Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several trials for chronic hepatitis B in children have shown the usefulness of interferon-alpha (IFN-alpha) in eliminating hepatitis B virus (HBV) replication, by an improvement in the liver damage. Optimal doses of IFN-alpha are 10 MU/m2 of body surface, three times a week for 24 weeks. With this schedule, clearance of HBV-DNA was achieved in 58% of treated children. In nonresponder children, because of the progression of the disease, there is a need to try new antiviral approaches. In a pilot study, 11 nonresponder children were retreated with IFN-alpha 10 MU/m2 body surface, three times a week for 24 weeks. At the end of treatment, 27% of the children had cleared serum HBV-DNA. Thus, retreatment has some benefit in nonresponder children.
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PMID:Interferon treatment in children with chronic hepatitis B. 760 77

To study the mechanism of the effects of alpha-interferon (alpha-IFN) on chronic hepatitis B, we examined its effect on hepatitis B virus (HBV)-specific cytotoxic T cells (CTL). Using two different HBV-DNA transfected human myeloma cell lines, one expressing hepatitis B core antigen (HBcAg; C4) and the other expressing hepatitis B surface antigen (HBsAg; S6) as targets in cytotoxic tests in vitro, peripheral blood mononuclear cells obtained from chronic hepatitis B patients who were treated with alpha-IFN were examined for their cytotoxic activity against these transfectants. During the treatment with alpha-IFN, in association with a decline of serum alanine amino transferase levels, CTL activities were significantly reduced. An inhibition study in vitro revealed that alpha-IFN did not directly inhibit these CTL activities, indicating that alpha-IFN may inhibit the induction of CTL, and thereby may be related to the reduction of hepatocyte injury.
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PMID:Effect of alpha-interferon on hepatitis B virus-specific cytotoxic T cells. 762 Jan 3

In the 35 years since the discovery of interferon, significant biological activity has been described for interferon-alpha (IFN alpha) in various cancers, particularly haematological malignancies such as hairy cell leukaemia and chronic myelogenous leukaemia. Except for localised therapy in bladder and ovarian cancer, activity against most solid tumours has been disappointing. Other notable exceptions include Kaposi's sarcoma, renal cell carcinoma and malignant melanoma, tumours known to be susceptible to immunological attack. More recently, broad spectrum antiviral activity has been demonstrated for both recombinant and naturally occurring IFN alpha. Hepatitis C is responsive to IFN alpha in about 40% of patients, but long term remissions are rare. In contrast, long term suppression of hepatitis B is common following IFN alpha therapy. Both diseases respond in a dose proportional fashion, with daily doses of 5 million units (MU) significantly more effective than lower doses. The mechanism of action in viral diseases involves the expression of unique antiviral proteins such as endonuclease and 2'-5'-oligoadenylate synthetase which enhance the destruction of viral RNA. General cellular protein synthesis is also inhibited, including cytochrome P450 enzymes. This forms the basis for potential drug interactions, with IFN alpha slowing the clearance of highly metabolised drugs such as theophylline. As an antitumour agent, the mechanism of action of IFN alpha is unclear, particularly in haematological cancers. In melanoma and renal cell carcinoma, antitumour effects may be mediated by augmented immune responses including activation of natural killer lymphocytes and enhanced expression of cell surface antigens (e.g. MHC I and II). Conversely, antibody formation to recombinant IFN alpha may result in a loss of activity. This has been observed in both renal cell cancer and hepatitis B and C. The elimination half-life of IFN alpha is short, 4 to 5 hours, but biological activity extends for 2 to 3 days after administration, which facilitates daily or thrice weekly administration. Clearance of IFN alpha is mediated by catabolism in the renal tubules; no intact drug is excreted in the urine. It is probable that the antiviral indications of IFN alpha will expand as the agent is more clearly recognised as a primary endogenous defence against various viral conditions.
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PMID:Interferon-alpha in malignant and viral diseases. A review. 768 71

