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)

Recombinant human granulocyte-macrophage colony-stimulating factor therapy significantly reduces serum hepatitis B virus DNA levels, associated with increased 2',5'-oligoadenylate synthetase activity in cultured mononuclear cells of patients with chronic hepatitis B. To assess changes in immune function during therapy of chronic hepatitis B patients, spontaneous and mitogen-induced production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interferon-alpha and interferon-gamma were measured-along with serum levels of soluble CD4, soluble CD8, soluble interleukin-2 receptor and beta 2-microglobulin-before, during and after a 6-wk course of granulocyte-macrophage colony-stimulating factor in nine patients with chronic hepatitis B. Treatment statistically enhanced spontaneous production of tumor necrosis factor-alpha (p < 0.05) and interleukin-1 beta (p < 0.02). Furthermore, spontaneous interleukin-6 production correlated negatively with hepatitis B virus DNA levels (p < 0.03), and spontaneous interleukin-1 beta production correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.0005). In addition, statistically significant increases were found during therapy in serum levels of soluble interleukin-2 receptor (p < 0.01), soluble CD4 (p < 0.01) and beta 2-microglobulin (p < 0.05). Levels of soluble interleukin-2 receptor and soluble CD4 correlated negatively with levels of hepatitis B virus DNA (p < 0.05), and levels of soluble interleukin-2 receptor and beta 2-microglobulin correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.003 and p < 0.02, respectively). Thus recombinant human granulocyte-macrophage colony-stimulating factor administration may induce reductions in hepatitis B virus DNA levels, perhaps by altering the immune status and increasing cytokine production.
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PMID:Changes in cytokine production during therapy with granulocyte-macrophage colony-stimulating factor in patients with chronic hepatitis B. 792 47

In a prospective, non-randomized, pilot study, we evaluated the efficacy of hepatitis B virus (HBV) vaccination in inhibiting HBV replication of chronic hepatitis B. Fourteen consecutive chronic HBs antigen carriers received standard vaccination with three injections of the GenHevac B vaccine, one month apart. All the patients had active HBV replication with chronic hepatitis but not cirrhosis. They were compared to a historical group of 34 patients who fulfilled the same inclusion criteria. Over the 6-month follow-up period after the first injection, serum HBV DNA became undetectable in 3 patients (21.4%). Four additional patients (28.6%) showed a significant decrease in HBV replication. In 4 cases, the disappearance of or decrease in HBV DNA was preceded by an increase in transaminase activities, which was also observed in one patient who did not modify his viral replication. Vaccination was otherwise uneventful. By contrast, during a mean follow-up of 40 months, only 3 (9%) of the 34 unvaccinated patients who served as controls lost serum HBV DNA, giving a 6-month HBV DNA disappearance rate of 1%. In sum, vaccination appeared able to reduce or stop HBV replication in half of the chronic HBsAg carriers with chronic hepatitis. This additional therapeutic tool may enhance the rate of response to interferon-alpha therapy, which is dependent on the level of HBV replication. Thus, immunotherapy should be considered of potential importance for the treatment of HBV infection.
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PMID:[Efficacy of immunotherapy with vaccination against hepatitis B virus on virus B multiplication]. 801 91

Adults who had received 4 x 20 micrograms doses of hepatitis B (Engerix-B) vaccine (appropriately administered) and who had failed to develop detectable anti-HBs or who had had a minimal response (< 10 IU l-1) were randomized to receive either a fifth dose of Engerix-B (20 micrograms) plus 1 million units of interferon-alpha or a fifth dose of vaccine plus saline placebo intramuscularly (deltoid). Both vaccine and test material were given together in one syringe and participants were blind as to the syringe contents. Anti-HBs was tested (by enzyme immunoassay) one to three months following the injection. Anti-HBs results from the 150 non-responders (NR) and the 26 hyporesponders (HR) are reported. Of NRs receiving a fifth dose plus placebo, 41% developed anti-HBs, whilst 53% of those receiving interferon-alpha developed anti-HBs. The response rates did not differ significantly. Of HRs receiving vaccine plus placebo, 70% showed an increase in their anti-HBs titre, while 87.5% of those receiving interferon-alpha with vaccine had titre rises. Vaccinee groups were well matched for age, sex and body mass index and the interval between injection and venepuncture. Side-effects from interferon-alpha were of short duration and were tolerated by vaccines seeking protection from hepatitis B infection. On the basis of this study, a fifth dose of vaccine in non- and hyporesponsive vaccinees is recommended. Interferon-alpha was of unproven value but it may increase the likelihood of seroconversion in NRs and its use could be considered in subjects at continued high risk of contracting hepatitis B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Randomized comparative trial of interferon-alpha versus placebo in hepatitis B vaccine non-responders and hyporesponders. 802 48

