining stomach. Gastroduodenal intussusception is rare and mostly secondary to gastric lipoma. To prevent this rare but serious complication, the remaining stomach could be fixed at the crura of the diaphragm, tagged to the anterior abdominal wall by temporary gastrostomy tube, or resected.

  5. Microarray Study of Pathway Analysis Expression Profile Associated with MicroRNA-29a with Regard to Murine Cholestatic Liver Injuries

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    Sung-Chou Li

    2016-03-01

    Full Text Available Accumulating evidence demonstrates that microRNA-29 (miR-29 expression is prominently decreased in patients with hepatic fibrosis, which consequently stimulates hepatic stellate cells’ (HSCs activation. We used a cDNA microarray study to gain a more comprehensive understanding of genome-wide gene expressions by adjusting miR-29a expression in a bile duct-ligation (BDL animal model. Methods: Using miR-29a transgenic mice and wild-type littermates and applying the BDL mouse model, we characterized the function of miR-29a with regard to cholestatic liver fibrosis. Pathway enrichment analysis and/or specific validation were performed for differentially expressed genes found within the comparisons. Results: Analysis of the microarray data identified a number of differentially expressed genes due to the miR-29a transgene, BDL, or both. Additional pathway enrichment analysis revealed that TGF-β signaling had a significantly differential activated pathway depending on the occurrence of miR-29a overexpression or the lack thereof. Furthermore, overexpression was found to elicit changes in Wnt/β-catenin after BDL. Conclusion: This study verified that an elevated miR-29a level could alleviate liver fibrosis caused by cholestasis. Furthermore, the protective effects of miR-29a correlate with the downregulation of TGF-β and associated with Wnt/β-catenin signal pathway following BDL.

  6. Effects of bile acids and the bile acid receptor FXR agonist on the respiratory rhythm in the in vitro brainstem medulla slice of neonatal Sprague-Dawley rats.

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    Cong Zhao

    Full Text Available Intrahepatic cholestasis of pregnancy is always accompanied by adverse fetal outcomes such as malfunctions of respiration. Farnesoid X receptor (FXR plays a critical role in the homeostasis of bile acids. Thus, we are determined to explore the effects of farnesoid X receptor (FXR and five bile acids on respiratory rhythm generation and modulation of neonatal rats. Spontaneous periodic respiratory-related rhythmical discharge activity (RRDA was recorded from hypoglossal nerves during the perfusion of modified Krebs solution. Group 1-6 was each given GW4064 and five bile acids of chenodeoxycholic acid (CDCA, deoxycholic acid (DCA, lithocholic acid (LCA, cholic acid (CA as well as ursodeoxycholic acid (UDCA at different concentrations to identify their specific functions on respiratory rhythm modulations. Group 7 was applied to receive FXR blocker Z-guggulsterone and Z-guggulsterone with the above bile acids separately to explore the role of FXR in the respiratory rhythm modulation. Group 8 was given dimethyl sulfoxide (DMSO as controls. Apart from UDCA, CDCA, DCA LCA and CA all exerted effects on RRDA recorded from hypoglossal nerves in a concentration-dependent manner. Respiratory cycle (RC, Inspiratory time (TI, Expiratory Time (TE and Integral Amplitude (IA were influenced and such effects could be reversed by Z-guggulsterone. FXR may contribute to the effects on the modulation of respiratory rhythm exerted by bile acids.

  7. Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

    Institute of Scientific and Technical Information of China (English)

    Matthias Froh; Ronald G Thurman; Lars Conzelmann; Peter Walbrun; Susanne Netter; Reiner Wiest; Michael D Wheeler; Mark Lehnert; Takehiko Uesugi; Jurgen Scholmerich

    2007-01-01

    AIM: To investigate the effects of heme oxygenase-1(HO-1) against oxidant-induced injury caused by bile duct ligation (BDL).METHODS: Either cobalt protoporphyrin (CoPP), a HO-1 inducer, or saline were injected intraperitoneally in male SD-rats. Three days later, BDL or sham-operations were performed. Rats were sacrificed 3 wk after BDL and livers were harvested for histology. Fibrosis was evaluated by sirius red staining and image analysis.Alpha-smooth muscular actin, which indicates activation of stellate cells, was detected by immunohistochemical staining, and cytokine and collagen- Ⅰα (Col- Ⅰα) mRNA expression was detected using RNase protection assays.RESULTS: Serum alanine transaminase increased 8-fold above normal levels one day after BDL. Surprisingly,enzyme release was not reduced in rats receiving CoPP.Liver fibrosis was evaluated 3 wk after BDL and the sirius red-positive area was found to be increased to about 7.8%. However, in CoPP pretreated rats sirius redpositive areas were increased to about 11.7% after BDL.Collagen- Ⅰα and TGF-β mRNA increased significantly by BDL. Again, this effect was increased by HO-1overexpression.CONCLUSION: Hepatic fibrosis due to BDL is not reduced by the HO-1 inducer CoPP. In contrast, HO-1overexpression increases liver injury in rats under conditions of experimental chronic cholestasis.

  8. Liver disease in pregnancy

    Institute of Scientific and Technical Information of China (English)

    Noel M Lee; Carla W Brady

    2009-01-01

    Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy.

  9. Possible protective role of pregnenolone-16 alpha-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis.

    Science.gov (United States)

    Miyata, Masaaki; Nomoto, Masahiro; Sotodate, Fumiaki; Mizuki, Tomohiro; Hori, Wataru; Nagayasu, Miho; Yokokawa, Shinya; Ninomiya, Shin-ichi; Yamazoe, Yasushi

    2010-06-25

    Lithocholic acid (LCA) feeding causes both liver parenchymal and cholestatic damages in experimental animals. Although pregnenolone-16 alpha-carbonitrile (PCN)-mediated protection against LCA-induced hepatocyte injury may be explained by induction of drug metabolizing enzymes, the protection from the delayed cholestasis remains incompletely understood. Thus, the PCN-mediated protective mechanism has been studied from the point of modification of lipid metabolism. At an early stage of LCA feeding, an imbalance of biliary bile acid and phospholipid excretion was observed. Co-treatment with PCN reversed the increase in serum alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities and hepatic hydrophobic bile acid levels. LCA feeding decreased hepatic mRNA levels of several fatty acid- and phospholipid-related genes before elevation of serum ALT and ALP activities. On the other hand, PCN co-treatment reversed the decrease in the mRNA levels and hepatic levels of phospholipids, triglycerides and free fatty acids. PCN co-treatment also reversed the decrease in biliary phospholipid output in LCA-fed mice. Treatment with PCN alone increased hepatic phospholipid, triglyceride and free fatty acid concentrations. Hepatic fatty acid and phosphatidylcholine synthetic activities increased in mice treated with PCN alone or PCN and LCA, compared to control mice, whereas these activities decreased in LCA-fed mice. These results suggest the possibility that PCN-mediated stimulation of lipogenesis contributes to the protection from lithocholic acid-induced hepatotoxicity.