An open, randomized trial study on the therapeutic effect of recombinant alpha-interferon (IFN alpha) in 40 patients with hepatitis B virus membranous nephropathy (HBVMN) was conducted. All were pathologically proven to have HBVMN which showed no response to corticosteroid treatment represented by persistent heavy proteinuria. Both HBeAg and HBsAg were positive in all. Group 1 was composed of 20 patients who were treated with recombinant IFN alpha (5 subjects, body wt < 20 kg; 8 subjects, body weight > or = 20 kg) by subcutaneous (s.c.) injection three times a week for 12 months. In group 2 there were 20 patients who received supportive treatment only. At the end of the third month of treatment, all patients in Group 1 were free of proteinuria. In contrast, 10 patients (50%) in Group 2 had persistent heavy proteinuria and another 10 patients (50%) had light proteinuria with exacerbation during respiratory tract infection. At the end of the twelfth month, 8 patients (40%) in Group 2 still had persistent heavy proteinuria and 12 patients (60%) had light proteinuria with frequent relapses. Eight patients (40%) in Group 1 had HBeAg seroconversion between the fourth and sixth months and HBsAg seroconversion between the tenth and twelfth months. HBe seroconversion only [HBeAg (-)/HBsAg (+)] was found in four patients. Four patients had no change in HBV serological markers [HBeAg (+)/HBsAg (+)]. The remaining 4 patients had HBeAg (-)/HBeAb (+) HBsAg (-)/HBsAb (-) at the end of the twelfth month. In contrast, there was no seroconversion of HBeAg (+)/HBsAg (+) in Group 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of hepatitis B virus-associated membranous nephropathy with recombinant alpha-interferon. 773 Nov 50

Hepatitis B virus (HBV) DNA was evaluated in peripheral blood mononuclear cells (PBMC) from 50 individuals utilising Southern hybridisation analysis. HBV DNA sequences were detected in PBMC from 16/29 (55 percent) of chronic hepatitis B virus (HBV) carriers with serum HBeAg and HBV DNA, compared with 1/8 (13%) of carriers with anti-HBe and HBV DNA negative (P = NS). Two of 7 patients with previous HBV infection and chronic liver disease had detectable HBV DNA in PBMC. Of the 19 patients with HBV DNA in PBMC, 18 had high molecular weight species. In addition, five of these had free, monomeric HBV DNA and six patients had low molecular weight bands. For nine of the above patients, total peripheral blood leucocytes were separated into PBMC and polymorphonuclear cells. Four had HBV DNA in PBMC only, two only in polymorphonuclear cells and three in both types of cell. Eleven patients with chronic HBV infection were studied at monthly intervals for 6 months. Six were untreated and five received IFN-alpha. Three patients who responded to IFN-alpha had HBV DNA present in PBMC before therapy, and two became negative. Two of 3 untreated patients had intermittent HBV DNA in PBMC and the other remained persistently negative. Of the patients positive on more than one occasion, the pattern of HBV DNA was similar. Peripheral blood leucocytes often contain multimers of free HBV DNA, more commonly in patients with serum HBeAg and HBV DNA and may occur even in the absence of serum HBsAg. These findings have implications for recurrence of disease after hepatic transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Southern hybridisation analysis of HBV DNA in peripheral blood leucocytes and of different cell types: changes during the natural history and with interferon-alpha therapy in patients with hepatitis B virus infection. 793 Nov 89

Chronic hepatitis D is a usually severe and progressive liver disease due to infection with the hepatitis delta virus, a unique RNA virus requiring the hepatitis B virus helper function to exert its pathogenic potential. Alpha IFN is at present the treatment of choice for chronic viral hepatitis, but the results obtained in chronic hepatitis D are far from being satisfactory. Available data show that IFN is more likely to be effective if administered to patients with a recent infection (lasting less than 1 year) at high doses (9-10 MU thrice in a week) and for a prolonged length of time (at least 12 months). The optimal timing of IFN treatment remains to be addressed: apart from the clearance of HBsAg and seroconversion to anti-HBs (an event often occurring months to years after completion of a successful IFN treatment) no other early biochemical or virological events can predict a sustained response. Better therapeutic options are therefore needed. Unfortunately, antiviral agents, such as Ribavirin, active against HDV in cell cultures, have failed to confirm their attitude in the clinical setting. In vitro and in vivo evidence points to HBV as a possible target for antiviral therapy in chronic hepatitis D, providing the rationale for trying new deoxynucleotide analogues also in this severe form of hepatitis.
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PMID:Interferon in HDV infection. 797 16

A 19-year-old male healthy hepatitis B virus (HBV) carrier developed fulminant hepatitis following allogenic bone marrow transplantation (BMT) from his brother, who was also a healthy HBV carrier, during the first complete remission of acute myelogenic leukemia (M1, FAB classification). Serum markers related to both HBV and hepatitis C virus (HCV) were elevated during active liver injury when a point mutation in the precore (pre-C) region occurred in the HBV. The patient received low-dose interferon alpha (IFN-alpha), while the dose of cyclosporin A was tapered; the patient eventually recovered from the liver injury. Fulminant hepatitis due to HBV and/or HCV following BMT is rare, and it is considered to have a very poor prognosis. The rationale for the use of low-dose IFN-alpha with cyclosporin A (CyA) is discussed.
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PMID:Fulminant hepatitis following bone marrow transplantation in hepatitis B virus carrier siblings. 800 May 16

