[Severe anguilluliatis revealed by corticosteroid therapy. Case].
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Biomedical subjects
Publications and source records attributed to R Poupon.
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We studied the influence of posterior pituitary extract, vasopressin, and somatostatin on hepatic elimination function. Hepatic clearance and its two biological determinants, hepatic blood flow and metabolic activity (clearance Vmax/Km), were determined from hepatic indocyanine green elimination at steady-state in cirrhotic patients. Intravenous infusion of posterior pituitary extract (oxytocin, 59%; vasopressin, 41%) at the constant rate of 0.3 unit per kg per hr decreased hepatic clearance (p less than 0.05) and Vmax/Km (p less than 0.05) but did not change hepatic blood flow. Intravenous infusion of vasopressin (0.3 unit per kg per hr) decreased hepatic clearance (p less than 0.05), Vmax/Km (p less than 0.05) and hepatic blood flow (p less than 0.05). Intravenous infusion of somatostatin (250 micrograms per hr following a bolus i.v. injection of 250 micrograms) decreased hepatic clearance (p less than 0.05), Vmax/Km (p less than 0.05), and hepatic blood flow (p less than 0.05). This study shows that the vasoactive agents used in the management of upper digestive bleeding in cirrhotic patients may have deleterious effects on the metabolic activity of the liver in addition to their effects on hemodynamics. The results suggest that the vasoactive substances either increased the fraction of total hepatic blood which bypassed intact hepatocytes or directly impaired metabolic activity of hepatocytes. Reduction in the metabolic activity of the liver produced by vasoactive agents may have important implications in therapy of portal hypertension.
We have previously reported the results of a controlled trial showing that continuous oral administration of propranolol reduced the risk of recurrent gastrointestinal bleeding in patients with cirrhosis; only part of our patients had been followed for 1 year. This controlled trial was continued for an additional year; accordingly, all of our patients have now been followed for at least 2 years. The purpose of the present study is to determine whether prolonged administration enhances the efficacy of this therapy. Seventy-four patients with cirrhosis, admitted for an episode of gastrointestinal bleeding, were included in this study; ascites, jaundice and encephalopathy were absent or mild and transient. The patients were randomly assigned to two groups; one group of 38 patients received propranolol twice daily at doses that reduced the resting heart rate by 25%, the other group of 36 patients received a placebo twice daily. The cumulative percentages of patients free of recurrent gastrointestinal bleeding 1 and 2 years after inclusion were 87 and 79% in the propranolol group, and 42 and 32% in the placebo group; both differences were highly significant (p less than 0.0001). Furthermore, the cumulative percentages of surviving patients 1 and 2 years after inclusion were 94 and 90% in the propranolol group, and 84 and 57% in the placebo group; the difference between the two groups was not significant at 1 year, but was statistically significant at 2 years (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
A study from five hepatology units documenting 157 cases of drug-induced hepatitis and a second study from a laboratory of immunology which tested more than 100,000 sera permitted us to establish the frequency of antiorganelle antibodies and their diagnostic value in drug-induced hepatitis. In drug-induced hepatitis caused by a heterogenous group of drugs consisting of ajmaline, aminopterine, isaxonine, isoniazid, perhexiline, phenylbutazone and troleandromycine, antiorganelle antibodies were absent or rare. In drug-induced hepatitis caused by another heterogenous group of drugs, including clometacin, fenofibrate, oxyphenisatin and papaverine, antismooth muscle, antinucleus and antimitochondria antibodies were found in isolation or in different combinations in 70% of cases. From the presence of antismooth muscle antibodies in sera, we could trace 30 cases of clometacin-induced hepatitis. The third group included drug-induced hepatitis with special antibody:iproniazid-induced hepatitis with antimitochondrial antibody 6 and tienilic acid (ticrynafen)-induced hepatitis with antiliver/kidney microsome antibody 2 (anti-LKM2). These two antibodies are rare in routine sera and were absent in patients who received the drug and had no liver damage. From the presence of corresponding antibodies, we detected six cases of iproniazid-induced hepatitis and 67 cases of tienilic acid-induced hepatitis. Antiorganelle antibodies found in high titers disappeared in 2 to 24 months following withdrawal of the offending drug. The fourth group was represented by halothane-induced hepatitis; antiliver/kidney microsome antibody 1 was weak and infrequent. Similarities between drug-induced hepatitis of the second group and lupoïd hepatitis suggest that drugs may reveal this spontaneous disorder.(ABSTRACT TRUNCATED AT 250 WORDS)
Sixty-five patients with histologically proven chronic active hepatitis of unknown cause but associated with the antiliver/kidney microsome antibody type 1, confirmed by immunofluorescence and immunoprecipitation, were selected as forming a special entity. This disease was found to be rare with a prevalence of 5/1,000,000. The female to male ratio was 8:1. The condition occurred at all ages but was most common between the ages of 2 and 14 years. In 22 of the 65 cases, the hepatitis was associated with an autoimmune disease, most commonly insulin-dependent diabetes, autoimmune thyroid disease and vitiligo. The same autoimmune diseases were present in first-degree relatives from seven families. In 36 cases, the onset of disease resembled acute viral hepatitis. Serum biochemical tests showed marked elevation in aminotransaminases and hypergammaglobulinemia. Paradoxically, serum and salivary IgA levels were often normal or low. Histologic findings were multifocal hepatic necrosis with bridging in the acute stage, and aggressive hepatitis with mononuclear cell infiltration or macronodular cirrhosis in the late stages. Serologically, apart from the presence of antiliver/kidney microsome antibody type 1, the disease was characterized by the absence of antiactin, antimitochondria and antinucleus antibodies; however, organ-specific autoantibodies were often present. The clinical course was usually severe: six patients in the acute stage presented with fulminant hepatitis, and all, except two, other patients progressed to cirrhosis. Prolonged treatment with corticosteroids and immunosuppressants was usually effective in rendering the cirrhosis inactive. The cumulative survival rate was 51% at 14 years. We propose to call this entity "anti-LKM1 chronic active hepatitis" or "autoimmune hepatitis type II" to differentiate it from classical "lupoid hepatitis" or autoimmune hepatitis type I.
