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Öğe Awareness of Hepatitis B virus reactivation among physicians administering immunosuppressive treatment and related clinical practices(AVES, 2019) Korkmaz, Pınar; Demirtürk, Neşe; Aydın, Gule; Çeken, Sabahat; Aygen, Bilgehan; Toka, Onur; Gündoğdu, Kıymet; Çelikbaş, Aysel Kocagül; İnan, Dilara; Kuruüzüm, Ziya; Kutsoylu, Oya Özlem Eren; Batırel, Ayşe; Sırmatel, Fatma; Ersöz, Gülden; Hakyemez, İsmail Necati; Aşçı, Zerrin; Yeşilbağ, Zuhal; Sönmezer, Meliha Çağla; Tülek, Necla; Örmen, Bahar; Karadağ, Fatma Yılmaz; Yörük, Gülşen; Türker, Nesrin; Özkaya, Hacer Deniz; Kalkan, İrem Akdemir; Süer, Hüseyin Kaya; Tekin, Süda; Saltoğlu, Neşe; Şener, Alper; Yenilmez, Ercan; Çetinkaya, Rıza Aytaç; Özel, Selcan Arslan; Ayaz, Celal; Karagöz, Ergenekon; Aydın, Mehtap; Acar, Ali; Arslan, Eyüp; Ceylan, Mehmet Reşat; Demir, Nazlım Aktuğ; Çaylak, Selmin Dirgen; Günal, Özgür; Solay, Aslı Haykır; Öztürk, Sinan; Ural, Onur; Sümer, Şua; Kadanalı, Ayten; Altıparmak, Vuslat Ecem Güneş; Akhan, Sıla; Sayan, Murat; Köse, ŞükranObjective: This study aimed to evaluate the awareness and knowledge levels of all physicians administering immunosuppressive treatment concerning hepatitis B virus (HBV) reactivation, and draw attention to the importance of the subject through evaluation. Methods: The study was carried out by infectious diseases and clinical microbiology specialists in 37 health centers, and it was performed in Turkey between January and March 2017. All specialists providing a written consent and working in the departments of Medical Oncology, Hematology, Dermatology and Venereology, Physical Medicine and Rehabilitation, and Rheumatology of each study center were included in the study. Results: A total of 430 physicians participated in the study. Their mean age was 39.87 +/- 7.42 years, and 47.9% of them were males. During their career, 39.3% of these physicians had encountered patients developing HBV reactivation while receiving immunosuppressive treatment. The rate of encountering patients who died due to HBV reactivation was 6.5%. 97% of physicians who participated, considered the risk of HBV reactivation to be important. 70.2% of physicians stated that guidelines related to HBV reactivation and antiviral treatment for these patients were discussed in the congresses they participated, regarding their specialties. The rate of performing hepatitis screening among physicians whose patients developed HBV reactivation was statistically significantly higher than those physicians who had no patients with HBV reactivation (p<0.05). Physicians who used the guidelines related to HBV reactivation in their specialties performed screening for the HBV infection much more often than physicians who did not use the guidelines (p=0.002). Conclusions: According to the results obtained in our study, the rates of conducting screening and awareness of HBV reactivation among physicians administering immunosuppressive treatment were higher compared with similar studies; however, their awareness that HBV DNA and anti-HBc should be utilized much more frequently among the serological tests they use for screening of HBV infection, should be increased.Öğe First Case of Hepatitis B Virus Genotype H Infection in Turkey(ANKARA MICROBIOLOGY SOC, 2013) Ural, Onur; Sayan, Murat; Akhan, Sıla; Sümer, Sua; Şimşek, FundaClinical studies reported from Turkey indicate that hepatitis B virus (HBV) genotype D is more prevalent than other genotypes. Epidemiological and clinical information on genotype H infection is currently limited. Genotype H infection is most likely due to its regional (Central and South America) prevalence throughout the world. The aim of this report is to present the first HBV genotype H infection in a chronic hepatitis B patient in Turkey. Laboratory findings of a 42 years old male patient admitted