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)

Seven carriers of the Hepatitis B surface antigen who had acquired a form of chronic hepatitis D in the recent past were treated with lymphoblastoid alpha interferon (IFN) (10 MU three times weekly for 4 months, 6 MU three times weekly for other 8 months, with a 12 month follow-up after treatment). At the beginning of the study, these patients had a chronic active hepatitis with intrahepatic hepatitis D antigen but without signs of cirrhosis. By the end of therapy, five had normal amino-transferases and no trace of HDV-RNA in the serum. In two patients the liver enzymes and viremia relapsed during follow up; biochemical and virologic remission persisted after discontinuation of therapy in the other three patients. In the early non-cirrhotic stage of chronic hepatitis D, IFN may play a more consistent therapeutic role than in the average advanced case of the disease. Cytokine should be used as soon as a diagnosis of progressive hepatitis D is reached.
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PMID:Treatment of early chronic delta hepatitis with lymphoblastoid alpha interferon: a pilot study. 156 48

To evaluate the efficacy of recombinant interferon (IFN) alpha 2b in the treatment of Chinese patients with chronic hepatitis C, a randomized controlled trial was conducted in 50 chronic hepatitis C patients: 25 patients received 3 million units of subcutaneously injected recombinant IFN-alpha 2b three times per week for 6 months, and 25 patients received no specific treatment were used as controls. At the end of the IFN treatment, 19 patients (76%) in the IFN-treated group normalized serum ALT compared with only 6 patients (24%) in the control group (p < 0.01). Relapse within 6 months after the completion of treatment occurred in 13 IFN-treated patients (68%). Normalized serum ALT was seen in 6 patients (24%) in the IFN-treated group and 1 patient (4%) in the control group 6 months after discontinuation of IFN therapy (p = 0.10). The presence of serum hepatitis C virus (HCV) RNA measured by reverse transcription-polymerase chain reaction was detected at the end of the IFN treatment in all 13 patients who relapsed after cessation of therapy. In only 3 of 25 IFN-treated patients (12%) was the presence of serum HCV RNA not detectable at the end of the IFN treatment or 6 months after cessation of therapy. No patient in the control group had undetectable serum HCV RNA during the study period. Using multivariate logistic regression analysis, the low pretreatment levels of HCV RNA, measured by a quantitative branched DNA amplification assay, was the only independent predictor of a sustained response to IFN therapy (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
J Interferon Cytokine Res 1995 Jul
PMID:Randomized controlled trial of recombinant interferon-alpha 2b in the treatment of Chinese patients with chronic hepatitis C. 755 31

Glycoproteins are metabolized through an asialoglycoprotein metabolic pathway in vivo. They are desialylated and taken up by the liver via an asialoglycoprotein receptor. Fibroblast-derived natural human interferon-beta is a glycoprotein having a single asparagine-linked sugar chain. Although natural human interferon-beta may also be metabolized through this pathway, there is very little information about the biologic features of human asialointerferon-beta. We evaluated the pharmacokinetics and biologic activities of human native and asialointerferon-beta s. After intravenous administration to rabbits, human asialointerferon-beta was cleared from the blood circulation faster than the human native interferon-beta. More asialoprotein was distributed to the liver than the native type, but it induced less 2'5'-oligoadenylate synthetase. The human asialointerferon-beta had less activity than the human native interferon-beta on cell growth inhibition and 2'5'-oligoadenylate synthetase induction in Hep-G2 and HuH6 human hepatoblastoma cells. Southern blotting using a hepatitis B virus-transfected HuH6 cell line, HB611, revealed that the inhibition of hepatitis B virus DNA replication by the asialoprotein was weaker than that by the native protein. The results showed that the different effects exerted by the human native and asialointerferon-beta s may be a result of recognition of the sugar chains by rabbit hepatocytes or by human hepatoblastoma cells. The results also suggested that the terminal sialic acid of the sugar chains in natural human interferon-beta significantly affects its pharmacokinetics and biologic activities.
J Interferon Cytokine Res 1995 May
PMID:Pharmacokinetics and biologic activities of human native and asialointerferon-beta s. 764 42