We studied the effects of a series of 16 vasodilators on the intrahepatic vasoconstriction induced by norepinephrine in the isolated perfused rat liver. The vasodilators were nonselective alpha-adrenergic antagonists (phentolamine, ifenprofil, isoxsuprine and buflomedil), a nonselective beta-adrenergic antagonist (propranolol) and an agonist (isoproterenol), an alpha 2-adrenergic agonist (clonidine), calcium channel blockers (verapamil and diltiazem), nitrovasodilators (nitroglycerin, sodium nitroprusside), papaverine and other unclassified vasodilators, some of them with rheological properties (diazoxide, vincamine, cinepazide, naftidofuryl and pentoxifylline). The most potent drugs were ifenprofil, phentolamine, isoxsuprine, clonidine, sodium nitroprusside and buflomedil. Diazoxide, papaverine, pentoxifylline and trinitrine were less powerful. Verapamil, diltiazem, propranolol, isoproterenol, vincamine, cinepazide and naftidofuryl were ineffective. We conclude that different classes of pharmacological agents have significant vasodilatory properties on the hepatic microvasculature. This offers interesting perspectives in the treatment of cirrhosis and stressful states where high levels of circulating norepinephrine may contribute to the altered liver perfusion.
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Elevated serum gammaglobulin concentrations are frequently observed in patients with liver cirrhosis. Predominant elevation of the IgA is generally considered as suggestive of an alcoholic aetiology. The aim of this study was to define the factors that determine the serum concentration of IgA in alcoholic cirrhosis. Twenty-seven patients with alcoholic cirrhosis were studied. Serum concentrations of IgG, IgA and IgM were measured by immunonephelometry. Hepatocellular function was assessed by the Child-Turcotte score, the prothrombin time and the intrinsic clearance of indocyanine green. The importance of intra-hepatic shunts was estimated according to the intact hepatocyte theory, and the degree of hepatic necrosis by serum levels of transaminases. It was noted that: 1) the IgA concentration correlated significantly with the Child-Turcotte score and with the decrease of the prothrombin time, intrinsic clearance and the functional fraction of hepatic blood flow; 2) there was no such correlation between the serum concentration of IgA and the total hepatic blood flow or transaminase levels; 3) there was no correlation between serum concentration of IgG or IgM and the factors studied. These results suggest that in alcoholic cirrhosis, increase in serum IgA, reflects the degree of impairment of hepatic function and intrahepatic shunting.
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Interferon is the only treatment shown to be effective on hepatitis C in controlled trials. The response to treatment is generally assessed in terms of a return to normal transaminase activity, but also negative PCR testing for viral RNA and histopathological examination of the liver. At a dose of 3 MU three times a week for 6 months, 25% of patients have a persistent return to normal transaminase activity, 25% relapse when interferon is withdrawn, and the remaining 50% have persistently high levels at the end of treatment and are considered resistant. The rate of persistent responses increases to 40% when treatment is extended to one year. Viral RNA becomes undetectable in the serum of 80% of these responders. Most also have a histological improvement, but so do a number of patients who relapse or who are resistant. In the longer term, interferon could prevent the onset of liver cancer in patients with viral C cirrhosis. Interferon is generally well tolerated at the doses currently used, most side effects (hematologic, neuropsychiatric and thyroid disorders) resolving when treatment is stopped. The following factors are clearly predictive of the response to interferon : young age, short time since onset, absence of cirrhosis, lower-level viremia, and infection by HCV genotypes other than 1b. Interferon is markedly less effective in immunodeficient patients (transplant, HIV infection, etc.). Several add-on treatments have been tried, but ribavirin appears to be the most promising, both during initial interferon therapy and for patients who relapse or are resistant to a first course. Interferon therapy of the acute phase of hepatitis C significantly reduces the risk of chronic liver disease. There is no vaccine against HCV infection.