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)

Cross-sectional studies on the correlation between serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels in patients with chronic hepatitis C have yielded conflicting results. We conducted a longitudinal study to examine the correlation between HCV viremia and serum ALT levels in individual patients over time. Serial samples (mean 9) from 25 patients with chronic HCV infection, including interferon-treated and untreated immunocompetent and immunosuppressed patients, collected over a period of 1-4.8 years (mean 2.6 years) were tested for HCV RNA and ALT levels using a highly reproducible quantitative (bDNA) assay. A significant correlation was found between serum HCV RNA and ALT levels in the patients who received IFN therapy, but no correlation was observed in the untreated patients. Among the untreated patients, the immunosuppressed patients had significantly higher HCV RNA levels (39 +/- 4 vs 3.6 +/- 8 Meq/ml, P < 0.0001) but significantly lower ALT (56 +/- 11 vs 97 +/- 12 units/liter, P = 0.03) levels when compared to the immunocompetent ones. In summary, we found no correlation between serum HCV RNA and ALT levels in chronic hepatitis C patients who are not receiving interferon therapy. Immunosuppression results in higher HCV RNA but lower ALT levels.
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PMID:Correlation between serum HCV RNA and aminotransferase levels in patients with chronic HCV infection. 894 74

Liver transplantation for cirrhosis caused by hepatitis B virus (HBV) has a poor prognosis. This is primarily a consequence of the near universal reinfection of the allograft, subsequent accelerated hepatic disease while receiving immunosuppression, and a reduced long-term survival. Because interferon-alpha has been shown to have an antiviral effect on HBV, a study was initiated in 1986 to assess the effect of interferon-alpha therapy on the course of liver transplantation in HBV-positive recipients. Twenty-eight patients with decompensated endstage liver disease caused by HBV were treated with 5, 2.5 or 1.25 million units (MU) of human recombinant interferon-alpha 2b (r-IFN-alpha 2b) daily for a minimum of 14 days prior to transplantation and continuing for 42 days post-transplantation. HBV antigens, HBV antibodies, HBV DNA and serum transaminase levels were measured throughout the treatment and post-treatment period. HBV DNA was eliminated in 10 of 19 patients, who survived 3 months or more post-transplantation, and was associated with a significant flare of hepatitis as detected by symptoms and transaminase levels (P < 0.05). Patients who cleared HBV DNA had lower HBV DNA levels (P < 0.05) at entry compared with those who did not. While four of 10 patients with hepatitis B e antigen (HBeAg) converted to hepatitis B e antibody (HBeAb), no surviving patient cleared hepatitis B surface antigen (HBsAg) on a long-term basis. Nonetheless, post-transplant survival was significantly better (P < 0.0001, median follow-up 42 months) in the IFN-alpha treated patients as compared with historical controls, and was similar to that of patients transplanted for all causes of parenchymal liver disease other than HBV cancer. Hence IFN-alpha therapy in the perioperative liver transplantation period improves short-term survival but does not prevent HBV infection of the allograft.
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PMID:Interferon-alpha 2b improves short-term survival in patients transplanted for chronic liver failure caused by hepatitis B. 894 86

The immune system plays a crucial role in the control and eventual clearance of hepatitis B virus (HBV) infection. Immune mechanisms are now believed to participate in the pathogenesis of the hepatitis C virus (HCV) and to account perhaps for the high frequency of progression from acute to chronic disease. Although IFN-alpha has been proven effective in the treatment of viral chronic hepatitis B and C, response rates are low, reactivation of disease is appreciable and side effects of treatment are frequent. Both antiviral and immune modulatory activity have been ascribed to IFN-alpha and are believed to account for its therapeutic effect. Immune-active peptides including those derived from the thymus have also been evaluated over the past 15 years for the treatment of viral chronic hepatitis. This review summarizes clinical studies and experimental observations which provide the rationale for the use of these agents in the treatment of chronic hepatitis associated with HBV and HCV. Primary attention is focused on thymosin-alpha (T alpha 1), a synthetic peptide, which has been evaluated in clinical trials. T alpha 1 has in vivo and in vitro immune-modulatory activity on lymphoid populations as well as the potential of more direct antiviral activity. Preliminary results of clinical trials utilizing combinations of T alpha 1 with various IFN preparations are also reviewed.
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PMID:Thymus-derived peptides in the treatment of viral chronic hepatitis. 903 Apr 64

