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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of human recombinant interferon-alpha on lymphocyte proliferation and differentiation was studied in 18 patients with chronic type B hepatitis who were participating in a randomized controlled trial of interferon-alpha therapy. Peripheral blood mononuclear cells (PBMC) were obtained by lymphopheresis before and during a 4 mo course of interferon. Pokeweed mitogen-induced immunoglobulin synthesis by PBMC obtained from patients before therapy was similar to that of PBMC from normal individuals. However, after 2 wk treatment with human recombinant interferon-alpha mitogen-induced immunoglobulin production was decreased by an average of 50%. Staining for cytoplasmic immunoglobulin revealed decreases that paralleled secreted immunoglobulin, indicating that interferon-alpha treatment inhibited immunoglobulin synthesis. Mixing autologous T and B cell enriched populations from before and during interferon treatment revealed that the decrease in immunoglobulin synthesis involved a defect in the B cell-enriched population. In contrast to immunoglobulin synthesis, pokeweed mitogen-induced lymphocyte proliferation was not significantly affected by in vivo administration of interferon-alpha. Thus a major effect of in vivo interferon-alpha on immunoregulation in patients with chronic type B hepatitis appears to be an inhibition of the late stages of B cell differentiation into immunoglobulin producing and secreting plasma cells.
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PMID:Immunologic effects of interferon-alpha in man: treatment with human recombinant interferon-alpha suppresses in vitro immunoglobulin production in patients with chronic type B hepatitis. 349 May 13

Activation of the interferon system is an early antiviral immune defence mechanism. In 16 patients, whose viral hepatitis (A, B, and non-A, non-B) ran a normal course, blood interferon levels rose and cells were rapidly induced into an antiviral states. However, in 6 patients with acute fulminant hepatitis, the antiviral interferon system was grossly defective. Blood interferon levels were not measurable in 5 of them; in all 6, the mononuclear cells were not in an antiviral state and did not produce interferon-alpha or interferon-gamma when stimulated, but their intracellular antiviral mechanism was intact because small amounts of exogenous interferon induced an antiviral state in vitro. 5 of the patients with fulminant hepatitis received interferon-alpha therapy, with rapid activation of their interferon systems, accompanied by rapid and uncomplicated recoveries in 3. It is suggested that interferon be given a trial as an early treatment for severe viral hepatitis.
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PMID:Interferon system in acute viral hepatitis. 617 36

Variations in the serum levels of hepatitis C virus (HCV) RNA. IgM antibody against the HCV 'core' structural protein (c22) and alanine amino-transferase (ALT) were measured in 23 patients with chronic hepatitis C who underwent therapy with interferon-alpha 2a (IFN alpha 2a). Low pretreatment levels of viraemia and undetectable IgM anti-core were significantly associated with a long-term response to treatment. In patients with hepatitis relapses after the end of treatment, HCV RNA levels increased before or at the same time as ALT in 29 out of 34 cases (85%). ALT flares occurred before or simultaneously with IgM anti-core elevations in 18 out of 20 cases (90%). Therefore, post-treatment hepatitis C exacerbations show the same sequence of events seen as in hepatitis B exacerbations (increases of viraemia followed by those of ALT and IgM anti-'core'). These findings underscore the diagnostic and prognostic usefulness of monitoring anti-HCV-positive patients with quantitative assays for HCV markers.
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PMID:The fluctuations of hepatitis C virus RNA and IgM anti-HCV (core) serum levels correlate with those of alanine aminotransferases during the hepatitis relapses of patients treated with interferon. 748 43

Chronic coinfection with the hepatitis B (HBV) and hepatitis delta (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-alpha 2b (IFN-alpha) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied; 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheuer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-alpha 2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and delta coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coinfection with hepatitis B and C or B, C and delta viruses results in severe chronic liver disease and responds poorly to interferon-alpha treatment. 749 93

