[Intrahepatic cholestasis caused by biochemical errors of bile acids. Part I --Nosographic, pathogenetic, diagnostic features]. / Colestasi intraepatiche da errori biochimici degli acidi biliari. Parte I--Aspetti nosografici, patogenetici, diagnostici.

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. The diagnostic and clinical aspects of cholestasis with reference to the clinical symptoms, laboratory findings and to role of liver biopsy are synthesized, and the essential criteria for a methodological approach to cholestasis are proposed.

[Intrahepatic cholestasis due to biochemical errors of bile acids. II. Clinical and therapeutic aspects]. / Colestasi intraepatiche da errori biochimici degli acidi biliari. Parte II--Aspetti clinici e terapeutici.

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. The conditioned cholestasis group comprises cholestasis of pregnancy and drug-induced cholestasis. Benign recurrent cholestasis of pregnancy is a form induced "by" pregnancy and not a form occurring "in" pregnancy, such as cholestasis due to hepatitis, to primary biliary cirrhosis, to cholelithiasis. Drug-induced cholestasis is a chapter of great clinical relevance: forms due to steroid hormones and due to phenothiazines are discussed.

[Systemic mastocytosis: a case with diffuse bone involvement]. / Mastocitosi sistemica: un caso con diffuso coinvolgimento osseo.

The authors report the case of a 54-year-old woman with systemic mastocytosis with cutaneous, gastroenteric and skeletal involvement. The patient, who had presented wine-coloured skin lesions for years diagnosed as urticaria pigmentosa on the basis of the skin biopsy, was admitted to the Institute of Internal Medicine owing to the radiological findings of severe osteopenia. Instrumental and laboratory tests led to the correct diagnosis of type 1 systemic mastocytosis. The peculiarity of the case in question prompts the authors to recall the classification of mastocytosis, namely those pathological syndromes characterised by tissular infiltration by mast-cells, and to outline elements regarding its differential diagnosis in relation to disorders such as various forms of carcinoids and osteopenia, and in particular osteoporosis and osteolysis secondary to metastatic processes.

[Diphosphonates. Current trends and therapeutic prospects]. / I difosfonati. Attualità e prospettive terapeutiche.

Diphosphonates are compounds characterized by a P-C-P bond. They are thus analogs of pyrophosphate and can be useful for treating several bone diseases. The authors synthetically review the mechanism of action of these drugs and their most important clinical applications. The authors finally mention the interesting therapeutic possibilities deriving from the development of new members of this class.

[Liver pathologies due to peroxisome disorders]. / Patologie epatiche da disordini dei perossisomi.

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. From the biochemical point some diseases present alterations of the cholesterol side chain (Zellweger syndrome, pseudo-Zellweger syndrome, infantile Refsum's disease, neonatal adrenoleukodystrophy), other diseases present errors involving the steroid nucleus (familial giant cell hepatitis). Zellweger disease or cerebro-hepato-renal syndrome is characterized clinically by skeletal changes, muscle hypotonia, renal cysts, psychosomatic retardation and persistent cholestasis and from the ultrastructural standpoint by the virtual absence of liver cell peroxisomes. Pseudo-Zellweger disease shows many of the clinical features of Zellweger disease but differs from this condition on account of the presence of abundant peroxisomes in the liver cells. Infantile Refsum's disease and neonatal adrenoleukodystrophy show typical clinical disorders and liver damage leading to cirrhosis. "Familial giant cell hepatitis" is characterized by jaundice from the first days of life, hepatosplenomegaly, cholestasis, lack of physical malformations. The disorder is due to defective biosynthesis of the bile acids with formation of allo-bile acids.

[Intrahepatic cholestasis in hyperthyroidism]. / Colestasi intraepatica in corso di ipertiroidismo.

Three cases of cholestatic liver disease related to hyperthyroidism are reported. Features indicative of a role of the endocrine disease in the pathogenesis of the cholestatic syndrome were the appearance of liver damage in temporal relation with the clinical onset of thyroid hyperfunction and its disappearance with the amelioration of the hyperthyroidism; the absence of congestive heart failure and of infectious, toxic or obstructive agents of liver damage; the pathological and biochemical findings of intrahepatic cholestasis. Hyperthyroidism can be rarely complicated by a severe cholestatic syndrome that may dominate the clinical presentation and course.

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. This case is of great interest from these two points of view: 1) the histologic and electron microscopic findings 23 and 41 years after the first episode of cholestasis, respectively, failed to reveal evidence of the possible future development of cirrhosis; 2) treatment with ursodeoxycholic acid proved ineffective both therapeutically and in the prevention of episodes of bile stasis: on the contrary, calculosis of the common bile duct appeared after 8 months from the onset of the treatment.

Benign recurrent intrahepatic cholestasis. A clinico-pathologic study.

Authors report 6 cases of benign recurrent intrahepatic cholestasis (BRIC), a rare disease of unknown etiology first described 30 years ago by Summerskill and Walshe, and thought to represent a study model for human cholestasis. Clinical, biochemical and pathologic findings of BRIC are briefly summarized in this paper in order to emphasize some triggering factors of the cholestatic attack (e.g., flu-like episodes and pregnancy), the diagnostic problems and the importance to avoid a surgical procedure. Finally, the 'state of the art' of the pathogenesis of BRIC is briefly summarized.