摘要:

AbstractWe conducted a prospective, randomized single‐blind trial of propranolol for the prevention of recurrent variceal bleeding. Seventy‐nine patients shown to have variceal hemorrhage at endoscopy were included in the study within 72 hr following diagnosis. Fifty‐seven patients had alcoholic cirrhosis, 10 cryptogenic cirrhosis, 6 posthepatitic cirrhosis, 4 biliary cirrhosis, 1 portal vein thrombosis without cirrhosis and 1 idiopathic portal hypertension. The severity of liver disease at inclusion was assessed according to the Pugh modification of the Child‐Turcotte classification: 9 (11%) had Class A; 41 (52%) Class B and 29 (37%) Class C disease. Patients were randomly assigned by sealed envelope to the propranolol group (42 patients) or the placebo group (37 patients). Propranolol dosage was titrated in order to produce plasma concentrations of propranolol of 50 to 150 ng per ml. β‐blockade was also confirmed by isoproterenol testing. The cumulative percentages of patients free of rebleeding 1 and 2 years after inclusion were 31 and 21% in the propranolol group, and 25 and 17% in the placebo group; both differences were not significant. Cumulative 1 and 2 years survival were also comparable: 64 and 54% in the propranolol group vs. 70 and 63% in the placebo group. There was no evidence for a therapeutic effect of propranolol after adjusting for potential confounding variables by multiple logistic regression. We conclude that propranolol is not effective for the prevention of variceal rebleeding, when administered early following the initial bleed, in cirrhotics unselected with respect to the severity of the liv

ISSN:0270-9139    

DOI:10.1002/hep.1840060602

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractThe effects of pharmacological manipulation of the lower esophageal sphincter pressure on the esophageal circulation in patients with cirrhosis and portal hypertension were investigated in 33 patients by measuring the azygos venous blood flow, which is an index of blood flow through esophageal varices and periesophageal collaterals draining into the azygos venous system. Measurements were performed in baseline conditions and after the blind administration of metoclopramide (20 mg i.v.) (12 patients), domperidone (10 mg i.v.) (12 patients) and placebo (9 patients).Both metoclopramide and domperidone caused a significant reduction of azygos blood flow, that decreased by 11.5% (p<0.01) and 15.6% (p<0.02) respectively, while no change was observed in patients receiving placebo (+1.4%, not statistically significant). Reduction of azygos blood flow represents a selective effect of metoclopramide and domperidone on the esophageal circulation, since portal pressure, hepatic blood flow, cardiac output, heart rate and arterial blood pressure were unchanged by the administration of metoclopramide, domperidone or placebo.These results indicate that the administration of drugs that increase the lower esophageal sphincter pressure may reduce the inflow of blood into the esophageal varices in cirrhotic patients with portal hypertension.

ISSN:0270-9139    

DOI:10.1002/hep.1840060603

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractThe drugs currently under investigation in the prevention of recurrent gastrointestinal bleeding in cirrhosis are likely to decrease the portal pressure by means of a primary reduction of portal blood flow. The hemodynamic effects of β‐blocking agents and vasodilatory drugs were noninvasively measured in eight patients with cirrhosis by means of pulsed echo‐doppler equipment. Portal caliber, blood velocity and flow were recorded hourly after a single dose of propranolol (40 mg p.o.) or atenolol (100 mg p.o.), and every 5 min after treatment with isosorbide dinitrate (5 mg sublingually). The drugs were administered at random with an interval of 2 days or more. The portal caliber decreased after atenolol, but did not change after propranolol and isosorbide. The blood velocity decreased by 29 ± 2% 3 hr after propranolol, by 26 ± 2% 3 hr after atenolol and by 31 ± 3% 15 min after isosorbide. The portal blood flow decreased by 0.29 ± 0.03 liters per min after propranolol, by 0.34 ± 0.06 after atenolol and by 0.26 ± 0.03 after isosorbide, without any difference among the various treatments. β‐blockers and vasodilatory drugs have comparable effects on portal blood flow. β1‐selective and nonselective β‐blockers are similarly effective in keeping with the hypothesis that changes in portal blood flow are mainly due to the bl