The inability to mount a protective level (> or = 10 IU/l) of hepatitis B surface antigen (HBsAg)-specific antibodies after vaccination is presumably the consequence of a defect in the cellular immune regulation. We compared the in vitro immune responses of peripheral blood mononuclear cells (PBMC) from high, intermediate and non-responders, after stimulation with recombinant HBsAg. The absence of a proliferative response in non-responders was not reversed by removal of CD8+ T cells, indicating that HBsAg-specific CD8+ T-cell-induced suppression was not the underlying cause of non-responsiveness. Non-responders did not produce cytokines after HBsAg stimulation. High responders displayed a typical Th1-like profile since their PBMC produced interleukin-2 (IL-2) and gamma-interferon (IFN gamma) and no detectable IL-4 or IL-5 upon stimulation with HBsAg.
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PMID:Deficient T-cell responses in non-responders to hepatitis B vaccination: absence of TH1 cytokine production. 801 62

Hepatic expression of interferon-alpha (IFN-alpha) was examined by immunohistochemistry in 90 Chinese patients (M/F 67:23, age: 14-69) with a spectrum of hepatitis B virus (HBV)-related chronic liver diseases. Immunoreactive IFN-alpha was detected in sinusoidal cells in 79 patients (88%) and in mononuclear cells in 59 patients (65.6%). Patients with active liver diseases (chronic active hepatitis, active cirrhosis, N = 55) had a higher level of IFN-alpha expression compared to patients with inactive histology (N = 35; sinusoidal cells, P < 0.01; mononuclear cells, P < 0.01). Cytoplasmic HBsAg, nuclear HBcAg, and cytoplasmic HBcAg were detected in 79 (88%), 42 (47%), and 23 (27%) patients respectively. Expression of IFN-alpha in mononuclear cells correlated with the expression of cytoplasmic HBcAg (P < 0.05) but not with nuclear HBcAg or cytoplasmic HBsAg. When the patients were divided into four different phases according to the natural history of chronic HBV infection, patients in the active liver disease phase had higher IFN-alpha expression compared to the immunotolerant and late phase patients (P < 0.01). Using double immunohistochemical staining, both IFN-alpha and cytoplasmic HBcAg were frequently detected near inflammatory infiltrates but no correlation existed between the hepatic expression of HBsAg and IFN-alpha. These data indicate that IFN-alpha is expressed in the liver in HBV-related active liver diseases and that the reported suboptimal production of IFN-alpha by PBMC in HBV-related chronic active liver diseases may be due to a redistribution of the IFN-alpha-producing mononuclear cells into the liver, the site of inflammation.
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PMID:Hepatic expression of interferon-alpha in chronic hepatitis B virus infection. 808 12

We have recently reported that administration of recombinant tumor necrosis factor alpha (TNF-alpha) to hepatitis B virus (HBV) transgenic mice reduces the hepatic steady-state content of HBV-specific mRNA by up to 80% in the absence of liver cell injury. In the current study, we analyzed the regulatory effects of several other inflammatory cytokines in the same transgenic model system. Hepatic HBV mRNA content was reduced by up to 90% following administration of a single noncytopathic dose (100,000 U) of interleukin 2 (IL-2). Comparable effects were produced by administration of alpha and beta interferons (IFN-alpha and IFN-beta), but only after multiple injections of at least 500,000 U per mouse. Importantly, the regulatory effect of IL-2 was completely blocked by the prior administration of antibodies to tumor necrosis factor alpha (TNF-alpha), which did not block the effect of IFN-alpha or IFN-beta. In contrast to these observations, recombinant IFN-gamma, IL-1, IL-3, IL-6, TNF-beta, transforming growth factor beta, and granulocyte-monocyte colony-stimulating factor were inactive in this system. These results suggest that selected inflammatory cytokines can down-regulate HBV gene expression in vivo by at least two pathways, one that is dependent on TNF-alpha and another that is not. These results imply that antigen-nonspecific products of the intrahepatic HBV-specific inflammatory response may contribute to viral clearance or persistence during HBV infection.
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PMID:Interleukin-2 and alpha/beta interferon down-regulate hepatitis B virus gene expression in vivo by tumor necrosis factor-dependent and -independent pathways. 810 92


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