[Immunologic mechanisms of cell damage and pathogenetic correlations in acute and chronic hepatitis].
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Biomedical subjects
Publications and source records attributed to F Tremolada.
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Cell-mediated immunity to a liver specific membrane protein (LP1) has been studied in patients with different types of liver diseases, using the leucocyte migration inhibition test. A high frequency of cellular sensitization to LP1 was detected in untreated chronic active hepatitis, with no significant differences between HBsAg-positive and negative cases. Inhibition of migration is a long-lasting reaction in the spontaneous evolution of the disease, while immunosuppressive treatment normalizes the test only in cases with complete remission. In viral hepatitis B cell-mediated immunity to the liver specific membrane protein can be detected in the acute phase of the disease as a time-limited reaction, exhausted with the clearance of the virus from the liver. An inhibition of migration with LP1 was found also in some cases of HBsAg-positive post-hepatitis patients, in chronic persistant hepatitis, mainly HBsAg-positive, and in asymptomatic chronic carriers of the antigen B. Most of these cases showed a progression to chronic active hepatitis, in clinical and histopathological prospective studies. Our results suggest that cell-mediated immune response to liver specific antigens plays a major role in the pathogenesis of chronic active hepatitis. Moreover the evaluation of these reactions in chronic liver diseases may help in the diagnosis and in the control of the immunosuppressive therapy. Hepatitis B virus infection must be considered one of the possible cause responsible for the rising of autoimmunity to the liver.
This paper describes immunofluorescence studies on liver cell surface localization of hepatitis B surface antigen (HBsAg) and of IgG in acute and chronic hepatitis and in cirrhosis. In acute hepatitis B, HBsAg was found at the surface of hepatocytes in an early phase of the disease, but not during the recovery. This finding is consistent with the hypothesis that immune reactions to HBsAg may be responsible for the liver cell lysis. In HBsAg-positive chronic hepatitis and cirrhosis the antigen was found in the cytoplasm, but not on the surface of the hepatocytes, while in HBsAg-negative cases the antigen could not be detected in the liver cells. Both in HBsAg-positive and in HBsAg-negative chronic active hepatitis (CAH) and cryptogenic cirrhosis IgG bound to the membrane of the hepatocytes could be detected, suggesting a role of antibodies in the pathogenesis of the disease.
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Among the several methods employed for the detection of hepatitis B antigen (HBAg) and hepatitis B antibody (HBAb), radioimmunoassay is considered to be the most sensitive and specific. This paper describes a radioimmunoprecipitation test (RIP) for HBAg and HBAb standardized in our laboratory; it consists of a double-antibody precipitation test in a micro-titer system employing 125I-labeled HBAg. The test is compared with double immunodiffusion (ID) and with counterimmunoelectrophoresis (CEP) in the detection of HBAg and HBAb in healthy persons and in patients with acute and chronic liver disease. RIP is 20,000 times more sensitive than ID and 2,500 times than CEP when HBAg is tested, and 40,000 times more sensitive than ID and 10,000 times than CEP for the antibody detection. Moreover the method is reproducible and specific for HBAg and HBAb. With this test the frequency of HBAg in healthy persons was 0% in subjects without any known contact with antigenic material, 0.80% in hospital personnel and 1.17% in high risk personnel (laboratory technicians, blood products workers, ecc.). In acute viral hepatitis the frequency of HBAg was 90% at the admittance to the hospital and 70% at the dimission, while CEP detected a frequency of 85% and 20% respectively. In chronic liver disease the frequency of HBAg with the RIP method was 83.3% in chronic persistent hepatitis, 42.8% in chronic aggressive hepatitis, 23% in cryptogenic cirrhosis and 16.6% in alcoholic cirrhosis. The frequency of HBAb detected with RIP was 4.50% in subjects without any known contact with antigenic material, 6.45% in hospital personnel, 0.41% in high risk personnel, 20% in acute viral hepatitis at the admittance to the hospital and 50% at the discharge, 25% in chronic persistent hepatitis, 14.2% in chronic aggressive hepatitis, 15.3% in cryptogenic cirrhosis and 50% in alcoholic cirrhosis. The high frequency of antibody in healthy persons with no history of hepatitis or parenteral exposure to blood transfusion suggests a widespread diffusion of hepatitis B infection and the possibility of a nonparenteral route transmission. The frequency of HBAg and HBAb in chronic liver disease as detected by a very sensitive method rises the question of a possible role of hepatitis B virus in the pathogenesis of the disease.
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The role of familial environment in the spreading of hepatitis C virus (HCV) infection is not well established. We studied 1670 family members for 578 anti-HCV+ subjects enrolled in 8 centres distributed throughout Italy. The prevalence of anti-HCV positivity was significantly higher in spouses than in offspring (15.6% and 2.1% respectively; p < 0.01), with no difference between northern and central-southern regions of Italy. Anti-HCV positivity was found almost exclusively in adults; among offspring, during the first two decades of life, the prevalence of anti-HCV positivity was significantly lower than in subjects over 20 years old (0.6% vs 3.1%, respectively).