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)

Ten patients with chronic hepatitis B received increasing doses of nIL-2 (30,000 U, 100,000 U, 300,000 U, 1.0 million U) subcutaneously in a phase I trial. Each dose was applied once per week over 3 weeks. Serum samples were taken before and 2, 12, 24, 48 and 72 h after the first application of each dose level. Serum concentrations of interleukin-1 (IL-1), IL-2, IL-6, interferon-alfa (IFN-alpha), IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and GM-CSF as well as the cytokine-dependent serum components neopterin, beta-2-microglobulin (B2M), C-reactive protein (CPR), soluble IL-2-receptor (sIL-2R) and 2'-5'-oligoadenylate synthetase (2-5 OA) were assayed using ELISAs and RIAs. None of the samples tested contained measurable cytokine levels other than IL-2. A low and non-toxic dose of 300,000 U nIL-2 was already biologically active with induction of neopterin, B2M and sIL-2R. Dose-dependent changes peaked 24-48 h after application. The same patients were then enrolled in a phase II trial. Treatment in five of the patients was continued twice per week for 3 months with a biologically active dose of 300,000 U nIL-2 subcutaneously. Two of these patients as well as another five patients from the original group were treated with 1.0 million U nIL-2 subcutaneously, twice weekly for 3 months. Neither a biologically active but non-toxic dose of 300,000 U nIL-2, nor a toxic dose of 1.0 million U resulted in permanent clearance of hepatitis B early antigen (HBeAg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pilot study of natural human interleukin-2 in patients with chronic hepatitis B. Immunomodulatory and antiviral effects. 830 Oct 59

Hepatitis B virus (HBV) infection is thought to be controlled by virus-specific cytotoxic T lymphocytes (CTL). We have recently shown that HBV-specific CTL can abolish HBV replication noncytopathically in the liver of transgenic mice by secreting tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) after antigen recognition. We now demonstrate that hepatocellular HBV replication is also abolished noncytopathically during lymphocytic choriomeningitis virus (LCMV) infection, and we show that this process is mediated by TNF-alpha and IFN-alpha/beta produced by LCMV-infected hepatic macrophages. These results confirm the ability of these inflammatory cytokines to abolish HBV replication; they elucidate the mechanism likely to be responsible for clearance of HBV in chronically infected patients who become superinfected by other hepatotropic viruses; they suggest that pharmacological activation of intrahepatic macrophages may have therapeutic value in chronic HBV infection; and they raise the possibility that conceptually similar events may be operative in other viral infections as well.
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PMID:Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver. 864 48

The comparative efficacy of prednisolone followed by interferon alfa (IFN-alpha) versus IFN-alpha alone in enhancing the rate of antibody to hepatitis B e antigen (anti-HBe) seroconversion has not been evaluated in a large cohort of white children. To determine this, a multicenter-controlled trial was conducted in 95 hepatitis B virus (HBV)-DNA/hepatitis B e antigen (HBeAg)-positive children (median age, 9 years [range, 2-16 years]; 56 boys; 84 [89 percent] white), all having inflammatory changes on liver biopsy. Patients were randomized to receive either prednisolone followed by IFN-alpha (n = 34); placebo followed by IFN-alpha (n = 30); or no treatment (n = 31). The prednisolone/placebo was given on a double-blind basis. Lymphoblastoid IFN-alpha was given at 5 MU/m(2) three times a week for 12 weeks. Baseline clinical, biochemical, and histological features were similar for the three groups. The majority (85 percent) had a baseline aspartate aminotransferase (AST) level < or = 100 IU/L. On follow-up between 12 and 18 months (median, 15 months) after treatment, the loss of HBeAg with anti-HBe seroconversion was more common in patients pretreated with steroids (12 of 34 [35 percent]) or placebo [12 of 30 (40 percent)] as against controls (4 of 31 [13 percent], P< .05). Factors predictive of anti-HBe seroconversion were baseline HBV-DNA concentration of < or = 1,000 pg/mL and a greater degree of portal tract inflammation on pretrial biopsy. Our results show that in white children treatment with IFN-alpha, at the dose and duration used in this study, improves the rate of anti-HBe seroconversion. Steroid priming does not potentiate the effect of IFN-alpha.
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PMID:Lymphoblastoid interferon alfa with or without steroid pretreatment in children with chronic hepatitis B: a multicenter controlled trial. 866 20