  10. Biliary tract obstruction secondary to Burkitt lymphoma; Linfoma de Burkitt associado a obstrucao de vias biliares

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Wellington L.; Bezerra, Alanna Mara P.S.; Carvalho Filho, Nevicolino P.; Coelho, Robson C. [Hospital do Cancer, Sao Paulo, SP (Brazil). Centro de Tratamento e Pesquisa. Dept. de Pediatria; Soares, Fernando A. [Hospital do Cancer, Sao Paulo, SP (Brazil). Centro de Tratamento e Pesquisa. Dept. de Patologia; Pecora, Marcela S. [Hospital do Cancer, Sao Paulo, SP (Brazil). Centro de Tratamento e Pesquisa. Dept. de Imagem; Chapchap, Paulo [Hospital do Cancer, Sao Paulo, SP (Brazil). Centro de Tratamento e Pesquisa. Servico de Cirurgia Pediatrica

    2004-09-01

    The abdomen, in particular the ileocecal region, appendix and colon, is the most common primary site for Burkitt non Hodgkin's lymphoma (NHL). Involvement of the bile duct is rare. The authors describe a patient with abdominal NHL in which jaundice due to bile duct obstruction was the first clinical sign. Case report: a 3 year old white boy presented with one month of progressive jaundice, clay-colored stools, tea colored urine and increase of abdominal volume. Physical examination showed jaundice 3+/4+ and pale mucosa. The abdomen was moderately distended and timpanous and the liver was enlarged. Laboratory examinations confirmed cholestasis with total bilirubin of 8.2 mg/dl (direct bilirubin of 7.8 mg/dl), and microcytic and hypochromic anemia. Ultrasonography (US) and abdominal CT showed two solid tumors in hepatic hilar topography, and dilated intrahepatic biliary tree. The Doppler US showed hepatic artery and portal vein dislocation by the nodules. Comment: although jaundice occurs frequently as a late manifestation of NHL, it is rarely seen as the presenting sign. When jaundice is the first clinical sign and image studies show hepatic hilar tumor and bile duct obstruction, NHL should be considered in the differential diagnosis. (author)

  11. Intramural Duodenal Haematoma after Endoscopic Biopsy: Case Report and Review of the Literature

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    Claudia Grasshof

    2012-01-01

    Full Text Available The development of intramural duodenal haematoma (IDH after small bowel biopsy is an unusual lesion and has only been reported in 18 children. Coagulopathy, thrombocytopenia and some special features of duodenal anatomy, e.g. relatively fixed position in the retroperitoneum and numerous submucosal blood vessels, have been suggested as a cause for IDH. The typical clinical presentation of IDH is severe abdominal pain and vomiting due to duodenal obstruction. In addition, it is often associated with pancreatitis and cholestasis. Diagnosis is confirmed using imaging techniques such as ultrasound, magnetic resonance imaging or computed tomography and upper intestinal series. Once diagnosis is confirmed and intestinal perforation excluded, conservative treatment with nasogastric tube and parenteral nutrition is sufficient. We present a case of massive IDH following endoscopic grasp forceps biopsy in a 5-year-old girl without bleeding disorder or other risk for IDH, which caused duodenal obstruction and mild pancreatitis and resolved within 2 weeks of conservative management. Since duodenal biopsies have become the common way to evaluate children or adults for suspected enteropathy, the occurrence of this complication is likely to increase. In conclusion, the review of the literature points out the risk for IDH especially in children with a history of bone marrow transplantation or leukaemia.

  12. Graft-Versus-Host Disease after Liver Transplantation Complicated by Systemic Aspergillosis with Pancarditis

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    Joseph Romagnuolo

    2000-01-01

    Full Text Available Acute graft-versus-host disease (GVHD is a common complication after bone marrow transplantation, with characteristic rash and diarrhea being the most common features. After liver transplantation, however, this phenomenon is very rare. Most transplant patients are on a variety of medications, including immunosuppressants; therefore, the differential diagnosis of skin rash or diarrhea is broad. A 37-year-old man who underwent liver transplantation for primary biliary cirrhosis, and developed a rash and watery diarrhea, is presented. Skin and colonic biopsies confirmed acute GVHD. A pulse of intravenous steroids was given. The skin rash improved, but he developed pancytopenia. His course was complicated by central line infection, jugular and subclavian vein thrombosis, pseudomembranous colitis, recurrent bacteremia, cholestasis on total parenteral nutrition and cytomegalovirus infection. After the onset of pleuritic chest pain and clinical sepsis, spiral computed tomography scan of his chest and abdomen revealed septic infarcts in multiple organs. Despite empirical treatment with amphotericin B, he died of multiorgan dysfunction syndrome within 72 h. Autopsy revealed systemic aspergillosis with pancarditis, endocardial vegetations, and septic pulmonary, splenic, hepatic and renal infarcts. The pathogenesis and experience with this rare, but often fatal, complication of liver transplantation are reviewed. In contrast to GVHD after bone marrow transplantation, pancytopenia is common and liver dysfunction is rare. One should have a high level of suspicion in the liver transplant recipient presenting with rash and/or diarrhea.

