Lege Artis Medicinae

[NEW MODALITIES IN THE TREATMENT OF CHRONIC VIRAL HEPATITIS C: PEGYLATED INTERFERONS]

GERVAIN Judit, NEMESÁNSZKY Elemér, CSEPREGI Antal

OCTOBER 20, 2003

Lege Artis Medicinae - 2003;13(07)

[Interferon-α proved to be the most effective therapy of chronic hepatitis C. Its combination with ribavirin enhances the antiviral activity and this modality has become the therapeutic standard recommended worldwide during the past few years. Metaanalysis of the international studies revealed that only 12-19% of the patients became virus-free following a 48-week long course of α interferon monotherapy. The combination treatment with ribavirin for 48 weeks increased the proportion of sustained responders to 35-45%. The introduction of pegylated interferons resulted in significantly higher response rates. The new therapeutic possibilities are due to the modified pharmacokinetic characteristics of the drug by changing the size and the structure of the molecules. Multicentre studies investigating the clinical effectiveness of the 40 kD sized pegylated interferon α-2a as well as the 12 kD sized pegylated interferon α-2b in combination with ribavirin reported 56% and 54% response rate, respectively. However, there is significant heterogeneity in the results according to the type of drug administered and to the genotype of the hepatitis C virus, as well as in the basal viral level and the stage of hepatic fibrosis, respectively. The message and the conclusion of the viral kinetic studies are worth remembering: if the result of the HCV nucleic acid test is still positive at week 12 or 24, therapy should be ceased due to the patient non-responder status. Since pegylated interferons are also available in Hungary the authors felt useful to give an overview of the current knowledge, summarizing the results of the relevant studies and provide a suggested state-of-the-art therapeutic protocol based on international consensus.]

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[AGRESSIVE STRATEGIES IN THE TREATMENT OF INFECTIVE ENDOCARDITIS]

LENGYEL Mária

[Without treatment, infective endocarditis (IE) is a fatal disease and in spite of contemporary diagnostic and therapeutic tools its prognosis is still poor. The most important first step is the early rise of clinical suspicion which should be confirmed by the new clinical criteria. Echocardiography is a major criterium: transesophageal echocardiography (TEE) is superior to transthoracic echocardiography (TTE) both in the diagnosis and in the detection of complications of infective endocarditis. Complications can be valvular (embolism, valvular dysfunction) or perivalvular (abscess, pseudoaneurysm formation) with hemodynamic consequences. TEE is recommended as the first line diagnostic technique (mostly in prosthetic valve infective endocarditis) or as a second study following negative TTE or positive TTE with high clinical risk factors or to define embolic risk. In addition to classical surgical indications, early ”preventive” indications are emphasized which can decrease the still high operative mortality. Improvement of outcome in infective endocarditis can only be expected with agressive management meaning early suspicion, early TEE and early operation.]

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[Antibiotic Treatment of Community-Acquired Respiratory Infections: Strategies Intended to Ensure Optimal Outcome and to Minimize the Development of Resistance]

P. Ball, F. Baquero, O. Cars, T. File, J. Garau, K. Klugman, E. Low, E. Rubinstein, R. Wise

Lege Artis Medicinae

[OBESITY: THE EPIDEMIC OF OUR TIMES]

SIDÓ Zoltán

[The influence of changes in lifestyle on treatment and prevention of cardiovascular diseases are the objects of surveys in many places of the world. On the basis of clinical trials one can underline that the Mediterranean diet, with enhanced physical activity, changing lifestyle, cessation of smoking, reducing alcohol intake, maintaining normal weight can decrease dyslipidaemia, atherosclerosis and prevent cardiovascular diseases.]

Lege Artis Medicinae

[THE USE OF EARLY BIOMARKERS IN PREVENTION. - THE MARKERS OF THE EXPOSITION, EARLY EFFECT AND INDIVIDUAL SENSITIVITY]

EMBER István, KISS István, SÁNDOR János, FEHÉR Katalin, NÉMETH Katalin, LUKÁCS Péter

[The molecular and predictive epidemiology plays more and more important role in the prevention of cancer. With the help of early biomarkers, high risk population could be identified for primary preventive intervention modalities. It uses both molecular biological methods and elements of risk assessment plus a testing system based on animal experiments. Its specificity is not high enough to establish the diagnosis but it can be used to monitor the disease and to follow the effectivity of the therapy (e.g. "minimal residual disease") and the preventive interventions. It is also suitable for risk assessment with the markers of individual susceptibility. As to everyday practice there are many problems because of limited therapeutic possibilities, but we hope that the molecular and predictive epidemiology becomes an important part of medicine in the near future.]

