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Jay H. Hoofnagle - One of the best experts on this subject based on the ideXlab platform.
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Seizures during Alpha Interferon therapy
Journal of hepatology, 1996Co-Authors: A.obaid Shakil, Adrian M. Di Bisceglie, Jay H. HoofnagleAbstract:Abstract Background/Aims: Alpha Interferon is now used widely in the therapy of chronic viral hepatitis. The common side effects of Interferon are well known; the uncommon side effects are less well defined. We have evaluated the incidence and characteristics of seizures that occurred during Alpha Interferon therapy. Methods: A retrospective chart review was done on 311 patients with chronic hepatitis treated with Alpha Interferon between 1983 and 1994 at the National Institutes of Health. Results: Four of 311 patients (1.3%) developed grand mal seizures while on therapy with Alpha Interferon. Three patients had chronic hepatitis B (two had an accompanying glomerulonephritis) and one chronic delta hepatitis. Interferon had been given in doses of 5–10 million units each day or three times weekly for 2–14 months before the onset of seizures. No other obvious cause for seizures was identified. Seizures resolved once Interferon was stopped, and did not recur even without chronic anticonvulsant therapy. Conclusions: Alpha Interferon in the doses used to treat chronic viral hepatitis caused seizures in approximately 1% of patients.
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decrease in serum hepatitis c viral rna during Alpha Interferon therapy for chronic hepatitis c
Annals of Internal Medicine, 1991Co-Authors: Michiko Shindo, Adrian M. Di Bisceglie, Ling Cheung, Waikuo J Shih, Karen Cristiano, Stephen M Feinstone, Jay H. HoofnagleAbstract:Abstract ▪Objective:To assess the effect of Alpha-Interferon therapy on hepatitis C viral RNA in serum of patients with chronic hepatitis C. ▪Design:Retrospective testing for hepatitis C viral (HCV...
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long term remission of chronic hepatitis b after Alpha Interferon therapy
Annals of Internal Medicine, 1991Co-Authors: Julia C Korenman, Adrian M. Di Bisceglie, Bennie L Baker, Jeanne G Waggoner, James E Everhart, Jay H. HoofnagleAbstract:Objective: To evaluate whether remissions of chronic hepatitis B induced by Alpha-Interferon therapy are of long duration. Design: Cohort study. Setting: Clinical Center of the National Institutes ...
Geoffrey Dusheiko - One of the best experts on this subject based on the ideXlab platform.
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Impact of Alpha Interferon and Ribavirin on the Function of Maturing Dendritic Cells
Antimicrobial agents and chemotherapy, 2004Co-Authors: Eleanor Barnes, Geoffrey Dusheiko, Mariolina Salio, Vincenzo Cerundolo, Joanne Medlin, Shona Murphy, Paul KlenermanAbstract:Alpha Interferon and ribavirin are required in combination to achieve a sustained virological response in the treatment of hepatitis C virus (HCV) infection. Alpha Interferon has direct antiviral activity and also enhances HCV-specific T-cell responses. Ribavirin has little direct activity against HCV but reduces hepatic inflammation. It is therefore likely that these drugs in combination have hitherto unidentified immunological effects. In the present study we investigated the effects of Alpha Interferon and ribavirin on dendritic cell (DC) maturation and cytokine production induced by double-stranded RNA in vitro. Alpha Interferon alone enhanced the expression of HLA class I, HLA class II, and CD86 on immature DCs but did not stimulate full DC maturation, which requires the expression of CD83. Alpha Interferon enhanced the production of interleukin 12 p70 [IL-12(p70)] and tumor necrosis factor Alpha (TNF-Alpha) but had no effect on IL-10 production. In contrast, ribavirin at physiological doses had no effect on DC maturation but markedly suppressed the production of TNF-Alpha, IL-10, and IL-12(p70). The suppression of cytokines by ribavirin cannot be explained by the induction of DC apoptosis or cell death. Quantitative PCR confirmed that cytokine suppression occurs at the level of mRNA. The suppression of IL-12(p70) and TNF-Alpha in maturing DCs may explain the reduction in hepatic inflammation observed during ribavirin monotherapy. Combination Alpha Interferon-ribavirin therapy may alter the cytokine profile of maturing DCs overall by suppressing IL-10 production but maintaining IL-12(p70) and TNF-Alpha production, a pattern that would favor viral elimination through downstream effects on T cells.
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Long-term efficacy of treatment of chronic hepatitis C with Alpha Interferon or Alpha Interferon and ribavirin.