  13. Two- and Three-Dimensional Quantitative Structure-Activity Relationships Studies on a Series of Liver X Receptor Ligands

    Science.gov (United States)

    Honório, Káthia M; Salum, Lívia B; Garratt, Richard C; Polikarpov, Igor; Andricopulo, Adriano D

    2008-01-01

    Liver X receptor (LXR) is an attractive drug target for the development of novel therapeutic agents for the treatment of dyslipidaemia and cholestasis. In the present work, comparative molecular field analysis (CoMFA) and hologram quantitative structure-activity relationship (HQSAR) studies were conducted on a series of potent LXR ligands. Significant correlation coefficients (CoMFA, r2 = 0.98 and q2 = 0.69; HQSAR, r2 = 0.99 and q2 = 0.85) were obtained, indicating the potential of the models for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values obtained from the 2D and 3D models were in good agreement with the experimental results. The final QSAR models, along with the information obtained from 3D steric and electrostatic contour maps and 2D contribution maps should be useful for the design of novel LXR ligands having improved potency. PMID:19696872

  14. Voriconazole and the liver

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Voriconazole is an azole useful for the prophylaxis andthe treatment of aspergillosis and other fungal infectionsin immunosuppressed subjects, as those found in aplasiaafter aggressive polychemotherapy treatments, afterhematopoietic stem cell, liver or lung transplantation.Its administration in therapeutic doses lead to extremelyvaried serum levels from patient to patient and even tothe same patient. The explanations are varied nonlinearpharmacokinetics, certain patient-related factors,including genetic polymorphisms in the cytochrome P4502C19 gene, the kidney and liver function, simultaneousadministration with other drugs metabolised by the samecytochrome. It is recommended to maintain the serumconcentrations of voriconazole between 1.5 and 4 μg/mL.At lower values its efficacy decreases and at highervalues the risk of neurological toxicity increases. Evenat these concentrations it is not excluded the possibleappearance of a variety of toxic effects, including onthe liver, manifested by cholestasis, hepatocytolisis, ortheir combination. It is recommended to monitor theclinical and laboratory evolution of all patients treatedwith voriconazole, and of the serum levels of the drugof those who belong to risk groups, even if there is stillno consensus on this issue, given the lack of correlationbetween the serum level and the occurrence of adverseeffects in many patients.

  15. Biochemical mechanisms in drug-induced liver injury: Certainties and doubts

    Institute of Scientific and Technical Information of China (English)

    Ignazio Grattagliano; Leonilde Bonfrate; Catia V Diogo; Helen H Wang; David QH Wang; Piero Portincasa

    2009-01-01

    Drug-induced liver injury is a significant and still unresolved clinical problem. Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development. Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites. Aging, preexisting liver disease, enzyme induction or inhibition, genetic variances, local O_2 supply and, above all, the intrinsic molecular properties of the drug may affect this process. Necrotic death follows antioxidant consumption and oxidation of intracellular proteins, which determine increased permeability of mitochondrial membranes, loss of potential, decreased ATP synthesis, inhibition of Ca~(2+)-dependent ATPase, reduced capability to sequester Ca~(2+) within mitochondria, and membrane bleb formation. Conversely, activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis. Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage. Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis, in which different HLA genotypes might play a major role. This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage. Future perspectives including new frontiers for research are discussed.

  16. Nosocomial Staphylococcal Toxic Shock. Case Report

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    Arbune Manuela

    2016-07-01

    Full Text Available Staphylococcal toxic shock syndrome (STSS is a rare, potentially lethal infection, with a clinical picture of multiple organ dysfunction and shock. The etiology is Staphylococcus aureus exotoxin, while enterotoxins act as superantigens. Most cases are identified in women using a vaginal tampon. A 51-year-old female, with a past medical history of biliary dyskinesia, presented in the emergency room complaining of sudden onset of abdominal pain, vomiting, headache, myalgia, and chills. The initial diagnosis was biliary colic and was treated parenterally with Amoxi-clavulanate and fluid replacement. Initially, progress was unsatisfactory. Four days after admission she developed a systemic inflammatory syndrome, diffuse rash, jaundice, oliguria, confusion, persistent hypotension and biological evidence of thrombocytopenia, nitrogen retention, and cholestasis. She was admitted to the intensive care unit. A gluteal phlegmon induced after intramuscular injections was identified and surgically treated. Blood bacteriological cultures were negative, though MRSA was isolated in phlegmon pus. A diagnosis of STSS was based on CDC criteria.

  17. Complications and Monitoring – Guidelines on Parenteral Nutrition, Chapter 11

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    Working group for developing the guidelines for parenteral nutrition of The German Association for Nutritional Medicine

    2009-11-01

    Full Text Available Compared to enteral or hypocaloric oral nutrition, the use of PN (parenteral nutrition is not associated with increased mortality, overall frequency of complications, or longer length of hospital stay (LOS. The risk of PN complications (e.g. refeeding-syndrome, hyperglycaemia, bone demineralisation, catheter infections can be minimised by carefully monitoring patients and the use of nutrition support teams particularly during long-term PN. Occuring complications are e.g. the refeeding-syndrome in patients suffering from severe malnutrition with the initiation of refeeding or metabolic, hypertriglyceridemia, hyperglycaemia, osteomalacia and osteoporosis, and hepatic complications including fatty liver, non-alcoholic fatty liver disease, cholestasis, cholecystitis, and cholelithiasis. Efficient monitoring in all types of PN can result in reduced PN-associated complications and reduced costs. Water and electrolyte balance, blood sugar, and cardiovascular function should regularly be monitored during PN. Regular checks of serum electrolytes and triglycerides as well as additional monitoring measures are necessary in patients with altered renal function, electrolyte-free substrate intake, lipid infusions, and in intensive care patients. The metabolic monitoring of patients under long-term PN should be carried out according to standardised procedures. Monitoring metabolic determinants of bone metabolism is particularly important in patients receiving long-term PN. Markers of intermediary, electrolyte and trace element metabolism require regular checks.

