Effect Of Interferon-alpha Treatment Research Articles

Comparison of depressive, anxiety, and somatic symptoms in patients with essential thrombocythemia, polycythemia vera, and myelofibrosis treated with interferon alpha

Introduction: The study aims to analyze the occurrence of depression, anxiety, and somatic symptoms in patients with chronic myeloproliferative neoplasms (essential thrombocythemia, polycythemia vera, and myelofibrosis) and to check whether individual side effects of interferon alpha treatment may contribute to the occurrence of depression, anxiety, and somatic symptoms. In addition, it was decided to check whether there were any relationships between age, gender, duration of treatment, and the intensity of anxiety, divided by the occurrence of individual side effects. Material and methods: The study involved 84 patients and was conducted at the Hematology Clinic of the University Hospital in Krakow and the Clinic of Hematology, Blood Cancer and Bone Marrow Transplantation in Wrocław. The following questionnaires were used: created by the author, David Goldberg General Health Questionnaire 28 (GHQ-28), and the Four-Dimensional Questionnaire (4DSQ). Results: The most frequently reported side effects of treatment were abdominal pain, fatigue, and bone and joint pain. Almost 40% of the respondents obtained a moderately and strongly increased result on the depression scale, less than 50% on the anxiety scale, and over 60% on the somatization scale. Somatic symptoms had the greatest impact on the occurrence of mental disorders, with anxiety symptoms being second in significance. There are differences in the severity of depressive, anxiety, and somatic symptoms depending on the side effects of interferon alpha treatment. Conclusions: The finding of the above study indicates the need for further research into the importance of detecting depressive, anxiety, and somatic disorders, and to addressing concomitant physical symptoms, both in patients with myeloproliferative neoplasms receiving interferon alpha and treated with other methods. In patients treated chronically, the occurrence of side effects of high intensity and lasting for a long time should alert medical personnel. The collected data on patients with myeloproliferative neoplasms who have to suffered from mental and physical symptoms of the disease or its treatment justifies the need for caring psychological, psychiatric, and educational care.

Detrimental Impact of Interferon-Based Regimens for Chronic Hepatitis C on Vitamin D/Parathyroid Hormone Homeostasis

Background: Both the anti-infective and anti-inflammatory properties of vitamin D, an essential hormone of calcium homeostasis, have ample support in the literature. The high rates of vitamin D deficiency among patients with chronic hepatitis C are also well known. That supplementation with vitamin D may boost sustained viral response rates in vitamin D deficient, hepatitis C virus (HCV) infected patients undergoing Interferon-alpha (IFN) treatment, on the other hand, is controversial. Surprisingly, studies considering in this latter setting what are the effects of IFN treatment (with or without vitamin D supplementation) on the other major regulator of mineral metabolism, i.e. the Parathyroid hormone (PTH), are lacking. Aim: Evaluate the impact of interferon-based treatment against HCV (±cholecalciferol supplementation) on vitamin D and PTH homeostasis. Methods: A series of 40 consecutive patients received pegylated IFN plus ribavirin to treat chronic hepatitis C. At the discretion of their physician, some of them (N. = 27) received vitamin D supplementation while others did not (N. = 13). All had measured plasma 25-hydroxycholecalciferol and PTH concentrations at baseline, at completion of the 4th (TW4) and 12th treatment week (TW12) and at 24 weeks after the end of therapy (SVR24). Results: Plasma PTH concentration increased significantly from baseline during treatment, raising to 44.8 [30.7-57.2] pg/mL at TW4 (p=0.01), 47.0 [37.1-63.2] pg/mL at TW12 (p=0.006) to return to baseline levels in the follow-up (34.5 [27.6-43.0]; p=0.16). The proportion of patients who satisfied criteria for hyperparathyroidism was higher at TW12 (N=10, 25%) than at TW4 (N=6, 15%). There was no statistical correlation between vitamin D and PTH blood levels (ρ=-0.07; p=0.65). Conclusion: An increase in plasma PTH occurs systematically during IFN treatment of HCV patients and cannot be prevented by vitamin D supplementation.