to our hospital revealed HBsAg (+), anti-HBs (-), HBeAg (-), anti-HBe (+), anti-HBc IgM (-), anti-HBc IgG (+), anti-HAV IgG (+), HBV-DNA: 5.689.776 IU/ml and high liver enzymes (ALT: 223 U/L, AST: 121 U/L). History of the patient indicated no risk factor (intravenous drug use, blood transfusion, suspicious sexual contact) related to HBV transmission. Since liver ultrasonography showed multiple hemangiomas, biopsy was performed and histologic activity index was found as 6/18 and fibrosis as 2/6, according to modified Knodell score system. HBV DNA isolated from the serum sample of the patient was amplified by polymerase chain reaction and polynnerase gene segment of HBV was directly sequenced. UPGMA method was used for phylogenetic analysis, and the genotype of the virus was identified accordingly. The nucleotide sequence was compared to those from the international DNA data bank (GenBank). The genotyping of the patient revealed that the isolated HBV was genotype H. Treatment with tenofovir disoproxil fumarate was initiated and the patient responded to the treatment. This finding suggested that other HBV genotypes, except the predominant genotype D may also be in circulation in Turkey. In conclusion, detection of epidemiologic and molecular characteristics of HBV genotype H which is related to chronic hepatitis, seems to be necessary in order to better understand its circulation and progression around the world.Öğe First case of hepatitis B virus genotype H Infection in Turkey [Türkiye'de Ilk Kez Saptanan Hepatit B Virus Genotip H Enfeksiyonu Olgusu](2013) Ural, Onur; Sayan, Murat; Akhan, Sıla; Sümer, Şua; Şimşek, FundaClinical studies reported from Turkey indicate that hepatitis B virus (HBV) genotype D is more prevalent than other genotypes. Epidemiological and clinical information on genotype H infection is currently limited. Genotype H infection is most likely due to its regional (Central and South America) prevalence throughout the world. The aim of this report is to present the first HBV genotype H infection in a chronic hepatitis B patient in Turkey. Laboratory findings of a 42 years old male patient admitted to our hospital revealed HBsAg (+), anti-HBs (-), HBeAg (-), anti-HBe (+), anti-HBc IgM (-), anti-HBc IgC (+), anti-HAV IgG (+), HBV-DNA: 5.689.776 IU/ml and high liver enzymes (ALT: 223 U/L, AST: 121 U/L). History of the patient indicated no risk factor (intravenous drug use, blood transfusion, suspicious sexual contact) related to HBV transmission. Since liver ultrasonography showed multiple hemangiomas, biopsy was performed and histologic activity index was found as 6/18 and fibrosis as 2/6, according to modified Knodell score system. HBV DNA isolated from the serum sample of the patient was amplified by polymerase chain reaction and polymerase gene segment of HBV was directly sequenced. UPGMA method was used for phylogenetic analysis, and the genotype of the virus was identified accordingly. The nucleotide sequence was compared to those from the international DNA data bank (GenBank). The genotyping of the patient revealed that the isolated HBV was genotype H. Treatment with tenofovir disoproxil fumarate was initiated and the patient responded to the treatment. This finding suggested that other HBV genotypes, except the predominant genotype D may also be in circulation in Turkey. In conclusion, detection of epidemiologic and molecular characteristics of HBV genotype H which is related to chronic hepatitis, seems to be necessary in order to better understand its circulation and progression around the world.