Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Short-term interferon treatment of serum hepatitis B e antigen (HBeAg)-negative carriers with serum hepatitis B virus (HBV) DNA and histological features of chronic hepatitis B has been largely unsuccessful. In a pilot study of long-term treatment, 42 such patients were randomly assigned to 6 million units of interferon alfa 2b (IFN-alpha2b) three times per week for 24 consecutive months (n = 21, 4 with cirrhosis) or to no therapy (n = 21, 3 with cirrhosis). Five patients (24%) discontinued therapy because of treatment-related adverse reactions. Serum levels of alanine transaminase (ALT) became persistently normal and HBV DNA undetectable by dot-blot assay in 8 patients receiving interferon and in 2 untreated controls (38% vs. 10%; P = .03). Hepatitis flare-ups disappeared in 17 patients during therapy compared with 6 controls (81% vs. 29%; P < .001). During a median period of 22 months after interferon was stopped, 2 treated patients (10%) lost serum hepatitis B surface antigen (HBsAg) and seroconverted to antibodies to hepatitis B surface antigen (anti-HBs). Serum ALT remained persistently normal and HBV DNA undetectable by dot-blot assay in 6 initial responders and 1 initial nonresponder, compared with none of the 21 untreated controls (sustained response: 33% vs. 0; P < .001). Comparative analysis of pre- and posttreatment liver biopsies showed that mean Knodell scores dropped in the treated group (10.3 to 5.3; P = .01), but not in the untreated group (9.3 to 9.8; not significant). In conclusion, a 24-month course of treatment with 6 MU IFN-alpha2b was well tolerated by most patients, led to sustained suppression of HBV in one third, and attenuated hepatitis in 81% of patients.
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PMID:A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum. 939 7

One hundred patients with severe Chronic C Hepatitis, > 60 years of age and a life expectancy > 10 yrs were randomised to receive a course of lymphoblastoid a-IFN or a non specific support therapy as control. Patients randomised to IFN (no. 50) were treated with 3MU i.m. every two days for 2 months and then with 6MU i.m. every second two days for additional 10 months. All patients were followed-up for 12 months at the end of treatment. At the end of treatment, 30/50 patients in the IFN group showed a complete remission with normalisation of ALT and AST values (60%). Partial remission occurred in 11 patients (22%) whose transaminase values improved but did not normalise. No response was seen in 9 cases (18%) who showed similar pre- and post- treatment transaminase levels. On the contrary, normalisation of ALT-AST was observed in just two patients assigned to the non-specific therapy, whereas pre- and post-treatment values were similar in the remaining 48 patients. In patients receiving IFN a marked histological improvement was observed at the end of therapy in 22 responders (73.3%) and in 6 partial or non responders (30%) treated with IFN. No histological improvement was observed in control patients. At the end of the 12-month follow-up (24 months from the beginning of the study), 12 responders relapsed (40%) showing levels of transaminase which returned to the pre-treatment values within the second month from the IFN discontinuation. Therefore 18 out of 50 patients (36%) showed a long-term response to lymphoblastoid interferon. Lymphoblastoid a-IFN is an effective and safe therapy in elderly patients whose life expectancy justify its use and generates responses which are similar to those observed in younger subjects.
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PMID:Treatment of chronic hepatitis C with lymphoblastoid interferon alpha in elderly patients. 944 98

Two forms of recombinant interferon-alpha (IFN-alpha2a and IFN-alpha2b) have been approved by the Food and Drug Administration for a variety of clinical indications, including hairy cell leukemia, hepatitis, acquired immunodeficiency syndrome-related Kaposi's sarcoma, chronic myelogenous leukemia (IFN-alpha2a only), and adjuvant therapy for melanoma (IFN-alpha2b only), based on their proven clinical efficacy and acceptable safety profiles. The continued postmarketing monitoring of adverse reactions associated with IFN-alpha therapy has revealed some new toxicities. The most common adverse events associated with IFN-alpha therapy are flu-like symptoms, fatigue, anorexia, and central nervous system and psychiatric reactions. In particular, the incidence of depression has only recently been fully appreciated. Some of these side effects, particularly chronic fatigue, anorexia, and neuropsychiatric reactions, may become dose limiting. New approaches to minimize and manage the side effects of IFN-alpha therapy are needed.
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PMID:Safety profile of interferon-alpha therapy. 948 35

The aim of this study was to assess the efficacy and tolerance of interferon alpha (IFN alpha) treatment of chronic hepatitis C in HIV-seropositive patients. Seventeen patients with actively replicating hepatitis C were consecutively enrolled and treated with IFN alpha 5 MIU three times a week and followed up for at least 6 months after cessation of treatment. Eight patients responded to IFN alpha therapy with a complete remission of signs of active hepatitis and viral replication (ALT, HCV-RNA) at the end of treatment with IFN alpha. A sustained complete remission (ALT, HCV-RNA) for at least 6 months after the end of treatment was achieved in five of these eight patients. Complete responders had higher CD4+ cell counts (median 525/microliter) compared to non-responders (median 245/microliter) (p < 0.001). All patients but one completed at least 4 months of treatment. No severe toxicity (> WHO grade 2) due to IFN alpha treatment occurred. The results indicate that IFN alpha treatment of chronic hepatitis C in HIV-seropositive patients is successful in a considerable number of cases. Success of treatment with IFN alpha is related to higher CD4+ cell counts.
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PMID:Response to treatment of chronic hepatitis C with interferon alpha in patients infected with HIV-1 is associated with higher CD4+ cell count. 950 74