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon-alpha (IFN alpha) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR-SR), as evidenced by the absence of serum hepatitis C virus (HCV)-RNA during the administration period and at 6 months after the final administration of IFN alpha and normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR-SR cases, significant improvements (P < 0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR-SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type 1b. A comparison by virus concentration revealed that CR-SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 10(5) copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 10(5) copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre-administration virus concentration (P = 0.0061) and genotype (P = 0.0015). These results suggest that the pre-administration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.
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PMID:Long-term administration of natural interferon-alpha in patients with chronic hepatitis C: relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus. 867 62

Nine children suffering from chronic hepatitis due to hepatitis B virus (HBV) infection were treated with recombinant IFN-alpha-2C for 16 weeks. Replication of HBV was inhibited in 5 cases while a decreased inflammatory process in the liver was attained in 3. The treatment was very well tolerated in all of the studied children. A significant increase of ALT activity in the fourth week of treatment seems to be a positive prognostic factor.
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PMID:[Interferon alpha in the treatment of chronic hepatitis B in children]. 869 95

Recombinant interferon-alpha 2a (IFN-alpha 2a) in a total dose of 702 MU was given to 31 patients: nine with wild-type hepatitis B virus (HBV) and hepatitis B e antigen (HBeAg) (A); four with HBeAg and a mixed infection with wild-type HB and precore mutants (B); 11 with antibody to HBeAg (HBeAb) and a mixed infection (C); and seven with HBeAb and precore mutants alone (D). HBV DNA was not cleared in any patient in groups A and B. By contrast, in patients with HBeAb, HBV DNA was ultimately lost in four patients in group C, as well as in 10 patients in group D. Thus, patients with HBeAb and infected with precore mutants alone (D) lost serum HBV DNA more often than those with HBeAg and wild-type HBV (A). Patients with low pretreatment levels of HBV DNA cleared virus more frequently, and the response of precore mutant to IFN was comparable with that of wild-type HBV in patients who had a mixed infection. Based on these results, precore mutants do respond to IFN, and therefore, IFN is indicated in patients with HBeAb, especially those with low serum HBV DNA levels.
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PMID:Interferon-alpha 2a for chronic hepatitis B with e antigen or antibody:comparable antiviral effects on wild-type virus and precore mutant. 874 16

Precore mutants of hepatitis B virus (HBV) were looked for in 18 hepatitis B e antigen (HBeAg) carriers who were treated with recombinant interferon-alpha (rIFN) and the results were compared with those obtained in 12 untreated carriers who underwent spontaneous HBeAb seroconversion. Molecular analysis of the HBV precore region was carried out by polymerase chain reaction (PCR) amplification and direct sequencing. Precore mutants with a stop codon at codon 28 were detectable at baseline in 19/30 carriers. However, wild-type strains predominated in the baseline sera of both treated (n = 16) and untreated (n = 10) patients. Sera from the remaining four patients contained predominantly or exclusively mutant virions. Following IFN treatment, there was a shift from the wild-type pattern to the mutant pattern in all patients, with the precore pattern prevailing in long-term responders (six out of nine) compared with the non-responders (none of nine). The wild-type pattern predominated among the non-responders (eight vs three), suggesting that the long-term response to IFN was associated with take-over of precore mutants. There were no relationships between any pretreatment precore molecular pattern and disease severity or outcome of treatment. Precore mutants also took over in 10 of the 12 untreated patients (83%), who underwent spontaneous HBeAb seroconversion. Thus, a shift from wild-type to precore mutant pattern occurs in most Italian patients undergoing IFN-induced or spontaneous HBeAb seroconversion.
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PMID:Hepatitis B virus precore mutants in HBeAg carriers with chronic hepatitis treated with interferon. 874 17