ISSN:0270-9139    

DOI:10.1002/hep.1840060604

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractWe quantitated α1‐antitrypsin mRNA in normal, α1‐antitrypsin‐deficient cirrhotic and biliary cirrhotic livers using two‐dimensional electrophoretograms of [35S] methionine‐labeled translational products of total hepatic RNA and RNA/DNA hybridization. α1‐antitrypsin precursor product was identified by immunoprecipitation. The relative abundance of α1‐antitrypsin product from normal (0.989 ± 0.197), cirrhotic (0.956 ± 0.062) and α1‐antitrypsin deficient (0.818 ± 0.12) livers was not significantly different. Although (RNA/DNA) was decreased in the PiZZ cirrhotic livers compared to normal (0.56 ± 0.045 vs. 0.95 ± 0.225), it equaled that found in the PiM cirrhotic livers (0.56 ± 0.055). The concentration of α1‐antitrypsin mRNA [relative abundance × (RNA/DNA)], while decreased in PiZZ compared to normal liver, is thus no different in PiZZ cirrhotics than in PiM cirrhotics. We confirmed this observation by quantitation of the α1‐antitrypsin mRNA using an α1‐antitrypsin genomic probe. By RNA/DNA hybridization, α1‐antitrypsin mRNA was equal in PiM cirrhotic and PiZZ cirrhotic (38.48 ± 4.5 vs. 31.93 ± 2.1), but significantly decreased from noncirrhotic PiM liver (58.36 ± 12.7). We conclude that α1‐antitrypsin mRNA is decreased in cirrhosis of any etiology, and this decrease appears to represent a general response of the liver to injury. Since the decreased α1‐antitrypsin mRNA in PiM cirrhotics is associated with normal serum α1‐antitrypsin levels, it is unlikely that the decreased α1‐antitrypsin mRNA in PiZ

ISSN:0270-9139    

DOI:10.1002/hep.1840060605

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractA neurologically normal 3‐year‐old girl with Type I Crigler‐Najjar syndrome was successfully treated with orthotopic liver transplantation. Preoperative serum bilirubin concentrations as high as 31 mg per dl were not diminished with phenobarbital or phototherapy. Bilirubin fractionation of duodenal bile prior to transplantation revealed 87.1% unconjugated bilirubin and 12.9% monoconjugates as determined by alkaline methanolysis‐high‐performance liquid chromatography. Postoperatively, the serum bilirubin concentration quickly fell to normal. Uridine diphosphate glucuronyl transferase activity in the recipient liver was not detectable. The gallbladder bile bilirubin concentration of 23.9 mg per dl was less than 15% of previously reported normal values. Since devastating kernicteric brain injury is the invariable outcome of Type I Crigler‐Najjar syndrome, liver transplantation should be performed when phototherapy cannot maintain the serum bilirubin concentration at an unequivocally

ISSN:0270-9139    

DOI:10.1002/hep.1840060606

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractAlthough secondary vitamin E deficiency causes a reversible neurologic disorder in children with chronic cholestasis, the effect of this deficiency state on other organ systems is unknown. We studied the effects of vitamin E therapy on selected gastrointestinal and hepatic functions in five children with chronic cholestasis and well‐documented biochemical and neurologic evidence of vitamin E deficiency. After 2 to 3 years of oral or parenteral vitamin E therapy, there was no improvement in fecal fat losses, severity of vitamin E malabsorption (as measured by an oral vitamin E tolerance test) or total serum fatty acid concentrations. Serial analyses of liver function blood tests demonstrated a marked decline in fasting serum cholylglycine concentrations during 18 to 31 months of vitamin E therapy, while other liver function tests showed no consistent changes. We conclude that vitamin E deficiency does not appear to alter intestinal absorption of fat or vitamin E; however, vitamin E deficiency may further impair already compromised hepatic function during pathologic conditions such as cholestasi

ISSN:0270-9139    

DOI:10.1002/hep.1840060607

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractThe clinical and pathologic findings in 12 patients with medium‐chain acyl CoA dehydrogenase deficiency and three patients with long‐chain acyl CoA dehydrogenase deficiency are summarized. Although these inborn errors of intramitochondrial β‐oxidation of fatty acids present with similar findings to Reye's syndrome, there are clinical, laboratory and hepatic histologic differences. Younger age at presentation, history of unexplained sibling death, a previous episode of lethargy, hypoglycemia or acidosis precipitated by fasting stress and only mildly elevated serum transaminases with normal or only mildly prolonged prothrombin time may all suggest an acyl CoA dehydrogenase deficiency. Long‐chain acyl CoA dehydrogenase deficiency is differentiated from medium‐chain acyl CoA dehydrogenase deficiency by younger age at presentation, more profound cardiorespiratory depression, evidence of cardiomyopathy, and sequelae of muscle weakness, hypotonia and developmental delay. Definitive diagnosis is made by assay of medium‐chain or long‐chain enzyme activity in cultured skin fibroblasts or in leukocytes.Hepatic light microscopic alterations are essentially limited to steatosis, which may be either macro‐ or microvesicular. The cases with microvesicular steatosis can be differentiated morphologically from Reye's syndrome by electron microscopy, showing the absence of the mitochondrial changes characteristic of Reye's. Four of seven cases of acyl CoA dehydrogenase deficiency showed some variations from normal in the appearance of the hepatocyte mitochondria. The relationship of these variations to the basic metabolic defect(s) remains