  18. Portal biliopathy.

    Science.gov (United States)

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-09-21

    Portal biliopathy refers to cholangiographic abnormalities which occur in patients with portal cavernoma. These changes occur as a result of pressure on bile ducts from bridging tortuous paracholedochal, epicholedochal and cholecystic veins. Bile duct ischemia may occur due prolonged venous pressure effect or result from insufficient blood supply. In addition, encasement of ducts may occur due fibrotic cavernoma. Majority of patients are asymptomatic. Portal biliopathy is a progressive disease and patients who have long standing disease and more severe bile duct abnormalities present with recurrent episodes of biliary pain, cholangitis and cholestasis. Serum chemistry, ultrasound with color Doppler imaging, magnetic resonance imaging with magnetic resonance cholangiopancreatography and magnetic resonance portovenography are modalities of choice for evaluation of portal biliopathy. Endoscopic retrograde cholangiography being an invasive procedure is indicated for endotherapy only. Management of portal biliopathy is done in a stepwise manner. First, endotherapy is done for dilation of biliary strictures, placement of biliary stents to facilitate drainage and removal of bile duct calculi. Next portal venous pressure is reduced by formation of surgical porto-systemic shunt or transjugular intrahepatic portosystemic shunt. This causes significant resolution of biliary changes. Patients who persist with biliary symptoms and bile duct changes may benefit from surgical biliary drainage procedures (hepaticojejunostomy or choledechoduodenostomy).

  19. A transcriptomics-based hepatotoxicity comparison between the zebrafish embryo and established human and rodent in vitro and in vivo models using cyclosporine A, amiodarone and acetaminophen.

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    Driessen, Marja; Vitins, Alexa P; Pennings, Jeroen L A; Kienhuis, Anne S; Water, Bob van de; van der Ven, Leo T M

    2015-01-22

    The zebrafish embryo (ZFE) is a promising alternative, non-rodent model in toxicology, which has an advantage over the traditionally used models as it contains complete biological complexity and provides a medium to high-throughput setting. Here, we assess how the ZFE compares to the traditionally used models for liver toxicity testing, i.e., in vivo mouse and rat liver, in vitro mouse and rat hepatocytes, and primary human hepatocytes. For this comparison, we analyzed gene expression changes induced by three model compounds for cholestasis, steatosis, and necrosis. The three compounds, cyclosporine A, amiodarone, and acetaminophen, were chosen because of their relevance to human toxicity and these compounds displayed hepatotoxic-specific changes in the mouse in vivo data. Compound induced expression changes in the ZFE model shared similarity with both in vivo and in vitro. Comparison on single gene level revealed the presence of model specific changes and no clear concordance across models. However, concordance was identified on the pathway level. Specifically, the pathway "regulation of metabolism - bile acids regulation of glucose and lipid metabolism via FXR" was affected across all models and compounds. In conclusion, our study with three hepatotoxic model compounds shows that the ZFE model is at least as comparable to traditional models in identifying hepatotoxic activity and has the potential for use as a pre-screen to determine the hepatotoxic potential of compounds.

  20. Obstructive jaundice activates nitroxidergic neurons of the vago-vagal neural circuit that regulates the hepatobiliary system in rabbits.

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    Hu, Ming-E; Lin, Yung-Chang; Chang, Hung-Ming; Tyan, Yeu-Sheng; Lan, Chyn-Tair

    2012-01-01

    In this study, we investigated the expression of neuronal nitric oxide synthase (nNOS) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), two specific enzymes for nitric oxide (NO) synthesis, in the development of liver fibrosis induced by chronic bile duct ligation (BDL) in the rabbit. We specifically studied the liver-innervated nitroxidergic neurons that originate in the nodose ganglion (NG), nucleus of the solitary tract (NTS) and dorsal motor vagal nucleus (DMV). Our data showed that BDL resulted in overexpression of NADPH-d/nNOS in the NG, NTS and DMV neurons. Using densitometric analysis, we found a significant increase in NADPH-d expression as a result of BDL in the NG, NTS and DMV (72.6, 79.4 and 57.4% increase, respectively). These findings were corroborated by serum biochemistry and hepatic histopathological examination, which were influenced by NADPH-d/nNOS-generated NO in the liver following BDL. Upregulation of NADPH-d/nNOS expression may have important implications, including (1) facilitation of extrahepatic biliary parasympathetic tone that promotes gallbladder emptying of excess stagnant bile; (2) relaxation of smooth muscles of bile canaliculi thus participating in the pathogenesis of cholestasis; (3) dilation of hepatic sinusoids to counter BDL-induced intrahepatic portal hypertension in which endothelia may be damaged, and (4) alterations in hepatic metabolism, such as glycogenesis, bile formation and secretion, and bilirubin clearance.

  1. Physiology of bile secretion

    Institute of Scientific and Technical Information of China (English)

    Alejandro Esteller

    2008-01-01

    The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment,in different situations,results in the syndrome of cholestasis.The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed.Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane.This review summarizes recent data on the molecular determinants of this primary bile formation.The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bileduct epithelial cells (cholangiocytes) as bile passes through bile ducts.The mechanisms of fluid and solute transport in cholangiocytes will also be discussed.In contrast to hepatocytes where secretion is constant and poorly controlled,cholangiocyte secretion is regulated by hormones and nerves.A short section dedicated to these regulatory mechanisms of bile secretion has been included.The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology.

  2. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element

    Science.gov (United States)

    Claudel, Thierry; Sturm, Ekkehard; Duez, Hélène; Torra, Inés Pineda; Sirvent, Audrey; Kosykh, Vladimir; Fruchart, Jean-Charles; Dallongeville, Jean; Hum, Dean W.; Kuipers, Folkert; Staels, Bart

    2002-01-01

    Serum levels of HDL are inversely correlated with the risk of coronary heart disease. The anti-atherogenic effect of HDL is partially mediated by its major protein constituent apoA-I. In this study, we identify bile acids that are activators of the nuclear receptor farnesoid X receptor (FXR) as negative regulators of human apoA-I expression. Intrahepatocellular accumulation of bile acids, as seen in patients with progressive familial intrahepatic cholestasis and biliary atresia, was associated with diminished apoA-I serum levels. In human apoA-I transgenic mice, treatment with the FXR agonist taurocholic acid strongly decreased serum concentrations and liver mRNA levels of human apoA-I, which was associated with reduced serum HDL levels. Incubation of human primary hepatocytes and hepatoblastoma HepG2 cells with bile acids resulted in a dose-dependent downregulation of apoA-I expression. Promoter mutation analysis and gel-shift experiments in HepG2 cells demonstrated that bile acid–activated FXR decreases human apoA-I promoter activity by a negative FXR response element mapped to the C site. FXR bound this site and repressed transcription in a manner independent of retinoid X receptor. The nonsteroidal synthetic FXR agonist GW4064 likewise decreased apoA-I mRNA levels and promoter activity in HepG2 cells. PMID:11927623

