Lege Artis Medicinae

[THE SAFETY OF TREATMENT WITH PEGYLATED INTERFERON-ALPHA-2A AND RIBAVIRIN IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION, BASED ON HUNGARIAN EXPERIENCE]

WERLING Klára, DALMI Lajos, GERVAIN Judit, HORVÁTH Gábor, NAGY István, NEMESÁNSZKY Elemér, RIBICZEY Pál, TELEGDY László, VARGA Márta, TORNAI István, TULASSAY Zsolt

JULY 14, 2007

Lege Artis Medicinae - 2007;17(06-07)

[INTRODUCTION - Adverse effects of treatment for chronic C virus hepatitis present an important problem both for the patient and the clinician. The reduction of drug doses or the suspension of therapy lessen the likelihood of recovery. PATIENTS, METHODS - Between 2001 and 2004, 66 patients with chronic hepatitis C received 180 μg pegylated interferon-alpha-2a per week and 800-1200 mg ribavirin per day, 6 of whom for 24 weeks and 60 patients for 48 weeks. During treatment, patients were closely followed in order to recognize any adverse effects early. RESULTS - Of the patients treated for 48 weeks, 48.3% developed adverse effects, with changes in the differential in 41.7%, and anaemia, low platelet count, neutropenia in similar rates. Further side effects included cardiac complications, skin symptoms, persisting high fever, autoimmune thyroiditis and liver failure, altogether in 9 cases. Dose reduction or temporary suspension of pegylated interferon-alpha-2a was necessary in 21 cases (31.7%), while complete cessation of this treatment was decided in 7 cases, most of them because of blood count changes. The 1000 to 1200 mg per day ribavirin had to be reduced in 30.8% of patients, while treatment was stopped in 3 cases. Long-term virological remission occurred in 48% of patients who received treatment for 48 weeks, whereas no such result was observed among any of those treated for 24 weeks. CONCLUSION - Adverse effects of variable severity developed in nearly half of the patients with chronic hepatitis C infection who received antiviral treatment for 48 weeks, but treatment had to be stopped in only a small proportion of this group. Early treatment of adverse effects can prevent the need to cease therapy and may improve its efficiency.]

COMMENTS

0 comments

Further articles in this publication

Lege Artis Medicinae

[Lorenzo da Ponte The Librettist of Mozart]

KÖVES Péter

Lege Artis Medicinae

[Coalition pathology]

FRENKL Róbert

Lege Artis Medicinae

[THE USE OF DIURETICS AND ALDOSTERONE RECEPTOR ANTAGONISTS IN CHRONIC HEART FAILURE]

NYOLCZAS Noémi

[Diuretics are an integral part of the management of chronic heart failure. Although there are no large, randomized, placebo-controlled, multicentric studies available to show that loop- and thiazid diuretics improve survival, the efficacy of these drugs in relieving heart failure symptoms and fluid retention is indisputable. The third class of diuretics used in heart failure is aldosterone antagonists, whose beneficial effects on mortality and morbidity were demonstrated in the RALES and EPHESUS trials. In this paper, the effects and side effects of the various diuretics, as well as the indications and recommendations on their use are reviewed. New options in diuretic treatment, including adenosine receptor blockers, vasopressin antagonists, atrial natriuretic peptide analogues and ultrafiltration are also presented.]

Lege Artis Medicinae

[ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN-2 RECEPTOR BLOCKERS IN CHRONIC HEART FAILURE]