The major target organ for Hepatitis B Virus (HBV) is the liver, but extrahepatic sites including monocytes express receptors for HBV and may become infected. Therefore, we investigated the effect of HBV on the in vitro expression of interleukin-beta (IL-1 beta) and interleukin-6 (IL-6) by the monocytoid cell line THP-1, exposed to various stimuli (LPS, PMA or both). Nonstimulated THP-1 cells did not synthesize IL-1 beta and IL-6, even after in vitro exposure to HBV. LPS stimulation alone induced moderate secretion of both IL-1 beta and IL-6 (300 pg/ml). After induction of macrophage differentiation by PMA, THP-1 cells acquired adherence and expressed a higher level of IL-1 beta (up to 2 ng/ml) but did not synthesize IL-6. Treatment of THP-1 cells with PMA and LPS caused the highest production of both IL-1 beta and IL-6 (> 5ng/ml). In vitro exposure of PMA + LPS-stimulated THP-1 cells to HBV resulted in secretion of both HBsAg and preS2Ag which was maintained over 10 days of culture. Southern blot technique was used to study the state of HBV DNA in the cells. Hybridization of non-digested cellular DNA showed only high molecular weight HBV DNA forms. The HindIII restriction pattern revealed bands corresponding to large DNA fragments and the presence of bands at the 3.2 kb position. Under these conditions (PMA + LPS), HBV inhibited the production of IL-1 beta and IL-6 proteins and completely suppressed the IL-1 beta and IL-6 mRNA. Thus, our findings (i) strongly support a relationship between the state of cell differentiation and susceptibility of cells to HBV infection, and (ii) demonstrate that HBV exerts an inhibitory effect on the induction of IL-1 beta and IL-6 genes expression in monocytic THP-1 cells. These results suggest that HBV leads to a fall of pro-inflammatory cytokine production by monocytes/macrophages, which may contribute to impaired host immune response during infection.
Eur Cytokine Netw 1996 Dec
PMID:Suppressive effect of hepatitis B virus on the induction of interleukin-1 beta and interleukin-6 gene expression in the THP-1 human monocytic cell line. 901 Jun 83

Secretion of the hepatitis B virus (HBV) e antigen (HBeAg) has been conserved throughout the evolution of hepadnaviruses. However, the function of this secreted form of the viral nucleoprotein remains enigmatic. It has been suggested that HBeAg functions as an immunomodulator. We therefore examined the possibility that the two structural forms of the viral nucleoprotein, the particulate HBV core (HBcAg) and the nonparticulate HBeAg, may preferentially elicit different T helper (Th) cell subsets. For this purpose, mice were immunized with recombinant HBcAg and HBeAg in the presence and absence of adjuvants, and the immunoglobulin G (IgG) isotype profiles of anti-HBc and anti-HBe antibodies were determined. Second, in vitro cytokine production by HBcAg- and HBeAg-primed Th cells was measured. The immunogenicity of HBcAg, in contrast to that of HBeAg, did not require the use of adjuvants. Furthermore, HBcAg elicited primarily IgG2a and IgG2b anti-HBc antibodies, with a low level of IgG3, and no IgG1 anti-HBc antibodies. In contrast, the anti-HBe antibody response was dominated by the IgG1 isotype; low levels of IgG2a or IgG2b anti-HBe antibodies and no IgG3 anti-HBe antibodies were produced. Cytokine production by HBcAg- and HBeAg-primed Th cells was consistent with the IgG isotype profiles. HBcAg-primed Th cells efficiently produced interleukin-2 (IL-2) and gamma interferon (IFN-gamma) and low levels of IL-4. Conversely, efficient IL-4 production and lesser amounts of IFN-gamma were elicited by HBeAg immunization. The results indicate that HBcAg preferentially, but not exclusively, elicits Th1-like cells and that HBeAg preferentially, but not exclusively, elicits Th0 or Th2-like cells. Because HBcAg and the HBeAg are cross-reactive in terms of Th cell recognition, these findings demonstrate that Th cells with the same specificity can develop into different Th subsets based on the structural form of the immunogen. These results may have relevance to chronic HBV infection. Circulating HBeAg may downregulate antiviral clearance mechanisms by virtue of eliciting anti-inflammatory Th2-like cytokine production. Last, the influence of antigen structure on Th cell phenotype was not absolute and could be modulated by in vivo cytokine treatment. For example, IFN-alpha treatment inhibited HBeAg-specific Th2-mediated antibody production and altered the IgG anti-HBe isotype profile toward the Th1 phenotype.
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PMID:The hepatitis B virus core and e antigens elicit different Th cell subsets: antigen structure can affect Th cell phenotype. 903 53