We conducted a prospective controlled study of the efficacy of recombinant interferon-alpha 2a in 77 children (44 boys, 33 girls, mean age 8 yr) with chronic hepatitis B. All patients had seropositive results for HBeAg and hepatitis B virus DNA; 52 had chronic persistent or nonspecific reactive hepatitis, and 25 had mild active hepatitis. Twenty-one children (group 1) received recombinant interferon-alpha 2a 7.5 megaunits/m2 three times weekly for 6 mo, 19 children (group 2) received megaunits/m2 on the same schedule and 37 (group 3) remained untreated. At 6 mo, HBe antigen-to-antibody seroconversion associated with biochemical remission was seen in 24% of patients in group 1, 5% in group 2 and 3% in group 3 (p < 0.05 vs. group 1). At 18 mo, seroconversion rates were 30% in group 1, 21% in group 2 and 13.5% in group 3. These results suggest that a course of recombinant interferon-alpha 2a accelerates HBeAg-HBe antibody seroconversion in children. High baseline ALT levels were sensitive predictors of seroconversion in both treated and untreated patients. In contrast, baseline IgM HBc antibody levels influenced the rate of anti-HBe seroconversion only in untreated patients. These findings suggest that, in children as well as in adults, recombinant interferon-alpha 2a favors the clearance of hepatitis B virus replication, enhancing the host antiviral immunoresponse.
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PMID:Recombinant interferon-alpha 2a hastens the rate of HBeAg clearance in children with chronic hepatitis B. 804 88

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

UDP-N-acetylglucosamine: beta-D-mannoside beta-1,4-N-acetylglucosaminyl-transferase III (GnT-III) is a key enzyme in the branching of asparagine-linked oligosaccharides, which are present in surface membrane proteins of various tissues and in secretory glycoproteins. The activity of GnT-III was assayed in 2 human hepatoblastoma cell lines, Huh6, which was the parental cell line, and HB611, which was established by transfection of 3 tandem copies of the hepatitis B virus genome into Huh6. A significant difference in GnT-III activity was found between Huh6 and HB611 (136 +/- 18.3 pmol/h/mg versus 6.7 +/- 2.4 pmol/h/mg; mean +/- SD, P < 0.001), whereas levels of the glycosyltransferases alpha-3-D-mannoside beta-1,4-N-acetylglucosaminyltransferase IV, alpha-6-D-mannoside beta-1,6-N-acetylglucosaminyltransferase-V, and beta-1,4-galactosyltransferase were almost the same in both cell lines. Northern blot analysis indicated that the decreased activity of GnT-III in HB611 was due to the decreased transcript. When HB611 was treated with interferon-alpha, expression of hepatitis B virus-related mRNA decreased, and the activity of GnT-III increased from 8.5 +/- 3.8 to 22.0 +/- 7.2 pmol/h/mg (mean +/- SD, P < 0.05). This increase was not found in Huh6. Binding capacity with erythrocyte phytohemagglutinin in these cells using fluorescence-activated cell sorter analysis was different, suggesting that the structure of sugar chain on the cell surface might be altered by suppression of GnT-III activity. This is the first report that hepatitis B virus selectively suppressed the GnT-III activity in hepatoblastoma cells.
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PMID:Selective suppression of N-acetylglucosaminyltransferase III activity in a human hepatoblastoma cell line transfected with hepatitis B virus. 813

Interferon-alpha induces remission in 30% to 40% of patients with chronic hepatitis B, but its effect on hepatic connective tissue turnover has not been well documented. We studied the changes in serum procollagen III propeptide and laminin-P1 peptide (Lam-P1) in 33 patients with chronic hepatitis B (11 nontreated controls and 22 treated patients) during a 4-mo randomized trial of interferon-alpha. Liver biopsy specimens were obtained at the start of treatment and 12 mo later. Liver biochemical tests, procollagen III propeptide, laminin-P1 peptide and hepatitis B virus DNA polymerase were determined before treatment with interferon was begun (mo -3), at the initiation (0 time) and completion of treatment (mo 4) and also at 8, 12 and 18 mo. Treated patients were classified as "responders" and "nonresponders" on the basis of clearance of HBV e antigen from serum. There were no significant changes in the control group, whereas the responders had persistent decreases in ALT, AST, hepatitis B virus dna polymerase, procollagen III propeptide and laminin-P1 peptide. The nonresponders had transient ALT, AST and hepatitis B virus dna polymerase reductions that returned toward baseline levels during follow-up, but procollagen III propeptide and laminin-P1 peptide persisted below the baseline at mo 18. Significant correlations between procollagen III propeptide and laminin-P1 peptide with ALT, AST and liver histologic specimens were noted at baseline but not after 12 mo. Changes in procollagen III propeptide levels also correlated with changes in AST, ALT and liver histologic specimens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decrease in serum levels of markers of hepatic connective tissue turnover during and after treatment of chronic hepatitis B with interferon-alpha. 813 56