ZÁMOLYI Károly

[The rennin-angiotensin system plays a major role in cardiovascular diseases. In the past decade, extensive research investigated the possible clinical benefit of the use of angiotensin-converting enzyme inhibitors in various clinical conditions. Their benefits have been clearly demonstrated in many cardiovascular conditions and agreement as to their potential usefulness has been established in chronic heart failure, asymptomatic left ventricular dysfunction, acute myocardial infarction and hypertension, and in the primary prevention in patients with high risk for cardiovascular events. Numerous randomised clinical trials over the past two decades established their efficacy in reducing adverse outcomes (mortality, hospitalitazion, and physical limitation) in patients with heart failure and left ventricular systolic dysfunction. Based on these results, angiotensin-converting enzyme inhibitors are indicated in all patients with left ventricular systolic dysfunction regardless of etiology, in the absence of intolerance or a contraindication. Despite the recent improvements in the treatment of heart failure, mortality remains high, with approximately 50% patients dead at five years. Although angiotensinconverting enzyme inhibitors decrease mortality, they incompletely suppress angiotenzin-2 when used chronically. Since angiotensin receptor blockers block the biologic effects of angiotenzin-2 more completely than angiotensin-converting enzyme inhibitors, they may be beneficial in the treatment of heart failure. In comparison trials, angiotensin receptor blockers were found to have no benefit over angiotensin-converting enzyme inhibitor therapy. Thus, angiotensin-converting enzyme inhibitors should remain first-line treatment for heart failure. However, in case of intolerance, angiotensin receptor blocker therapy is a reasonable substitute and provides excellent tolerability.]

Lege Artis Medicinae

[THE USE OF BETA RECEPTOR BLOCKERS IN CHRONIC HEART FAILURE]

CZURIGA István

[The beneficial effects of treatment with betablockers in patients with chronic heart failure have been demonstrated in several large, prospective, randomised, placebo-controlled clinical trials. In large trials with mortality as the endpoint, the long-term use of bisoprolol, carvedilol, nevibolol and metoprolol succinate have been associated with a reduction in total mortality, cardiovascular mortality, sudden cardiac death and death due to progression of heart failure in patients of functional classes II-IV. These favorable clinical experiences warrant a recommendation that beta-blockers should be used in all haemodynamically stable heart failure patients with reduced left ventricular systolic function who are on standard treatment, unless contraindicated. In this review, the most important data of clinical trials and practical considerations of therapy with beta-blockers in heart failure are summarized.]

All articles in the issue

Related contents

Lege Artis Medicinae

[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.]

Lege Artis Medicinae

[Successful treatment of chronic hepatitis C infection accompanied by rare but reversible adverse effects]

ERŐSS Bálint Mihály, NEMESÁNSZKY Elemér

[INTRODUCTION - In absence of signs and symptoms characteristic of chronic hepatic disease caused by hepatitis C viral infection, its diagnosis is generally suggested by abnormal liver function tests. If viral serological activity is confirmed, combined antiviral treatment (pegylated interferon plus ribavirin) has to be considered. Antiviral treatment is accompanied by several, usually reversible adverse effects. CASE REPORT - The 62 year-old woman has had waveringly abnormal liver function results for decades. Her anamnesis included transfusions for polytraumatization that resulted in a hepatitis C virus infection. We started treatment with interferon alpha-2a plus ribavirin. At week 4 of therapy, a significant decrease in virulence and at week 12, viral negativity was confirmed, accompanied by a normalization of hepatic function markers. Because of a gradually developing anemia, beginning from month 4, the former optimal dose of ribavirin had to be reduced. At the end of week 42, severe dermatitis with fever, muscle weakness and malaise (Sweetsyndrome) developed, and antiviral therapy had to be discontinued and steroids had to be given. During a short travel abroad, the patient suffered a collaptiform episode caused by extremely high blood glucose (28.0 mmol/l). She received temporarily fractioned insulin and then combined oral antidiabetic treatment. Then, dermatosis symptoms rapidly resolved, glycemic status gradually improved, and could be controlled by low-dose metformin. Liver function tests were normal. At the end of antiretroviral treatment and 6 months later, HCV-RNA by PCR proved negative, meaning that hepatitis C virus has been eradicated successfully. CONCLUSION - Treatment with pegylated interferon alpha-2a plus ribavirin rendered viral replication undetectable at 3 months, which is - together with the normalization of abnormal liver function tests - the strongest predictor of a good outcome. The patient’s exemplary good compliance contributed to successful treatment of hepatitis C and control of these rare but reversible adverse effects.]