Öğe HCV NS3 inhibitors resistance mutations in the telaprevir started Turkish patients with chronic HCV(ELSEVIER SCI LTD, 2014) Sayan, Murat; Akhan, Sıla; Aygen, Bilgehan; Koruk, Süda Tekin; Mıstık, Reşit; Demirturk, N.; Ural, Onur[Abstract not Available]Öğe Molecular Characterization of Drug Resistance in Hepatitis B Viruses Isolated from Patients with Chronical Infection in Turkey(KOWSAR PUBL, 2018) Asan, Ali; Sayan, Murat; Akhan, Sıla; Koruk, Suda Tekin; Aygen, Bilgehan; Sırmatel, Fatma; Eraksoy, HalukBackground: Hepatitis B virus (HBV) has a high mutation rate due to its unusual replication strategy leading to the production of a large number of virions with single and double mutations. The mutations, in turn, are associated with the development of drug resistance to nucleos(t)ide analogs (NUCs) in patients before and during NUCs therapy. Objectives: The current study aimed at investigating the molecular characterization of HBV in Turkish patients with chronic hepatitis B (CHB) infection. Methods: Polymerase chain reaction (PCR) amplification and direct sequencing procedures were used to analyze mutations. The detected drug resistance mutations were divided into the nucleos(t) ide analogs primary, partial, and compensatory resistance groups. The amino acid substitutions of hepatitis B surface antigen (HBsAg) were categorized into antiviral drug - associated potential vaccine-escape mutations (ADAPVEMs) and typical HBsAg amino acid substitutions, which included hepatitis B hyperimmunoglobulin (HBIg) - selected escape mutation, vaccine escape mutation, hepatitis B misdiagnosis, and immune - selected amino acid substitutions. Results: The number of patients included in the study was 528 out of which 271 (51.3%) were treatment - naive and 351 (66.3%) were hepatitis B e antigen (HBeAg) - negative. Moreover, 325 (61.6%) were males with a mean age of 38 years (range: 18 - 69). Primary, partial, and compensatory resistance to NUCs was reported in 174 (32.9%) patients. Six different ADAPVEM motifs were determined in both treatment - naive and treatment - experienced patients, namely, sF161L/rtI169X, sE164D/rtV173L, sL172L/rtA181T, sL173F/rtA181V, sS195M/rtM204V, and sS196L/rtM204I. The prevalence of ADAPVEMs and typical HBsAg escape mutations was 5.3% (n = 28) and 34.8% (n = 184), respectively. Conclusions: The analysis of drug resistance should constitute a fundamental part of the follow - up period of patients with CHB undergone treatment with NUCs. The surveillance of development of drug resistance mutations, while receiving treatment for hepatitis B is of paramount importance to monitor and control the emerging resistance.Öğe Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C(ELSEVIER SCI LTD, 2016) Altunok, Elif Sargın; Sayan, Murat; Akhan, Sıla; Aygen, Bilgehan; Yıldız, Orhan; Koruk, Suda Tekin; Mistik, ReşitBackground: Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals. Materials and methods: 178 antiviral-naive patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed. Results: In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation. Conclusion: We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.Öğe Retreatment of chronic hepatitis c infection with telaprevir: Preliminary results in Turkey(GALENOS YAYINCILIK, 2015) Aygen, Bilgehan; Yıldız, Orhan; Akhan, Sıla; Çelen, Mustafa Kemal; Ural, Onur; Koruk, Süda Tekin; Köse, Şukran; Korkmaz, Fatime; Kuruüzüm, Ziya; Tuna, Nazan; Taheri, Serpil; Sayan, Murat; Demir, Nazlım Aktuğ; Sümer, Şua; Altınok, Elif SargınBackground: The use of pegylated interferon alpha and ribavirin (PegIFN/RBV) for the retreatment of chronic hepatitis C virus (HCV) infection without a sustained virological response (SVR) prior to PegIFN/RBV treatment has resulted in low success rates. Aims: To investigate the efficacy and safety of telaprevir (TVR) in combination with PegIFN/RBV in patients infected with HCV genotypes 1 and 4 who were previously treated with PegIFN/RBV and failed to achieve SVR. Study Design: Multi-center, retrospective, cross-sectional study. Methods: The study included 111 patients: 80 prior relapsers, 25 prior null responders, and six