Effects of Interferon-Alpha Treatment on the Incidence of Hyperglycemia in Chronic Hepatitis C Patients: A Systematic Review and Meta-Analysis

BackgroundThere is a significant association between effects of interferon-alpha treatment and the risk of developing hyperglycemia in patients with chronic hepatitis C virus (HCV) infection. The objective of this systematic review and meta-analysis on the basis of published observational studies was to estimate risk of hyperglycemia in chronic HCV patients who had acquired sustained virological responses (SVR) compared to those without SVR.MethodologyWe identified eligible studies by searching the relevant databases, including PubMed, Embase, and Google, for papers published between January 1990 and April 2011. The selection of eligible papers was carried out using a scoring system based on guidelines and inclusion criteria that were established before the articles were identified. Heterogeneity across studies was determined and the meta-analysis was performed following standard guidelines.ConclusionsEleven eligible studies provided data of the incidence of hyperglycemia in chronic hepatitis C patients with SVR in comparison with patients without these conditions. The results demonstrated that SVR was associated with a lower risk of hyperglycemia (odds ratio = 0.497, 95% confidence interval 0.421–0.587, p<0.001), and there was no evidence of any substantial between-study heterogeneity (I2 = 24.4%, p>0.1). Results of meta-regression showed patients with different baseline glucose (normal vs. abnormal) and patients with co-infected HIV (presence vs. absence) as the sources of low heterogeneity (p<0.15).The lowest risk of hyperglycemia was described in patients with normal glucose baseline (OR = 0.402, 95%CI 0.297–0.543, p<0.001). This is the first systematic review and meta-analysis performed to examine the association between SVR and risk of hyperglycemia in patients with HCV infection. Our meta-analysis suggests that SVR reduce the risk of developing glucose abnormalities, especially in patients with normal glucose baseline.

A polymorphism in NFKB1 is associated with improved effect of interferon- maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support

Maintenance therapy with interferon-alpha after high-dose treatment with stem cell support in multiple myeloma has been intensively debated. In this study, we evaluated the response to treatment with interferon-alpha in relation to genetic variation in genes related to inflammation. In a retrospective study of 296 patients with multiple myeloma undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon-alpha as maintenance therapy. We tested the polymorphisms IL1B T-31C, IL6 G-174C, NFKB1-94ins/delATTG, CD3EAP G-21A and PPP1R13L IVS1 A4364G for associations with time to treatment failure and overall survival with and without interferon-alpha treatment. The wild type ins-allele of polymorphism NFKB1-94 ins/delATTG was, by multivariate Cox analysis, associated with longer time to treatment failure (p=0.01) and overall survival (p=0.0084) when tested between treatment arms and in the subgroup of patients treated with interferon-alpha the wild type ins-allele was associated with longer overall survival (p=0.002). In the absence of interferon-alpha treatment, there was no association between the polymorphisms and treatment outcome, except for patients homozygous for the wild type G allele of IL6 G-174C who survived longer (p= 0.0074) than variant allele carriers. There was no association between the polymorphisms IL1B T-31C, CD3EAP G-21A and PPP1R13L IVS1 A4364G and treatment outcome for interferon-alpha. Patients who are homozygous carriers of the wild type ins-allele of the NFKB1 -94ins/delATTG polymorphism may benefit from treatment with interferon-alpha, in contrast to patients carrying the variant allele. This result may indicate that the effect of interferon-alpha treatment is dependent on the availability of nuclear factor-kappaB and the polymorphism in NFKB1 may, therefore, be a good prognostic marker for multiple myeloma patients on maintenance treatment with interferon-alpha after high-dose therapy. A prospective study of interferon-alpha treatment in relation to NFKB1 -94ins/delATTG is highly warranted.