Journal of Hepatology, 1999Co-Authors: Eleanor Barnes, George Webster, Ruth Jacobs, Geoffrey DusheikoAbstract:The major objective of treatment of chronic hepatitis C virus (HCV) infection is to prevent progression to cirrhosis, and thereby prevent complications of end-stage liver disease. The established treatment of chronic HCV is with Alpha Interferon. Recent results with ribavirin and Alpha Interferon together suggest that combination antiviral therapy will become the benchmark treatment. For both naive and relapsed patients, however, it has become important to assess the long-term outcome of treatment, in order to gauge whether treatment has indeed modified the natural history of chronic hepatitis C virus infection. It seems likely that most sustained responders (85-90%) treated with combination ribavirin and Alpha Interferon will continue to have a long-term biochemical and virological response, as has been demonstrated with Alpha Interferon alone, but further long-term follow-up of patients treated with combination therapy is required.
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Side effects of Alpha Interferon in chronic hepatitis C.
Hepatology (Baltimore Md.), 1997Co-Authors: Geoffrey DusheikoAbstract:Alpha Interferons have been used widely to treat chronic hepatitis C virus infection. These include recombinant Interferons, purified natural leukocyte, and lymphoblastoid Interferons. Alpha Interferon is administered by subcutaneous or intramuscular injection either daily or three times weekly for a period of 6 to as long as 24 months. A wide array of adverse effects of Alpha Interferon have been described. Several side effects such as fever, headache fatigue, arthralgias, and myalgias are common, especially with the initial injections. These early side effects of Interferon are predictable and are encountered in the majority of patients. These may not require dose modification, but can be problematic for a significant proportion of patients. Other adverse events effects may require dose modification or even discontinuation of therapy in 2% to 10% of patients. Neuropsychiatric side effects such as depression and irritability can be most troublesome; their mechanisms are not well understood. Granulocytes, platelets, and red blood cell counts decrease during treatment, but the decreases are usually mild, although they can be dose limiting if cell counts are low initially. Interferon has important immunomodulatory properties, and treatment can induce autoimmune phenomena, the most frequent being autoimmune thyroiditis with either hypothyroidism or hyperthyroidism, especially in predisposed patients. Other autoimmune disease can be aggravated by Interferon therapy. Severe and even life-threatening side effects of Interferon occur in 0.1% to 1% of patients; these include thyroid, visual, auditory, renal, and cardiac impairment, and pulmonary interstitial fibrosis. Some of these side effects may be irreversible. Higher doses of Interferon (above 5 million units three times weekly) cause higher rates of adverse events than standard doses. Contraindications to Alpha Interferon have been recognized.
Adrian M. Di Bisceglie - One of the best experts on this subject based on the ideXlab platform.
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Seizures during Alpha Interferon therapy
Journal of hepatology, 1996Co-Authors: A.obaid Shakil, Adrian M. Di Bisceglie, Jay H. HoofnagleAbstract:Abstract Background/Aims: Alpha Interferon is now used widely in the therapy of chronic viral hepatitis. The common side effects of Interferon are well known; the uncommon side effects are less well defined. We have evaluated the incidence and characteristics of seizures that occurred during Alpha Interferon therapy. Methods: A retrospective chart review was done on 311 patients with chronic hepatitis treated with Alpha Interferon between 1983 and 1994 at the National Institutes of Health. Results: Four of 311 patients (1.3%) developed grand mal seizures while on therapy with Alpha Interferon. Three patients had chronic hepatitis B (two had an accompanying glomerulonephritis) and one chronic delta hepatitis. Interferon had been given in doses of 5–10 million units each day or three times weekly for 2–14 months before the onset of seizures. No other obvious cause for seizures was identified. Seizures resolved once Interferon was stopped, and did not recur even without chronic anticonvulsant therapy. Conclusions: Alpha Interferon in the doses used to treat chronic viral hepatitis caused seizures in approximately 1% of patients.
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decrease in serum hepatitis c viral rna during Alpha Interferon therapy for chronic hepatitis c
Annals of Internal Medicine, 1991Co-Authors: Michiko Shindo, Adrian M. Di Bisceglie, Ling Cheung, Waikuo J Shih, Karen Cristiano, Stephen M Feinstone, Jay H. HoofnagleAbstract:Abstract ▪Objective:To assess the effect of Alpha-Interferon therapy on hepatitis C viral RNA in serum of patients with chronic hepatitis C. ▪Design:Retrospective testing for hepatitis C viral (HCV...
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long term remission of chronic hepatitis b after Alpha Interferon therapy
Annals of Internal Medicine, 1991Co-Authors: Julia C Korenman, Adrian M. Di Bisceglie, Bennie L Baker, Jeanne G Waggoner, James E Everhart, Jay H. HoofnagleAbstract:Objective: To evaluate whether remissions of chronic hepatitis B induced by Alpha-Interferon therapy are of long duration. Design: Cohort study. Setting: Clinical Center of the National Institutes ...
Kjell Öberg - One of the best experts on this subject based on the ideXlab platform.
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Treatment of malignant endocrine pancreatic tumors with a combination of Alpha-Interferon and somatostatin analogs.