  3. An emerging, recognizable facial phenotype in association with mutations in GLI-similar 3 (GLIS3).

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    Dimitri, Paul; De Franco, Elisa; Habeb, Abdelhadi M; Gurbuz, Fatih; Moussa, Khairya; Taha, Doris; Wales, Jerry K H; Hogue, Jacob; Slavotinek, Anne; Shetty, Ambika; Balasubramanian, Meena

    2016-07-01

    Neonatal diabetes and hypothyroidism (NDH) syndrome was first described in 2003 in a consanguineous Saudi Arabian family where two out of four siblings were reported to have presented with proportionate IUGR, neonatal non-autoimmune diabetes mellitus, severe congenital hypothyroidism, cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by enlarged kidneys and multiple small cysts with deficient cortico-medullary junction differentiation and normal kidney function. There was minor facial dysmorphism (depressed nasal bridge, large anterior fontanelle, long philtrum) reported but no facial photographs were published. Mutations in the transcription factor GLI-similar 3 (GLIS3) gene in the original family and two other families were subsequently reported in 2006. All affected individuals had neonatal diabetes, congenital hypothyroidism but glaucoma and liver and kidney involvement were less consistent features. Detailed descriptions of the facial dysmorphism have not been reported previously. In this report, we describe the common facial dysmorphism consisting of bilateral low-set ears, depressed nasal bridge with overhanging columella, elongated, upslanted palpebral fissures, persistent long philtrum with a thin vermilion border of the upper lip in a cohort of seven patients with GLIS3 mutations and report the emergence of a distinct, probably recognizable facial gestalt in this group which evolves with age. © 2016 Wiley Periodicals, Inc.

  4. Alagille Syndrome and Wilson Disease in Siblings: A Diagnostic Conundrum

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    Meghan Amson

    2012-01-01

    Full Text Available The authors describe two siblings, each with a different, rare genetic condition that affects liver function. The index case, the 18-year-old asymptomatic brother of a young man recently diagnosed with Wilson disease, presented for Wilson disease screening and was also found to have abnormal liver function suggestive of cholestasis. However, ceruloplasmin level, 24 h urine copper concentration and liver synthetic function were normal. Further hepatic investigations and genetic mutation analysis were performed, ultimately leading to a diagnosis of Alagille syndrome. He was treated with ursodiol, which resulted in normalization of his liver function tests. Subsequently, he was found to be a carrier for a mutation in the Wilson disease gene, ATP7B. In the present report, the potential implications of being a heterozygote for Wilson disease in the context of Alagille syndrome are discussed. Also stressed is that care must be exercised by the clinician when diagnosing family members who may present with two different disorders closely mimicking one another.

  5. Waking action of ursodeoxycholic acid (UDCA involves histamine and GABAA receptor block.

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    Yevgenij Yanovsky

    Full Text Available Since ancient times ursodeoxycholic acid (UDCA, a constituent of bile, is used against gallstone formation and cholestasis. A neuroprotective action of UDCA was demonstrated recently in models of Alzheimer's disease and retinal degeneration. The mechanisms of UDCA action in the nervous system are poorly understood. We show now that UDCA promotes wakefulness during the active period of the day, lacking this activity in histamine-deficient mice. In cultured hypothalamic neurons UDCA did not affect firing rate but synchronized the firing, an effect abolished by the GABA(AR antagonist gabazine. In histaminergic neurons recorded in slices UDCA reduced amplitude and duration of spontaneous and evoked IPSCs. In acutely isolated histaminergic neurons UDCA inhibited GABA-evoked currents and sIPSCs starting at 10 µM (IC(50 = 70 µM and did not affect NMDA- and AMPA-receptor mediated currents at 100 µM. Recombinant GABA(A receptors composed of α1, β1-3 and γ2L subunits expressed in HEK293 cells displayed a sensitivity to UDCA similar to that of native GABA(A receptors. The mutation α1V256S, known to reduce the inhibitory action of pregnenolone sulphate, reduced the potency of UDCA. The mutation α1Q241L, which abolishes GABA(AR potentiation by several neurosteroids, had no effect on GABA(AR inhibition by UDCA. In conclusion, UDCA enhances alertness through disinhibition, at least partially of the histaminergic system via GABA(A receptors.

  6. Predictors of Fetal and Maternal Outcome in the Crucible of Hepatic Dysfunction During Pregnancy

    Science.gov (United States)

    Suresh, Indrajit; TR, Vijaykumar; HP, Nandeesh

    2017-01-01

    Background Hepatic dysfunction during pregnancy places both the mother and the fetus at risk. Investigations which are efficient, cost effective and easily available for prognostication are required to tackle this global problem. We studied the etiologies and evaluated investigations for predictive efficiency. Methods One hundred ninety-seven pregnant women with hepatic dysfunction during pregnancy were identified. All patients were followed up till 8 weeks after termination of pregnancy or death. Clinico-demographic, biochemical and hematological data were collected and analyzed. Results One hundred ninety-seven of 6,122 females had abnormal liver function tests. Pre-eclampsia (57%), eclampsia (19%), HELLP syndrome (8%), viral infection (6%), hyperemesis gravidarum (5%), intrahepatic cholestasis of pregnancy (4%), chronic liver disease (1%) and sepsis were encountered. There were 41 fetal deaths, 42% preterm deliveries, and NICU admission rate was 27%. Five maternal deaths occurred. Maternal anemia, thrombocytopenia, hyperbilirubinemia and coagulopathy were statistically significant in adverse fetal outcomes. Serum bilirubin performed better than INR as a predictor of both maternal and fetal outcomes. Conclusions Hepatic dysfunction during pregnancy is associated with adverse events for both the mother and the fetus and hypertensive disorders remain the major cause. Maternal bilirubin levels and INR have a role in predicting adverse feto-maternal outcome. PMID:28270873

  7. Ictericia secundaria a cistoadenoma seroso pancreático gigante Jaundice secondary to giant pancreatic serous cystoadenoma

