Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The occurrence of antibodies against recombinant human interferon-alpha 2a (IFN-alpha 2a) in patients with acute viral hepatitis (AVH) was examined by ELISA. Naturally occurring IgG anti-IFN-alpha 2a were found in 50% of patients with type A, 50% of those with type B and in 8.3% of those with non-A, non-B AVH. The corresponding frequencies of IgM antibodies were 80%, 30% and 33.3%, respectively. IgM anti-IFN-alpha 2a were found more frequently in patients with AVH type A than in normal control subjects (P less than 0.01). Anti-IFN-alpha 2a were detectable at the highest frequency 3 weeks after acute onset and then became negative. An absorption experiment revealed that IgM anti-IFN-alpha 2a did not cross-react with recombinant human IFN-alpha 2b. Immunoblotting analysis confirmed the binding of antibodies to IFN-alpha 2a. Sera positive for IgG and/or IgM anti-IFN-alpha 2a were unable to neutralize IFN-alpha 2a. The appearance of anti-IFN-alpha 2a was not correlated with disease severity. There was no evidence to suggest that anti-IFN-alpha 2a impaired the elimination of hepatitis virus. This is the first study to demonstrate the occurrence of anti-IFN-alpha 2a in patients with AVH. Detection of anti-IFN-alpha 2a may be useful for clarifying any underlying immune events in various diseases.
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PMID:Naturally occurring anti-interferon-alpha 2a antibodies in patients with acute viral hepatitis. 190 85

To determine whether long-term therapy with recombinant interferon-alpha can improve the course of chronic delta hepatitis, 61 Italian patients with this disease were randomly assigned to receive either interferon-alpha-2b three times a week (5 MU/m2 for 4 mo and then 3 MU/m2 for another 8 mo) or no treatment. At the end of the 12-mo study, all patients were followed-up for 12 additional months. Normalization or decrease of more than 50% from baseline of serum ALT levels occurred in 42% of treated patients the fourth month of therapy, 26% the twelfth month and 3% the twenty-fourth month vs. 7%, 7% and 0%, respectively, in the control group. However, relapses occurred in 7 of 8 (87.5%) responders 1 to 10 mo (mean = 3.5 mo) after cessation of therapy. Liver biopsies were carried out at baseline and during the twelfth month of treatment. Histological improvement, mostly caused by decrease of portal inflammation, was observed in 57% of treated and 36% of untreated patients. Measures of antiviral activity (serum hepatitis delta virus RNA and intrahepatic hepatitis delta antigen) showed similar levels in treated and control patients. In treated patients the percentage of patients who were negative for HDV RNA never exceeded that of baseline. Although interferon-alpha in the dosage given in this study had no antiviral effect on patients with chronic hepatitis D, it reduced hepatic inflammation as measured by ALT levels. Whether a longer duration or reinstitution of interferon-alpha therapy would achieve long-term control of ALT levels and prevent chronic liver damage is not known.
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PMID:A randomized controlled trial of a 12-month course of recombinant human interferon-alpha in chronic delta (type D) hepatitis: a multicenter Italian study. 205 Mar 21

To determine whether natural human interferon administered under the usual therapeutic dosing scheme would inhibit the hepatic drug metabolism, we performed an antipyrine test in eight patients with chronic B or non-A, non-B hepatitis before and after a subchronic interferon therapy (6 megaunits/day for 17 +/- 4 days, mean +/- SD). Six patients received interferon-beta and 2 received interferon-alpha. To circumvent a possible influence of interferon-induced fever on the hepatic drug metabolism, the antipyrine test during the interferon therapy was performed at least 14 days after the interferon-induced fever disappeared. The kinetic parameters of antipyrine were obtained from seven saliva samples over 32 hours postdose. There were no significant differences in any kinetic parameters of antipyrine observed before and during the interferon therapy. With the sample size of the study, there was only a 20% chance (i.e., beta-power = 0.8 at alpha = 0.05) that we might have missed a 17% reduction in antipyrine clearance by the interferon therapy (type II error). On the other hand, the subchronic interferon therapy lowered serum aminotransferases and DNA polymerase activity significantly (P less than .05) compared with the respective baseline values. Our results suggest that the subchronic therapeutic dosing scheme of interferon as conducted in the present study does not cause the inhibitory effect on the oxidative drug metabolism to a statistically significant or clinically relevant degree in patients with chronic hepatitis, while it improves their liver function. Further studies are required for determining if different types of interferons administered under the different dosing schemes would alter the hepatic drug metabolism and the inhibitory effect would be time-dependent.
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PMID:Effects of subchronic treatment with natural human interferons on antipyrine clearance and liver function in patients with chronic hepatitis. 211 64

