What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define "related stricture" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.
Child ; Humans ; Cholangitis, Sclerosing/diagnosis* ; Constriction, Pathologic/complications* ; In Situ Hybridization, Fluorescence ; Cholangiocarcinoma/therapy* ; Liver Diseases/complications* ; Cholestasis ; Inflammatory Bowel Diseases/therapy* ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/therapy*

OBJECTIVETo investigate the protective effect of emodin in young rats with intrahepatic cholestasis.

METHODSA total of 120 young Sprague-Dawley rats were randomly divided into control, model, and high-, medium-, and low-dose emodin groups, with 24 rats in each group. The rats in the control and model groups were given sodium carboxymethyl cellulose solution by gavage, while the other groups were given different doses of emodin solution by gavage. On the 5th day of experiment, alpha-naphthylisothiocyanate (ANIT, 50 mg/kg) was applied by gavage to establish the model of intrahepatic cholestasis in all groups except the control group. At 24, 48, and 72 hours after gavage, 8 rats in each group were sacrificed. Colorimetry was used to measure the serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in each group, and hematoxylin-eosin staining was applied to observe the morphological changes of the liver under a light microscope at different time points.

RESULTSCompared with the control group, the model group had significantly increased serum levels of TBIL, DBIL, TBA, ALP, GGT, ALT, and AST at the 24-hour, 48-hour, and 72-hour time points (P<0.01). In the model group, the serum levels of TBIL, DBIL, TBA, ALT, and AST showed varying degrees of increase at 48 hours after establishment of model, compared with the values at 24 and 72 hours (P<0.05). At 24, 48, and 72 hours, the high-, medium-, and low-dose emodin groups had varying degrees of reductions in the serum levels of TBIL and TBA compared with the model group (P<0.05); the high- and low-dose emodin groups had significantly increased serum levels of TBA compared with the medium-dose emodin group (P<0.05). The model group had the most severe pathological changes at 48 hours. Compared with the model group, the high-, medium-, and low-dose emodin groups showed certain improvement in pathological changes of the liver at each time point, and the medium-dose emodin group had better improvement compared with the high- and low-dose emodin groups.

CONCLUSIONSEmodin can effectively improve ANIT-induced intrahepatic cholestasis in young rats, and medium-dose emodin shows the best effect.

Alanine Transaminase ; genetics ; metabolism ; Animals ; Aspartate Aminotransferases ; genetics ; metabolism ; Bilirubin ; metabolism ; Cholestasis, Intrahepatic ; drug therapy ; genetics ; metabolism ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Emodin ; administration & dosage ; Female ; Humans ; Liver ; enzymology ; pathology ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo establish a prediction model of fetal meconium-stained amniotic fluid in re-pregnant women with intrahepatic cholestasis of pregnancy (ICP).

METHODSClinical data of 180 re-pregnant women with ICP delivering in Women's Hospital, Zhejiang University School of Medicine between January 2009 to August 2014 were collected. An artificial neural network model (ANN) for risk evaluation of fetal meconium-stained fluid was established and assessed.

RESULTSThe sensitivity, specificity and accuracy of ANN for predicting fetal meconium-stained fluid were 68.0%, 85.0% and 80.3%, respectively. The risk factors with effect weight >10% were pregnancy complications, serum cholyglycine level,maternal age.

CONCLUSIONThe established ANN model can be used for predicting fetal meconium-stained amniotic fluid in re-pregnant women with ICP.

Amniotic Fluid ; chemistry ; Cholestasis, Intrahepatic ; pathology ; Female ; Fetus ; Humans ; Infant, Newborn ; Meconium ; chemistry ; Neural Networks (Computer) ; Pregnancy ; Pregnancy Complications ; pathology ; Sensitivity and Specificity

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disorder of cholestasis of hepatocellular origin, typically seen in infancy or childhood caused by a defect in the ABCB4 located on chromosome 7. Here we report on an older patient, aged 15, who presented with biochemical testing that led to an initial consideration of a diagnosis of Wilson disease (WD) resulting in a delayed diagnosis of PFIC3. Diagnosis of PFIC3 was later confirmed by molecular studies that identified novel mutations in the ABCB4 gene. Cholestasis due to PFIC3 can cause elevated hepatic copper and increased urine copper excretion that overlap with current diagnostic criteria for WD. Molecular diagnostics are very useful for establishing the diagnosis of PFIC3. Ursodeoxycholic acid ameliorates cholestasis in PFIC3, and may help mediate a reduction in hepatic copper content in response to treatment.
Cholestasis ; Cholestasis, Intrahepatic* ; Chromosomes, Human, Pair 7 ; Copper ; Delayed Diagnosis ; Diagnosis* ; Hepatolenticular Degeneration* ; Humans ; Molecular Biology* ; Pathology, Molecular ; Ursodeoxycholic Acid