Medical oncology (Northwood London England), 2002Co-Authors: Marie-louise Fjällskog, Anders Sundin, J.-e. Westlin, Kjell Öberg, Eva Tiensuu Janson, Barbro ErikssonAbstract:Somatostatin analogs and Alpha-Interferon induce good responses as single drugs in the treatment of endocrine pancreatic tumors. We examined the efficacy and tolerability of the combination of Alpha-Interferon and somatostatin analogs in 16 patients with metastatic endocrine pancreatic tumors. All patients except one had received prior treatment and were in a progressive state. Doses of Alpha-Interferon and somatostatin analogs were individually titrated. The Alpha-Interferon doses varied between 9 and 25 million units per week and were combined with 100-1500 microg of octreotide or 6000 microg of lanreotide daily. Radiological response was seen in 3 of 16 (19%) patients (median duration 23 mo). Biochemical response was seen in 10 of 16 (62.5%) patients (median duration 22 mo). All three patients previously progressing on both Alpha-Interferon and somatostatin analog as single drugs achieved a stabilization of the disease when treated with the combination (median duration 10 mo). Seven of eight (88%) patients previously progressing on Alpha-Interferon treatment benefited from the combination with biochemical partial response or stabilization. All six patients previously progressing during somatostatin analog treatment achieved biochemical partial response or stabilization. More than 80% of patients who progressed during previous treatment with either drug benefited from the combined treatment, which also was well tolerated. Thus, a combination of Alpha-Interferon and somatostatin analogs may be considered for patients previously progressing on treatment with Alpha-Interferon or somatostatin analogs. However, in this study, the value of sequential treatment has not been evaluated.
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long term management of the carcinoid syndrome treatment with octreotide alone and in combination with Alpha Interferon
Acta Oncologica, 1993Co-Authors: Eva Tiensuu Janson, Kjell ÖbergAbstract:Fifty-five patients with metastatic carcinoid tumor were treated with the long-acting somatostatin analogue octreotide. Nineteen received in addition Alpha-Interferon when octreotide had failed. During octreotide treatment reduced flush and/or diarrhea was seen in 70% of the patients, 37% showed > 50% decrease in urinary 5-HIAA for a median of 8 months. A further 49% experienced stabilization of their disease and only 14% progressed. One patient showed reduced tumor size. Of the 19 patients given Alpha-Interferon in combination with octreotide, 72% showed significant reduction in urinary 5-HIAA for a median of 10 months. Twenty-two percent became stabilized and only 6% progressed. A symptomatic improvement was seen in 49%. The combination was well tolerated. Our data confirm previous studies, showing that octreotide is useful for treatment of the carcinoid syndrome. Our results also indicate that the combination of octreotide and Alpha-Interferon might be of beneficial value for long-term management of th...
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autoimmunity after Alpha Interferon therapy for malignant carcinoid tumors
Annals of Internal Medicine, 1991Co-Authors: L Ronnblom, Gunnar V Alm, Kjell ÖbergAbstract:▪ Objective: To determine the incidence of autoantibodies and autoimmune disease and their influence on therapeutic results during Alpha-Interferon treatment in patients with malignant midgut carci...
J Cassidy - One of the best experts on this subject based on the ideXlab platform.
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A feasibility study of roquinimex (Linomide) and Alpha Interferon in patients with advanced malignant melanoma or renal carcinoma
British Journal of Cancer, 1998Co-Authors: Mj Mackean, Alf Svedberg, F Hansson, D Jodrell, Máté Leskó, D. Kerr, J CassidyAbstract:Thirty-one patients with advanced renal carcinoma or malignant melanoma were treated in the first feasibility study of Alpha-Interferon (Roferon) and the new oral immunomodulating agent, Linomide. Linomide 5 mg or 10 mg p.o. daily was given for 2 weeks; Alpha-Interferon was then added at 3 MU s.c. three times weekly, escalating in each patient by 3 MU per week, if tolerable, up to 12 MJ. The combination was poorly tolerated with nausea, vomiting, somnolence and myalgia commonly reported. Adverse events accounted for treatment withdrawal in ten patients and contributed to withdrawal in four other patients. Treatment with Linomide alone in the first 2 weeks led to a significant increase in white blood cells, neutrophils and platelets. When Alpha-Interferon was added, the platelet count decreased significantly over the following 6 weeks. Nineteen patients had white cell phenotype and function measured. After 2 weeks of 5 mg Linomide, a transient but significant decrease in the absolute number of activated T-helper cells (CD4+DR+) was observed. No changes in natural killer (NK) cell number or activity were observed. Twenty-two patients were evaluable for response. One with metastatic renal cell carcinoma had a complete response and six had stable disease. This study does not support the use of the combination because significant toxicity was seen without the anticipated immunological benefits.