Lege Artis Medicinae

[Crucial points in the therapy of hepatitis C]

MAKARA Mihály, HUNYADY Béla

MARCH 20, 2014

Lege Artis Medicinae - 2014;24(03)

[The first generation of direct acting antivirals represented a milestone in the therapy of hepatitis C but other breakthroughs are on the way with imminent authorization of new antiviral drugs and interferon-free combinations. The prices of these new agents necessitate the rational use of limited financial capacities: relatively cheaper interferon-based treatments could be used first for those who can be cured with these combinations, while the most expensive treatments are to be reserved for those with no other options. In the future, interferonfree regimens will likely be used first in those patients who did not respond to firstgeneration interferon-based regimens and in whom interferon therapy is contraindicated. To avoid complications of the disease, currently it is reasonable to treat all eligible patients with advanced fibrosis, particularly those with compensated cirrhosis, with interferon-based treatments. In some instances other medical or social conditions warrant prompt treatment. The triage of treatments is based on the Priority Index in Hungary. Current triple therapies with protease inhibitors are complicated by drug and food interactions as well as by frequent (sometimes severe) side effects. General practitioners and other specialists need to be involved in managing these issues. It is of utmost importance to refer patients to hepatology care before decompensation or development of hepatocellular carcinoma. The key of timely and accurate diagnosis is organized anti-HCV screening in populations at risk and in the age group with the highest prevalence.]

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[Once Again about the Cathedral of the Heart – Paradigms for the Symbolism of the Heart ]

LOZSÁDI Károly, KIRÁLY László

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[Resection of colonic polypoid cavernous hemangioma with help of rubber rings]

ÁCSNÉ Tóth Andrea, LUKOVICH Péter, LAKATOS Péter László, KARDOS Magdolna, ARANY Andrea Szilvia, HARSÁNYI László

[INTRODUCTION - Cavernous hemangioma is a benign, rare disorder, usually localized in the distal part of the gastrointestinal system. CASE REPORT - In a 19-year-old woman treated for Crohn’s disease localized to the colon, a polypoid lesion was found during routine colonoscopy. The lesion appeared to be vascularized, purple in color and could be localized 25 cm above the anal sphincter. MSCT examination confirmed vascularization of the lesion. Considering the high risk for severe bleeding, resection was performed with surgical assistance. At first, two rubber rings were placed around the polypoid lesion. Thereafter 1 ml of epinephrine was injected into the neck of the lesion above the rubber rings, followed by polypectomy with a standard hook. No complications were present during the observation period. Histological examination of the polypoid lesion confirmed it to be cavernous hemangioma. CONCLUSION - On the basis of previous cases and the present case there might be a connection between inflammatory bowel disease and the development of cavernous hemangioma. We have not found any previous reports of a similar application of rubber rings. However, in cases where the risk of bleeding is high, this method is safe and easy to apply.]

Lege Artis Medicinae

[In memoriam dr. András Szalka]

PRINCZ Gyula

Lege Artis Medicinae

[Measurement of therapeutic response during the primary systemic therapy of breast cancer]

TŐKÉS Tímea, SZENTMÁRTONI Gyöngyvér, LENGYEL Zsolt, GYÖRKE Tamás, DANK Magdolna

[Primary systemic therapy (PST), also called as neoadjuvant therapy has a substantial role in the treatment of patients with breast cancer. There is an increasing need among clinicians for the monitoring of therapeutic effectiveness. Beyond simple physical examination, diagnostic imaging tools have the most important role in the measurement of the therapeutic response. Selecting the appropriate imaging method is crucial for the correct evaluation of the therapeutic response and for planning further therapy. In this paper we review breast imaging modalities currently available in Hungary and detail the efficiency of these modalities in the evaluation of the therapeutic response.]

Lege Artis Medicinae

[The 50th Anniversary of the Helsinki Declaration: Commentary to the 2013 Amendment ]

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LAM Extra for General Practicioners

[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. ]

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.]

Lege Artis Medicinae

[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. ]

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.]

Lege Artis Medicinae

[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.]