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1.
Dig Dis Sci ; 40(1): 33-40, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7529673

ABSTRACT

To determine if hepatitis C virus infection influences the behavior of type 1 autoimmune hepatitis and to assess the performance parameters of third-generation immunoassays for viral infection in this disease, 64 patients with different patterns of disease behavior were assessed retrospectively for antibodies to hepatitis C virus by third-generation enzyme-linked immunosorbent assay and recombinant immunoblot assay and for HCV RNA by polymerase chain reaction. Hepatitis C virus RNA was detected in seven patients (11%) and antibodies to hepatitis C virus were found in five (8%). All patients who had an acute onset of illness or who sustained remission after therapy lacked HCV RNA in serum. In contrast, four of 31 patients who relapsed (13%) and three of 17 patients who failed treatment (18%) had HCV RNA in serum. Patients with HCV RNA were indistinguishable from those without HCV RNA; in three patients, infection was recognized only by testing for HCV RNA. Four of seven patients with HCV RNA responded fully to corticosteroids, although each relapsed after drug withdrawal. Smooth muscle antibodies (43% versus 91%, P = 0.006) and concurrent smooth muscle and antinuclear antibodies (0% versus 60%, P = 0.003) occurred less frequently in patients with HCV RNA than in counterparts without HCV RNA. The specificity of the third-generation enzyme immunoassay was 98% and its overall predictability was 94%. Its sensitivity, however, was 57% and false positive results occurred in 20%. Hepatitis C virus infection is an uncommon determinant of disease behavior in type 1 autoimmune hepatitis, but it may be present in relapse or treatment failure.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Autoimmune Diseases/microbiology , Hepatitis C/complications , Hepatitis/immunology , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Autoantibodies/analysis , Autoimmune Diseases/diagnosis , Autoimmune Diseases/drug therapy , Chronic Disease , Enzyme-Linked Immunosorbent Assay , Female , Hepacivirus/genetics , Hepacivirus/immunology , Hepatitis Antibodies/analysis , Hepatitis C/diagnosis , Hepatitis C/microbiology , Hepatitis C Antibodies , Humans , Immunoblotting , Male , Middle Aged , Polymerase Chain Reaction , Predictive Value of Tests , RNA, Viral/analysis , Recurrence , Retrospective Studies , Sensitivity and Specificity
2.
J Hepatol ; 21(5): 730-4, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7890886

ABSTRACT

This study evaluated the performance of third-generation anti-HCV assays in blood donors who were positive by second-generation anti-HCV, and assessed any possible relationship between antibody patterns, HCV replication and liver damage. Fifty-two second-generation enzyme immunoassay-positive asymptomatic Italian blood donors were retested for anti-HCV by third-generation enzyme immunoassay and recombinant immunoblot assay (Ortho third-generation enzyme immunoassay, third-generation recombinant immunoblot assay), utilising recombinant C33c and NS5 and synthetic peptide C100 and C22 antigens, and for HCV-RNA by "nested" polymerase chain reaction with 5' region primers. Alanine aminotransferases were tested monthly for 6 months. Two out of 52 second-generation enzyme immunoassay-positive donors were third-generation enzyme immunoassay, third-generation recombinant immunoblot assay and HCV-RNA negative. Among 50 third-generation enzyme immunoassay-positive cases, two had a third-generation enzyme immunoassay optical density < or = 1: one was third-generation recombinant immunoblot assay and HCV-RNA negative, and the other was third-generation recombinant immunoblot assay "indeterminate" and HCV-RNA-positive. The remaining 48 cases had third-generation enzyme immunoassay optical density > 1: six were third-generation recombinant immunoblot assay negative (one HCV-RNA+ve), eight "indeterminate" (two HCV-RNA+ve) and 34 positive (22 HCV-RNA+ve). All "indeterminate" subjects reacted only to C22. HCV-RNA was positive in 22/34 cases with positive third-generation recombinant immunoblot assay (two or more Ags), 3/9 "indeterminate" and 1/11 negative. Alanine amino-transferases were abnormal in 13 cases with positive third-generation recombinant immunoblot assay, one was "indeterminate" and three were negative.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Blood Donors , Hepacivirus/immunology , Hepatitis Antibodies/analysis , Microbiological Techniques , Adult , Cohort Studies , Female , Hepacivirus/genetics , Humans , Immunoblotting/methods , Immunoenzyme Techniques , Male , Middle Aged , RNA, Viral/analysis
3.
Hepatology ; 19(2): 273-9, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8294085