Cells respond to tumour necrosis factor-alpha (TNF-alpha) via binding to 75-kDa (type A) and 55-kDa (type B) receptors which have different intracellular signalling pathways and can also circulate as soluble molecules. Both receptors are co-expressed in many tissues, but their relative contributions to cellular TNF responses is for most situations unknown. In patients with viral and non-viral inflammatory liver diseases serum TNF-alpha was determined by an immunoenzymetric assay and soluble type A and B TNF receptors (TNF-alpha r) by enzyme-linked immunological and biological assays (ELIBA). In addition, cellular expression of TNF and its binding proteins were studied in liver biopsies by an indirect immunoperoxidase technique. Secretion of TNF-alpha and upregulation of TNF-alpha r-A were particularly prominent in viral hepatitis. Strong TNF-alpha in-situ production by mononuclear cells could be demonstrated in liver biopsies from patients with acute viral hepatitis. However, TNF-alpha r-A was detected only on hepatocytes. Serum TNF-alpha r-A was elevated two-fold in relative abundance over TNF-alpha r-B and was correlated to serum TNF-alpha (r = 0.6464, P < 0.0001). Soluble TNF-alpha r levels normalized, when the viral hepatitis was cleared, and successful therapy of hepatitis B was associated with a temporary rise of TNF-alpha r-A during the initial flare of aminotransferase. Patients with alcoholic hepatitis had also evidence of TNF-alpha activation but clearly differed from patients with viral induced liver diseases: Soluble TNF-alpha r-A and TNF-alpha r-B were highly elevated in equal proportions. In situ analysis in liver biopsies revealed a distinctive pattern of TNF-alpha r expression with strong cytoplasmic staining for both TNF-alpha r-A and B on scattered hepatocytes in addition to infiltrating mononuclear cells. The data propose that TNF release during antiviral immune responses is predominantly associated with TNF-alpha r-A upregulation and shedding, whereas upregulation and shedding of TNF-alpha r-B is more prominent in alcoholic hepatitis. As cytotoxicity and apoptosis by TNF are mediated mainly via TNF-alpha r-B, our results are consistent with more severe TNF-alpha induced liver damage in alcoholic hepatitis as compared to viral hepatitis.
Cytokine 1996 Nov
PMID:Serum levels and in situ expression of TNF-alpha and TNF-alpha binding proteins in inflammatory liver diseases. 904 83

Patients with dual infection with hepatitis B virus (HBV) and delta virus (HDV) responded poorly to interferon (IFN) therapy. Little is known about the effect of IFN therapy in patients with HBV and hepatitis C virus (HCV) dual infection. The patients in two randomized controlled trials with chronic HBV infection were retrospectively assayed for HCV markers. The HBV responses to IFN therapy in patients with and without HCV markers were compared. An open trial was conducted in 4 patients who had lost their serum HBV surface antigen (HBsAg) but had continuing HCV viremia and hepatitis. Of the 15 patients seropositive for HCV marker(s), only 1 (6.7%) responded with seroclearance of HBV DNA and HBV e antigen, as compared with 46 (28%) of 164 HCV-negative patients (p = 0.058). Icteric hepatitis developed in 1 patient on emergence of serum HCV RNA in association with seroclearance of HBV DNA. In contrast, good response was demonstrated in 3 of the 4 patients who had lost serum HBsAg before therapy. The results suggest that IFN therapy is not only of limited value in patients with dual infection with HBV and HCV but also has a potential risk of severe hepatitis if the clearance of one virus removes its suppressive effect on and facilitates the emergence of the other. However, patients with continuing HCV hepatitis after termination of the chronic HBsAg carrier state responded well to IFN therapy.
J Interferon Cytokine Res 1997 Aug
PMID:Response of patients with dual hepatitis B virus and C virus infection to interferon therapy. 928 24

The aim of this study was to determine what factors correlate with a favorable response to interferon-alpha2a (IFN-alpha2a) treatment in chronic hepatitis C. Fifty patients with chronic hepatitis C who received a 26-week treatment with IFN-alpha2a (474 million units in total) were assessed for pretreatment parameters and biochemical and virologic events during the treatment. According to biochemical and virologic responses to the treatment, 16 patients (32%) were categorized as sustained complete responders (SR), 13 (26%) as initial complete responders (IR), and 21 (42%) as nonresponders (NR). By multivariate analysis, a low viremia level was the only independent predictor of SR among pretreatment parameters (p = 0.0088). The percentage of patients showing hepatitis C virus RNA negativity at 2 and 12 weeks of treatment was significantly higher in SR (94% and 100%, respectively) or IR (69% and 92%, respectively) than in NR (14% and 33%, respectively) (p = 0.001). In contrast, the normalization of serum alanine aminotransferase levels at both time points failed to differentiate among SR, IR, and NR. These results indicate that monitoring of serum hepatitis C virus RNA at an appropriate time during treatment in addition to determination of pretreatment viral load is important in predicting responses to IFN-alpha2a treatment.
J Interferon Cytokine Res 1997 Nov
PMID:Importance of pretreatment viral load and monitoring of serum hepatitis C virus RNA in predicting responses to interferon-alpha2a treatment of chronic hepatitis C. Hanshin Chronic Hepatitis C Study Group. 940 9

Cytokine-mediated apoptotic destruction of viral-infected cells, downregulation of virus production and inhibition of anchorage dependent (clonal) cell growth were evaluated using virus-transfected human hepatoblastoma (HepG2) cells. The cytokines evaluated were interferon alpha (IFN-alpha), tumour necrosis factor alpha (TNF-alpha) and thymosin alpha 1 (T alpha 1), all of which have previously been implicated in control of various viral infections. The viruses evaluated were Hepatitis B (HBV) and the transforming virus, SV-40. TNF-alpha-induced apoptosis in the HBV-transfected cell line and the control HepG2 cells but not the HepG2 cells transfected with SV-40 virus. IFN-alpha and T alpha 1 had no effect on apoptosis. TNF-alpha also prevented the clonal growth of the HBV-HepG2 and control HepG2 but enhanced the growth of the SV-40-transfected HepG2 cells. IFN-alpha inhibited the clonal growth of all three cell lines in contrast to T alpha 1 which inhibited the clonal growth of only the HBV-transfected cells. Although TNF-alpha, IFN-alpha, and T alpha 1 when given alone did not significantly inhibit HBV-DNA production in the culture supernatant from HBV-HepG2 cells, the combination of T alpha 1 and IFN-alpha resulted in a statistically significant inhibition of virus production. These studies demonstrate that HepG2 cells transfected with HBV and SV-40 are useful for defining the mechanisms of cytokine activity. The HBV-transfected cells are especially useful in defining possible in vivo differences in responses to cytokines with respect to HBV production, apoptosis and clonal cell growth. Multiple mechanisms through which different cytokines can influence HBV infection and hepatoblastoma growth were identified and the importance of defining effective combinations to improve therapy in vivo demonstrated.
Cytokine 1998 Aug
PMID:Cytokine-mediated apoptosis and inhibition of virus production and anchorage independent growth of viral transfected hepatoblastoma cells. 972 31

The influence of hepatitis B (HBV) and hepatitis C virus (HCV) infection on blood hemoglobin (Hb) and serum erythropoietin (Epo) and interleukin-6 (IL-6) concentrations was studied in 48 anemic patients on regular hemodialysis. They were grouped as follows: (I) 19 patients whose Hb values improved after infection (Hb > 85 g/L), (II) 10 patients with persisting anemia after infection (Hb < 75 g/L), and, without hepatitis virus markers (III) 8 patients with Hb > 85 g/L and (IV) 11 patients with Hb < 75 g/L. Serum immunoreactive Epo levels were significantly higher in group I (34.4+/-47.1 U/L) than in the other groups (II, 10.8+/-6.0; III, 7.9+/-3.2; IV, 8.4+/-4.3). Serum IL-6 was higher in group I than group III (7.7+/-7.8 pg/ml vs. 3.6+/-2.4; p = 0.05) but similar to the other groups. Hb levels in group I were maximal at the time of serum alanine aminotransferase normalization. Red cell production increases as a result of elevated circulating Epo during hepatic regeneration after HBV or HCV infection.
J Interferon Cytokine Res 1999 Apr
PMID:Serum erythropoietin and interleukin-6 levels in hemodialysis patients with hepatitis virus infection. 1033 88


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