The study of chronic liver disease has been hampered by insufficient information relative to the pathogenesis of the many forms of hepatitis. Consequently, well-designed treatment strategies are frequently lacking. Wilson's disease is characterised by excessive copper accumulation in the liver and other organs. While d-penicillamine is clearly effective, many patients may not tolerate its many adverse effects. Trientine, oral zinc and unithiol have all shown promise as therapeutic alternatives. Autoimmune chronic active hepatitis responds well to prednisone and azathioprine. Cyclosporin has also produced clinical improvement in several case reports but no comparison has yet been made with the current standard therapy. Recombinant interferon-alpha (IFN alpha) has demonstrated the ability to inhibit hepatitis B viral replication, and the combination of oral corticosteroids followed by IFN alpha is more effective than either agent alone in eliminating viral replication in patients with chronic active hepatitis B. Currently, primary sclerosing cholangitis (PSC) has no standard medical management, but corticosteroids and methotrexate may each have a future role in its treatment. Drug treatment for primary biliary cirrhosis (PBC) has been disappointing, and early reports of success with d-penicillamine were not confirmed in large well-controlled trials. While some reports of improvement with several agents have been described, larger studies are still needed. Alcoholic liver disease continues to be associated with significant morbidity and mortality and numerous investigators have researched several different medical avenues of treatment. Success reported with androgens and the antithyroid agent propylthiouracil in alcoholic liver disease will need confirmation by other research before these agents can be recommended for routine use. Finally, colchicine may prove to be effective in slowing the rate of fibrosis in cirrhosis, but this has yet to be conclusively proven.
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PMID:Current therapy of chronic liver disease. 219 64

Twenty patients with metastatic renal cell cancer were treated with a combination of recombinant interferon-alpha 2a (Roferon-A), 18 MU intramuscularly three times weekly and vinblastine 0.1 mg/kg intravenously once every 3 weeks. Three patients experienced a complete response (CR) (15%) and three a partial response (PR) (15%). The response duration was 3, 13, and 15 months in the CR group, and PRs lasted 11, 13, and 14 months. Constitutional symptoms like fever, anorexia, and fatigue were the most common side effects. One patient had reversible hepatitis, which was probably unrelated to antineoplastic therapy. Dose modifications had to be made in seven patients due to leukopenia or thrombocytopenia. No very serious side effects were noticed. In view of what has been reported previously, the overall response rate (30%) of this regimen is good and tolerance of the treatment is acceptable.
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PMID:Recombinant interferon-alpha 2a and vinblastine in advanced renal cell cancer: a clinical phase I-II study. 239 8

A small proportion of patients with acute viral hepatitis run a progressive fulminant course ending in acute liver failure with encephalopathy, and with a mortality rate of 75-80%. In small children and pregnant women mortality is even higher. We have treated 32 patients of all ages with acute progressive and fulminant hepatitis over the last 7 years in an uncontrolled trial with human interferon-alpha (HulFN-alpha), with i.m. doses of 3 x 10(6) u/day (70,000 u/kg per day for infants) for 8 +/- 3 days (mean +/- SD.) In 17 patients hepatitis was due to hepatitis A virus, in 7 to hepatitis B virus, in 6 to non A-non B virus and in 1 case each to herpes and cytomegalovirus. Sixteen patients (50%) recovered including 9 of 22 (41%) who were in Grades III-IV coma when treatment was started. Only 1 of 8 children less than 4 years of age recovered, whereas 15 of 24 (62%) older children and adults survived. Two of three pregnant women with acute fulminant hepatitis survived. In patients who recovered, improvement was often noted on about the fifth day of IFN treatment: 9 of 16 patients died before completing 5 days of therapy. Our studies of the IFN system response to hepatitis viruses showed that the greater majority of patients produce IFN in the acute stage of the infection. However, a minority have a defective IFN response that is more severe and more common in progressive fulminant hepatitis, and in several of these patients IFN response was completely lacking. It is in these cases that IFN treatment is likely to have the greatest value. On the basis of these encouraging preliminary results, it is suggested that a well-controlled, double-blind study be done to evaluate the effectiveness of HulFN-alpha treatment when given early during the course of acute progressive viral hepatitis.
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PMID:Interferon treatment in acute progressive and fulminant hepatitis. 247 21

Six patients with chronic type B hepatitis and concurrent infection with the immunodeficiency virus were treated with 600 mg azidothymidine (AZT)/day and 3 X 10(6) units of interferon-alpha (IFN-alpha) every other day for a total of 4 months. None of the patients treated lost the hepatitis B virus (HBV). HBV-DNA concentrations were not significantly influenced by this treatment. Human immunodeficiency virus (HIV) infection was also not affected except for a transient rise in CD 4-positive cells in 2 individuals, who had initially low CD 4-positive cells. Treatment did not influence the presence of HIV-Ag in the serum. In conclusion, a combination therapy of IFN and AZT does not seem to be beneficial at the doses given and the time involved.
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PMID:Treatment of patients with chronic type B hepatitis and concurrent human immunodeficiency virus infection with a combination of interferon alpha and azidothymidine: a pilot study. 257 96

