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      Aproximación al diagnóstico patológico de las enfermedades colestásicas Translated title: Approaches to Pathological Diagnosis of Cholestatic Diseases

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          Abstract

          Cualquier enfermedad que lleve a la alteración del flujo biliar o del metabolismo de las sales biliares se traduce en colestasis. Son múltiples las causas que pueden producirla, sea por su localización anatómica intrahepática o extrahepática, agudas o crónicas, con o sin lesión hepatocelular acompañante, o primarias o secundarias, por lo que resultan numerosas las entidades que deben ser consideradas como parte del diagnóstico diferencial de las enfermedades colestásicas y que plantean un gran reto diagnóstico tanto para el clínico, como para el patólogo (1). En el presente estudio se plantea una aproximación diagnóstica basada en patrones histológicos, haciendo énfasis en las enfermedades colestásicas crónicas del adulto, en próximos estudios se tratarán las de la población pediátrica

          Translated abstract

          Any disease that leads to impaired bile flow or impaired bile salt metabolism results in cholestasis. There are several causes of the disease related to intrahepatic or extrahepatic anatomical locations, to whether the disease is acute or chronic, to whether or not hepatocellular damage occurs, and to whether or not the condition is primary or secondary. The large number of entities that must be considered in the differential diagnosis of cholestatic diseases poses a major diagnostic challenge for both the clinician and the pathologist (1). This article establishes a diagnostic approach based on histologic patterns which emphasizes adult chronic cholestatic diseases. The next article will focus on the pediatric population

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          Primary biliary cirrhosis.

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            Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families.

            Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in such patients and correlated genotypes with residual protein detection and risk of malignancy. Patients with intrahepatic cholestasis suggestive of BSEP deficiency were investigated by single-strand conformation polymorphism analysis and sequencing of ABCB11. Genotypes sorted by likely phenotypic severity were correlated with data on BSEP immunohistochemistry and clinical outcome. Eighty-two different mutations (52 novel) were identified in 109 families (9 nonsense mutations, 10 small insertions and deletions, 15 splice-site changes, 3 whole-gene deletions, 45 missense changes). In 7 families, only a single heterozygous mutation was identified despite complete sequence analysis. Thirty-two percent of mutations occurred in >1 family, with E297G and/or D482G present in 58% of European families (52/89). On immunohistochemical analysis (88 patients), 93% had abnormal or absent BSEP staining. Expression varied most for E297G and D482G, with some BSEP detected in 45% of patients (19/42) with these mutations. Hepatocellular carcinoma or cholangiocarcinoma developed in 15% of patients (19/128). Two protein-truncating mutations conferred particular risk; 38% (8/21) of such patients developed malignancy versus 10% (11/107) with potentially less severe genotypes (relative risk, 3.7 [confidence limits, 1.7-8.1; P = .003]). With this study, >100 ABCB11 mutations are now identified. Immunohistochemically detectable BSEP is typically absent, or much reduced, in severe disease. BSEP deficiency confers risk of hepatobiliary malignancy. Close surveillance of BSEP-deficient patients retaining their native liver, particularly those carrying 2 null mutations, is essential.
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              Primary sclerosing cholangitis: summary of a workshop.

              Primary sclerosing cholangitis (PSC) is a rare but important liver disease that leads to cirrhosis and need for liver transplantation in a high proportion of cases. The disease occurs in approximately 1 per 100,000 population per year, usually presents in adulthood, and affects men more often than women. Typical serum biochemical results, autoantibodies and liver biopsy are suggestive but not diagnostic of PSC, the diagnosis requiring cholangiographic demonstration of stricturing and dilatation of the intra- and/or extra-hepatic bile ducts. The natural history of PSC is variable, the average survival being 12 to 17 years. The cause of PSC is still unknown. Although considered an autoimmune disease, PSC has several atypical features and a strong genetic component. The therapy of PSC is unsatisfactory. Standard doses of ursodeoxycholic acid (UDCA) lead to improvements in biochemical abnormalities but not in histology, cholangiographic appearance or survival. Several innovative therapies have been tried in PSC, but with scant evidence of benefit. For patients with high grade strictures, endoscopic dilatation is beneficial. Liver transplantation is successful for end-stage liver disease due to PSC and improves survival. PSC may recur after transplantation but is rarely progressive. The most dreaded complication of PSC is cholangiocarcinoma. Diagnosis of this highly malignant tumor is difficult, and there are no biomarkers for its early detection. Liver transplantation for cholangiocarcinoma has an exceedingly poor outcome, although transplantation with neoadjuvant chemoirradiation holds promise in selected patients. Thus, significant opportunities remain for basic and clinical research into the cause, natural history, and therapy of PSC.
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                Author and article information

                Contributors
                Role: ND
                Journal
                rcg
                Revista Colombiana de Gastroenterologia
                Rev Col Gastroenterol
                Asociación Colombiana de Gastroenterología (Bogotá )
                0120-9957
                June 2014
                : 29
                : 2
                : 189-199
                Affiliations
                [1 ] Hospital Universitario Fundación Santa Fé de Bogotá Colombia
                Article
                S0120-99572014000200016
                8037b891-49e3-443b-a704-a68705eb0fdf

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Colombia

                Self URI (journal page): http://www.scielo.org.co/scielo.php?script=sci_serial&pid=0120-9957&lng=en
                Categories
                GASTROENTEROLOGY & HEPATOLOGY

                Gastroenterology & Hepatology
                Cholestasis,acute cholestasis,chronic cholestasis,liver biopsy,acute cholangitis,primary biliary cirrhosis,primary sclerosing cholangitis,IgG4 cholangitis,Colestasis,colestasis aguda,colestasis crónica,biopsia hepática,colangitis aguda,cirrosis biliar primaria,colangitis esclerosante primaria,colangitis IgG4

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