The human MxA protein is a new specific marker for type I interferon activity both in vitro and in vivo. In the study presented here, this interferon-induced marker, as well as the 2',5'-oligoadenylate synthetases, was measured in circulating mononuclear cells from 21 patients with acute hepatitis A, 20 patients with acute hepatitis B and 14 patients with acute hepatitis C for determination of the activation of the interferon system in these viral diseases. In acute hepatitis A a strong expression (10 of 10 patients) of the MxA protein and the 2',5'-oligoadenylate synthetase activity in peripheral-blood mononuclear cells was observed during the first 2 wk after onset of clinical symptoms. In this period the MxA protein concentrations reached levels similar to those measured in patients treated with up to 5 x 10(6) IU interferon-alpha three times a week. Beyond wk 3, in eight of eight patients with hepatitis A no increased MxA protein levels were found. In contrast, peripheral-blood mononuclear cells from patients with acute hepatitis B contained either no measurable MxA protein or only slightly higher levels of the MxA protein, as did those of most patients (12 of 14) with acute hepatitis C. The MxA protein levels of both hepatitis B and C patients were significantly lower (p < 0.05) than those found in hepatitis A patients. Furthermore, sera from 6 of 10 patients with hepatitis A, but none of 10 patients with acute hepatitis B and C, contained measurable MxA protein. This serum MxA protein may originate from interferon-exposed and subsequently damaged liver cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Strong transient expression of the type I interferon-induced MxA protein in hepatitis A but not in acute hepatitis B and C. 813 57

Hepatitis B virus (HBV) infection is recognised as an important cause of nephrotic syndrome in endemic areas. This paper retrospectively examines the natural history and treatment of 70 patients with membranous glomerulonephritis and 1 with mesangiocapillary glomerulonephritis associated with HBV infection. Thirty-seven patients were in complete remission by the end of the study. The average duration of proteinuria in these patients was 30 months. The cumulative probability of remission was 64% at 4 years and 84% at 10 years. Three patients were still nephrotic after more than 90 months of follow-up and 2 others had reached end-stage renal failure. Remission occurred within 6 months of clearing the antigen (HBeAg) in the majority of cases. Steroids alone were given to 10 patients and 2 received steroids and cyclophosphamide, with no beneficial effect. Three patients received interferon-alpha 2b. One cleared the HBeAg from the circulation and had a significant fall in proteinuria, but defaulted from follow-up a month after completing treatment. One had a reduction of proteinuria but remained HBeAg positive. There was no change in the condition of the third. Although the majority of children eventually enter remission, there is a significant morbidity associated with the disease. Steroids and other immunosuppressive therapy are of no benefit. Interferon therapy may be useful, but has not been adequately assessed.
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PMID:The clinical course of hepatitis B virus-associated nephropathy. 814 8

We examined the efficacy of decreasing high doses (beginning at 18 MU/day) of interferon-alpha 2a vs. that of daily low doses (3 MU) in the treatment of chronic hepatitis delta virus infection. Patients treated with 18 MU had a somewhat higher frequency of normalization of serum ALT levels than patients treated with low doses (31% and 12%, respectively, on an intention-to-treat basis). A decrease in the percentage of hepatitis D virus RNA positivity was observed in both groups at the end of treatment. Thus, whereas in baseline samples 10 (62%) of the patients in each group were positive for hepatitis D virus RNA in serum on slot-blot hybridization, these numbers decreased to 5 (31%) and 4 (25%) patients in groups 1 and 2, respectively, at the end of therapy. However, hepatitis D virus RNA, detected by means of nested polymerase chain reaction, remained in all but two (one in each group) patients who completed the treatment. Finally, during posttreatment follow-up, hepatitis D virus RNA levels returned to baseline values, and only one patient remained negative for this marker. The beneficial effect of interferon-alpha was only transient. Only two patients (one from each treatment group) had persistently normal serum ALT levels after 18 mo of follow-up. Finally, the presence of serum hepatitis D virus RNA at the end of therapy, detected with nested polymerase chain reaction, might be a good marker for the prediction of viral replication relapse.
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PMID:Treatment of chronic hepatitis D virus infection with low and high doses of interferon-alpha 2a: utility of polymerase chain reaction in monitoring antiviral response. 818 63


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