Effects of interferon alpha treatment on recurrence and survival after complete resection or ablation of hepatocellular carcinoma: A meta‐analysis of randomized controlled trials

Available literature on the benefit of interferon alpha (IFN-alpha) as adjuvant postsurgical or ablative treatment of hepatocellular carcinoma reports discordant results. By meta-analysis of the available data, we evaluated the effects of IFN-alpha on recurrence and survival after complete resection or ablation of hepatocellular carcinoma. All randomized controlled trials comparing IFN-alpha with placebo or no treatment after tumor resection or ablation were selected. Finally, 6 studies published in 2001 or later with a total of 600 patients were included in this meta-analysis. Data on postsurgical or ablative early recurrence and 1 year survival of hepatocellular carcinoma in IFN-alpha treated and untreated patients were extracted from each study. Proportions were combined, and the odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Analysis results show that IFN-alpha significantly decreased postsurgical or ablative overall early recurrence (OR = 0.62; 95% CI = 0.42-0.93; p = 0.02) and improved overall 1 year survival (OR = 3.14; 95% CI = 1.79-5.52; p < 0.0001). Subgroup analyses show that IFN-alpha decreased postsurgical early recurrence (OR = 0.58; 95% CI = 0.37-0.91; p = 0.02) and improved 1 year survival (OR = 3.19; 95% CI = 1.80-5.67; p < 0.0001) evidently. Subgroup analyses also show that IFN-alpha reduced early recurrence after resection without pre-resection ablation therapy (OR = 0.58; 95% CI = 0.37-0.91; p = 0.02) and improved 1 year survival (OR = 3.83; 95% CI = 2.01-7.27; p < 0.0001). These results suggest that IFN-alpha treatment could significantly decrease early recurrence and improve 1 year survival of patients with hepatocellular carcinoma after complete resection or ablation. The use of IFN-alpha as adjuvant postsurgical or ablative treatment seems promising but requires further study. (c) 2009 UICC.

Pulmonale Sarkoidose: eine seltene Nebenwirkung einer Interferon-α-Therapie bei chronischer Hepatitis-C-Infektion

This is a case report of a 44-year-old woman who received a 1-year-treatment with interferon-alpha for chronic hepatitis C virus infection. 3 months after cessation of the therapy she relapsed and was successfully retreated 12 months with a combination of interferon-alpha and ribavirin thereafter. During the treatment the patient developed a typical flue-like syndrome, dry cough with exertional dyspnea that was initially interpreted as a typical side effect of interferon-alpha treatment. Due to the persisting cough, further radiologic and histologic work up was done and results were significant for interstitial sarcoidosis. After interferon-treatment was stopped the pulmonary symptoms resolved completely while pathologic changes in radiographic imaging persisted. Interferon-alpha may have contributed to the development and progression of sarcoidosis by activation of cellular immunity. Although there are only few reports about pulmonary sarcoidosis associated with interferon-alpha treatment, this entity should be included in the differential diagnosis of putative side effects of interferon-alpha therapy.

Effect of interferon-alpha treatment in hemodialysis patients and renal transplant recipients with chronic hepatitis C

Effect of interferon-alpha treatment in hemodialysis patients and renal transplant recipients with chronic hepatitis C