ABSTRACT

We assessed the pattern of hepatitis C viremia in chronic liver disease by studying 100 hepatitis C virus antibody-positive patients: 48 with chronic hepatitis, 21 with cirrhosis and 31 with hepatocellular carcinoma and cirrhosis. Serum hepatitis C virus RNA was detected by means of both the conventional nested polymerase chain reaction and a newly developed assay based on branched DNA that can also quantify viremia. Hepatitis C virus RNA was found in 94 of 100 patients with polymerase chain reaction and in 71 of 100 patients with branched-DNA (p < 0.001). Mean viremia level (x 10(3) genome equivalents/ml +/- S.D.), as assessed with the branched-DNA test, was 5,700 +/- 7,618 in the 48 patients with chronic hepatitis, 3,340 +/- 3,633 in the 21 patients with cirrhosis and 1,768 +/- 2,770 in the 31 patients with hepatocellular carcinoma (p < 0.02). We also analyzed retrospectively the relationship between viremia and treatment. Fifty-five patients (41 chronic hepatitis, 14 cirrhosis) underwent interferon-alpha treatment. Mean viremia level was comparable among the 30 responders (5,644 +/- 8,207) and the 25 nonresponders (5,519 +/- 6,208) to interferon, but it was significantly lower (1,841 +/- 1,864) in the 12 of 30 responders (11 chronic hepatitis, 1 cirrhosis) who maintained remission up to 1 yr after cessation of interferon treatment. Fourteen patients (7 chronic hepatitis, 7 cirrhosis) with autoantibodies (12 antinuclear, 2 anti-liver-kidney microsomal) were treated with prednisone. The mean viremia level significantly increased after 3 mo of treatment, even in face of ALT decrease.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Hepatitis C/blood , Interferon-alpha/therapeutic use , Prednisone/therapeutic use , Viremia/blood , Adult , Alanine Transaminase/blood , Carcinoma, Hepatocellular/blood , Chronic Disease , DNA, Viral/blood , Female , Hepacivirus/genetics , Hepatitis C/drug therapy , Humans , Interferon alpha-2 , Liver Cirrhosis/blood , Liver Cirrhosis/drug therapy , Liver Neoplasms/blood , Male , Middle Aged , Polymerase Chain Reaction , RNA, Viral/blood , Recombinant Proteins , Retrospective Studies , Viremia/drug therapy
4.
Gut ; 34(4): 544-8, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8491404

ABSTRACT

Primary biliary cirrhosis is characterised by the presence of antimitochondrial antibodies which are directed against components of mitochondrial dehydrogenase complexes. The specificity of antimitochondrial antibodies for primary biliary cirrhosis as detected by immunoblotting was investigated. Commercially available preparations of pyruvate and oxo-glutarate dehydrogenases and beef-heart mitochondria were used as source of antigens. Sera from 47 primary biliary cirrhosis patients (46 of whom were antimitochondrial antibody positive by immunofluorescence), 16 non-primary biliary cirrhosis patients (antimitochondrial antibody positive by immunofluorescence), 23 liver-kidney microsomal antibody positive chronic active hepatitis patients, and 32 patients with connective tissue diseases were examined. Of the 47 subjects with primary biliary cirrhosis, 43 (91%) and 13 (28%) tested positive by immunoblotting for pyruvate and oxo-glutarate dehydrogenase, respectively. Only three primary biliary cirrhosis patients were negative for both antigens, including the only one shown to be antimitochondrial antibody negative by immunofluorescence. The other two patients were positive by immunoblotting with beef-heart mitochondria. In contrast, only three of 16 (19%) non-primary biliary cirrhosis patients who were antimitochondrial antibody positive by immunofluorescence tested positive by immunoblotting (for both pyruvate dehydrogenase and beef-heart mitochondria). None of the 23 liver-kidney microsomal antibody positive and the 32 patients with rheumatic diseases were positive by immunoblotting with any antigen. Our data show that immunoblotting with commercially available oxo-acid dehydrogenases is a reproducible method for the detection of antimitochondrial antibodies highly specific for primary biliary cirrhosis.


Subject(s)
Autoantibodies/analysis , Liver Cirrhosis, Biliary/immunology , Mitochondria/immunology , Adult , Animals , Antibody Specificity , Cattle , Female , Fluorescent Antibody Technique , Humans , Immunoblotting/methods , Ketoglutarate Dehydrogenase Complex/immunology , Middle Aged , Mitochondria, Heart/immunology , Pyruvate Dehydrogenase Complex/immunology
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