Lege Artis Medicinae

[MOTOR VEHICLE ACCIDENT WITH COMPLETE LOSS OF CONSCIOUSNESS DUE TO VASOVAGAL SYNCOPE]

VARGA Emma, WÓRUM Ferenc, SZABÓ Zoltán, VARGA Mihály, BARTA Kitti, LŐRINCZ István

[INTRODUCTION - Vasovagal syncope is one of the most common causes of complete or partial loss of consciousness, thus it might cause harm to the patients themselves or innocent bystanders while driving a car. CASE REPORT - In our case report we introduce the case of a 60-year-old man who was admitted to hospital after a serious motor vehicle accident due to loss of consciousness. We demonstrate the process and results of complete cardiologic and neurological assessment. Our case report illustrates the importance of recognition of patients with a high risk for incapacitating symptoms due to vasodepressor type vaso vagal syncope and the use of head-up tilt-table test to determine the diagnosis and to guide combined management. CONCLUSION - As transient loss of consciousness during driving may cause potentially fatal accident, it has to be taken into consideration during decision making for issue of driving license in patients with vaso vagal syncope.]

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[AIMS - In this trial we have analyzed the data of cirrhotic naiv as well as treatment experienced patients with chronic hepatitis C, treated in the East-Hungarian hepatology centers, between 2004 and 2010, because in the era of triple combinations, we mostly treat cirrhotic patients. PATIENTS AND METHODS - We have found 272 patients and in most of them the cirrhosis was proven by biopsy. These patients were treated with pegylated interferon (pegIFN) alpha plus ribavirin in combination, 172 were naiv and 100 patients were treatment experienced. Data were collected retrospectively and the pretreatment parameters like age, sex, body weight, transaminase level, genotype, initial viral load, comorbidities, and proportion of first and repeated treatments have been analyzed. We have investigated the influence of the initial parameters as well as the type of pegIFN on the complete early virologic response (cEVR) and on the sustained virological response (SVR). RESULTS - The cEVR was 27% (74/272) and the SVR was 21% (58/272) in the whole patient population. With pegIFN a-2a, 32% (45/141) cEVR and 28% (39/141) SVR, whereas with pegIFN a-2b 22% (29/131) cEVR and 15% (19/131) SVR were achieved. Among this patient population the largest subgroup was the naiv patients with high viral load (HVL). In this subgroup the SVR was 21% (28/132). However, with pegIFN a-2a SVR was 29% (21/73), whereas with pegIFN a-2b SVR was only 12% (7/59). The above differences found between the two pegIFNs proved to be statistically significant. Age <40 years, low viral load (LVL) and treatment with pegIFN a-2a proved to be independent positive factors influencing cEVR as well as SVR, by multiple logistic regression analysis. CONCLUSION - According to these results, cirrhotic patients with hepatitis C may benefit if pegIFN a-2a is used as backbone therapy in triple combinations. ]

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[The medical impact of hepatitis C (HCV) is significant worldwide. The main consequences are chronic hepatic injury, cirrhosis, and hepatocellular carcinoma formation. The estimated global prevalence is 3% with 180 million infected people worldwide. The prevalence <1% in Hungary. The prevalence increased between 1990 and 2005 in East Asia, Western Europe, and West sub-Saharan Africa. There is characteristic geographical distribution of the main HCV genotypes. The mode of transmission can not be identified of 40% of cases. The most frequent transmission is the intravénás drug injection in the developed countries, and unsafe health procedures in developing countries. The sensitive, nucleic acid amplification testing, identification of high-risk groups, development of vaccination would help the HCV prevalence in the future. ]

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[Vision or reality? Can Hungary become hepatitis C virus free by 2030?]