Studies in IL-12-deficient mice established the necessity for IL-12 to generate a Th1 cytokine response that is often required for elimination of intracellular pathogens. In this study, we demonstrate that mice with a targeted disruption of the IL-12p40 and/or p35 gene effectively control liver damage induced by mouse hepatitis virus (MHV) infection, similar to wild-type animals. In contrast, MHV-infected IFN-gamma receptor-deficient (IFN-gammaR[-/-]) mice showed an increased susceptibility to coronaviral hepatitis. Surprisingly, MHV-infected mice lacking IL-12 produced a polarized Th1-type cytokine response, as evidenced by high IFN-gamma and nondetectable IL-4 production by CD4+ splenocytes and normal virus-specific serum IgG2a/IgG1 ratios. The virus-induced type 1 cytokine secretion pattern was not reversed in IL-12-deficient mice by in vivo neutralization of IFN-gamma nor in IFN-gammaR(-/-) mice receiving IL-12-neutralizing Abs. In IL-12-deficient mice, Th1-type responses were also generated upon immunization with inactivated MHV. In contrast, following immunization with keyhole limpet hemocyanin, mice lacking IL-12 mounted strongly reduced specific IgG2a and increased IgE responses, indicative of a type 2-dominated cytokine pattern. These findings demonstrate that following a virus infection, IL-12 is not essential for the generation of polarized T cell type 1 cytokine expression and associated immune responses, which is in marked contrast to nonviral systems. Our data suggest that viruses may selectively induce IFN-gamma production and Th1-type immune reactions even in the absence of IL-12.
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PMID:Mice lacking IL-12 develop polarized Th1 cells during viral infection. 955 3

Interferon alfa-2b (IFN-alpha) therapy has been shown to be effective in the treatment of viral hepatitis B (HBV) or viral hepatitis C (HCV) in patients who did not undergo transplantation. However, in allograft recipients, treatment with IFN-alpha often leads to allograft rejection. The aim of the present study was to determine if IFN-alpha therapy increases the incidence or severity of acute rejection in human liver allograft recipients. One hundred five orthotopic liver transplant (OLT) recipients with HBV (n = 32), HCV (n = 58), or Non A Non B Non C (n = 15) viral infections were treated with a 6-month course of IFN-alpha, 5 million U subcutaneously three times a week, which began 2 to 97 months after transplantation. The mean hepatitis activity index (HAI) at the beginning of the therapy was 10.1 +/- 3.0. The baseline immunosuppression was achieved by tacrolimus in 77 patients and by cyclosporine A (CyA) in 28 patients. Contemporaneous controls consisted of 132 OLT patients (100 who received tacrolimus and 32 who received CyA) who did not receive IFN-alpha. A retrospective analysis was performed on this group of patients. The incidence of rejection and the baseline immunosuppression were compared. All biopsies were reviewed without knowledge of clinical data and scored for HAI and for rejection activity index (RAI). The biochemical response to IFN-alpha was also examined. The mean baseline maintenance dose of prednisone was greater by 2 mg daily in patients who received IFN-alpha with tacrolimus compared with control patients who did not receive IFN-alpha with tacrolimus (IFN-alpha 5. 3 +/- 5.2 mg daily v controls 3.3 +/- 4.9 mg daily; P </= .05). Similarly, the mean maintenance dose of prednisone was greater by 2.5 mg daily in patients who received IFN-alpha compared with controls who received CyA-based immunosuppression (IFN-alpha 9.8 +/- 3.1 mg daily v controls 7.3 +/- 3.3 mg daily; P = .01). Acute rejection episodes were detected in 10.5% (n = 11) of IFN-alpha-treated patients compared with 8.8% of controls for the similar time period from OLT and period of exposure to risk of rejection. Mean RAI was 2.0 +/- 2.4 for the IFN-alpha-treated group and 2.1 +/- 1.7 for controls. Rejection episodes with IFN-alpha treatment were mild and responded to steroid therapy. In OLT recipients, the risk of acute rejection was not increased by the introduction of IFN-alpha. However, in this study, patients were exposed to greater levels of immunosuppression.
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PMID:Incidence and severity of acute allograft rejection in liver transplant recipients treated with alfa interferon. 956 57

