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Chronic Cholestasis (chronic + cholestasi)
Selected AbstractsLack of evidence that bone marrow cells contribute to cholangiocyte repopulation during experimental cholestatic ductal hyperplasiaLIVER INTERNATIONAL, Issue 4 2006Yuki Moritoki Abstract: Background: Ductopenia is observed in end-stage human cholestatic diseases. The limited capability of cholangiocytes for proliferation is suggested to be the principal reason. Recently, bone marrow cells (BMCs) have been reported to behave as hepatic stem cells; however, their capability to differentiate into cholangiocytes in cholestasis remains unclear. Methods: Normal mice were lethally irradiated to suppress the proliferation of self-BMCs; thereafter, the BMCs from enhanced green fluorescent protein (EGFP)-transgenic mice were transferred to recipients. Chronic cholestasis was induced by 0.1%,-naphtylisothiocyanate (ANIT) feeding. The proliferation of cholangiocytes and oval cells was assessed morphologically and immunohistchemically (cytokeratin-7 (CK-7), A6). Proliferative activity (proliferating cell nuclear antigen (PCNA) protein expression), hepatic growth factor (HGF) receptor (c-Met), stem cell factor receptor (c-kit), Notch2 and Hes1 expression were also evaluated. Results: Marked cholangiocyte proliferation was observed in ANIT-fed mice. However, no EGFP/CK-7 double positive cells were identified in any of the liver specimens after BMCs transfer (Tx). In hepatic parenchyma, there were scattered EGFP-positive cells, although none of them were positive for CK-7. Conclusions: In spite of the significant ductular proliferations after ANIT feeding, no EGFP-positive cholangiocytes were confirmed by any other means in this chronic cholestasis model. Thus, different from hepatocytes, BMCs Tx seems not to contribute to the differentiation of cholangiocytes. Future studies are feasible to clarify the origin of proliferative cholangiocytes observed in this chronic cholestatic ductular hyperplasia model. [source] The amazing universe of hepatic microstructure,HEPATOLOGY, Issue 2 2009Valeer J. Desmet An informal review is presented by the author of his 50 years of involvement in practice and research in hepatopathology. Some background for the author's attitude and meandering pathway into his professional career serves as introduction to a short discussion of the main topics of his interest and expertise. Histogenesis of liver cancer was the theme of early work for a Ph.D. thesis, the results of which were lost into oblivion due to local rules and circumstances, but were rescued three decades later. His conclusions about the cells of origin of liver cancer remain concordant with the newer concepts in the field after nearly half a century. Studies in the field of chronic hepatitis became a long saga, involving the first classification of this syndrome by "the Gnomes" in 1968, histochemical investigations of viral antigens, lymphocyte subsets and adhesion molecules, and a quarter century later, the creation of a new classification presently in use. Cholestasis was a broadening field in diagnostic entities and involved the study of liver lesions, comprising pathways of bile regurgitation (including reversed secretory polarity of hepatocytes) and so-called ductular reaction. The latter topic has a high importance for the various roles it plays in modulating liver tissue of chronic cholestasis into biliary cirrhosis, and as the territory of hepatic progenitor cells, crucial for liver regeneration in adverse conditions and in development of liver cancer. Study of the embryology of intrahepatic bile ducts helped to clarify the strange appearance of the ducts in "ductal plate configuration" in several conditions, including some forms of biliary atresia with poor prognosis and all varieties of fibrocystic bile duct diseases with "ductal plate malformation" as the basic morphologic lesion. (HEPATOLOGY 2009;50:333,344.) [source] Can Turner syndrome teach us about the pathogenesis of chronic cholestasis?HEPATOLOGY, Issue 5 2004Piotr Milkiewicz The mechanisms that cause the female predominance of primary biliary cirrhosis (PBC) are uncertain, but the X chromosome includes genes involved in immunological tolerance. We assessed the rate of X monosomy in peripheral white blood cells from 100 women with PBC, 50 with chronic hepatitis C, and 50 healthy controls, by fluorescence in-situ hybridisation. Frequency of X monosomy increased with age in all groups, but was significantly higher in women with PBC than in controls (p<0.0001); age-adjusted back-transformed mean frequencies were 0.050 (95% CI 0.046-0.055) in women with PBC, 0.032 (0.028-0.036) in those with chronic hepatitis C, and 0.028 (0.025-0.032) in controls. We suggest that haploinsufficiency for specific X-linked genes leads to female susceptibility to PBC. [source] Characterization of mutations in ATP8B1 associated with hereditary cholestasisHEPATOLOGY, Issue 1 2004Leo W. J. Klomp Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BRIC) are clinically distinct hereditary disorders. PFIC patients suffer from chronic cholestasis and develop liver fibrosis. BRIC patients experience intermittent attacks of cholestasis that resolve spontaneously. Mutations in ATP8B1 (previously FIC1) may result in PFIC or BRIC. We report the genomic organization of ATP8B1 and mutation analyses of 180 families with PFIC or BRIC that identified 54 distinct disease mutations, including 10 mutations predicted to disrupt splicing, 6 nonsense mutations, 11 small insertion or deletion mutations predicted to induce frameshifts, 1 large genomic deletion, 2 small inframe deletions, and 24 missense mutations. Most mutations are rare, occurring in 1,3 families, or are limited to specific populations. Many patients are compound heterozygous for 2 mutations. Mutation type or location correlates overall with clinical severity: missense mutations are more common in BRIC (58% vs. 38% in PFIC), while nonsense, frameshifting, and large deletion mutations are more common in PFIC (41% vs. 16% in BRIC). Some mutations, however, lead to a wide range of phenotypes, from PFIC to BRIC or even no clinical disease. ATP8B1 mutations were detected in 30% and 41%, respectively, of the PFIC and BRIC patients screened. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html) and at www.atp8b1-primers.nl (HEPATOLOGY 2004;40:27,38.) [source] Lack of evidence that bone marrow cells contribute to cholangiocyte repopulation during experimental cholestatic ductal hyperplasiaLIVER INTERNATIONAL, Issue 4 2006Yuki Moritoki Abstract: Background: Ductopenia is observed in end-stage human cholestatic diseases. The limited capability of cholangiocytes for proliferation is suggested to be the principal reason. Recently, bone marrow cells (BMCs) have been reported to behave as hepatic stem cells; however, their capability to differentiate into cholangiocytes in cholestasis remains unclear. Methods: Normal mice were lethally irradiated to suppress the proliferation of self-BMCs; thereafter, the BMCs from enhanced green fluorescent protein (EGFP)-transgenic mice were transferred to recipients. Chronic cholestasis was induced by 0.1%,-naphtylisothiocyanate (ANIT) feeding. The proliferation of cholangiocytes and oval cells was assessed morphologically and immunohistchemically (cytokeratin-7 (CK-7), A6). Proliferative activity (proliferating cell nuclear antigen (PCNA) protein expression), hepatic growth factor (HGF) receptor (c-Met), stem cell factor receptor (c-kit), Notch2 and Hes1 expression were also evaluated. Results: Marked cholangiocyte proliferation was observed in ANIT-fed mice. However, no EGFP/CK-7 double positive cells were identified in any of the liver specimens after BMCs transfer (Tx). In hepatic parenchyma, there were scattered EGFP-positive cells, although none of them were positive for CK-7. Conclusions: In spite of the significant ductular proliferations after ANIT feeding, no EGFP-positive cholangiocytes were confirmed by any other means in this chronic cholestasis model. Thus, different from hepatocytes, BMCs Tx seems not to contribute to the differentiation of cholangiocytes. Future studies are feasible to clarify the origin of proliferative cholangiocytes observed in this chronic cholestatic ductular hyperplasia model. [source] Absence of glycochenodeoxycholic acid (GCDCA) in human bile is an indication of cholestasis: A 1H MRS studyNMR IN BIOMEDICINE, Issue 5 2009Omkar B. Ijare Abstract The utility of 1H MR spectroscopy in detecting chronic cholestasis has been investigated. The amide proton region of the 1H MR spectrum of human bile plays a major role in differentiating cholestatic (Ch) patterns from the normal ones. Bile obtained from normal bile ducts contains both taurine and glycine conjugates of bile acids , cholic acid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA). Absence of a glycine-conjugated bile acid glycochenodeoxycholic acid (GCDCA) has been observed in bile samples obtained from primary sclerosing cholangitis (PSC) patients. A total of 32 patients with various hepatobiliary diseases were included in the study. Twenty-one patients had PSC and 11 had normal cholangiograms. One PSC patient was excluded from the study because of a bad spectrum. Seventeen out of the 20 PSC patients showed an absence of GCDCA in their 1H MR spectrum of bile. Six of the 11 reference patients with normal cholangiogram also showed spectra similar to those of PSC, indicating the possibility of cholestasis. DQF-COSY and TOCSY experiments performed on bile samples from PSC patients also revealed absence of phosphatidylcholine (PC) in some of the bile samples, suggesting possible damage to the cholangiocytes by the toxic bile. These observations suggest that analysis of human bile by 1H MRS could be of value in the diagnosis of chronic Ch liver disorders. Copyright © 2008 John Wiley & Sons, Ltd. [source] Hepatic osteodystrophy in chronic cholestasis: Evidence for a multifactorial etiologyPEDIATRIC TRANSPLANTATION, Issue 2 2002Gordon L. Klein Abstract: Children with cholestatic liver disease have been thought to develop hepatic osteodystrophy resulting from vitamin D and calcium malabsorption, resulting in secondary hyperparathyroidism and osteomalacia or rickets. However, treatment with vitamin D has not always proven successful in improving the bone disturbance. The aim of our study was to determine the role of vitamin D deficiency in the pathogenesis of hepatic osteodystrophy. We studied five patients, three female and two male, ages 0.9,19 yr, with biopsy-proven chronic cholestatic liver disease and previously low serum levels of vitamin D despite oral intake of vitamin D preparations. Patients were admitted to the Clinical Research Center for 8 days for sunlight deprivation and ultraviolet light substitution and for determinations of serum 25-hyroxyvitamin D(25(OH)) D2 and -D3, osteocalcin, and type I collagen telopeptide (ICTP), the last two being markers of bone formation and resorption, respectively. Samples were taken on admission, at discharge, and 1 month later. Results demonstrated low serum levels of osteocalcin and normal circulating levels of ICTP. Admission serum 25(OH)D2 levels were uniformly low or undetectable and remained so. Admission levels of circulating 25(OH)D3 were normal or low and did not rise during ultraviolet light therapy or subsequent resumption of oral vitamin D therapy and remained low 1 month later. These results indicate that in the face of low,normal to low total 25(OH)D levels, the low osteocalcin and normal ICTP levels suggest that decreased bone formation and not increased bone resorption is the main determinant of bone loss in a subset of children with chronic cholestatic liver disease. [source] | ||||||||||