[Alcoholic cirrhosis. Pathologic anatomy, diagnosis, complications and their physiopathology, treatment].
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Biomedical subjects
Publications and source records attributed to M Doffoël.
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Mononuclear cells can be infected in vitro by hepatitis C virus and the viral RNA can be detected in mononuclear cells of chronically infected patients. It was suggested that the virus could persist in the mononuclear cells of some patients treated by interferon. The aim of this study was to follow the presence of viral RNA in the plasma and peripheral blood mononuclear cells of 16 chronically infected patients treated by alpha 2b interferon for 1 year. The RNA was detected by reverse transcription followed by nested PCR and quantified using the branched DNA method at regular intervals for at least one year. Before PCR, the mononuclear cells were treated by RNase and trypsin in order to eliminate the viral particles that could be stuck at the cell surface. Six patients were non responders and had persistent plasmatic viral RNA during the treatment. Two patients were good responders and had persistently negative PCR in both plasma and mononuclear cells. Eight patients had initial negativation of plasmatic hepatitis C virus RNA but showed a relapse characterized by positive plasmatic PCR. Positive PCR in mononuclear cells despite negativity of plasmatic PCR was noted 18 times in 8 patients. Persistently positive PCR in mononuclear cells in absence of detectable viraemia was followed by a virological relapse in 5 of these patients. This study confirms that hepatitis C virus RNA can be detected in mononuclear cells despite negative plasmatic PCR in patients treated by interferon. Moreover, the persistence of viral RNA in peripheral mononuclear cells could be a predictive factor of treatment failure. Our data also suggest that detection of viral RNA in mononuclear cells is probably not only due to passive virus adsorption from plasma.
OBJECTIVES: To assess information that general practitioners had on hepatitis C and on the hepatitis C network in hospitals and private practice. METHODOLOGY: A national telephone survey of 604 general practitioners was conducted between March 18 and 23, 1998. RESULTS: Screening and management of hepatitis C was important for 89% and 97% of general practitioners. Screening was performed in relation to the relative risk (IV drug users 89%, blood transfusion before 1991 88%). General practitioners wanted more information on treatment (54%), patient counselling (42%) and the potential risks of the disease (42%). Of 604 general practitioners, 6% were involved in a hepatitis C network, while 21% were involved in another network (drug users 9%, AIDS 8%). Of the 94% general practitioners who were not part of the network, 33% were willing to join a hepatitis C network. Only 56% were aware of a hepatitis C network (press article 30%, mailing 17% or local meeting 12%). The difficulties for the involvement of general practitioners were: lack of time, topics not adapted to daily practice and geographic constraints (74%), too few patients in their practice (52%), no need (38%), the idea itself of a network and lack of information (28%). CONCLUSION: General practitioners screen patients at risk of hepatitis C. They want to be better informed about treatment, patient counselling, and the potential risks of hepatitis C. They are less involved in hepatitis C networks than in other networks (drug, AIDS). However, one third of general practitioners would like to be involved in a hepatitis C network. These results could be useful for implementing post-graduate courses and general practitioner training.
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Transcatherter oily chemoembolisation, that should not be confused with other different and less effective techniques also called "chemoembolisation" is the most widely used therapy for loco-regional palliative treatment of hepatocellular carcinoma, which will become increasingly frequent, due to HCV infection; the cancer itself is often discovered at an advanced stage, when neoplastic extension precludes radical treatment that is liver transplantation. Performed with the best techniques, it offers a 1- and 5-yr survival of 60 and 30%, that is under confirmation by a randomized trial.
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Etiological treatment is based upon: abstinence in case of alcoholic cirrhosis; alpha-interferon in case of B or C viral cirrhosis; corticosteroids in case of autoimmune cirrhosis; ursodeoxycholic acid in case of primary biliary cirrhosis; stopping the drug in case of drug-induced cirrhosis; surgery in case of secondary biliary cirrhosis; venesections in case of genetic haemochromatosis; liver transplantation in cases of Wilson's disease and alpha 1-anti-trypsin deficiency. Overall, these treatment are more effective when undertaken early in the course of the liver disease.