BACKGROUND/AIMS: There are several methods for obtaining tissue samples to diagnose malignant biliary strictures during endoscopic retrograde cholangiopancreatography (ERCP). However, each method has only limited sensitivity. This study aimed to evaluate the diagnostic accuracy of a combined triple-tissue sampling (TTS) method (on-site bile aspiration cytology, brush cytology, and forceps biopsy). METHODS: We retrospectively reviewed 168 patients with suspicious malignant biliary strictures who underwent double-tissue sampling (DTS; n=121) or TTS (n=47) via ERCP at our institution from 2004 to 2011. RESULTS: Among the 168 patients reviewed, 117 patients (69.6%) were eventually diagnosed with malignancies. The diagnostic sensitivity for cancer was significantly higher in the TTS group than the DTS group (85.0% vs 64.9%, respectively; p=0.022). Furthermore, the combination of brush cytology and forceps biopsy was superior to the other method combinations in the DTS group. With respect to cancer type (cholangiocarcinoma vs noncholangiocarcinoma), interestingly, the diagnostic sensitivity was higher for cholangiocarcinoma in the TTS group than the DTS group (100% vs 69.4%, respectively; p<0.001) but not for the non-cholangiocarcinoma patients (57.1% vs 57.1%, respectively). CONCLUSIONS: TTS can provide an improved diagnostic accuracy in suspicious malignant biliary strictures, particularly for cholangiocarcinoma.
Aged ; Ampulla of Vater/*pathology ; Bile Duct Neoplasms/complications/diagnosis/pathology ; Bile Ducts, Intrahepatic/*pathology ; Biopsy/*methods ; Biopsy, Needle ; Carcinoma/complications/diagnosis/pathology ; Cholangiocarcinoma/complications/*diagnosis/pathology ; Cholangiopancreatography, Endoscopic Retrograde/*methods ; Cholestasis/etiology ; Common Bile Duct Neoplasms/complications/*diagnosis/pathology ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/complications/*diagnosis/pathology ; Retrospective Studies ; Sensitivity and Specificity

OBJECTIVETo investigate the expression of farnesoid X receptor (FXR) and the effect of emodin on FXR expression in a rat model of acute cholestatic hepatitis.

METHODSNinety adult Sprague-Dawley rats were randomly divided into normal control, model, and emodin groups (n=30 each). The model and emodin groups were given alpha-naphthylisothiocyanate (ANIT) 50 mg/kg by gavage to establish an animal model of cholestatic hepatitis, while the normal control group was given an equal volume of sesame oil. The emodin group was given emodin by gavage every day from 4 days before the model was prepared until the time of sacrifice, while the model and normal control groups were given an equal volume of sodium carboxymethyl cellulose solution. At 24, 48 and 72 hours after the model was prepared, serum level of total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT), and total bile acids (TBA) were measured by Aeroset automatic biochemical analyzer, and the mRNA expression of FXR in the liver tissue was measured by real-time PCR.

RESULTSAt all time points FXR mRNA expression in the model group decreased, but serum levels of TB, DB, ALT and TBA increased significantly compared with the normal control group (P<0.05). The emodin group had significantly higher mRNA expression of FXR and significantly lower serum levels of TB, DB, ALT, and TBA compared with the model group (P<0.05).

CONCLUSIONSEmodin can significantly reduce serum levels of TB, DB, ALT, and TBA in rats with ANIT-induced cholestatic hepatitis, probably by promoting FXR expression.

Acute Disease ; Alanine Transaminase ; blood ; Animals ; Cholestasis, Intrahepatic ; drug therapy ; metabolism ; Disease Models, Animal ; Emodin ; pharmacology ; therapeutic use ; Hepatitis ; drug therapy ; metabolism ; Liver ; pathology ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; genetics

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 of perinatal 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, umbilical 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.
Bile Acids and Salts ; metabolism ; Cholestasis, Intrahepatic ; metabolism ; pathology ; Female ; Fetal Diseases ; etiology ; metabolism ; Fetus ; metabolism ; Humans ; Maternal-Fetal Exchange ; Placenta ; pathology ; Pregnancy ; Pregnancy Complications ; metabolism ; pathology ; Umbilical Cord ; metabolism ; pathology

OBJECTIVETo detect the expression profiles of suppressor of cytokine signaling 3 (SOCS3), interleukin (IL)-10, and tumor necrosis factor-alpha (TNF-a) in the placenta of women with intrahepatic cholestasis of pregnancy (ICP) and determine the clinical significance of the differential expressions.

METHODSPlacentas were collected from 37 ICP gravidas who delivered through cesarean section at the First Teaching Hospital of Xingjiang Medical University from October 2010 to May 2011 and from 35 healthy pregnant women (controls). SOCS3, TNF-a, and IL-10 protein levels were detected by immunoblotting and the Envision immunohistochemical method.