Infection par le virus de l'hépatite C et pathologies thyroïdiennes

The combination of hepatitis C virus (HCV) infection and thyroid diseases raises several issues that are the prevalence of thyroid autoimmunity in patients with chronic hepatitis C, the prevalence of HCV infection in patients with autoimmune thyroid diseases, and the effects of interferon alpha treatment on thyroid function in chronic HCV hepatitis. The prevalence of anti-thyroid auto-antibodies ranges from 4.6 to 15% in HCV infection, which is considered as significant by various authors. Results have to be interpreted according to the following: the type of auto-antibodies detected, the age, sex, ethnic origin of the population studied, and characteristics of the control population. Recent data are suggestive of a high prevalence of anti-thyroid auto-antibodies in females with HCV infection. An increased prevalence of HCV infection in patients with Hashimoto's thyroiditis is not confirmed. During treatment of chronic hepatitis C, interferon alpha induces thyroid dysfunctions (3 to 15% of the cases) with various clinical presentations. Hypothyroidism is more common (two out of three cases) than hyperthyroidism (one out of three cases). Hyperthyroidism followed by hypothyroidism has also been described. Clinical symptoms vary, ranging from subclinical to severe manifestations. Thyroid dysfunction may be delayed after discontinuation of the interferon treatment. Hypothyroidism is easily cured by L-thyroxine replacement therapy when necessary, and regression may be observed following discontinuation of interferon treatment. Each case of hyperthyroidism has to be precisely evaluated. Development of anti-thyroid antibodies or an increase in anti-thyroid antibodies titers is often observed during interferon alpha treatment, thus suggesting the existence of immunological mechanisms at the origin of thyroid dysfunction. Furthermore, interferon would directly act on iodine. Clinical studies are still necessary to better clarify the links between HCV infection and thyroid autoimmunity, and to determine risk factors for the development of thyroid dysfunction during interferon alpha therapy. The effects of HCV and interferon alpha on thyroid autoimmunity and function have to be investigated in basic research.

Hepatic blood flow changes in chronic hepatitis C measured by duplex Doppler color sonography: relationship to histological features.

Our aim was to determine if portal vein and hepatic artery blood flow indices are a noninvasive index of severity of liver disease in chronic hepatitis C. The effect of interferon-alpha treatment on liver blood flow was also studied. Liver blood flow measurements were recorded by duplex Doppler color sonography in 39 patients with chronic hepatitis C, 50 healthy controls, and a single patient with hepatocellular carcinoma. Doppler perfusion index (DPI) (calculated as the ratio of hepatic artery flow to total hepatic flow) and the congestive index of the portal vein (area/velocity) were calculated. Liver biopsies were scored for hepatic inflammation and fibrosis. Hepatic arterial flow (415.7+/-329.1 ml/min vs 195.1+/-103.5 ml/min) and DPI (0.27+/-0.14 vs. 0.17+/-0.06) were elevated in chronic hepatitis C patients compared to controls (P = 0.0002 and 0.0003, respectively) while portal vein flow and total hepatic flow were similar. Portal vein congestive index was similar in chronic hepatitis C (0.106+/-0.05) compared to controls (0.125+/-0.08) P 0.52. Hepatic blood flow indices were not related to the grade of hepatic inflammation or the stage of hepatic fibrosis. Twelve weeks of treatment with interferon-alpha had no effect on liver blood flow. In conclusion, patients with chronic hepatitis C have elevated hepatic artery blood flow. Hepatic blood flow indices have no relationship to the severity of histological liver injury in chronic hepatitis C, and these flow indices are unaffected by a 12-week course of interferon-alpha.

Effect of interferon-alpha treatment of chronic hepatitis C on health-related quality of life.

Studies of interferon-alpha (IFN-alpha) therapy for chronic hepatitis C have focused on viral clearance; however, few have evaluated patient's health-related quality of life during therapy. This study evaluates health-related quality of life and the prevalence of anxiety and depression in patients with chronic hepatitis C before, during, and following IFN-alpha therapy. Patients undergoing IFN-alpha therapy for chronic hepatitis C were asked to complete health status measures as well as anxiety and depression inventories before, during, and following IFN-alpha therapy. These measures were compared to the results of healthy adults in the general US population. Thirty-eight of forty-eight eligible patients (79%) with chronic hepatitis C completed the questionnaires. Respondents demonstrated a significant increase in depression during the sixth month of interferon therapy in comparison to pretreatment results. Anxiety scores improved significantly after one month of IFN-alpha in comparison to pretreatment results. Scores on the health status measures did not vary with IFN-alpha therapy. Patient responses were analyzed with respect to biochemical response (normalized transaminases) to IFN-alpha. IFN-alpha responders, who were aware of their transaminase results, exhibited lower scores on anxiety subscales during and after therapy (P = 0.02-0.04). Scores on the health status subscale, role emotional, improved in IFN-alpha responders compared to nonresponders during the sixth month of therapy (P = 0.02). Response to IFN-alpha therapy was not associated with any other differences on subscale analysis. Patients with chronic hepatitis C exhibited health perceptions similar to the general US population, and these were unchanged during IFN-alpha therapy. However, the incidence of depression significantly increased during the sixth month of IFN-alpha therapy. IFN-alpha responders exhibited fewer emotional problems as well as a lower incidence of anxiety during and following therapy.