Lege Artis Medicinae

[TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS C, USING PEGYLATED INTERFERON ALFA-2A AND RIBAVIRIN - THE FIRST EXPERIENCES IN HUNGARY BASED UPON A MULTICENTRIC, OPEN, PROSPECTIVE STUDY]

TORNAI István, DALMI Lajos, GERVAIN Judit, HORVÁTH Gábor, NAGY István, NEMESÁNSZKY Elemér, RIBICZEY Pál, TELEGDY László, VÁRKONYI Tibor, WERLING Klára

[INTRODUCTION - The treatment of patients with hepatitis C virus infection is one of the most challenging tasks in hepatology nowadays. PATIENTS AND METHODS - Between 2001 and 2004, during a phase III, prospective, multicentric, international open trial 69 patients (35 naive and 34 non-responder or relapser) with chronic hepatitis C were treated, using 180 μg pegylated interferon alfa-2a once weekly and 800-1200 mg daily ribavirin. The inclusion and exclusion criteria were the same as in the normal daily practice. Five patients were treated for 24 weeks and 54 were treated for 48 weeks. The treatment was stopped in 10 additional patients. Sustained virological response was the main end-point of the trial, after 24 weeks of follow-up. RESULTS - The mean age of the patients was 46 years. In all the patients virus genotype 1 could be detected. In none of the patients, treated for 24 weeks, sustained remission could be obtained. In patients, treated for 48 weeks, the overall sustained virological remission was 48%. The outcome of the treatment was better, if the patient was naive to the treatment, could receive the full dosage of drugs and had no liver cirrhosis. The best result could be obtained if the patient was naive to the therapy and younger than age 40. Viral load, however, did not show any effect on viral remission in our patients. At week 24, a negative HCV RNA had a positive predictive value of 68%, while a positive virus test had a negative predictive value of 93%, regarding sustained remission. CONCLUSION - Considering the high rate of genotype 1, pegylated interferon alfa-2a and ribavirin proved to be a very effective therapy in Hungarian chronic hepatitis C patients.]

Lege Artis Medicinae

[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.]

Hypertension and nephrology

[Nebivolol’s unique molecule structure and its effect onthe quality of life]

KERKOVITS Gábor

[The β receptor blockers have very different effects depending on their receptor selectivity, ISA effect, which gives a wide opportunity of beneficial therapeutic choice. Resulting from its unique molecule structure nebivolol has its unique effects. It consists two isomers in 1:1 ratio. D-nebivolol is a highly β1 receptor blocker, while l-nebivolol causes NO release resulting vasodilatation. As a result of this dual effect, nebivolol more strongly reduces the blood pressure. The pressure reducing effect of nebivolol is stronger than 25 mg of atenolol, and is equal with the effect of 100 mg of atenolol. Nebivolol has a significantly higher responders’ rate than bisoprolol, and significantly fewer adverse effect. Comparing to losartan nebivolol produces significantly higher reduction in systolic and in diastolic blood pressure as well. Nebivolol has beneficial haemodynamic effects. It raises the stroke volume by 20.6 percent, the cardias output by 7.1 per cent, the ejection fraction by 7.8 per cent while reduces the peripheral resistance by 13.2 per cent. Both at rest and during exercise nebivolol cases significantly higher reduction in pulmonary wedge pressure than atenolol. Nebivolol has a better profile of adverse effects. The following adverse effects were observed: fatigue in 1.3 per cent, cold extremities in 0.8 per cent, impotence in 0.08 per cent and dyspnea in 0.05 per cent. It has also a beneficial effect on erectile dysfunction. It cases a significant elevation in erectile dysfunction score from 17.22 to 22.09. The number of sexual activity also raised from 3.41 to 6.38 during nebivolol treatment. The prevalence of erectile dysfunction is also significantly lower as compared to any β receptor blocker. Nebivolol has a synergic effect on PDE5 blockers, raises the cGMP concentration in the erectile tissue. There is also a significant difference among the β receptor blockers in the reduction of exercise tolerance. The nonselective β receptor blocker cause 40 per cent, carvedilol 35 per cent, the β1 selective receptor blocker 25 per cent while nebivolol 6 per cent reduction in the duration time.]