Biomedical subjects
Publications and source records attributed to C Degott.
Liver involvement is common in acute and chronic Q fever and consists of nonspecific hepatitis and granulomas without fibrosis. We report the case of a patient suffering from chronic Q fever with nonspecific hepatitis and granulomas, in whom progressive development of extensive liver fibrosis was documented by repeated biopsies.
We report the case of a female patient suffering from Waldenström's macroglobulinemia with three different liver lesions: peliosis hepatis, nodular regenerative hyperplasia, and light-chain deposits within the sinusoidal walls. We hypothesize that both peliosis hepatis and nodular regenerative hyperplasia might be the consequence of a disordered intrahepatic circulation determined by light-chain deposits infiltrating the sinusoidal walls.
Hepatitis B virus (HBV) infection may induce severe hepatitis and affect long-term survival of kidney transplant recipients. Persistent viral infection has been shown to occur despite the absence of usual serologic markers. The liver and serum HBV deoxyribonucleic acid (DNA) status of 90 patients were studied prospectively; recently transplanted patients, both hepatitis B virus surface antigen (HBsAg)-positive and negative, with and without liver disease, were investigated with HBV serology, serum HBV DNA, and liver histology. Thirty-four patients had detectable HBsAg, and 21 had viral multiplication at the time of transplantation. Serial HBV DNA determinations performed in 57 of 90 patients disclosed (a) reactivation of HBV replication in 11 of 12 HBsAg-positive patients, (b) increase of viral replication when positive on the initial sample in 6 of 11 patients, and (c) development of HBV replication in 7 of 35 of the HBsAg-negative patients. Moreover, liver HBV DNA studies showed a statistical correlation between the presence of integrated liver HBV DNA and chronic hepatitis in HBsAg-negative patients. This study demonstrates prospectively the significant association of HBsAg-positive as well as HBsAg-negative HBV infection with chronic hepatitis and suggests that immunosuppressive therapy may enhance the viral replication in both HBsAg-positive and negative subjects.
We report the case of a patient in whom amitriptyline administration for 5 wk was followed by prolonged cholestasis. Jaundice and pruritus lasted 19 and 20 mo, respectively. Three liver biopsies were performed at different stages of the disease showing the course of liver lesions. Cholestasis initially located in the region of the hepatic venule came to be associated with the progressive development of portal tract lesions consisting of inflammatory infiltration, fibrosis, and disappearance of interlobular bile ducts. Amitriptyline hydroxylation and dextromethorphan O-demethylation are deficient in subjects with the poor metabolizer phenotype of debrisoquine. Drug oxidation phenotyping with dextromethorphan showed that this patient had the extensive metabolizer phenotype. This observation demonstrates that amitriptyline can induce prolonged cholestasis and suggests that the susceptibility to develop liver injury while taking this drug may not be related to a genetic deficiency of its hydroxylation.
Five cases of epithelioid hemangioendothelioma of the liver are reported. This unusual type of vascular tumor is often difficult to diagnose; its angiogenic nature is not overt at the radiologic level and may be overlooked by conventional histologic examination. At imaging procedures, epithelioid hemangioendothelioma of the liver presents as multiple focal hypovascular areas, disseminated in both lobes. The combination of these imaging abnormalities with a peculiar set of demographic and clinical features, including young age, good general condition, and progressive course, is suggestive. However, the final diagnosis can be established only by histologic examination of appropriate material collected by guided liver biopsies and may be helped by immunohistochemistry and ultrastructural examination. The accurate diagnosis of epithelioid hemangioendothelioma of the liver is of clinical and therapeutic relevance. In view of its favorable clinical course, orthotopic liver transplantation may be considered for the treatment of this tumor when intrahepatic dissemination contraindicates partial hepatectomy and extrahepatic extension, excluded by exploratory laparotomy, is absent.
Three patients suffered from fulminant hepatitis within 23, 59 and 22 weeks after having ingested a total dose of 16, 26 and 15 g, respectively, of amodiaquine for the prophylaxis of malaria. Amodiaquine administration was continued for 44, 21 and 25 days after the onset of jaundice, respectively. One patient underwent emergency orthotopic liver transplantation and survived. The other two died. Fulminant hepatitis threatens patients in whom amodiaquine administration is protracted for several months and not interrupted when jaundice occurs.
A patient with acute myeloblastic leukaemia developed jaundice revealing peliosis hepatis after receiving 6-thioguanine for two months. Peliosis hepatis was severe and was associated with mild lesions of centrilobular veins. Withdrawal of 6-thioguanine was followed by a progressive improvement of liver dysfunction. This report shows that 6-thioguanine, a thiopurine already reported to be responsible for veno-occlusive disease of the liver, can induce peliosis hepatis. This suggests that some liver vascular disorders caused by thiopurines (6-thioguanine, azathioprine and 6-mercaptopurine), particularly peliosis hepatis, veno-occlusive disease, sinusoidal dilatation and perisinusoidal fibrosis, might be related syndromes caused by similar lesions at different sites.