Topical interferon alpha 2b for corneal haze after excimer laser photorefractive keratectomy

Purpose: To determine whether topical interferon alpha 2b (IFN-α) prevents corneal haze after excimer laser photorefractive keratectomy (PRK).Setting: Tertiary referral ophthalmic hospital.Method: A prospective, double-blind, placebo-controlled, randomized study of 31 patients was undertaken. After surgery in a single institution, patients received a drop of either a placebo or IFN-α (5 × 106 IU/ml) four times daily for 4 weeks. The main outcome measures were corneal haze, refraction, and visual acuity.Results: The major side effect of interferon alpha treatment was a significant delay in epithelial healing by a mean of 2 days. The means of the average post-treatment clinical scores for haze in all patients up to 12 months after surgery were 0.46 ± 0.25 for the IFN-α group and 0.64 ± 0.43 for the placebo group (P = .20). Of patients with a correction of greater than 5.00 diopters (D), the IFN-a group had significantly less haze over the course of the study (0.39 − 0.23 versus 0.98 ± 0.50; P = .03). After 12 months, the mean absolute spherical equivalent in the two groups was not significantly different (1.02 ± 1.13 D versus 1.44 ± 2.64 D). There was a tendency toward better uncorrected visual acuity in the INF-a group (P < .10, Kolmogorov-Smirnov).Conclusion: Topical IFN-α may merit further investigation as a treatment to reduce corneal haze after excimer laser PRK for corrections greater than 5.00 D.

Effects of interferon-alpha treatment on neutrophil oxidative metabolism, lymphocyte proliferation and monocyte HLA class I antigen expression in patients with chronic hepatitis C.

Polymorphonuclear cell (PMN) oxidative metabolism, lymphocyte polyclonal proliferation and monocyte HLA class I antigen expression were evaluated at different intervals of time in patients with chronic hepatitis C (CH-C) subjected to a 6 month interferon alpha (IFN-alpha) treatment and divided into Responder ('R') and Nonresponder ('NR') subsets according to clinical outcome. Before therapy, all subjects exhibited multiple immune alterations even if to a different extent between 'R' and 'NR' subsets: an elevated superoxide anion (O2-) generation by suspended PMN, a failure to further increase neutrophil oxidative responsiveness under adherence conditions, an augmented phytohaemagglutin-induced lymphocyte proliferative capacity and an enhanced HLA class I antigen expression on CD14+ cells. IFN-alpha administration gave rise to a modulation of oxidative response in 'R' group only, since these individuals displayed an O2- release by suspended and adherent PMN which fell within normal values. At the same time, a decrease of lymphocyte proliferation occurred in both groups of patients during IFN-alpha therapy, even if it reached statistical significance in 'R' group only. Finally, a more marked difference between 'R' and 'NR' individuals was noted in terms of HLA class I antigen induction on CD14+ cells at the end of therapy, as a consequence of a reduced expression of these structures in 'NR' subjects. Altogether, these findings suggest the occurrence of a strict relationship between immunoresponsiveness and IFN-alpha induced therapeutical effects in CH-C patients.