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

Interleukin-12 (IL-12) is a heterodimeric cytokine produced by antigen-presenting cells that has the ability to induce gamma interferon (IFN-gamma) secretion by T and natural killer cells and to generate normal Th1 responses. These properties suggest that IL-12 may play an important role in the immune response to many viruses, including hepatitis B virus (HBV). Recently, we have shown that HBV-specific cytotoxic T lymphocytes inhibit HBV replication in the livers of transgenic mice by a noncytolytic process that is mediated in part by IFN-gamma. In the current study, we demonstrated that the same antiviral response can be initiated by recombinant murine IL-12 and we showed that the antiviral effect of IL-12 extends to extrahepatic sites such as the kidney. Southern blot analyses revealed the complete disappearance of HBV replicative intermediates from liver and kidney tissues at IL-12 doses that induce little or no inflammation in these tissues. In addition, immunohistochemical analysis demonstrated the disappearance of cytoplasmic hepatitis B core antigen from both tissues after IL-12 treatment, suggesting that IL-12 either prevents the assembly or triggers the degradation of the nucleocapsid particles within which HBV replication occurs. Importantly, we demonstrated that although IFN-gamma, tumor necrosis factor alpha, and IFN-alpha/beta mRNA are induced in the liver and kidney after IL-12 administration, the antiviral effect of IL-12 is mediated principally by its ability to induce IFN-gamma production in this model. These results suggest that IL-12, through its ability to induce IFN-gamma, probably plays an important role in the antiviral immune response to HBV during natural infection. Further, since relatively nontoxic doses of recombinant IL-12 profoundly inhibit HBV replication in the liver and extrahepatic sites in this model, IL-12 may have therapeutic value as an antiviral agent for the treatment of chronic HBV infection.
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PMID:Interleukin-12 inhibits hepatitis B virus replication in transgenic mice. 906 Jun 87

To evaluate the therapeutic effect of recombinant human alpha-interferon (alpha-IFN) on hepatitis B virus associated glomerulonephritis (HBV-GN) and the relationship between the seroconversion of viral antigens and the change of proteinuria, the hepatitis B viral markers and urinary protein were monitored during alpha-IFN treatment in 8 male adult patients who (1) were positive in serum HBsAg and HBeAg, (2) had chronic hepatitis, (3) had persistent proteinuria > 1 g/day, and (4) showed glomerulonephritis on kidney biopsy. alpha-IFN was given at a dose of 3 million units, subcutaneously, three times a week for 6 months. Kidney biopsy specimens showed membranoproliferative glomerulonephritis (MPGN) in 4 patients, mesangial proliferative glomerulonephritis (MesPGN) in 2, and membranous glomerulonephritis (MGN) in 2 patients. Seven of the 8 patients received a 6-month course of alpha-IFN therapy; 1 patient with MGN quitted therapy 2 months after the initial dose because of side effects. In 5 of the 7 patients who received a 6-month therapy, serum HBeAg disappeared, and anti-HBe appeared during the therapy. In 2 of these 5 patients, HBeAg reappeared, in 1 during alpha-IFN therapy and in 1 9 months after the last dose of alpha-IFN. The hepatitis B viral markers of the patient who received a 2-month therapy did not change. HBs antigenemia persisted in all patients. In all 4 patients with MPGN, serum HBeAg was transiently or persistently converted to negative, but the proteinuria persisted. Both patients with MesPGN showed remission of proteinuria; however, only 1 patient had seroconversion of HBeAg. In 2 patients with MGN, proteinuria persisted. In conclusion, alpha-IFN at the doses given was not effective in MPGN type of HBV-GN. Improvement of proteinuria was achieved in MesPGN patients without disappearance of HBs antigenemia which is the finding against the possible role of HBsAg in the pathogenesis of this type of HBV-GN.
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PMID:Treatment of hepatitis B virus associated glomerulonephritis with recombinant human alpha interferon. 909 40

Interferon alpha therapy of hepatitis B virus-related decompensated cirrhosis with the dose and the duration generally used is frequently associated with severe side-effects and reactivations. Between 1989 and 1996, 15 patients with hepatitis B virus-related decompensated cirrhosis received prolonged (3-48 months) low-dose (3 million units) IFN-alpha therapy. Ten patients (66%) had a sustained loss of serum hepatitis B virus DNA and hepatitis Be antigen (if present initially) associated with a decrease of aminotransferase levels into the normal range. During follow-up of these 10 patients, seven had a marked clinical improvement and are alive and fully active. One has an hepatocellular carcinoma, and two died without reactivation. Among the five other patients, two had a transient loss of serum HBV DNA followed by reactivation and three did not respond to therapy. During follow-up, one of these five patients died and one underwent liver transplantation. Severe complications, possibly related to interferon were uncommon and included bacterial infection in one case and variceal bleeding in two cases. Eleven of the 15 patients treated are alive after 1.5-7 years of follow-up. Hence, in patients with hepatitis B-related cirrhosis, prolonged low-dose IFN-alpha therapy is relatively well tolerated and may induce a sustained inhibition of hepatitis B virus replication with marked clinical improvement.
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PMID:Prolonged interferon-alpha therapy of hepatitis B virus-related decompensated cirrhosis. 909 74

