Use Of Interferon Therapy Research Articles

Clinical and immunological efficacy of interferonotherapy in rotavirus infection in infants

Purpose: to improve the complex therapy of rotavirus infection in infants by including interferon and to evaluate its clinical and immunological effectiveness.Materials and methods. Infants without infectious pathology and with rotavirus infection, who were on standard therapy and treatment, including standard therapy and interferon (20 in each group), were examined using general clinical methods. The diagnosis of rotavirus infection was carried out by molecular-genetic method and immunochromatography. Indicators of cellular immunity were determined by flow cytometry. Statistical processing of the results was carried out using the STATISTICA 8.0 program for related and independent samples using the nonparametric Mann-Whitney test and χ2.Summary. In all infants with rotavirus infection, the disease occurred in a moderate form with symptoms of grade II exicosis. In the group of patients who received an additional interferon drug as part of complex therapy, the duration of intoxication symptoms was significantly less, and in the hemogram at discharge from the hospital, the relative content of neutrophils was higher and monocytes lower compared to infants who were only on standard treatment, which corresponded to the norm. In the acute period of rotavirus infection, the relative level of lymphocytes decreased, and NK cells and T-NK cells increased compared to healthy infants. The relative number of cells expressing TLR-3 at the beginning of the disease was lower than in the control group. The inclusion of interferon in the complex therapy contributes to normalization of the relative number of NK cells, while maintaining an increased content of T-NK cells in both relative and absolute terms compared to healthy infants, and a reduced content of cells expressing TLR-3.Conclusion. Currently, rotavirus infection in infants is typical, the most pronounced and long-lasting clinical symptom of the disease is watery diarrhea. The use of interferon in complex therapy helps to reduce the duration of intoxication and normalize the hemogram. Changes in the immune status in the acute period of rotavirus infection indicate increased antigenic stimulation of the cell link and inhibition of the synthesis of pro-inflammatory cytokines, including interferons, under the influence of rotavirus, which is the justification for the use of interferon therapy.

Opportunities of Interferon Therapy in Pregnant Women with Cervical Intraepithelial Neoplasia

Objective: Due to hormonal and immune response changes, pregnancy contributes to their adverse stimulating effect on the progress of already existing hyperplastic processes in the cervix. The resulting aggravation of severity in their clinical course and intensity of the pathological process relatively frequently leads to precancerous conditions and cervical cancer developing further on. Some authors note the upward trend in the number of pregnant women having been diagnosed with pre-cancer and cancer of the cervix, as women postpone their maternity decisions increasingly more often. Currently, the tactics of managing pregnant women with cervical dysplasia consists in dynamic observation, including cytological study, colposcopic assessment of the state of surface cervical epithelium taking into account physiological particularities which are characteristic of pregnancy. The use of interferon therapy in pregnant female patients with HPV-associated cervical neoplasia is also expedient owing to its positive effect for reducing the CIN progression frequency, the probability of infecting the fetus with human papillomavirus, and the frequency of perinatal complications. Methods: The study involved pregnant women in their second and third trimesters of gestation who have been diagnosed with cervical neoplasia (L-SIL, H-SIL). In comparison groups, behavior of cervical neoplasia was monitored against the background of the therapy conducted with interferon alpha-2b or without treatment. Results: Against the background of the therapy conducted with interferon alpha-2b drug, higher frequency of the pathological process improving and lower frequency of its progressing into more severe dysplasia forms have been registered in the pregnant women with HPV-associated cervical neoplasia. However, it must be noted that efficiency of the treatment is higher in the group of pregnant women with L-SIL than in the H-SIL female patients. Conclusion: In managing the CIN pregnant women, it is expedient to prescribe interferon therapy systemically and topically in the form of gel (Viferon®) which allows reducing inflammation, viral load, ensuring regression of L-SIL and stabilization of H-SIL.

Immunological Approaches to the Treatment of New Coronavirus Infection (Review).