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    S. Goñi

    2010-08-01

    Full Text Available El cistoadenoma seroso es el segundo tumor quístico más frecuente del páncreas y representa el 1-2% de todas las neoplasias exocrinas pancreáticas. Recientemente, gracias a las mejoras en las técnicas de imagen, la identificación de las lesiones quísticas pancreáticas es cada vez más frecuente. El diagnóstico diferencial ha de hacerse con el cistoadenoma mucinoso, debido al potencial maligno de esta última entidad. En esta nota clínica describimos el caso de una paciente con ictericia indolora y colestasis, con diagnóstico final de cistoadenoma seroso pancreático.Serous cystadenoma is the second most frequent pancreatic cystic neoplasm and accounts for 1-2% of exocrine neoplasms of the pancreas. Recently, they have been identified more frequently, due to the improvement in imaging techniques. Differential diagnosis should be performed with mucinous cystoadenoma, due to the latter's potential for malignant transformation. We present the case of a female patient who underwent examination for painless jaundice and cholestasis, with a final diagnosis of pancreatic serous cystoadenoma.

  8. Quantitative multivoxel {sup 1}H MR spectroscopy of the brain in children with acute liver failure

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    Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs [University Medical Center Groningen and University of Groningen, Department of Radiology, Beatrix Children' s Hospital, Groningen (Netherlands); Lunsing, Roelineke J. [University Medical Center Groningen and University of Groningen, Department of Child Neurology, Beatrix Children' s Hospital, Groningen (Netherlands); Spronsen, Francjan J. van; Verkade, Henkjan J. [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Beatrix Children' s Hospital, Groningen (Netherlands)

    2008-11-15

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, {gamma}-glutamyl transpeptidase, alkaline phosphatase). (orig.)

  9. Human placental lactogen levels during and after labor.

    Science.gov (United States)

    Ylikorkala, O; Kauppila, A; Pennanen, S

    1975-08-01

    In order to estimate the human placental lactogen (HPL) level and its value as an indicator of fetoplacental function during labor, we determined HPL levels (N equals 225) before, during, and after labor in normal (N equals 16) and preeclamptic (N equals 14) subjects or in patients with benign intrahepatic cholestasis of pregnancy (N equals 5). During labor, greater decreases in this value were found in preeclamptic than in normal subjects and similarly in mothers with fetoplacental dysfunction than with normal fetoplacental function. The rupture of the membranes had no effect on the level of HPL, which was not related to parity, oxytocin infusion, time interval from rupture of the membranes to delivery, nor to relative placental weight. The half-life of HPL varied in the range of 20-23 minutes immediately after delivery and in the range of 30-39 minutes some time later. During labor, greater decreases in HPL level in cases of preeclampsia or fetoplacental dysfunction may be caused by relative uteroplacental ischemia during uterine contractions, but from this finding it is hard to expect any advantage of HPL as a monitor of fetoplacental function during labor.

  10. Fibroblast growth factor (Fgf) signaling pathway regulates liver homeostasis in zebrafish.

    Science.gov (United States)

    Tsai, Su-Mei; Liu, Da-Wei; Wang, Wen-Pin

    2013-04-01

    In mammals, fibroblast growth factor (FGF) signaling controls liver specification and regulates the metabolism of lipids, cholesterol, and bile acids. FGF signaling also promotes hepatocyte proliferation, and helps detoxify hepatotoxin during liver regeneration after partial hepatectomy. However, the function of Fgf in zebrafish liver is not yet well understood, specifically for postnatal homeostasis. The current study analyzed the expression of fgf receptors (fgfrs) in the liver of zebrafish. We then investigated the function of Fgf signaling in the zebrafish liver by expressing a dominant-negative Fgf receptor in hepatocytes (lfabp:dnfgfr1-egfp, lf:dnfr). Histological analysis showed that our genetic intervention resulted in a small liver size with defected medial expansion of developing livers in transgenic (Tg) larvae. Morphologically, the liver lobe of lf:dnfr adult fish was shorter than that of control. Ballooning degeneration of hepatocytes was observed in fish as young as 3 months. Further examination revealed the development of hepatic steatosis and cholestasis. In adult Tg fish, we unexpectedly observed increased liver-to-body-weight ratios, with higher percentages of proliferating hepatocytes. Considering all these findings, we concluded that as in mammals, in adult zebrafish the metabolism of lipid and bile acids in the liver are regulated by Fgf signaling. Disruption of the Fgf signal-mediated metabolism might indirectly affect hepatocyte proliferation.

  11. Evaluation of a liver micronucleus assay in young rats (III): a study using nine hepatotoxicants by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Japanese Environmental Mutagen Society (JEMS)-Mammalian Mutagenicity Study Group (MMS).

    Science.gov (United States)

    Takasawa, Hironao; Suzuki, Hiroshi; Ogawa, Izumi; Shimada, Yasushi; Kobayashi, Kazuo; Terashima, Yukari; Matsumoto, Hirotaka; Aruga, Chinami; Oshida, Keiyu; Ohta, Ryo; Imamura, Tadashi; Miyazaki, Atsushi; Kawabata, Masayoshi; Minowa, Shigenori; Hayashi, Makoto

    2010-04-30

    We have been investigating a liver micronucleus assay to detect genotoxic chemicals using young rats for several years, and had established its advantages with respect to using autonomous proliferation of young rat hepatocytes. Nine chemicals known to induce hepatotoxic effects such as necrosis (2,6-dinitrotolune, bromobenzene, isoniazid, phenacetin, allyl alcohol and thioacetamide), cholestasis (chlorpromazine hydrochloride and alpha-naphthyl isothiocyanate) and oxidative stress (clofibrate) were selected for this study. A liver micronucleus assay was conducted in 4-week-old male F344 rats using two or three dose levels of test chemicals given orally by gavage to evaluate the compound's ability to induce micronucleated hepatocytes. Several of these test chemicals were additionally examined in a peripheral blood micronucleus assay conducted concurrently and in the same animals. The genotoxic rodent hepatocarcinogen, 2,6-dinitrotoluene showed a positive result in the liver micronucleus assay, but the nongenotoxic hepatocarcinogens, clofibrate and thioacetamide gave negative responses. Bromobenzene, known to produce DNA adducts but is noncarcinogenic in rodent liver, was judged equivocal in this assay. alpha-Naphthyl isothiocyanate is noncarcinogenic and showed negative response in the liver. The other four chemicals, known to be either noncarcinogenic or carcinogenic in other non-liver target organs, showed negative results in the liver micronucleus assay. Based on the results in the present study and previous report described above, it was concluded that this technique is able to effectively predict genotoxic rodent hepatocarcinogenicity, and does not give false positives due to hepatotoxicity.