prior partial responders to PegIFN/RBV treatment. The patients were given TVR/PegIFN/RBV for 12 weeks, followed by a 12-week PegIFN/RBV treatment; virological response results were assessed at weeks 4, 12, and 24. Treatment was discontinued in patients with HCV RNA >1000 IU/mL at week 4 or with negative RNA results at week 4 but >1000 IU/mL at week 12. Rapid virological response (RVR), early virological response (EVR), extended rapid virological response (eRVR), and virological response at 24th week of treatment were evaluated. The side effects of combination therapy and the rates of treatment discontinuation were investigated. Results: The mean age of the patients was 56.02 +/- 9.96 years and 45.9% were male. Ninety-one percent of the patients were infected with viral genotype 1, 69.6% with the interleukin (IL) 28B genotype CT and 20.2% were cirrhotic. The RVR rate was 86.3% in prior relapsers, 56% in prior null responders, and 50% in prior partial responders (p=0.002). EVR rates in those groups were 91.3%, 56%, and 83.3%, respectively (p<0.001). eRVR rates were 83.8% in prior relapsers, 48% in prior null responders, and 50% in prior partial responders (<0.001). The virological response at the 24th week of treatment was found to be the highest in prior relapsers (88.8%); it was 56% in prior null responders and 66.7% in prior partial responders (p<0.001). Common side effects were fatigue, headache, anorexia, malaise, anemia, pruritus, dry skin, rash, dyspepsia, nausea, pyrexia, stomachache, and anorectal discomfort. All treatments were discontinued due to side effects in 9.9% of patients. Conclusion: High virological response rates were obtained with TVR/PegIFN/RBV treatment. Although side effects were frequently observed, the discontinuation rate of combination therapy was low.Öğe Türkiye’de ilk kez saptanan hepatit B virus genotip H enfeksiyonu olgusu(2013) Ural, Onur; Sayan, Murat; Akhan, Sıla; Sümer, Şua; Şimşek, FundaGünümüzdeki klinik çalışmalar Türkiye’de hepatit B virus (HBV) genotip D’nin diğer genotiplere göre daha yaygın olduğunu göstermektedir. Genotip H enfeksiyonu ile ilgili epidemiyolojik ve klinik bilgiler halen sınırlıdır. Genotip H enfeksiyonu genellikle dünyada bölgesel (Orta ve Güney Amerika) prevalans gösterir. Bu raporda, Türkiye’de kronik hepatit B’li bir hastada ilk kez tanımlanan HBV genotip H enfeksiyonu olgusunun sunulması amaçlanmıştır. Kliniğimize başvuran 42 yaşındaki erkek hastanın laboratuvar bulguları; HBsAg (), anti-HBs (-), HBeAg (-), anti-HBe (), anti-HBc IgM (-), anti-HBc IgG (), anti- HAV IgG (), HBV-DNA: 5.689.776 IU/ml ve karaciğer enzimleri yüksek (ALT: 223 U/L, AST: 121 U/L) olarak belirlenmiştir. Hastanın öyküsünde HBV bulaşını açıklayacak intravenöz ilaç kullanımı, kan transfüzyonu, yurt dışı seyahat ve şüpheli cinsel ilişki tespit edilememiştir. Karaciğer ultrasonografisinde multipl hemanjiyomlar izlenen hastaya ultrasonografi eşliğinde karaciğer biyopsisi yapılmış ve modifiye Knodell skorlama sistemine göre histolojik aktivite indeksi 6/18 ve fibrozis 2/6 olarak belirlenmiştir. Hastanın serum örneğinden izole edilen HBV DNA’sı polimeraz zincir reaksiyonu ile çoğaltılmış ve HBV polimeraz gen bölgesi direkt dizileme yöntemiyle dizilenmiştir. Virusun genotipi UPGMA yöntemi ile yapılan filogenetik analiz sonucu belirlenmiştir. HBV izolatının nükleotid dizileri, uluslararası DNA veri bankası (GenBank) ile karşılaştırılmış ve suşun genotiplendirme sonucu genotip H olarak belirlenmiştir. Hastaya tenofovir disoproksil fumarat tedavisi başlanmış ve tedaviye yanıtı iyi olan hasta takibe alınmıştır. Bu bulgu, Türkiye’de yaygın olan HBV genotip D dışında diğer genotiplerin de bulunduğunu vurgulamaktadır. Kronik hepatite neden olan HBV genotip H’nin epidemiyolojik ve moleküler özelliklerini belirlemek dünyadaki yayılımının anlaşılmasına imkan tanıması açısından önemli olabilir.