The pandemic of the new coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus has spread all over the world. The large amount of information that appears every day requires comprehension and systematization. The immunological aspects of the virus-host interaction are the core issues in the effective treatment and prevention of COVID-19’ development.The review analyzes the known pathways of the viral invasion and evasion, the mechanisms of the cytokine storm, endothelial damage, and hypercoagulability associated with SARS-CoV-2 infection. Clinical data from previous SARS and MERS epidemics is discussed here. We also address the therapeutic approaches based on the basic knowledge of immune response and the blood cells’ immune functions, as well as the ways to reduce their hyperactivation. The use of interferon therapy, anti-inflammatory therapy, anti-cytokine therapy, neutralizing antibodies, convalescent plasma, and mesenchymal stem cells, as well as prophylactic vaccines, is discussed.

Awareness of interferon therapy among dental students

Interferon is perhaps the term given to antiviral material formed by many vertebrate cells in reaction to viral infections. Research has established a number of mechanisms involved, in therapeutic benefits of interferon together with antiviral, innate immunity-enhancing and functions. This survey was performed for assessing the awareness about interferon therapy amongst dental students. A cross-sectional survey was performed with a self-administered questionnaire with ten queries circulated among 100dental students. The questionnaire assessed the awareness about Interferon therapy, their medicinal uses, anticancer activity, mechanism of action and side effects. The responses were recorded and .91% of the respondents were not aware of medical uses of Interferon therapy .93%were not aware of anticancer activity of Interferon therapy.93 % were not aware of the mechanism of action of Interferon therapy .96% were not aware of side effects of Interferon therapy. The awareness about the use of interferon therapy is very less among dental students. Increased awareness programs and sensitization programs should be conducted to improve the awareness levels.

Thyrotoxic graves' disease-induced by interferon-ribavirin therapy in a patient with amiodarone-induced hypothyroidism on thyroxine replacement

An unusual type of drug-induced thyroid dysfunction is described. Thyrotoxicosis was seen in association with the use of interferon therapy despite prior established amiodarone-induced hypothyroidism. A 63-year-old female patient with a history of hypertension, high-grade ventricular arrhythmia on sotalol 80 mg daily was diagnosed to have amiodarone-induced hypothyroidism previously. She has been receiving thyroxine replacement therapy for 4 years. During the second cycle of interferon for hepatitis C virus relapse. She developed autonomous thyrotoxicosis. Her anti-thyroid peroxidase antibody was persistently negative before, during, and after either amiodarone or interferon while anti-thyroid stimulating hormone receptor antibody titer. Thyroid Tc-99m scan showed a high uptake during interferon therapy. To the best of the author's knowledge, this is the first report of a case of long-term hypothyroidism-induced by amiodarone therapy evolving into thyrotoxic Graves' disease-induced by interferon/ribavirin combination therapy in Libya reflecting an interaction of drugs and the background autoimmune disease.

Contemporary Use of Interferon Therapy in the Myeloproliferative Neoplasms.

The purpose of this article is to review the current evidence behind interferon therapy in patients with myeloproliferative neoplasms. Preliminary analysis suggests that interferon may be non-inferior to hydroxyurea in patients with polycythemia vera and essential thrombocytosis. Responses have been observed regardless of JAK2 mutational status, but the presence of non-JAK2 somatic mutations may negatively influence response rates. Pegylated interferon has proven efficacy for patients with myeloproliferative neoplasms. Both newly diagnosed and previously treated patients with polycythemia vera and essential thrombocytosis exhibit high hematologic response rates, and some of these patients achieve molecular responses as well. Interferon therapy leads to lower rates of hematologic response in MF patients, but patients earlier on in their disease course have a better chance of responding. There are ongoing trials comparing pegylated interferon to hydroxyurea in essential thrombocytosis (ET) and polycythemia vera (PV), and early analysis suggests non-inferiority. However, longer follow-up is needed before drawing any conclusions. Future research is needed to better define characteristics of the best responders and to determine whether novel forms of interferon therapy or combination therapy with interferon can enhance efficacy and tolerability.

Optimal therapy for polycythemia vera and essential thrombocythemia: Preferred use of interferon therapy based on phase 2 trials

Objectives: To determine the value of recombinant interferon-alfa (rIFNα) in the treatment of polycythemia vera (PV) and essential thrombocythemia (ET) based on its biological activities and phase 2 clinical studies, pending completion of phase 3 trials; to determine importance of the Internet in patient decision-making in treatment selection.Results: The value of rIFNα in PV and ET is based upon its biological effects on PV stem cells and megakaryocyte proliferation. Single-arm trials are useful for life-threatening diseases when there are relatively few patients to evaluate endpoints, such as rIFNα treatment of PV and ET. Proper diagnostic criteria are mandatory; for PV, the current World Health Organization criteria emphasizing increased hemoglobin values exclude approximately one-third of eligible patients.Importance of these data: Single-arm studies in diseases exemplified by rIFNα in PV require updated diagnostic criteria for research and for clinical practice. The influence of the Internet on patient decisions for treatment is noteworthy.Conclusion: The biologic basis for selecting therapy is exemplified by rIFNα in treating PV and ET. Current single-arm studies of rIFNα in PV and ET are relevant and acceptable. The importance of the Internet in patient decision-making is important.

Review article: depression and the use of antidepressants in patients with chronic liver disease or liver transplantation.

The scale of depression in patients with chronic liver disease (CLD) and those who have received orthotopic liver transplantation (OLT) is poorly characterised. Clinicians are uncertain of how best to manage depression within these patients. To review the literature evaluating both the prevalence and impact of depression in patients with CLD and post-OLT, and to assess the safety and efficacy of antidepressant use within this context. A PubMed search using the phrases 'chronic liver disease', 'cirrhosis', 'liver transplantation', 'depression', 'antidepressant' and the names of specific causes of liver disease and individual antidepressants. Over 30% of cirrhotic patients have depressive features, and they experience worse clinical outcomes than nondepressed cirrhotic patients. CLD patients with chronic hepatitis C are particularly prone to depression, partly related to the use of interferon therapy. OLT patients with depression have higher mortality rates than nondepressed patients; appropriate antidepressant use reverses this effect. Selective serotonin reuptake inhibitors (SSRIs) and selective noradrenaline reuptake inhibitors (SNRIs) are effective and generally safe in both CLD and OLT patients. Depression is much more prevalent in CLD or OLT patients than is generally recognised, and it adversely affects clinical outcomes. The reasons for this relationship are complex and multifactorial. Antidepressants are effective in both CLD and post-OLT, although lower doses or a reduced dosing frequency may be required to minimise side effects, e.g. exacerbation of hepatic encephalopathy. Further research is needed to establish optimal management of depression in these patients, including the potential role of nonpharmacological treatments.

Percutaneous Ethanol ablation of small Hepatocellular Carcinomas: Twenty years on

Percutaneous Ethanol ablation of small Hepatocellular Carcinomas: Twenty years on

Interferon-induced pulmonary sarcoidosis

A further new case of sarcoidosis associated with the use of interferon (IFN) in the classical treatment of chronic hepatitis C (CHC) is reported. During the last two years, more than 20 cases of interferon-induced sarcoidosis have been described in the literature and about half of these cases have involved CHC. Therefore this disorder appears more common than originally thought two years ago, possibly due to the more frequent use of interferon therapy and an improvement in the methods of diagnosis.

Spectrum of Pulmonary Toxicity Associated with the Use of Interferon Therapy for Hepatitis C: Case Report and Review of the Literature

Hepatitis C is one of the leading causes of liver disease in the United States, and current recommendations for its treatment include the use of interferon (IFN). Pulmonary side effects, although uncommon, have been reported in association with the use of IFN. We report a case of interstitial granulomatous pneumonitis that occurred after therapy with IFN and ribavirin, and we review the literature concerning this entity and other forms of IFN-associated pulmonary toxicity in patients with hepatitis C. The purpose of the present study is to increase awareness of the unusually wide spectrum of pulmonary toxicities associated with the use of IFN and ribavirin, with the anticipation that IFN will be used more frequently in the future for the treatment of hepatitis C.

Interferon Therapy for Acute Hepatitis C During Pregnancy

OBJECTIVE:Due to their antiproliferative activity, the probable effects of interferons on a fetus are a concern. We report on a pregnant patient who developed acute hepatitis C during pregnancy and was treated with a short course of interferon alfa therapy with a successful outcome.CASE SUMMARY:A 26-year-old woman was diagnosed with acute hepatitis C at the 16th week of pregnancy. She received a total dose of 72 million units of interferon alfa-2b during a 2 1/2 month period. Although the therapy was discontinued due to adverse effects, a complete biochemical and virologic response was obtained. Premature labor occurred and healthy, but growth-restricted, twin infants were born transvaginally. At 18 months of age, they had normal development, with a negative hepatitis C serology.DISCUSSION:The rate of transmission of hepatitis C virus from mother to infant is within the range of 1–5%. Although acute hepatitis C during pregnancy is a very rare occurrence, the mother is at a great risk for chronic infection. There is scarce literature about the probable effects of interferon use during pregnancy due to a lack of controlled studies in this special population. A total of 8 infants, including ours, exposed to interferon alfa and/or ribavirin during pregnancy showed no congenital anomalies or malformations.CONCLUSIONS:Patients with chronic hepatitis whose therapy can be delayed should not be treated with interferon due to a lack of controlled studies. However, women exposed to interferon inadvertently during pregnancy may be encouraged to continue pregnancy. In patients with acute hepatitis C during pregnancy, the use of interferon therapy should be considered with close monitoring.

Interferon therapy in primary care

Interferons are proteins produced by human blood cells in response to stimulation (viral infection). The natural roles of interferons are host defense and modulation of the immune system. Therapeutic uses are based on these roles. Interferon-α has been widely used for malignancies, skin conditions, viral infections, and myeloproliferative disorders. Interferon-β is a standard treatment for relapsing multiple sclerosis. Interferon-γ therapy is currently used for chronic granulomatous disease and skin lesions (human papilloma virus related and keloids), but further research is ongoing. Side effects of interferon therapy are common and limit utility. Flulike symptoms are reported by more than 75% and depression by 10–40% of interferon users. Severe adverse effects are less common but may be life threatening, including autoimmune diseases, thrombotic-thrombocytopenic purpura, and acute renal failure. Limited use of interferon therapy during pregnancy has been described, with successful maternal and neonatal outcomes. Use of interferon therapy during early pregnancy is not an indication for termination.

Natural history of hepatitis C

Ten years after the discovery of the hepatitis C virus (HCV) and its association with NANB hepatitis as a major cause of chronic liver disease worldwide, our knowledge of the natural history of hepatitis C is still limited. The asymptomatic course of the disease in most patients, its slow and silent progression and heterogeneous outcome and the widespread use of interferon therapy during the past decade explain why many questions are still unsolved. The changing epidemiological pattern of HCV and the significant contribution of several cofactors to the severity of liver disease also complicate the development of a general model describing the natural history of hepatitis C. Available data indicate that HCV infection may resolve without any clinical signs of liver disease in individuals exposed to low dose inoculum and that these cases may develop T cell immunity even in the absence of anti-HCV seroconversion. Rates of complete biochemical and virological resolution of acute hepatitis C range between 10 and 50%, and are probably affected by the route of infection, size and type of inoculum and acute phase clinical features. Chronic HCV infection may develop with or without ALT abnormalities and with or without chronic inflammation and increasing fibrosis in the liver. Studies conducted in patients who acquired hepatitis C by blood transfusion 15–25 years ago indicate that 20–30% of them have now progressed to cirrhosis, including 5–10% with end stage liver disease and 4–8% who died of liver-related causes. Similar studies conducted in patients infected by other routes have shown a more benign course of hepatitis C, with little evidence of cirrhosis and no liver-related mortality during the first two decades. Outcomes after longer follow-up need to be assessed. In patients presenting with chronic hepatitis C, fibrosis progression is extremely variable over time and can be partially predicted by the age at infection, disease duration, liver histologic activity and stage of fibrosis and by the ALT profile. However, it is often difficult to predict clinical outcomes in individual cases. In patients who have developed cirrhosis, the 5-year risk of decompensation is between 15 and 20% and that of hepatocellular carcinoma around 10%. Several variables have been shown to influence the natural course of shown C, the most significant being age at infection, alcohol consumption and coinfection with HBV and HIV. Studies are being performed to assess the role of host genetics. Viral factors, such as the HCV type and load, seem to have inconsistent or marginal effects.

Interferon therapy for acute hepatitis C viral infection--a review by meta-analysis.