Patients with biopsy-proven chronic hepatitis C, who failed to respond to a previous course of either recombinant (rIFN-alpha) or lymphoblastoid (Ly IFN-alpha) interferon-alpha, were randomized to receive either leucocyte (Le) IFN-alpha (patients) or a second course of the same IFN-alpha (controls), to compare the efficacy and safety of these treatment schedules. All patients received the same dose of IFN-alpha as was used during their previous treatment (3 million units (MU) or 6 MU three times weekly) for 6 months. Patients with a normal alanine aminotransferase (ALT) value at month 6 were treated for a further 6 months. All patients were followed-up for 12 months after treatment. A total of 69 patients were enrolled, 44 in the Le IFN-alpha group and 25 in the control group. At the end of the treatment period, 13 of the 44 patients (29.5%) in the Le IFN-alpha group had a biochemical response (normal ALT) and six of 44 (13.6%) patients had undetectable serum hepatitis C virus (HCV) RNA. At the end of the follow-up period, 10 patients (22.7%) had normal ALT values and serum HCV RNA was undetectable in three (6.8%). None of the patients in the control group showed normal ALT values at any time. Genotype 1b tended to be more frequent among non-responders (61 vs 45%): basal gamma-glutamyl transpeptidase (gamma-GT) values were lower in responders than in non-responders (33.3 +/- 11.70 Ul-1 vs 58.4 +/- 33.04; P = 0.01). Le IFN-alpha was well tolerated by all patients. These results support the use of Le IFN-alpha in patients with chronic hepatitis C who are non-responders to a previous treatment with recombinant or lymphoblastoid IFN-alpha.
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PMID:Human leucocyte interferon-alpha in chronic hepatitis C resistant to recombinant or lymphoblastoid interferon-alpha: a randomized controlled trial. 918 30

Allograft infection in hepatitis B surface antigen (HBsAg)-positive patients undergoing liver transplant (OLT) is still significant, despite post-transplant prophylaxis with high doses of immunoglobulin to HBsAg. Baseline status and post-OLT levels of viraemia and wild-type and hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) were correlated with the clinical course of 16 consecutive HBsAg carriers. positive for hepatitis B e antibody, with hepatocellular carcinoma who underwent OLT and received permanent post-OLT prophylaxis with antibody to HBsAg (HBsAb). Fourteen patients had less than 10(3) HBV genome equivalents ml(-1) (eq ml[-1]) at baseline and remained HBV free after a median of 36 months following OLT. Two patients with mean pre-OLT viraemia higher than 10(5) genome eq ml(-1) and prevalent HBeAg-negative HBV viraemia before OLT suffered a severe graft hepatitis. Interferon-alpha2b (3 MU m(-2) per day) was able to reduce viraemia in both patients and to revert the clinical course of the infection in one, who remained infection-free 22 months after IFN treatment. Fourteen patients had less than 10(3) HBV genome eq ml(-1) at baseline and remained HBV free, after a median of 36 months following OLT, with permanent HBsAb immunoprophylaxis. These observations suggest that the quantitative analysis of HBV pre-OLT viraemia levels may provide a very useful tool for predicting the ideal time of liver replacement. Clinical trials on the use of antiviral drugs capable of inhibiting HBV serum levels before liver transplantation should be pursued on this premise.
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PMID:Preoperative serum levels of wild-type and hepatitis B e antigen-negative hepatitis B virus (HBV) and graft infection after liver transplantation for HBV-related hepatocellular carcinoma. 927 21

Virological response to treatment of chronic hepatitis B is defined as the loss of serum hepatitis B virus DNA (HBV DNA) and hepatitis B e antigen (HBeAg). The quantitative measurement of HBV DNA is useful for monitoring and predicting the response to therapy with interferon-alpha (IFN-alpha). In this study, we evaluated whether quantitative measurement of serum HBeAg and IgM antibody to hepatitis B core antigen (HBcAb) could also be used in this manner. Using a microparticle-capture enzyme immunoassay (IMx), a standard curve of fluorescence rate vs HBeAg concentration was constructed to provide quantitative results. The IgM HBcAb index was also measured using a microparticle enzyme immunoassay and serum HBV DNA was measured by a solution hybridization assay. We studied 48 patients who were initially positive for HBeAg and HBV DNA and who were treated with IFN-alpha2b. Their sera were serially evaluated for HBeAg concentration, and results were compared with HBV DNA levels. In the 14 patients who responded to IFN, similar disappearance curves were observed with good intraindividual correlation between the levels of the two markers. In the 34 non-responders, HBeAg levels decreased during treatment but never became negative; HBV DNA levels also decreased during treatment and became transiently undetectable in six patients, falsely suggesting treatment success. The IgM HBcAb index paralleled changes in alanine aminotransferase (ALT) concentration and did not provide additional information. Multiple logistic regression indicated that baseline ALT and HBeAg concentrations were independent predictors of the response to treatment and the addition of neither HBV DNA nor IgM HBcAb improved the model. We conclude that quantitative measurement of HBeAg provides information similar to that of HBV DNA in monitoring and predicting the response to treatment; this technique could be readily adaptable to clinical laboratories.
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PMID:Quantitative assessment of serum hepatitis B e antigen, IgM hepatitis B core antibody and HBV DNA in monitoring the response to treatment in patients with chronic hepatitis B. 927 24


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