We characterized liver-infiltrating leucocytes (LIL) from BALB/c and C57BL/6 mice 0-56 days after murine cytomegalovirus (MCMV) infection. Inflammation clears from C57BL/6 mice 4-5 weeks post infection (pi), but persists for several months in BALB/c mice. The LIL obtained were 60-80% Thy 1.2+ by flow cytometry. The percentage of CD8+ cells rose sharply in all mice 7 days pi, with little decrease in BALB/c mice by day 56. CD4-CD8-Thy 1.2+/TCR alpha beta + cells were more prevalent in LIL than lymph node cells (LNC) irrespective of MCMV infection, whilst infection increased the proportion of CD8+ L-selectin- LIL (but not LNC). LIL from both mouse strains demonstrated cytotoxic activity against YAC-1 cells, but only LIL from BALB/c mice proliferated spontaneously ex vivo 21 days pi, as measured by tritiated thymidine incorporation. BALB/c LIL produced IFN gamma and IgG2a 7-21 days pi, whilst IL-10 secretion was similar in both strains. Thus, persistent hepatitis in BALB/c mice is associated with activation and proliferation of intrahepatic leucocytes with some bias towards a Th1 response.
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PMID:Contrasting phenotypes of liver-infiltrating leucocytes isolated from MCMV-infected BALB/c and C57BL/6 mice. 961 48

HCV infection and interferon-alpha (IFN-alpha) therapy have been associated with autoimmunity. To assess whether chronic liver disease (CLD) due to HCV infection or its treatment with IFN-alpha cause autoimmune manifestations, the prevalence of tissue autoantibodies in 51 children with chronic HCV infection and 84 with other CLD was analysed by standard techniques. Sixty-five percent of patients with chronic HCV infection, 66% with chronic hepatitis B infection and 60% with Wilson's disease were positive for at least one autoantibody. In the 51 subjects with chronic HCV infection (29 treated with IFN-alpha, 22 untreated), tested on 165 occasions over a median of 9 months (range 5-42 months), autoantibodies to nuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC) and/or liver kidney microsomal type 1 (LKM-1) were similarly prevalent in treated and untreated patients (90% versus 68%, P = 0.12). Positivity for SMA was present in 67%, GPC in 32%, ANA in 10%, LKM-1 in 8% of cases. Treatment with IFN-alpha had to be suspended due to transaminase elevation in one SMA-positive, one ANA-positive but in three of four LKM-1-positive patients. Our results show that: (i) autoantibodies are common in viral-induced hepatitis and Wilson's disease; (ii) positivity for SMA, GPC, ANA is part of the natural course of chronic HCV infection, their prevalence being unaffected by IFN-alpha; and (iii) IFN-alpha should be used cautiously in the treatment of LKM-1/HCV-positive patients.
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PMID:Autoantibody prevalence in children with liver disease due to chronic hepatitis C virus (HCV) infection. 964 17

Thirty-five outpatients (7 F, 28 M, mean age 39.8 years) with histologically confirmed active chronic B hepatitis, have been immunised with specific anti-HBV vaccine (Engerix B 20 mcg, SmithKline Beecham Biologicals, Rioxensart, Belgium) on days 0, 30 and 60. Hepatitis B markers, HBV-DNA and anti-HDV antibodies were determined on the same day of vaccination. One week after the last dose of anti-HBV vaccine, 15 and 10 patients have been treated respectively with alpha-leukocyte-IFN and beta-natural-IFN at the dose of 6 mU three times/week for one year; the remaining 10 patients were included in the control group. Hepatitis B and D markers and transaminases were monitored monthly during IFN therapy. Within one month from the last dose of anti-HBV vaccine, 20 patients out 35 have shown a transitory disappearance of HBV-DNA. After the 2nd dose in 4 patients a marked increase in AST and ALT levels was observed (up to 10 times the normal values). After the 3rd dose (last dose) five HBV-DNA-negative patients have shown transitory low levels of anti-HBs antibodies; moreover, after the last dose of anti-HBV, one HBV-DNA-negative patient resulted HBV-DNA-positive. After one year of IFN-therapy, 8 patients out 15 treated with alpha-leukocyte-IFN and 2 treated with beta-natural-IFN, have shown normalisation of transaminases. These results confirm the effectiveness of an anti-HBV vaccination before an IFN treatment and a better response achieved with alpha-leukocyte-IFN.
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PMID:Anti-HBV vaccination before therapy with interferon (IFN) in chronic B hepatitis. 971 55

A patient with chronic myeloid leukemia (CML) treated with interferon alpha (IFN alpha) and who developed autoimmune hepatitis (AIH) is described. The patient was treated with IFN alpha 2a, a complete cytogenetic response was achieved 5 months later, and this response has lasted now more than 7 years. Autoimmune hypothyroidism appeared at 18 months of treatment, and 1 year later severe type I autoimmune hepatitis developed. To our knowledge this is the first report of such complication in an IFN alpha-treated CML patient.
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PMID:Severe autoimmune hepatitis in a chronic myeloid leukemia patient treated with interferon alpha and with complete genetic response. 972 86


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