To assess whether interferon-alpha might prevent non-A, non-B hepatitis from becoming chronic, 45 consecutive patients with transfusion-associated hepatitis were enrolled in a randomized clinical trial. Thirty-eight patients had hepatitis C virus infection, and 7 had non-A, non-B, non-C hepatitis. Twenty-six patients (22 with HCV) were given 3 MU of recombinant interferon-alpha 2b three times a week for 12 wk, whereas 19 (16 with HCV) were not. Biochemical and virological parameters were monitored at regular intervals during an 18-mo follow-up. At the end of the 3-mo therapy, 16 (73%) patients with hepatitis C had normal serum ALT activity, compared with 7 (44%) who were not treated (NS). Fifty-three percent of the treated patients and none of the untreated patients had normal ALT levels and no HCV RNA (p = 0.0087). At the end of the 18-mo follow-up, 13 (59%) treated patients had normal ALT levels, compared with 6 (37%) untreated controls (NS). Thirty-nine percent had normal ALT and no HCV RNA, compared with none of the controls (p = 0.035). Four patients (22%) had had sustained complete responses to interferon, defined as normal ALT levels and no HCV RNA at the end of the 3-mo treatment period and the 18-mo follow-up period. All seven patients with non-A, non-B, non-C hepatitis, treated and untreated, recovered uneventfully from hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A multicenter randomized controlled trial of recombinant interferon-alpha 2b in patients with acute transfusion-associated hepatitis C. 750 25

Formerly the diagnosis of acute and chronic non-A, non-B hepatitis was made by the exclusion of other causes. However, in 1989 cloning of an antigenic component of the hepatitis C virus (HCV) was reported. This led to first- and second-generation tests for antibody to HCV (anti-HCV) in serum. HCV has been associated with acute and chronic posttransfusion and sporadic non-A, non-B hepatitis, and with hepatocellular carcinoma. Viral HCV RNA can be estimated with the polymerase chain reaction test, but this technically difficult test is not generally available. The entire viral genome has been sequenced. The envelope region shows considerable variation, and mutant HCV infections are being described already. There are geographic variations in the prevalence of anti-HCV, but usually about 0.5% to 1% of healthy blood donors test positive. Parenteral exposure to blood, especially by transfusion or drug abuse, remains a certain means of acquiring HCV infection. The method by which millions without parenteral risk factors acquire HCV remains uncertain. Vertical transmission and sexual and family spread occur only rarely. Body secretions are free of the virus. The mode of transmission may become clarified when tests for viral HCV as opposed to anti-HCV become generally available. Acute HCV infection usually is mild, and the chronic disease is also indolent. Carriers of hepatitis B virus or alcoholics who also test positive for HCV have more serious disease. Chronic HCV infection must be distinguished from autoimmune chronic active hepatitis. The most important difference is the response to corticosteroid therapy, which is good in autoimmune hepatitis and poor in HCV-related disease. Hepatocellular carcinoma can complicate HCV-related cirrhosis, usually about 20 years after infection with HCV. Recombinant interferon-alpha is used to treat chronic HCV disease, but selection of patients, dose, and duration of therapy are uncertain. In general, 50% of patients respond to the treatment, but 50% of these will have a relapse, with an overall response rate of 25%. Liver transplantation in patients with end-stage HCV disease usually is followed by infection of the graft.
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PMID:Chronic hepatitis C. 751 76

Hepatitis viruses and alcohol are major causes of liver disease. This study was aimed at investigating the effect of alcohol intake on the replication of hepatitis C virus and the efficacy of interferon therapy. Fifty-three patients who were histologically proved to have chronic hepatitis C were tested. Of these, 16 were diagnosed as habitual drinkers whose cumulative total consumption of alcohol was more than 100 kg or who had consumed at least 60 gm of ethanol daily for at least 5 yr. The quantities of hepatitis C virus RNA in serum were measured with a competitive assay that combined reverse transcription and polymerase chain reaction. The subjects received a 26-wk course of interferon-alpha therapy. There were no significant differences in age and ALT levels between habitual drinkers and nonhabitual drinkers. The titer of viral RNA (logarithmic transformed copy numbers per milliliter of serum) of habitual drinkers (8.5 +/- 0.5) was higher than that of nonhabitual drinkers (7.7 +/- 0.8) (p < 0.01). Neopterin levels in serum, a marker for the activation of cell-mediated immunity, were lower for habitual drinkers (5.7 +/- 1.5 pmol/ml) than for nonhabitual drinkers (8.1 +/- 5.0 pmol/ml) (p < 0.01). Eleven of the nonhabitual drinkers (30%) were long-term responders whose alanine aminotransferase levels remained within normal range during the 24 wk after interferon therapy, whereas only one (6%) of the habitual drinkers was a long-term responder (p = 0.06). These findings suggest that alcohol intake increases hepatitis C virus RNA levels in serum--at least in part--impairment of cellular immunity, and modulates the efficacy of interferon therapy.
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PMID:Increased serum hepatitis C virus RNA levels among alcoholic patients with chronic hepatitis C. 752 70