The high worldwide prevalence of chronic viral hepatitis, as well as its progressive course, have led to the performance of multiple clinical studies. The natural history of the disease is different depending on the infecting virus; thus, the evolution to liver cirrhosis and/or hepatocellular carcinoma for the hepatitis B, C and delta (D) viruses in chronic hepatitis is 15, 20 and 75%, respectively. Different therapeutic agents have been used in attempts to modify the natural course of these diseases, interferon-alpha (IFN alpha) having proved to be the most effective. In 30 to 50% of patients, treatment with IFN alpha has achieved inhibition of viral replication, as well as normalisation of aminotransferase levels. Moreover, in a majority of patients, histological improvement is observed, principally in piece-meal necrosis and portal inflammation. The dosage currently recommended for treatment of chronic hepatitis B is 30 to 35MU weekly for a minimum of 4 months; when there is a co-existing delta virus infection, the total dosage employed should be greater. For hepatitis C, the minimum effective dosage is 9MU weekly, and a treatment duration of 12 months is recommended. The administration of IFN alpha produces a series of dose-dependent adverse effects, which are reversible on suspension of the medication. The most frequent of these adverse reactions is the 'flu-like' syndrome, which is self-limited and generally well tolerated. Secondary haematological alterations (leucopenia and thrombocytopenia) are the most frequent cause of reduction in dosage or suspension of treatment, although the latter is not normally necessary. The proportion of patients requiring dosage modification or suspension of treatment fluctuates between 5 and 15%. Taking the evolution of chronic hepatitis into account, there can be no doubt that all patients with this disease should be offered treatment. At present, the drug of choice is IFN alpha, as it slows disease progression and it is generally well tolerated.
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PMID:Risks and benefits of interferon-alpha in the treatment of hepatitis. 878 18

Among the six species of hepatitis viruses, HBV (hepatitis B virus) and HCV (hepatitis C virus) can induce persistent infection. HBV and HCV are transmitted parenterally, of which maternal transmission and transfusion-associated infection is a major route respectively. We opened the special clinic for carriers detected through blood donation, and followed them at regular intervals for their health care. The prevalence rate of HBV carriers decreased from 3.0% to 1.2% in these 10 years, and that of HCV decreased from 0.9 to 0.4% in these 4 years. Prevalence rate of HBV peaks at 50s and that of HCV peaks at 60s. Due to nearly complete screening of donated blood, post-transfusion hepatitis almost disappeared. HBV vaccine for neonates born from infected mothers reduced the new incidence of HBV carriers. In HBV carriers seroconversion of HBeAg to HBeAb occurs at teens with transient hepatitis and appearance of mutant virus. Ninety percent of the carriers remains healthy for the lifetime but some of them aggravate into chronic hepatitis leading to HCC (hepatocellular carcinoma). In HCV acute infection at adult age succeeds to chronic infection and eventually to liver cirrhosis with sporadic appearance of HCC. On the other hand, less than 50% of HCV carriers seem to be asymptomatic and do not lead to grave disease. In HBV carriers tendency to reject the virus occurs and eventually HBV is cleared in some percentage of the population. In contrast HCV does not tend to be cleared. HBsAb is a defensive antibody. In contrast HCVAb is not a defensive antibody but an infective antibody like HBcAb. DNA polymerase is a good marker of disease state in HBV, and HCV RNA is a good marker of HCV proliferation. Treatment with IFN is sometimes effective for seroconversion in HBV, and for eradication of virus in HCV.
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PMID:[Basic and clinical aspects of hepatitis virus carriers]. 880 69

A meta-analysis of six randomized clinical trials involving 240 children with chronic hepatitis B treated with recombinant interferon-alpha (IFN-alpha) was performed. IFN-alpha treatment was effective in blocking viral replication. Clearance of hepatitis B virus (HBV) DNA from sera occurred in 44 of 127 treated patients (P < .00001), and clearance of hepatitis B e antigen (HBeAg) occurred in seven of 74 treated patients (P = .099). IFN-alpha normalized serum levels of alanine aminotransferase (ALT) in 33 of 85 treated patients (P = .017). At the end of the follow-up period, viral replication was still reduced in IFN-alpha-treated patients, HBV DNA clearance occurred in 36 of 126 patients (P = .014), and HBeAg clearance occurred in 29 of 126 patients (P = .026). Regarding these virological and biochemical endpoints, we found that prolonged therapy (> 6 months) was associated with a better response, whereas high dosages of IFN-alpha were not. These findings could be biased by limited follow-up. Children with high ALT levels had a better response. However, these randomized clinical trials had some methodological flaws, including the lack of information on histologic response to IFN-alpha treatment by pediatric patients and the absence of "hard outcomes" (such as survival or development of cirrhosis or hepatocellular carcinoma).
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PMID:Interferon-alpha therapy for chronic hepatitis B in children: a meta-analysis. 881 42


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