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

NOVEMBER 20, 2005

Lege Artis Medicinae - 2005;15(11)

[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.]

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[MANAGEMENT OF LIFE-THREATENING ENDOSCOPIC THERAPY-RESISTENT OESOPHAGUS VARICEAL BLEEDING]

ERŐSS Bálint Mihály, SZÉKELY György, SIKET Ferenc, LÁZÁR István

[INTRODUCTION - Liver cirrhosis has two serious consequences: hepatic failure and portal hypertension. Portal hypertension has two important clinical appearances: variceal bleeding and therapy resistant ascites. Variceal bleeding can be recurrent and resistant to endoscopic treatment. These complications can be prevented by implantation of Transjugular Intrahepatic Portosystemic Shunt (TIPS). CLINICAL CASE - A 59 year old male with cirrhosis due to hepatitis C, was hospitalized in our department in April 2004 with variceal bleeding. We tried to control the bleeding twice by band ligation, once by sclerotherapy and with the use of Sengstaken-Blakemore tube, but bleeding continued for three weeks despite the endoscopic treatment. The patient needed intensive care therapy and was treated with more than forty units of packed red cells and plasma. At that point we decided to implant a TIPS, which was carried out succesfully. After TIPS implantation no rebleeding occured and the shunt had good patency. Moderate hepatic encephalopathy was observed, which is a well known phenomenon, but it could be treated with pharmacologic therapy. CONCLUSIONS - In case of portal hypertension TIPS implantation can prevent from variceal rebleedings and may caus significant improvement in the quality of life.]

Lege Artis Medicinae

[SCREENING OF PSYCHIATRIC SIDE EFFECT OF INTERFERON THERAPY WITH QUESTIONNAIRE]

GAZDAG Gábor, SZABÓ Zsuzsa

[INTRODUCTION - Interferon therapy is an effective treatment of several oncological, hematological and viral diseases but it can precipitate serious side effects too. Among others the most frequent are the psychiatric symptoms. These symptoms are also the most frequent reasons of non-compliance and early cessation of treatment which can be avoided with rapid recognition and adequate treatment. Therefore, the early recognition of the psychiatric symptoms is of high importance. METHODS AND RESULTS - Authors report a self-administered questionnaire developed to screen the most frequent psychiatric symptoms precipitated by interferon treatment. They also present the evaluation method for the questionnaire, which makes the evaluation of the data easier for non-psychiatrist doctors as well. Between September 2004 and July 2005 all interferon treated patients who also had psychiatric consultation filled in the questionnaire. The number of patients was 26. Authors set up a decision-making algorhythm for the evaluation, so the non-psychiatrist doctors were able to judge whether a psychiatric consultation was needed as well as its urgency. With the data of 26 interferon treated patients who all went through a psychiatric consultation during a 10 months period, authors discuss their first experience, going into details in the three false positive and the two false negative cases. CONCLUSION - Authors founded the questionnaire helpful in the clinical practice and recommended the use for doctors working in general practice. They also suggest to carry it further research with more patients to strengthen the results.]

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WERLING Klára

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[MEDICAL TREATMENT OF LOWER URINARY TRACT SYMPTOMS DUE TO BENIGN PROSTATIC HYPERPLASIA - RISK FACTORS AND SIDE-EFFECTS]

KARSZA Attila

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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

[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.]

Lege Artis Medicinae

[RETREATMENT OF CHRONIC HEPATITIS C IN PREVIOUS NONRESPONDERS]

TORNAI István

[Only approximately 50% of patients with chronic hepatitis C virus (HCV) genotype 1, the prevailing genotype in Hungary, show a sustained virologic response (SVR) when treated with the combination of peginterferon alfa and ribavirin. The number of patients who do not respond to this treatment is continuously increasing. The appearance of increasingly efficient treatment modalities was seen in the past 15 years, but now no new drugs are expected for a few years. There is a growing need for retreatment to prevent possible progression of the disease. The best candidates for retreatment are identified based on the data of the previous treatment; the dosage of the drugs used, dose reductions and their causes, the kinetics of the virologic response, the patient’s compliance, and every correctable and non-correctable factor should be carefully analysed. When the previous treatment with peginterferon and ribavirin failed to induce response, retreatment is only recommended if correctable factors can be identified. Repeated treatment may result in sustained virologic response usually if a longer duration and/or higher dose of ribavirin is applied. Since the best possible outcome of retreatment is sustained virologic response in 10 to 30% of patients, which is significantly lower than the results achieved in naive patients, every effort has to be made to increase the efficacy of the first treatment. For patients in whom no sustained virologic response can be achieved, a maintenance therapy with low dose interferon may be considered, although its benefit is yet to be proven. New small molecules are under development, which may bring further hope for nonresponders to current standard therapy.]

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

[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

[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.]