ISSN:0270-9139    

DOI:10.1002/hep.1840060608

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractTwenty‐nine patients with a positive antimitochondrial antibody titer ≥1/40, who were detected during screening for other autoimmune disease, are described who had a normal serum bilirubin, alkaline phosphatase and transaminase and who had no symptoms of liver disease at presentation. Liver biopsies in 12 of the 29 fulfilled diagnostic criteria for primary biliary cirrhosis; a further 12 were consistent with primary biliary cirrhosis, but only 2 were normal. There was a high incidence of other autoantibodies and autoimmune diseases, especially thyroid antibodies and disorders. Sixteen of these patients have been followed for over 4 years since diagnosis (mean = 6 years, range = 4 to 9 years) and for a mean of 8.7 years since initial detection of the antimitochondrial antibody (range = 4 to 13). Five of 16 developed symptoms suggestive of primary biliary cirrhosis, and 11 of 16 developed elevation of alkaline phosphatase. The antimitochondrial antibody activity in these patients was in the same IgG subclasses (predominantly IgG1and IgG3) as that seen in a group of 23 patients with clinically, biochemically and histologically advanced primary biliary cirrhosis. All showed the same abnormalities on quantitative estimation of the total IgG subclasses in serum; relative excess of IgG3and, to a lesser extent, IgG2was exhibited. It is concluded that, in this study, the finding of an antimitochondrial antibody titer ≥1/40 is strongly suggestive of primary biliary cirrhosis even in the absence of symptoms and the presence of a normal alkaline phosph

ISSN:0270-9139    

DOI:10.1002/hep.1840060609

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractStimulated by observations in an outbreak of hepatitis δ‐virus infection among Yucpa Indians in Venezuela, in which unusual histologic features were found, we studied 100 cases of fatal hepatitis from Colombia, South America, which had been obtained by autopsy or viscerotomy. These cases were considered to be “Santa Marta hepatitis,” or “hepatitis of the Sierra Nevada de Santa Marta,” which has been observed in this region for more than 40 years. Of the 100 cases, 19 had a variety of histologic lesions or were normal, and hepatitis δ‐virus antigen was not demonstrated immunocytochemically in any of them. By contrast, 81 cases had a characteristic histologic picture with intense microvesicular steatosis associated with conspicuous eosinophilic necrosis of the hepatocytes, which apparently were sluggishly removed by cytolysis. Hepatitis δ‐virus antigen was detected in 70% of the 81 cases, and the absence of detection of this antigen was often associated with poor tissue preservation and more extensive hepatocyte necrosis. A smaller percentage of patients had hepatitis B virus antigens detectable in liver tissue. The characteristic lesion in these 81 cases could be distinguished from other causes of microvesicular steatosis by the extensive eosinophilic necrosis. Other variable accompanying features included intraacinar, mainly macrophagic, scavenger cell inflammation, intense portal inflammation, parenchymal regeneration, and ductular and arteriolar proliferation. Santa Marta hepatitis as a severe form of hepatitis δ‐virus infection differs markedly from fulminant δ‐hepatitis in Europe and the United States in which the microsteatosis with marked eosinophilic degeneration is not found. The causes for these differences are unknown but may relate to nutritional factors or environmental toxins. Hepatitis δ‐viral infection appears to be endemic in the indigent, rural populations of Northern South America where hepatitis B virus is also endemic. The severity of Santa Marta hepatitis stresses the importance of preventive measures against hepatitis B v

ISSN:0270-9139    

DOI:10.1002/hep.1840060610

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

Abstract“Santa Marta” hepatitis has been recognized as an unusual type of severe hepatitis occurring in northern Colombia since 1930. Liver specimens from a historic viscerotomy series, used by Gast‐Galvis to identify cases and describe epidemiologic features of this disease, were available for review and histopathologic staining for δ‐virus. Of 86 liver specimens examined from cases of fulminant Santa Marta hepatitis, 81 showed a distinct histopathologic picture, in various stages of progression, with features of eosinophilic necrosis, microvesicular fat infiltration of the liver parenchyma and morula cells; 69% were positive for δ‐antigen by immunoperoxidase staining. This disease occurred predominantly in several small towns within 50 km of Santa Marta, with mortality reaching 1.25 per 1,000 inhabitants per year during the 1940′s. Children under age 15 were most commonly affected and males affected twice as frequently as females. Liver specimens obtained from children, or within 15 hr of death, or which showed early histologic stages of disease were most likely to be positive for δ‐antigen.This and the accompanying study confirm the existence of a distinct type of fulminant hepatitis in Colombia for over 50 years. The epidemiologic and histopathologic features are comparable to severe hepatitis in Venezuela Indians and in the Amazon basin of Brazil, suggesting that all are caused by δ‐superinfection of hepatit

ISSN:0270-9139    

DOI:10.1002/hep.1840060611

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY