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Clinical Neuroscience

NOVEMBER 30, 2017

[Role of peginterferon-β-1a in the therapy of multiplex sclerosis]

SIMÓ Magdolna, ILJICSOV Anna

[The subcutaneous peginterferon-b-1a is recently introduced in the therapy of relapsing-remitting multiplex sclerosis (RRMS) patients. Pegylation of IFN b-1a improved pharmacodynamic and pharmacokinetic properties, resulting in, increased biologic activity and a longer half-life. The efficacy of peginterferon-b-1a was proved by the ADVANCE study - a 2-year Phase 3, multicenter, randomized, double-blind study with a 1-year placebocontrolled period evaluating the efficacy and safety of subcutaneous peginterferon-b-1a administered every 2 or 4 weeks in patients with RRMS. Peginterferon-b-1a efficacy was maintained during the two years, with greater effects observed with every 2 week versus every 4 week dosing. Annualized relapse rate and confirmed disability progression was reduced comparing with patients on delayed treatment. Patients treated with continuous peginterferon-b-1a had fewer new or newly enlarging T2 lesions over 2 years than patients in the delayed treatment group. Adverse events were consistent with the known profiles of IFN b therapies in MS. The most commonly reported adverse events were injection site erythema, influenza-like illness. The less frequent administration is associated with fewer flu-like adverse events, which may improve patients’ compliance and adherence. Peginter-feron-b-1a could be an effective and safe treatment option for RRMS patients.]

Lege Artis Medicinae

JULY 20, 2017

[Relationship between adipokinome and lipid parameters in Hungarian obese patients]

LŐRINCZ Hajnalka

[Since the prevalence of obesity has been dramatically increasing worldwide, a better understanding of obesity-related comorbidities leading to carbohydrate and lipid metabolism disorders has become essential. As an active endocrine organ, white adipose tissue secretes adipokines with diverse biological functions. We have found strong correlations between serum chemerin level and atherogenic lipoprotein sub-fractions in obese non-diabetic patients. To better characterize obese patients with and without manifest insulin resistance, we plan to determine serum levels of novel adipokines (omentin-1, vaspin, visfatin, lipocalin-2 and plasminogen activator inhibitor-1) and various oxidative stress markers including paraoxonase-1 activity, tumor necrosis factor-alfa and interleukin-6 levels, as well as low- and high-density lipoprotein subfractions in them and compare their data with lean individuals. We plan to determine correlations between the levels of novel adipokines and oxidative stress markers and lipoprotein subfractions. Furthermore, based upon our previous observations, we plan to study the potential alterations in the adipokine profile and the ratios of lipoprotein subfractions during a 5-year follow-up in obese patients. Our expected results may help to characterize the involvement of the adipokine profile in the regulation of lipoprotein metabolism. Early screening and treatment of lipid abnormalities may help to reduce the risk of cardiovascular events in obesity. ]

Lege Artis Medicinae

FEBRUARY 14, 2014

[Treatment of hungarian chronic hepatitis C genotype 1 patients with severe fibrosis or compensated cirrhosis in the international telaprevir Early Access Program: Interim analysis of the week 16 results]

TORNAI István, BÁNYAI Tivadar, GERVAIN Judit, HORVÁTH Gábor, MAKARA Mihály, MARTYIN Tibor, NEMES Zsuzsanna, PÁR Alajos, PÁR Gabriella, PÉTERFI Zoltán, SZALAY Ferenc, SZINKU Zsolt, TÓTH Tamás, VINCZE Áron, ISABELLE Lonj

[The approval of the first two direct acting antiviral agents, boceprevir and telaprevir, has been a major step forward in the treatment of chronic hepatitis C. Both protease inhibitors must be added to the dual peginterferon and ribavirin combination therapy. The triple combination therapy resulted in significantly higher rates of recovery both in naive patients and in those previously unresponsive to therapy. Following the approval of telaprevir, an Early Access Program has been initiated in 16 countries. In Hungary 132 patients were enrolled into this program. In the first interim analysis, data from the first 16 weeks of treatment of 92 patients are included. Liver cirrhosis (F4) was detected in 70% of the patients and severe fibrosis (F3) was found in the other 30%, on the basis of either liver biopsy or transient elastography. During their previous antiviral treatment, 64% of the patients were non-responders (partial and nullresponders), 26% were relapsers, and only 10% were treatment naives. The efficacy of the triple combination was excellent, as 82% of the patients had undetectable HCV RNA at week 12. Further - more, 48% had negative HCV RNA at week 4 as well as at week 12. Cessation of i.e. negative HCV RNA at week 4 through week 12. Only 5.4% of the patients had virologic failure and needed to stop therapy prematurely. The most frequent adverse event was anemia, hemoglobin level decreased below 100 g/l in 40% of the patients. In the majority of these patients ribavirin dose reduction was sufficient to treat anemia, only 16% needed blood transfusion. The rate of severe rash was 6%. Although this group of patients represents a difficult-to-treat population, both efficacy and safety data are similar to published data in international clinical trials. A very effective, triple combination therapy with telaprevir, peginterferon and ribavirin can be provided for patients with advanced liver disease, to reduce the risk of liver failure and hepatocellular carcinoma.]

Lege Artis Medicinae

JUNE 20, 2013

[Optimizing the efficacy of triple combination therapy of chronic hepatitis C]

TORNAI István

[The outcome of chronic hepatitis C (CHC) therapy has been improved significantly. If sustained virologic response (SVR) is achieved, then it may prevent the occurrence of liver failure and hepatocellular carcinoma. With the currently used double combination therapy (peginterferon and ribavirin) SVR can be achieved in 40-50% of patients with genotype 1. In treatment naive patients, triple combination with protease inhibitors can result in 70-75% SVR. In treatment experienced patients, however, the result of the previous therapy, which mostly depends on the reaction to interferon (IFN), has a significant influence on the outcome of triple combination. INF sensitivity is the highest in relapsers, triple combination can achieve about 85% SVR, while in null responders this is only 30%. Viral resistance is a new phenomenon during triple combination therapy of CHC. In poorly IFN responsive patients the virus is effectively exposed to protease inhibitor functional monotherapy, leading to the rapid emergence of resistant virus. IFN sensitivity is well represented by the on-treatment viral response, therefore the knowledge of the previous viral response, relapse, a partial response or a null response is absolutely important. Optimization of triple therapy is crucial, since for a lot of patients with advanced liver disease it might be the last chance to achieve an SVR. The selection of the patients seems very important. Relapsers are the best candidates, there is no doubt with the indication. However, there are many debates for cirrhotic nullresponders, since the most virological failures are expected in this group. Prevention of viral resistance is crucial. PegIFN and ribavirin suppress both wild-type and resistant virus. PegIFN α-2a based treatment proved to be the most effective backbone for triple combination. This combination should be preferred especially for treatment experienced patients. Adherence to therapy is also critically important to prevent resistance. If resistant mutants appear, treatment should be stopped promptly.]

Lege Artis Medicinae

JANUARY 27, 2009

[Efficacy of peginterferon alfa-2a and -2b plus ribavirin in the routine treatment of patients with chronic hepatitis C]