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The detection of hepatitis B viral antigens and the hepatitis delta viral antigen on liver section is currently facilitated by the production and marketing of good quality antisera and revelation systems. Moreover, the routine application of these techniques in histology departments has become more widespread. The detection of HBs and HBc antigens may be useful in the diagnosis of chronic hepatitis. It allows evaluation of replication of HBV (in the same way as HBe antigen and serum DNA) and the examination of a liver needle biopsy should include, in addition to analysis and classification of the lesions, tests for the presence of these antigens. The detection of the delta antigen is particularly useful for the diagnosis of acute hepatitis delta (in cases of co-infection or secondary infection). On the other hand, it is disappointing for the diagnosis of chronic hepatitis delta.
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In order to specify the factors responsible for the hepatic changes occurring during total parenteral nutrition (TPN) and to propose a preventive treatment, 30 infants treated for severe protracted diarrhea were prospectively distributed into 4 groups: I (n = 10): controls; II (n = 7): oral administration of human milk since the 15th day of TPN; III (n = 5): oral metronidazole since the 15th day; IV (n = 8): parenteral antibiotic therapy for septicemia since the 1st day. Contrary to group IV, the first 3 groups were randomly constituted on the 15th day. Liver function tests, bile and serum biliary acids, duodenal flora, hepato-biliary ultrasonography and, in 12 cases, liver histology were sequentially studied. Liver function changes were observed on the 15th day in all groups. An improvement occurred 15 days later in the infants treated, when the control group worsened (p less than 0.02). A significant increase of bile chenodeoxycholic acid levels was observed in the control group only (p less than 0.01), without change in lithocholic acid levels. These results lead the authors to recommend the preventive use of metronidazole or human milk during prolonged TPN in infants.
Microvesicular steatosis of the liver has been reported in two subjects receiving amineptine (a tricyclic antidepressant metabolized by beta-oxidation of its acyl chain). A similar disease is observed after ingestion of drugs which inhibit hepatic mitochondrial fatty acid beta-oxidation, or in subjects with various inborn defects in this metabolic pathway. We therefore determined the effects of amineptine on the mitochondrial oxidation of fatty acids in mice. In vitro, the formation of beta-oxidation products during incubation of palmitic acid with mouse liver mitochondria and the various cofactors necessary for beta-oxidation was inhibited by 27, 33, 46 and 57% respectively, in the presence of 0.25, 0.5, 1 and 2 mM of amineptine. Inhibition was reversible. Tricarboxylic acid cycle activity, assessed by the in vitro formation of [14C]CO2 from [1-14C]acetyl coenzyme A by mouse liver mitochondria, was inhibited by 22, 23, 47, 54, 60 and 62%, respectively, in the presence of 0.0625, 0.125, 0.25, 0.5, 1 and 2 mM of amineptine. In vivo, administration of amineptine, 0.5 and 0.75 mmol.kg-1, inhibited by 70 and 84%, respectively, the exhalation of [14C] CO2 during the first 3 hr after the administration of a tracer dose of [U-14C]palmitic acid. Administration of amineptine, 0.0625, 0.25, 0.5 or 1 mmol.kg-1, 6 hr before the measurement, increased hepatic triglycerides by 73, 139, 295 and 320%, respectively. After 1 mmol.kg-1, accumulation of hepatic triglycerides was maximum at 24 hr, reaching 5-fold the control value; liver histology at that time showed microvesicular steatosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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The prevalence of cholelithiasis was estimated in 434 cirrhotic patients and 1582 non cirrhotic patients necropsied at Hôpital Beaujon from 1976 to 1984. The overall prevalence of cholelithiasis was significantly higher in cirrhotic than in non cirrhotic patients, 26.3 p. 100 and 20.3 p. 100, respectively. The prevalence of cholelithiasis was higher in cirrhotic than in non cirrhotic patients, whether male or female and at any age, except in women over 60 years and in men over 80 years; in these groups, the prevalence of cholelithiasis in non cirrhotic patients was especially high and therefore did not significantly differ from that in cirrhotic patients. The cause of cirrhosis did not significantly influence the prevalence of cholelithiasis; however, although the number of studied patients was small, the prevalence of cholelithiasis seemed to be particularly high in primary biliary cirrhosis. The prevalence of cholecystectomy was lower in cirrhotic than in non cirrhotic patients, which suggests that cholelithiasis might be less often symptomatic and/or less often complicated in the former than in the latter.
