Fine-resolution mapping by haplotype evaluation: the examples of PFIC1 and BRIC.

Loci for two inherited liver diseases, benign recurrent intrahepatic cholestasis (BRIC) and progressive familial intrahepatic cholestasis type 1 (PFIC1), have previously been mapped to 18q21 by a search for shared haplotypes in patients in two isolated populations. This paper describes the use of further haplotype evaluation with a larger sample of patients for both disorders, drawn from several different populations. Our assessment places both loci in the same interval of less than 1 cM and has led to the discovery of the PFIC1/BRIC gene, FIC1; this discovery permits retrospective examination of the general utility of haplotype evaluation and highlights possible caveats regarding this method of genetic mapping.

Benign recurrent intrahepatic cholestasis. Some reflections on a case followed for 20 years.

Benign recurrent intrahepatic cholestasis (BRIC) is a form of cholestasis of obscure aetiology characterized by recurrent episodes of jaundice and itching associated with a morphological picture of pure intrahepatic cholestasis. No effective treatment has yet been found among the many that have been proposed and the invariably benign nature of the condition has been questioned. A case of BRIC followed for a period of 20 years is described.

[Intrahepatic cholestasis due to biochemical errors of bile acids. II. Clinical and therapeutic aspects].

Within the "primary" cholestasis we can discriminate "essential" forms due to an endogenous biochemical error of bile acid metabolism and/or secretion and "conditioned" forms, in which a known precipitating factor is required to elicit the functional disorder responsible for cholestasis. Among the essential forms of cholestasis must be included benign recurrent intrahepatic cholestasis or Summerskill-Walshe disease, Aagenaes disease, progressive familial intrahepatic cholestasis or Byler's disease, and forms due to disorders of the peroxisomes. Benign recurrent intrahepatic cholestasis, the best known form, is characterized by recurrent episodes of itching and jaundice with an acute onset separated by symptom-free intervals, which shows no tendency to progress to liver failure.

[Intrahepatic cholestasis caused by biochemical errors of bile acids. Part I --Nosographic, pathogenetic, diagnostic features].

Intrahepatic cholestasis occurs in certain conditions characterized by a biochemical error of bile acid metabolism, resulting from a disorder of the hepatic canalicular system responsible for synthesis or secretion of the bile acids. As regards the pathogenesis of these "primary" forms of cholestasis, it must be remembered that cholestasis represents the outcome of various factors capable of interfering with the mechanism of bile flow. Therefore the factors known to be involved in cholestasis, such as the metabolic steps in bile acid metabolism, the cytoplasmic membrane, the mitochondria, the cytoskeleton of the liver cell, the intercellular junctions, the physicochemical state of the canalicular bile, are discussed briefly.

[Liver pathologies due to peroxisome disorders].

Peroxisomes or microbodies are peculiar subcellular organelles with an important role in the metabolism of a variety of different organic compounds. Particularly they are an important site of bile acids synthesis. Some hepatic diseases, mainly cholestatic, can to be reconnected at disorders of bile acids synthesis by these organelles.