RESULTSTNF-a and IL-10 expression was detected in placentas of both groups, and was present mainly in the cytoplasm of trophoeytes. IL-10 expression was obviously lower in the ICP placentas than in the control placentas; meanwhile, TNF-a expression was obviously higher than in the control placentas (Z=-2.63, P less than 0.01). SOCS3 protein was significantly more abundant in the control placentas than in the ICP placentas. Furthermore, SOCS3 and IL-10 placental expressions were positively correlated (r=0.494, P less than 0.01), but there was a negative correlation between SOCS3 and TNF-a placental expressions (r=-0.472, P less than 0.01).

CONCLUSIONIn ICP, an increase of the type 1 cytokine, TNF-a, is associated with decreases of the type 2 cytokine, IL-10, and of SOCS3, which may reduce the secretion of IL-10. Furthermore, SOCS3 may contribute to ICP pathogenesis by modulating the Th1/Th2 cytokine balance.

Adult ; Case-Control Studies ; Cholestasis, Intrahepatic ; metabolism ; pathology ; Female ; Humans ; Interleukin-10 ; metabolism ; Placenta ; metabolism ; Pregnancy ; Pregnancy Complications ; metabolism ; pathology ; Pregnancy Trimester, Third ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Young Adult

OBJECTIVETo investigate the diagnostic value of histopathological changes in the liver of patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD).

METHODSLiver specimens from 10 cases of NICCD were evaluated by hematoxylin-eosin stain, histochemistry and immunohistochemistry (EnVision method). SLC25A13 mutation analysis was performed to correlate with histopathology.

RESULTSMost specimens showed varying degrees of fat deposition in hepatocytes, necrotic inflammation, cholestasis and fibrosis (so-called tetralogy). The combination of the above four histological changes was highly characteristic for NICCD. With the progression of the disease, hepatic fibrosis deteriorated and ultimately led to cirrhosis.

CONCLUSIONSNICCD should be suspected in the presence of cholestasis during infancy. A liver biopsy must be performed to rule out other liver diseases. The tetralogy of the hepatic histopathological changes has a highly diagnostic value for NICCD, which is also practical for accurately assessing the degree of inflammation and fibrosis, and similarly the progression of hepatic cirrhosis.

Biopsy ; Calcium-Binding Proteins ; deficiency ; genetics ; metabolism ; Cholestasis, Intrahepatic ; etiology ; genetics ; pathology ; Disease Progression ; Female ; Hepatocytes ; pathology ; Humans ; Infant ; Liver ; pathology ; Liver Cirrhosis ; pathology ; Male ; Mitochondrial Membrane Transport Proteins ; genetics ; Mutation ; Organic Anion Transporters ; deficiency ; genetics ; metabolism

OBJECTIVETo investigate the effect and mechanism of emodin on acute intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT) in rats.

METHODAcute cholestatic model in rats was induced by ANIT. Normal control group, emodin group without ANIT treatment, model group and emodin group with ANIT treatment were set up. Liver function and pathological changes of hepatic tissue were examined. Real-time fluorescent quantitative RT-PCR was used to detect the mRNA levels of the hepatic transport protein genes mdr1a (multidrug resistance protein 1a), mdr1b (multidrug resistance protein 1b) mdr2 (multidrug resistance protein 2), The expression of P-gp were determined by Western blotting analysis.

RESULTCompared to the model group, Emodin treatment resulted in significant reductions in serum total bilirubin (TBiL), direct bilirubin (DBiL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid (TBA) (P < 0.01 or P < 0.05). By examining the liver pathology, it was found that hepatic cellular change and necrosis, inflammatory cell infiltration and bile duct proliferation were notably alleviated in emodin model with ANIT treatment. Analysis of gene expression in livers from emodin-treated cholestatic rats revealed that mdr1a, mdr1b and mdr2 could be up-regulated (P < 0.01 or P < 0.05), expression of P-gp was increased in accordance with its mRNA (P < 0.05).

CONCLUSIONEmodin has a protective effect on hepatocytes and a restoring activity on cholestatic hepatitis. Mechanism of its action may be related to induce expression of the bile-metabolism-related transporter P-gp in the liver to prevent bile acids and other toxic compounds overaccumulation in hepatocytes and hepatic toxicity.

1-Naphthylisothiocyanate ; pharmacology ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bile Acids and Salts ; blood ; Bilirubin ; blood ; Cholestasis, Intrahepatic ; chemically induced ; drug therapy ; genetics ; metabolism ; Emodin ; pharmacology ; therapeutic use ; Gene Expression Regulation ; drug effects ; Liver ; drug effects ; metabolism ; pathology ; physiopathology ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley