SUMMARY Twenty-nine patients with primary sclerosing cholangitis were reviewed. Males predominated (2:1). Seventy-six per cent presented with cholestasis and cholangitis, 17 % with cirrhosis and portal hypertension, and 7% were asymptomatic, presenting with a raised serum alkaline phosphatase. The serum immunoglobulin IgM concentration was raised in 45 % of the patients, but no patient had serum mitochondrial antibody present. Seventy-two per cent had ulcerative proctocolitis. There was no relationship between either duration or severity of ulcerative proctocolitis and the development of primary sclerosing cholangitis. Four patients were not benefited by colectomy. None of the patients had Crohn's disease. The prognosis was variable. Corticosteroids and azathioprine were ineffective. Eleven patients (38 %) had died with a mean survival time of seven years from diagnosis. Three patients with ulcerative proctocolitis developed bile duct carcinoma. The cholangiograms and liver biopsies were reported without reference to clinical information together with 41 patients with other biliary diseases. Cholangiography was diagnostic in 18/22 (82 %). Hepatic histology was diagnostic in 8/22 (36 %). Ten showed features of large bile duct disease and three were misdiagnosed as primary biliary cirrhosis. Reduced numbers of bile ducts, ductular proliferation, portal inflammation, and substantial copper deposition, in combination with piecemeal necrosis, are commonly seen in primary sclerosing cholangitis and indicate the need for cholangiography.Primary sclerosing cholangitis (PSC), first described by Delbett in 1924, is a rare disease of unknown aetiology. It is characterised by an intense inflammatory fibrosis usually affecting both the intra-and extrahepatic biliary tree.2Reported series of patients with PSC have been small34 and until the advent of percutaneous and endoscopic cholangiography did not include detailed descriptions of the biliary tree. The present paper describes the clinical features, natural history, and treatment of 29 patients with primary sclerosing cholangitis.Cholangiographic and hepatic histological appear-

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In the course of examining liver biopsy specimens, certain larger than normal liver cells whose cytoplasm is finely granular and strikingly acidophilic have been seen. These cells are called "oxyphilic granular hepatocytes" (oxyphils) because of their similarities to the "oncocytes" of the salivary glands and other endocrine organs. Oxyphilic liver cells can be readily differentiated from acidophilic bodies and groundglass hepatocytes by light and electron microscpy, the latter showing them to be extraordinarily rich in mitochondria. A retrospective study of 214 consecutive liver biopsies was undertaken to determine the prevalence of oxyphilic cells in a variety of liver diseases. Oxyphils were identified in 15% of the biopsy specimens, and were most strongly associated with chronic active hepatitis and cirrhosis in hepatitis B surface antigen (HBsAg)-positive patients. Subsequent reevaluation of 77 biopsy specimens from HBsAg-positive patients showed oxyphils in 28.6%. Their pathogenesis and significance in chronic liver disease are unknown.

SUMMARY Ten cases are reported of short incubation (one to four weeks) non-A, non-B hepatitis occurring after infusion of various preparations of factor VIII concentrates into patients with coagulation disorders. Five patients were symptomatic and, in all, serum transaminase levels were increased for at least six months. These cases of chronic hepatitis exhibited none of the features of autoimmune chronic hepatitis: autoantibodies were negative and serum immunoglobulins were normal. Hepatic histology confirmed acute hepatitis in two cases biopsied early in the illness, and thronic active hepatitis (three) or chronic persistent hepatitis (two) in five cases studied later. Lobular inflammation was a prominent feature in all cases. Other features not commonly associated with type A or B hepatitis included fatty change and damaged bile ducts.Patients with congenital coagulation disorders receive large quantities of blood derivatives and acute hepatitis is not an uncommon occurrence.

Lipid peroxidation was initiated by the addition of either ADP-complexed Fe3 + or cumene hydroperoxide to isolated rat hepatocytes and the resultant biochemical and morphological alterations investigated. As previously observed with microsomes, malonaldehyde formation was associated with the inactivation of glucose-6-phosphatase. Inhibition of microsomal oxidative drug metabolism was correlated with the release and subsequent inactivation of NADPH-cytochrome c reductase, whereas cytochrome P-450 destruction occurred only in the presence of high concentrations of the organic hydroperoxide which were associated with extensive malonaldehyde formation. Under these conditions there were also marked ultrastructural alterations in the hepatocytes which were not apparent after incubation in the presence ofiron (I 187pM Fe3+). The latter treatment was, however, associated with moderate biochemical effects such as glucose-6-phosphatase inactivation and increased membrane permeability. The cellular defence system against lipid peroxidation is discussed and it is concluded that the isolated liver cell system provides a valuable tool for the study of lipid peroxidation and its pathological implications. Because of its widespread toxic effects lipid peroxidation might have pathological implications as has been proposed in connection with iron toxicity [6] and CCI, toxicity [7]. However, the role of lipid peroxidation during the early stages of cell damage leading to cell necrosis has yet to be established.Isolated liver cells produce malonaldehyde, a metabolite of lipid peroxides, upon exposer to ADP-complexed iron or the organic peroxide cumene hydroEn:ymc.s. Collagenase (EC 3.4.24.3); Hyaluronidase or hyaluronate 4-glycanohydrolase (EC 3.2.1.35); NADPH-cytcchrome c reductase (EC 1.6.2.4); Glucose 6-phosphatase (EC 3.1.3.9).peroxide [8]. Malonaldehyde production, which is readily monitored in this isolated-cell system, is probably catalyzed by the drug-hydroxylating enzyme system located in the endoplasmic reticulum and is thus comparable with the enzyme-dependent lipid peroxidation reactions of isolated microsomes [9,10]. The isolated cell system, however, differs from a microsomal system in being fortified with natural inhibitors, which alter the response to agents that stimulate lipid peroxidation [8,11]. The purpose of this work was to characterize some early alterations in isolated hepatocytes in which malonaldehyde production had been induced. MATERIALS AND METHODSThe cell preparation and incubation techniques were the same as described previously [8,11]. Lipid peroxide formation was initiated by addition of ADPcomplexediron(stocksolution50mMADP + 1.87mM FeC1,) or an aqueous solution of cumene hydroperoxide (stock solution 30 mM). The reaction was followed by the withdrawal of aliquots (0.2 ml) of the whole incubation mixture for spectrophotometric measurements of thiobarbituric-acid-reacting substances at 535 nm (malonaldehyde) [12].