Spleen cells from uninfected control mice selectively lysed BALB/c 3T3 fibroblasts infected with mouse hepatitis virus (MHV), a murine coronavirus. Lysis of infected cells occurred within 3 hr, and histocompatibility between effector and target cells was not required. This natural, cell-mediated, virus-associated cytotoxicity differed from NK cell- and T cell-mediated lysis. Spleen cells from animals infected with MHV were enriched in NK activity and were more cytotoxic to YAC-1 target cells, but did not show enhanced cytotoxicity for MHV-infected target cells. Spleen cells from beige mice, which are deficient in NK cell activity, were able to lyse MHV-infected target cells, as were spleen cells from nude mice, which are deficient in T cell activity. Lysis of MHV-infected target cells could be mediated by cells from the spleen and, to a lesser extent, by cells from the bone marrow, but not by resident peritoneal cells or thymocytes. We suggest the term "virus killer (VK) activity" for this phenomenon. VK activity of splenocytes from different mouse strains correlated with the ability of the splenocytes to bind purified radiolabeled MHV virions. MHV virions caused agglutination of spleen leukocytes from susceptible mouse strains, indicating that leukocyte agglutination or adsorption may provide a useful assay for coronaviruses such as MHV which lack hemagglutinating activity. SJL mouse splenocytes did not bind MHV and did not lyse infected targets. MHV bound relatively well to splenocytes of other mouse strains, but poorly to thymocytes and erythrocytes. Binding of MHV to leukocytes was not influenced by 6 mM EDTA or EGTA, indicating a lack of requirement for Mg++ or Ca++. VK activity was also resistant to EDTA and EGTA, in contrast to NK activity, which was sensitive to those chelating agents. VK activity was also unaffected by actinomycin D, cycloheximide, or puromycin, indicating that new protein synthesis was not required for lysis. Antibody to interferon-alpha/beta did not block lysis, nor was there substantially enhanced lysis mediated by leukocytes from mice infected with virus and thus exposed to high levels of interferon. VK activity was blocked by antibody directed against the peplomeric glycoprotein E2 of MHV. VK activity required infected target cells, because cells with adsorbed MHV virions were not lysed by splenocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Natural cytotoxicity against mouse hepatitis virus-infected target cells. I. Correlation of cytotoxicity with virus binding to leukocytes. 300 98

For patients with chronic hepatitis B e (HBe)-positive hepatitis, long-term results of pilot studies with lymphoblastoid interferon-alpha, acyclovir, or a combination, and of a randomized controlled trial of interferon/desciclovir combination therapy are presented. HBe seroconversion was observed in more than 40 percent of patients treated with combination therapy, 30 percent with interferon therapy, 18 percent with acyclovir, and 0 percent with no treatment. HBe reactivation occurred in two patients with cirrhosis. Hepatitis B surface seroconversion followed HBe seroconversion in 11 to 30 percent of treated patients. HBe seroconversion was significantly related to initial low levels of viral replication and to transient aminotransferase elevation during the second half of the interferon treatment of 16 weeks. Clinical improvement and persistent normalization of aspartate aminotransferase was observed in all patients with HBe seroconversion. Conversion to a state of virus latency (HBe negative) mostly occurred after therapy, suggesting that the specific immunologic host response had been brought about by the suppression of virus replication through antiviral agents. Recommendations for selection of patients for antiviral combination therapy are made on the basis of these long-term results.
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PMID:Long-term follow-up of antiviral combination therapy in chronic hepatitis B. 304 80

Changes in the host interferon system during short-term steroid hormone (prednisolone) withdrawal therapy in seven patients with HBeAg-positive chronic hepatitis B were investigated by estimating the in vitro interferon-alpha production in peripheral blood lymphocytes and 2-5 oligoadenylate synthetase activity in the serum. The interferon-alpha production induced by the Sendai virus and estimated in lymphocyte cultures was rapidly and significantly (p less than 0.01) reduced by prednisolone administration and subsequently followed by a recovery corresponding to its withdrawal. The serum 2-5 oligoadenylate synthetase activity showed a similar tendency to diminish under prednisolone administration and to revive during its withdrawal. In all four patients who developed an acute and transient post-prednisolone withdrawal exacerbation a significant initial increase in serum HBV-DNA levels was noted in accordance with the reduction in the host interferon system activity. The results suggest that the changes in the host interferon system activity, i.e. an initial fall and subsequent recovery as caused by a short-term steroid administration with gradual withdrawal, appear to promote viral replication in the early phase and the development of acute and transient exacerbation of hepatitis in the post-steroid withdrawal phase, which may lead to HBeAg/anti-HBe seroconversion in HBeAg-positive chronic hepatitis B patients.
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PMID:Activities of the interferon system in patients with HBsAg-positive chronic hepatitis B during short-term steroid withdrawal therapy. 339 63


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