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OBJECTIVES: The association of anti-HBs immunoglobulins and anti-HBV vaccine could increase the immunogenicity of the latter. The aim of this prospective randomized trial was to compare the immunogenicity of anti-HBs vaccination and serovaccination in alcoholic patients with cirrhosis. METHODS: Alcoholic patients with cirrhosis were randomized in 2 groups: a) Vaccination group: 3 i.m. injections of GenHevac B followed by one booster at month 9; b) Serovaccination group: same vaccination schedule followed by one i.m. injection of anti-HBs immunoglobulins (500 IU). RESULTS: Twenty-five patients (17 males and 8 females, mean age 56 years) were included in the study: 13 received a vaccination and 12 received a serovaccination. After 12 months, the seroconversion rates were 69% and 67% in vaccination and in serovaccination groups, respectively. The predictive factors of non responsiveness were as following: Child B cirrhosis, low number of CD8, a high CD4/CD8 rate, the existence of HLA DR7 antigen, and the absence of HLA DR1 antigen. CONCLUSION: In alcoholic patients with cirrhosis, serovaccination does not increase the immunogenicity of anti-HBs vaccination and should not be recommended.
OBJECTIVE: Although portal obstruction is a complication in cirrhosis which is usually associated with hepatocellular carcinoma, its precise neoplastic or thrombotic nature is not easy to determine. Serum antiphospholipid antibodies could be involved in thrombosis-related portal obstruction. PATIENTS AND METHODS: The presence of serum anticardiolipid antibodies was investigated by an immunoenzymatic technique in 129 patients with alcoholic cirrhosis, 47 patients with hepatocellular carcinoma with (n = 18) or without (n = 29) portal obstruction, and 82 patients without hepatocellular carcinoma or portal obstruction. Five control groups were included: patients with non alcoholic cirrhosis (n = 21), non cirrhotic alcoholic liver disease (n = 21), chronic viral hepatitis (n = 14), extra-hepatic cholestasis (n = 9), and hypergammaglobulinemia associated with human immunodeficiency virus infection without liver disease (n = 28). RESULTS: The prevalence of serum anticardiolipid antibodies was 57% in patients with alcoholic cirrhosis, which was significantly different from the prevalence in the control groups which ranged from 0 to 32%. Anticardiolipid antibodies were of IgA isotypes in 90.5% of the cases, mainly related to the degree of liver failure but not to hepatocellular carcinoma or portal obstruction. CONCLUSION: In alcoholic cirrhosis, serum anticardiolipid antibodies do not seem to be related to the pathogenesis of portal obstruction in patients with hepatocellular carcinoma. They could rather reflect liver lesions and immunological dysfunctions.
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Gastrointestinal hormones and neuropeptides are known to regulate growth of various normal gastrointestinal tissues and many cancers. Since cholecystokinin (CCK) is considered the most potent trophic factor for the exocrine pancreas, we studied its effect on growth of an acinar cell tumor, initially induced by azaserine and transplanted to the rat, in comparison with the normal pancreas. When tumors became palpable, rats were treated three times daily for 12 or 14 days with CCK-8 or NaCl 0.9% (controls) alone or in combination with the CCK receptor antagonist CR1409 (10 mg/kg) administered subcutaneously twice daily. Then tumors and pancreata were analyzed for their size, composition, and CCK receptors. Tumor volume, weight, and protein content, RNA, DNA, and enzymes decreased after CCK-8 treatment in a dose-dependent manner, the maximal effect being observed with 4-micrograms/kg treatment. This inhibitory effect was partially suppressed by CR1409, which by itself also reduced tumor growth, but to a lesser degree. CCK-8 exerted a stimulating effect on growth of the normal pancreas with low doses (1 and 2 micrograms/kg) and an inhibitory effect or no effect with a higher dose (4 micrograms/kg). CR1409 prevented this latter effect, but did not affect by itself the normal pancreas. These findings suggest that CCK-8 inhibits growth of an acinar cell tumor grafted to the rat; this effect is mediated by the occupation of specific CCK receptors present in high density on these cells. In contrast, CCK-8 exerts a biphasic effect on the normal pancreas as a function of its dose.
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