  12. Distribution of electrophoretically separated serum high density lipoprotein subfraction levels among healthy students and its alteration in patients with liver diseases.

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    Ikeda,Satoru

    1986-06-01

    Full Text Available In an attempt to evaluate high density lipoprotein (HDL subfraction levels in liver diseases, HDL was separated by a precipitation method with dextran sulfate-Mg2+ from sera of 289 healthy adults and 50 patients with liver diseases. The HDL was subdivided into HDL2e and HDL3e by Utermann's polyacrylamide gel electrophoresis with lauric acid. Ultracentrifugally separated HDL2 and HDL3 roughly corresponded to HDL2e and HDL3e, respectively. Male and female groups had different distributions of HDL2e/HDL3e ratios. Among healthy males, 121 cases had ratios less than 1.0 (mean +/- SD = 0.72 +/- 0.39, n = 150, while among healthy females, the ratios were generally larger than those of males and varied widely from 0.2 to 6.6 (mean +/- SD = 1.77 +/- 1.05, n = 139. Low levels of HDL-cholesterol were found in patients with liver diseases, except those with mild alcoholic liver injury and intrahepatic cholestasis. Apparent decreases in HDL3e, but not in HDL2e, were found in all cases with liver diseases investigated, even in those who did not show decreases in the total HDL level, when male and female patients were analyzed separately. The analysis of HDL subfractions by the present method is simple and useful for the study on altered lipid metabolism in liver diseases.

  13. Serum lipase determination in the dog: a comparison of a titrimetric method with an automated kinetic method.

    Science.gov (United States)

    Walter, Gail L.; McGraw, Pamela; Tvedten, Harold W.

    1992-01-01

    An enzymatic, kinetic method for determining serum lipase activity was evaluated and compared to a standard manual method for use in dogs. The kinetic method was a commercial kit adapted for use on a tandem access clinical chemistry analyzer and utilized a series of coupled enzymatic reactions based on the hydrolysis of 1,2-diglyceride by lipase. The manual method was the Cherry-Crandall technique based on the titration of base against the acid formed by hydrolysis of an olive oil substrate by lipase. The correlation between the two methods was very good (r = 0.94). The reference range for 56 clinically healthy dogs assayed by the kinetic method was 90 to 527 U/L. Diseases associated with a greater than twofold elevation in serum lipase activity as determined by the kinetic method included pancreatitis, gastritis with liver disease, and oliguric renal failure with metabolic acidosis. In some cases, pancreatitis was seen with other clinical problems, such as gastroenteritis, diabetic ketoacidosis, duodenal mass, disseminated intravascular coagulation, and septic peritonitis. Diseases associated with serum lipase activity within the reference range or elevated less than twofold included gastritis, gastric ulcer, cholestasis, phenobarbital-induced hepatopathy, colitis, copper hepatopathy, abdominal hematoma, apocrine gland adenocarcinoma, and thrombocytopenia with pneumonia.

  14. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis

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    Ludwig, J.; Barham, S.S.; LaRusso, N.F.; Elveback, L.R.; Wiesner, R.H.; McCall, J.T.

    Histologic, ultrastructural, chemical, and statistical methods were used to study liver biopsy and autopsy specimens from 43 patients who had primary sclerosing cholangitis (PSC), with or without chronic ulcerative colitis (CUC), and from 19 patients who had CUC without PSC. In all study groups, essentially the same abnormalities were found in the hepatic parenchyma outside the major bile ducts, although nondiagnostic tissue samples were observed also. Specimens from patients with extrahepatic PSC were indistinguishable from those patients with combined extra- and intrahepatic PSC. Common findings included periductal fibrosis and inflammation, portal edema and fibrosis, focal proliferation of bile ducts and ductules, focal bile duct obliteration and loss of bile ducts, copper deposition, and cholestasis. Proliferation of bile ducts in some portal tracts and obliteration or absence of bile duct in others were the most characteristic changes. In most specimens, inflammatory changes appeared mild, yet biliary cirrhosis had developed in 34% of the patients. Specimens from patients with PSC, with or without CUC, more often contained bile and strikingly increased stainable copper (Grades 2 and 3) than did specimens from patients with CUC without PSC. Hepatic copper contents, measured by atomic absorption spectrophotometry, also were higher in specimens from patients with PSC. Study of PCS specimens by transmission electron microscopy and by energy-dispersive X-ray microanalysis revealed that most copper was sequestered in lipolysosomes. The recognition of strikingly similar morphologic features in many liver specimens from patients with either PSC or CUC or both suggests that the causes of these conditions are closely related.

  15. Coexistence of primary sclerosing cholangitis in a patient with myasthenia gravis

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    P J Lorenzoni

    2011-01-01

    Full Text Available Myasthenia gravis (MG is an immune-mediated disease that compromises the postsynaptic membrane of the neuromuscular junction. Primary sclerosing cholangitis (PSC is considered an immune-mediated cholestatic liver disease. Both MG and PSC include an autoimmune pathogenesis, so there is some evidence that patients with MG or PSC have a higher risk of developing autoantibodies and other immune disorders than normal controls, but the coexistence of these two disorders has never been documented. We report a 40-year-old woman who presented with MG when she was 20 years old and developed PSC 20 years after a thymectomy. Liver biochemistry revealed cholestasis. Magnetic resonance imaging showed multifocal strictures and beads involving the intrahepatic bile ducts. A liver biopsy confirmed sclerosing cholangitis. Serological analysis demonstrated positive autoantibodies (Anti-nuclear antibodies, anti-smooth muscle antibodies. Repetitive stimulation had a decremental response, and antibodies to acetylcholine receptors were detectable. To our knowledge, this is the first case of PSC in a patient with MG. The main characteristics of both MG and PSC combination are discussed.