GERVAIN Judit

[According to the WHO, there are 71 million people worldwide and 3 million people in the EU who are infected with hepatitis C virus. Most of these infections, however, remain undiagnosed and only 6-7% of them received antiviral therapy. In Hun-gary, there are an estimated 50.000 infections, out of these 20.000 are identified, the remaining 30.000 infections are outside the reach of the health care sector. Early diagnosis and therapy are of utmost importance as late diagnosis leads to se-vere liver insufficiency, hepatocellular carcinoma and multiple other extrahepatic organ impacts. In Hungary, second generation direct acting enzyme inhibitor antiviral medications with a recovery rate of almost 100% are available since 2015. Since 2018, all patients are treated with this type of therapy. Nevertheless, there are several remaining professional, organisational and health policy issues to solve. Firstly, Hungary should join the EU’s HCV elimination programme which aims to eradicate hepatitis C virus from Europe by 2030. Secondly, the frequency and efficiency of national screening should be increased. Furthermore, better information of the general population, inclusion of general practitioners and civil organisations, and introduction of the compulsory screening of high risk groups and health care professionals would be necessary. This review summarises the evolution of hepatitis C virus diagnostics and therapy over the past three decades, current best practice and the still outstanding tasks. ]

Lege Artis Medicinae

[“War of numbers” and the facts about pegylated interferon based treatment of chronic hepatitis C]

MAKARA Mihály, HUNYADY Béla

[Further to the traditional pegylated interferon and ribavirin products, used since 2001 in the treatment of chronic hepatitis C, two new direct antiviral protease inhibitors were licensed in 2011: telaprevir and boceprevir. Added to the traditional dual combination either of these drugs increase significantly the rate of sustained viral response. Discussions over the relative efficacy of two different bands of interferons with different pharmacokinetic properties as well as of the different protease inhibitors are arising regularly. After critical review of the relevant literature the authors did not identify any clinically meaningful differences in efficacy of the two pegylated interferons (α 2a or α 2b) neither in dual nor in triple combination therapies. There has been no convincing evidence found to support superiority of one protease inhibitor over the other, either: Generally both drugs can be recommended for patients previously or actually not responding to dual therapy. However, there is a tendency towards a potential difference between the relapse rates after treatments with the two pegylated interferons in dual therapy, attributable potentially to the difference of their pharmacokinetic profiles. In special cases the choice of protease inhibitors can be influenced by cost-effectiveness and side effect profile.]

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[Treatment of hepatits C virus infected patients with cirrhosis in real-life conditions in Hungary with the two pegylated interferons]

[AIMS - In this trial we have analyzed the data of cirrhotic naiv as well as treatment experienced patients with chronic hepatitis C, treated in the East-Hungarian hepatology centers, between 2004 and 2010, because in the era of triple combinations, we mostly treat cirrhotic patients. PATIENTS AND METHODS - We have found 272 patients and in most of them the cirrhosis was proven by biopsy. These patients were treated with pegylated interferon (pegIFN) alpha plus ribavirin in combination, 172 were naiv and 100 patients were treatment experienced. Data were collected retrospectively and the pretreatment parameters like age, sex, body weight, transaminase level, genotype, initial viral load, comorbidities, and proportion of first and repeated treatments have been analyzed. We have investigated the influence of the initial parameters as well as the type of pegIFN on the complete early virologic response (cEVR) and on the sustained virological response (SVR). RESULTS - The cEVR was 27% (74/272) and the SVR was 21% (58/272) in the whole patient population. With pegIFN a-2a, 32% (45/141) cEVR and 28% (39/141) SVR, whereas with pegIFN a-2b 22% (29/131) cEVR and 15% (19/131) SVR were achieved. Among this patient population the largest subgroup was the naiv patients with high viral load (HVL). In this subgroup the SVR was 21% (28/132). However, with pegIFN a-2a SVR was 29% (21/73), whereas with pegIFN a-2b SVR was only 12% (7/59). The above differences found between the two pegIFNs proved to be statistically significant. Age <40 years, low viral load (LVL) and treatment with pegIFN a-2a proved to be independent positive factors influencing cEVR as well as SVR, by multiple logistic regression analysis. CONCLUSION - According to these results, cirrhotic patients with hepatitis C may benefit if pegIFN a-2a is used as backbone therapy in triple combinations. ]