Soon after the isolation of the hepatitis C virus (HCV) genome in 1988 it became evident that HCV is the most important cause of non-A, non-B-hepatitis. In recent years the structure of this (+)-stranded RNA-virus, the different genotypes of HCV and the replication in hepatic and extrahepatic sites have been investigated. HCV has a remarkable degree of genetic heterogeneity, mutates rapidly, leading to the simultaneous coexistence of different genoms in the same individual (quasispecies) and most likely to the generation of neutralization escape mutants. The cytotoxicity of the hepatitis C virus appears to be mainly immune-mediated. This review article summarizes basic, diagnostic and clinical aspects of acute and chronic HCV-infection, association with other diseases and complications such as liver cirrhosis and hepatocellular carcinoma. Interferon-alpha has been shown useful in normalizing serum aminotransferases and decreasing liver inflammatory lesions in about half of the patients with chronic hepatitis C. However, relapses after the cessation of interferon-alpha are frequent, leading to a sustained response in less than 30% of treated patients. Several clinical and biochemical parameters for response to interferon-alpha have been proposed. In patients with orthotopic liver transplantation due to progressive chronic hepatitis C and decompensated liver cirrhosis, reinfection of the donor organ frequently occurs. However, in transplanted patients under immunosuppression the course of hepatitis C reinfection is usually mild. Due to screening programs of blood and blood products the incidence of posttransfusion-acquired hepatitis C has declined. However, further efforts in understanding the transmission of community-acquired hepatitis C are necessary. The development of a hepatitis C vaccine will be difficult due to the high degree of viral genetic heterogeneity.
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PMID:[Viral hepatitis C]. 753 96

A 42-year-old man was treated with interferon-alpha for chronic hepatitis B; during the fourth week of treatment he developed an exacerbation of liver disease, and nuclear and smooth muscle autoantibodies, which were previously negative, were detected in very high titers. After discontinuation of interferon therapy, ALT values subsided promptly and autoantibodies disappeared within a few months. This sequence of events strongly suggests a direct relationship between IFN treatment and a self-limited hepatitis with autoimmune markers in this case.
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PMID:Development of transient autoimmune hepatitis during interferon treatment of chronic hepatitis B. 764 89

We quantified IgG antibodies to structural (core) and nonstructural (C100-3) hepatitis C virus proteins in 42 patients with chronic hepatitis C treated with a 6-mo course of interferon-alpha. Sera were drawn before and at the end of therapy and also 6 mo after therapy withdrawal; they were stored for later analysis of antibodies and serum hepatitis C virus RNA. Sustained virus clearance was observed at the end of therapy and 6 mo after therapy withdrawal in nine cases; it was accompanied with sustained reductions of antibody to hepatitis C virus core protein and antibody to C100-3 protein. A sustained reduction of antibody to hepatitis C virus core protein was specific to sustained virus clearance, although that of antibody to C100-3 protein was not. None of the patients who did not show reductions of levels of both antibodies at the end of therapy displayed sustained virus clearance. Five patients showed hepatitis C virus RNA negativity and normal aminotransferase levels at the end of therapy without reduction of antibody to hepatitis C virus core protein levels. Of these five patients, relapse of hepatitis occurred in four, and viremia was present 6 mo after therapy withdrawal in all cases. These results demonstrate that testing for antibody titers may add information for evaluating virus clearance after interferon therapy.
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PMID:Quantitative analysis of antibodies to hepatitis C virus during interferon-alpha therapy. 768 34


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