Idiopathic adulthood ductopenia (IAD) is a chronic cholestatic liver disease of unknown etiology characterized by adult onset, an absence of autoantibodies, inflammatory bowel disease, and a loss of interlobular bile ducts. In the present report, a case fulfilling the IAD criteria is described. A 19-year-old man was admitted to the hospital for persistent elevation of transaminases and alkaline phosphatase without clinical symptoms. Viral hepatitis markers and autoantibodies were absent. The patient had a normal extrahepatic biliary tree and had no evidence of inflammatory bowel disease. A liver biopsy specimen showed absence of interlobular bile ducts from 58% of the portal tracts. He was diagnosed with IAD and was treated with ursodeoxycholic acid.
Adult ; Cholestasis, Intrahepatic/*diagnosis/etiology/pathology ; Chronic Disease ; Humans ; Male

Cholestasis, Intrahepatic ; diagnosis ; pathology ; therapy ; Female ; Humans ; Pregnancy ; Pregnancy Complications ; diagnosis ; pathology ; therapy

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

To assess the extent of microfilaments in cholestatic liver diseases we examined the cytoplasmic microfilaments in intrahepatic and extrahepatic cholestasis in man by electron microscopy. Study subjects were two patients with drug-induced intrahepatic cholestasis, three patients with intrahepatic cholestasis due to viral hepatitis, four patients with extrahepatic cholestasis due to stones of the common bile duct and two patients with primary biliary cirrhosis. Two biopsied specimens from patients without clinical or histological evidence of liver disease served as noncholestatic controls. The microfilaments in hepatocytes and biliary ductular cells were significantly increased in cholestasis compared with those in non-cholestatic controls. Well developed bundles of microfilaments were noted around the pericanalicular ectoplasm and seemed to be parallel to plasma membrane of the hepatocytes in cholestasis. In cholestasis, there were increased bundles of microfilaments around the periluminal region, lateral cell wall, and nucleus of biliary ductular cells. Two patterns of microfilaments bundles (fine microfilamentous network and spindle-shaped dense or clusters of microfilaments) were associated with cholestasis. The clustered form of microfilaments also seemed to be clearly associated with intracytoplasmic vacuoles containing bile salts. In conclusion, the increase of microfilaments in hepatocytes and biliary ductular cells may be the consequence of various forms of cholestasis. Further studies are needed to clarify the functional significance of increased microfilaments in cholestasis.
Bile Canaliculi/*pathology/ultrastructure ; Biopsy ; Cholestasis, Intrahepatic/*pathology ; Hepatocytes/*pathology/ultrastructure ; Humans ; Microfilaments/*pathology/ultrastructure ; Microscopy, Electron

Bile Duct Neoplasms ; pathology ; surgery ; Carcinoma, Hepatocellular ; complications ; pathology ; surgery ; Cholestasis, Intrahepatic ; etiology ; pathology ; surgery ; Humans ; Liver Neoplasms ; complications ; pathology ; surgery ; Neoplasm Invasiveness

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

OBJECTIVETo summarize the Chinese experience in pathologic diagnosis of liver biopsies after orthotopic liver transplantation (OLTx).

METHODS1123 post-transplant liver biopsies from 665 OLTx patients from the Shanghai Eastern Hepatobiliary Surgery Hospital, Tianjin First Central Hospital, Guangzhou Sun Yat-sen University and Chongqing Southwest Hospital were retrospectively analyzed. All liver biopsies were stained with hematoxylin and eosin. Immunohistochemical studies for cytomegalovirus, HBsAg, CK19, CD4 and CD8 were also performed in selected examples.

RESULTSIn the involved hospitals, 4 to 12 types of complications were encountered after OLTx. The number of liver biopsies performed for each patient ranged from 1 to 9 (mean = 2.2). The timing of these biopsies varied from the second to the 2877 th post-transplant day. The 5 most common complications were acute cellular rejection (35.6%), ischemic-reperfusion injury (13.4%), biliary stricture (5.6%), drug complication (5.0%) and chronic rejection (4.7%). The 5 earliest complications after OLTx were primary non-function (occurring at day 4.7 +/- 2.1), ischemic-reperfusion injury (occurring at day 14.0 +/- 4.0), acute cellular rejection (occurring at day 32.1 +/- 62.9), hepatic artery thrombosis / stricture (occurring at day 62.9 +/- 74.2) and cytomegalovirus infection (occurring at day 107.7 +/- 93.0).

CONCLUSIONSThis study has evaluated the types, incidence and timing of major complications occurring after OLTx. The most important issue is the distinction between rejection and non-rejection pathology. Thorough understanding of atypical pathologic features of these complications is necessary. The Banff Schema (rejection activity index) for grading liver allograft rejection is useful for monitoring anti-rejection therapy and should be used routinely.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Child ; Child, Preschool ; Cholestasis, Intrahepatic ; pathology ; Female ; Graft Rejection ; pathology ; Hepatic Artery ; pathology ; Humans ; Infant ; Liver Transplantation ; pathology ; Male ; Middle Aged ; Postoperative Complications ; pathology ; Reperfusion Injury ; pathology ; Retrospective Studies ; Thrombosis ; pathology

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

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