  16. Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis.

    Science.gov (United States)

    Kato, Takehiro; Komori, Atsumasa; Bae, Sung-Kwan; Migita, Kiyoshi; Ito, Masahiro; Motoyoshi, Yasuhide; Abiru, Seigo; Ishibashi, Hiromi

    2012-01-14

    Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis, except epidemic schistosomiasis. Among them, primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues, giving rise to systemic amyloidosis, due to a progressive and unresolved inflammatory process, and its possible association with inflammatory bowel diseases. Nevertheless, only one such case has been reported in the literature to date. We report a 69-year-old Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis, without any evidence of other inflammatory disorders. As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4, the presence of IgG4(+) plasma cells was examined systemically, resulting in unexpected documentation of Congo-red-positive amyloid deposits, but not IgG4(+) plasma cells, in the liver, stomach and salivary glands. Elevated serum IgG4 is the hallmark of IgG4-related disease, including IgG4-associated cholangitis, but it has also been demonstrated in certain patients with PSC. Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.

  17. Primary Sclerosing Cholangitis as a Premalignant Biliary Tract Disease: Surveillance and Management.

    Science.gov (United States)

    Rizvi, Sumera; Eaton, John E; Gores, Gregory J

    2015-11-01

    Primary sclerosing cholangitis (PSC) is a premalignant biliary tract disease that confers a significant risk for the development of cholangiocarcinoma (CCA). The chronic biliary tract inflammation of PSC promotes pro-oncogenic processes such as cellular proliferation, induction of DNA damage, alterations of the extracellular matrix, and cholestasis. The diagnosis of malignancy in PSC can be challenging because inflammation-related changes in PSC may produce dominant biliary tract strictures mimicking CCA. Biomarkers such as detection of methylated genes in biliary specimens represent noninvasive techniques that may discriminate malignant biliary ductal changes from PSC strictures. However, conventional cytology and advanced cytologic techniques such as fluorescence in situ hybridization for polysomy remain the practice standard for diagnosing CCA in PSC. Curative treatment options of malignancy arising in PSC are limited. For a subset of patients selected by using stringent criteria, liver transplantation after neoadjuvant chemoradiation is a potential curative therapy. However, most patients have advanced malignancy at the time of diagnosis. Advances directed at identifying high-risk patients, early cancer detection, and development of chemopreventive strategies will be essential to better manage the cancer risk in this premalignant disease. A better understanding of dysplasia definition and especially its natural history is also needed in this disease. Herein, we review recent developments in our understanding of the risk factors, pathogenic mechanisms of PSC associated with CCA, as well as advances in early detection and therapies.

  18. Citrin deficiency: A treatable cause of acute psychosis in adults

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    Sunita Bijarnia-Mahay

    2015-01-01

    Full Text Available Citrin deficiency is an autosomal recessive genetic disorder caused by a defect in the mitochondrial aspartate/glutamate antiporter, citrin. The disorder manifests either as neonatal intra-hepatic cholestasis or occurs in adulthood with recurrent hyperammonemia and neuropsychiatric disturbances. It has a high prevalence in the East Asian population, but is actually pan-ethnic. We report the case of a 26-year-old male patient presenting with episodes of abnormal neuro-psychiatric behavior associated with hyperammonemia, who was diagnosed to be having citrin deficiency. Sequencing of the SLC25A13 gene revealed two novel mutations, a single base pair deletion, c. 650delT (p.Phe217SerfsFNx0133 in exon 7, and a missense mutation, c. 869T>C (p.Ile290Thr in exon 9. Confirmation of the diagnosis allowed establishment of the appropriate management. The latter is an essential pre-requisite for obtaining a good prognosis as well as for family counseling.

  19. A fatal case of bupropion (Zyban hepatotoxicity with autoimmune features: Case report

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    Humayun Fawwaz

    2007-09-01

    Full Text Available Abstract Background Bupropion is approved for the treatment of mood disorders and as an adjuvant medication for smoking cessation. Bupropion is generally well tolerated and considered safe. Two randomized controlled trials of bupropion therapy for smoking cessation did not report any hepatic adverse events. However, there are three reports of severe but non-fatal bupropion hepatotoxicity published in the literature. Case Presentation We present the case of a 55-year old man who presented with jaundice and severe hepatic injury approximately 6 months after starting bupropion for smoking cessation. Laboratory evaluation demonstrated a mixed picture of hepatocellular injury and cholestasis. Liver biopsy demonstrated findings consistent with severe hepatotoxic injury due to drug induced liver injury. Laboratory testing was also notable for positive autoimmune markers. The patient initially had clinical improvement with steroid therapy but eventually died of infectious complications. Conclusion This report represents the first fatal report of bupropion related hepatotoxicity and the second case of bupropion related liver injury demonstrating autoimmune features. The common use of this medication for multiple indications makes it important for physicians to consider this medication as an etiologic agent in patients with otherwise unexplained hepatocellular jaundice.

  20. Necrotizing Enterocolitis: A dreadful condition of premature babies

    Directory of Open Access Journals (Sweden)

    Deepak sharma

    2014-12-01

    Full Text Available NEC is inflammatory necrosis of intestine with most common site being terminal ileum and ascending colon in preterm babies (1. The condition is typically seen in premature infants, and the timing of its onset is generally inversely proportional to the gestational age of the baby at birth, i.e. The earlier a baby is born, longer is the time of risk for NEC in premature babies. The incidence of NEC is inversely proportional to the gestational age and birth weight (2. Baby have initial symptoms which include feeding intolerance, increased gastric residuals, abdominal distension and bloody stools (3. The laboratory triad includes metabolic acidosis, hyponatremia and thrombocytopenia. Pneumatosis intestinalis is the pathognomonic radiological finding in the NEC. Modified Bell’s staging is used to stage the NEC. Treatment involves Nil per Oral, supportive care, antibiotics, surgery in advanced stages and parenteral nutrition (4,5. Complication of NEC includes mortality, prolonged NICU stay, intestinal strictures, enterocutaneous fistula, intra-abdominal abscess, cholestasis, and short-bowel syndrome (6,7, neurodevelopmental, motor, sensory, and cognitive problems (8,9.