TUSNÁDI Anna, SZABÓ Anna

[INTRODUCTION - Combination of peginterferon plus ribavirin is the standard treatment for chronic hepatitis C virus (HCV) infection. Two types of peginterferon are available. The aim of this retrospective study was to find out whether the choice of peginterferon influenced the patient’s chance of recovery. PATIENTS AND METHODS - Between 2004 and 2007, 142 patients with HCV genotype 1 hepatitis with or without cirrhosis (107 treatmentnaive, 35 previously treated) were treated with 180 ug/week peginterferon alfa-2a (Group A) or 1.5 ug/kg/week peginterferon alfa-2b (Group B) plus ribavirin. Examination and treatment of patients followed the rules of the national guideline. Patients were not randomized in any way. Group A consisted of 78 patients and Group B included 64 patients. Eight patients dropped out for various reasons (5 from Group A, 3 from Group B). There was no statistically significant difference in the baseline characteristics and the cumulative doses of the drugs between Group A and B, so the treatment results were comparable. RESULTS - Sustained virological response (undetectable HCV ribonucleic acid serum levels 24 weeks after the end of treatment) occurred in 42.5% of patients from Group A and 37.7% from Group B. When focusing on treatment-naive patients only, sustained virological response was found in 48.2% of patients in Group A and 46.7% in Group B. Result of the treatment was better if the patient was treatment-naive, if there was no cirrhosis, and if early virological response at 12 weeks was achieved. CONCLUSION - Patients treated with peginterferon alfa-2a plus ribavirin achieved sustained virological response at a higher rate than those with peginterferon alfa-2b plus ribavirin, however, the difference was not statistically significant.]

AUGUST 15, 2011

Lege Artis Medicinae

NOVEMBER 19, 2006

[TREATMENT APPROACHES OF CHRONIC HEPATITIS B IN HUNGARY]

TORNAI István, NEMESÁNSZKY Elemér

[Today, there are less patients with active chronic hepatitis B requiring treatment than patients with chronic hepatitis C. However, the course and outcome of chronic hepatitis B is usually more severe, therefore, the disease has not lost importance. The most dangerous risks are the development of liver cirrhosis and hepatocellular carcinoma. The disease may present in various forms. Symptom-free carriers only need follow-up and hepatologic care. In the active stages with elevated liver enzymes and high level of viral nucleic acid (either HBeAg negative or positive), however, antiviral treatment is strongly indicated. There are two main forms of treatment. Alfa-interferon-based therapy, which is applied for a defined period of time, has a direct antiviral and immunomodulatory effect, but has several adverse effects. Long-term nucleoside analogue treatment represent the other treatment modality. These drugs are administered orally, have minimal side effects, but after some time resistant mutants may develop. Traditional interferon has recently been replaced by pegylated interferon alfa-2a with much better pharmacokinetic properties. Lamivudine has been in use for the longest time of the nucleoside analogues. Its efficacy is high, but after 3 to 4 years of treatment, resistant mutants appear in about 70% of cases. Of the most recent compounds, adefovir dipivoxil has recently become available in Hungary; it is primarily recommended in cases with lamivudine resistant mutants. There are promising new drugs in the stages of clinical trial; of these, entecavir has already been approved in the United States.]

Lege Artis Medicinae

JUNE 20, 2010

[The treatment of chronic hepatitis C with peginterferon - Peginterferon alfa-2a or alfa-2b?]

TORNAI István

[The main purpose of the treatment of patients with chronic hepatitis C is to achieve a sustained virologic remission (SVR), which means that no hepatitis C virus ribonucleic acid (HCV RNA) is detectable 24 weeks after the cessation of treatment. In patients infected by genotype 1 virus, the chance of achieving SVR by a combination treatment with peginterferon alfa-2a or alfa-2b plus ribavirin is about 40-50%. The pharmacokinetic properties of the two peginterferons are significantly different from each other. A number of clinical trials have been performed in the past eight years to clarify whether this difference influences the clinical efficiency or safety of these drugs. Several prospective, comparative studies have been completed recently. Among these, the American IDEAL study is the largest and most important one, however, the results of numberous smaller studies are also available. More than 3000 patients with genotype 1 HCV were treated in the IDEAL study and no significant difference was found in SVR rates between the peginterferon alfa-2a and alfa-2b treatment arms. However, the doses of ribavirin used in this study raise several questions in this study. In two smaller Italian studies, significantly higher SVR was achieved with peginterferon alfa-2a plus ribavarin treatment. According to a Cochrane metaanalysis, in which reviewed data of 4335 patients from eight randomized trails have been reviewed, treatment with peginterferon alfa-2a is significantly more effective. Besides efficiency, the cost/effectiveness of the two therapies were also compared in a large American study, which also showed that peginterferon alfa-2a treatment was superior to peginterferon alfa-2b treatment.]