Seven patients developed acute hepatitis after receiving Plethoryl for obesity for 4 to 16 weeks. Jaundice was generally associated with or preceded by asthenia, nausea and pruritus. Serum aminotransferase activities were markedly increased whereas alkaline phosphatase and gamma-glutamyltransferase activities were moderately elevated. There was no hepatic failure. In all cases, Plethoryl administration was promptly discontinued. In 6 cases, jaundice disappeared within 2 to 4 weeks, and recovery occurred within 2 to 5 months. In one case, however, jaundice disappeared within 12 weeks and recovery took 10 months.
Methoxsalen, a potent suicide inhibitor of cytochrome P-450 that can be used in humans, might be of value for the prevention of hepatitis in subjects with carbon tetrachloride poisoning. As a preliminary step, we have determined its effects on the hepatotoxicity of carbon tetrachloride in mice. Several monooxygenase activities, the in vitro covalent binding of carbon tetrachloride metabolites to microsomal proteins, and in vitro microsomal lipid peroxidation initiated by carbon tetrachloride metabolites were decreased by 60-90% in microsomes from mice killed 2 hr after the administration of methoxsalen (250 mumol X kg-1); microsomal lipid peroxidation mediated by endogenous iron and NADPH was not modified. Administration of methoxsalen (250 mumol X kg-1) 30 min before carbon tetrachloride (0.1 ml X kg-1) decreased both the in vivo formation of conjugated dienes in microsomal lipids and the in vivo covalent binding of carbon tetrachloride metabolites to lipids and proteins. This pretreatment completely prevented the hepatotoxicity of carbon tetrachloride. Other cytochrome P-450 inhibitors (cimetidine, SKF 525-A or piperonyl butoxide) given at this low molar dose (250 mumol X kg-1) exerted no protective effect. Methoxsalen (500 mumol X kg-1) was also effective, but only partially, when given 30 min after carbon tetrachloride (0.025 ml X kg-1). We conclude that pretreatment with methoxsalen decreases the metabolic activation of carbon tetrachloride, and completely prevents its hepatotoxicity in mice. Post-treatment with methoxsalen must be given early and is only partially effective in mice.
Incubation of [11-14C]amineptine (1 mM) with an NADPH-generating system and hamster liver microsomes resulted in the in vitro covalent binding of an amineptine metabolite to microsomal proteins; this binding was decreased by 41-71% in the presence of cysteine, lysine, glycine or glutathione (0.5 mM). An inverse relationship was found between the concentration of glutathione in the incubation mixture (0.25-4 mM) and the extent of covalent binding in vitro, which became undetectable at concentrations of glutathione of 2 mM and higher. Administration of [11-14C]amineptine (300 mg/kg-1 i.p.) to hamsters pretreated with phorone (500 mg/kg i.p.) resulted in the in vivo covalent binding of an amineptine metabolite to hepatic proteins. This binding was increased by phenobarbital-pretreatment and decreased by piperonyl butoxide-pretreatment. After various doses of phorone (150-500 mg/kg), an inverse relationship was found between hepatic glutathione content and in vivo covalent binding. Administration of amineptine alone (300 mg/kg i.p.) depleted hepatic glutathione by 16% only; in these animals, in vivo covalent binding was undetectable from background. Amineptine (300 mg/kg i.p.) did not produce hepatic necrosis, even in hamsters pretreated with phorone and/or phenobarbital. We conclude that physiologic concentrations of glutathione essentially prevent the in vivo covalent binding of an amineptine metabolite to hepatic proteins, and that this binding does not produce liver cell necrosis in hamsters.
The relationship between the degree of portal hypertension and histologic liver lesions was studied in a group of 84 patients with histologically proven alcoholic cirrhosis. The degree of portal hypertension was evaluated by the gradient between wedged and free hepatic venous pressures. Five histologic lesions were quantified: liver cell necrosis, Mallory bodies, neutrophilic infiltrate, fibrosis, and fatty infiltration. The gradient between wedged and free hepatic venous pressures was significantly correlated with the degree of liver cell necrosis and the degree of neutrophilic infiltrate. The stepwise regression analysis showed that only liver cell necrosis has a significant and independent correlation for the degree of portal hypertension. The value for the gradient between wedged and free hepatic venous pressures was significantly higher in patients with (N = 48) than in those without (N = 36) acute alcoholic hepatitis (19.4 +/- 0.8 and 16.5 +/- 0.7 mmHg, respectively). Thus, histologic liver lesions observed in acute alcoholic hepatitis may play a role in the risk of complications of portal hypertension in patients with alcoholic cirrhosis.