Hepatitis C viral (HCV) infection poses a major health problem for Australia. Currently interferon therapy is approved only for people with chronic infection, yet the literature contains a number of studies that show that there is a better response to interferon in symptomatic acute HCV. To review the response to interferon therapy in acute HCV by way of meta-analysis. This study was a retrospective review of the data on the use of interferon therapy in acute HCV. The meta-analysis was performed using the methods of DerSimonian and Laird. Data were presented by calculating the risk difference which estimated efficacy by calculating the proportion of patients in treatment groups who responded better (0 to +1.0) or worse (0 to -1.0) than untreated control groups. A meta-analysis of six studies on the use of 3MU of interferon alpha 2b (IFN-alpha 2b) three times a week for six to 24 weeks showed a significant response as measured by long term (> 12 months) normalisation of alanine aminotransferase (ALT) and clearance of HCV RNA (as measured by polymerase chain reaction). The risk of difference was +0.31 (95% CI of +0.19 to +0.43, p < 0.01) and +0.33 (95% CI of +0.08 to +0.58, p < 0.001) respectively. Slightly better results were seen with daily doses of 3MU of interferon beta (IFN-beta) given intravenously over four to seven weeks. This produced a risk difference of +0.57 (95% CI of +0.26 to +0.88, p < 0.02) for normalisation of ALT and +0.83 (95% CI of +0.61 to 1.00, p < 0.001) for clearance of HCV. Results for higher daily doses of both IFN alpha and beta were limited to a few studies and most were uncontrolled. 6MU of IFN-alpha 2b three times a week for 16 to 24 weeks produced a risk difference of +0.53 (95% CI +0.17 to +0.89, p < 0.05) for normalisation of ALT and +0.44 (95% CI +0.06 to +0.82) for clearance of HCV RNA. Results with 6MU daily for eight weeks of IFN-beta in an uncontrolled study, showed up to 90% patients cleared HCV long term. Preliminary results with 10MU of IFN-alpha 2b daily for four to six weeks also showed long term clearance of HCV RNA and normalisation of ALT in 90% of treated patients. Short term (six weeks to six months) treatment of symptomatic acute HCV with interferon (both alpha and beta) produced a better long term response rate than prolonged therapy (> 12 months) in chronic HCV. Daily doses of 6MU and 10MU produced better responses than 3MU but more studies are needed to determine the optimum regime.

Loss of serum HBsAg after interferon-A therapy in liver transplant patients with recurrent hepatitis-B infection

Reinfection with hepatitis B virus after orthotopic liver transplantation is nearly universal in patients who have not received posttransplant immunoprophylaxis. Recurrence almost invariably leads to chronic liver disease. Interferon has been used both prophylactically and therapeutically but has not been effective. We treated 2 liver transplant patients with recurrent hepatitis B virus (HBV) infection (serum hepatitis B surface antigen [HBsAg] and HBV DNA positive on polymerase chain reaction, and positive liver biopsy result) with interferon, 3 to 6 MU three times weekly for 6 to 22 months. A full response to therapy was manifested in both patients by normalized serum alanine aminotransferase levels and the loss of serum HBsAg and HBV DNA. The effectiveness of interferon in our patients may have been related to coinfection with hepatitis D virus in the first case and the high interferon dose (6 MU, three times weekly) and long treatment period (22 months) in the second. No episodes of rejection were noted during therapy. We conclude that interferon can induce a complete response in liver transplant patients with recurrent HBV infection. Future studies should investigate the use of interferon therapy at higher doses and/or for longer periods. (Liver Transpl Surg 1997 Jul;3(4):394-7)

Intraventricular administration of interferon and administration of methisoprinol by mouth in the treatment of adult‐onset subacute sclerosing panencephalitis

This is thought to be the first report of the use of interferon therapy by intraventricular administration in adult-onset subacute sclerosing panencephalitis. A 22-year-old female patient with subacute sclerosing panencephalitis was treated for three months with interferon by the intraventricular route and methisoprinol (inosiplex) by mouth. There was no obvious clinical improvement during this time, and the cerebrospinal-fluid measles antibody titre remained elevated. The lack of effect of therapy could be attributed partly to the patient's age and to the rapidly progressive deterioration in her condition before treatment. No significant side-effects were associated with this therapy. Further trials of these medications in adult-onset subacute sclerosing panencephalitis are indicated.