Çukurova Üniversitesi Tıp Fakültesi Hastanesi’nde Hepatit C virus genotiplerinin ve HCV enfeksiyonu bulaş yollarının belirlenmesi

Öz

Amaç: HCV’nin neden olduğu kronik karaciğer hastalığının tedavi ve takibinde genotiplerin belirlenmesi kritik öneme sahiptir. Bu çalışmada, HCV genotiplemesi için Çukurova Üniversitesi Tıp Fakültesi Hastanesi Merkez Laboratuvarına gönderilen kan örneklerinde elde edilen sonuçlar ve hasta dosya bilgileri kayıtlardan incelenerek bölgemizdeki HCV genotiplerinin dağılımı ve bulaş yolları belirlenmiştir. Yöntem: Ocak 2015-Ağustos 2016 tarihleri arasında Çukurova Üniversitesi Tıp Fakültesi Hastanesi Merkez Laboratuvarında, HCV-RNA COBAS AmpliPrep/COBAS Taq Man HCV real-time PCR, Roche Diagnostics, Germany pozitif saptanan hastalardan HCV genotip tayini yapılan 119 hastaya ait sonuçlar kayıtlardan incelendi. Hastaların demografik verileri, hastane elektronik bilgi sisteminden ve hasta dosyalarından elde edildi. Genotipleme için genotip 1a, 1b, 2, 3, 4, 5a ve 6’yı gerçek zamanlı PCR yöntemi ile saptayan “Sacace HCV Genotype Plus Real TM” kiti kullanıldı. Bulgular: 119 hastadan oluşan çalışma grubunda %71,4 genotip 1 %12,6 genotip 1a, %58,8 genotip 1b , %16,8 genotip 3, %7,6 genotip 2, %3,4 genotip 4 enfeksiyonu saptandı. Suriyeli kadın hastada,Adana’da daha önce bildirilmemiş olan genotip 5a %0,8 enfeksiyonuna rastlandı. Genotip 3 enfeksiyonu saptanan hastaların %45,0’inde ve genotip 2 enfeksiyonu saptanan hastaların %33,3’ünde damar içi uyuşturucu DIU kullanımı söz konusu olup çoğunluğunu genç erkek %83,3 hastalar oluşturmakta idi. Ayrıca psikiyatrik hastalığı ve intihar girişimi öyküsü olan ve DIU kullanımı açısından riskli dört hastada da genotip 3 enfeksiyonu tespit edildi. Tamamına yakını tıbbi uygulamalarla ilişkili olan Suriyeli 11 hastadaki HCV genotiplerinin dağılımı sırasıyla %63,6 genotip 1a, %27,3 genotip 4 ve %9,1 genotip 5a olarak belirlendi. Sonuç: Türkiye’de HCV enfeksiyonunun epidemiyolojisi son yıllarda değişiklik göstermektedir. Her ne kadar ülkemizde tıbbi uygulamalar temel risk faktörü ve genotip 1b enfeksiyonu prevalansı %85-90’larda olsa da son yıllarda genotip 1b enfeksiyonunun prevalansı azalmaktadır. Diğer genotiplerin görülme sıklığı artmakta ve Suriyeli göçmenlerde daha önce ülkemizde saptanmayan genotip 5 enfeksiyonlarına rastlanmaktadır. Adana gibi Türkiye’nin güneyindeki illerde DIU kullanımı ile ilişkili genotip 2 ve özellikle genotip 3 enfeksiyonlarında artış görülmektedir. Tıbbi uygulamalarda güvenliğin artırılması HCV enfeksiyonu riskini azaltsa da, DIU kullanımının artması, gelecekte de HCV enfeksiyonunun önemini koruyacağını göstermektedir.

Anahtar Kelimeler

• HCV genotipleri, risk faktörleri, damar içi uyuşturucu kullanımı, genotip 5 enfeksiyonu

Determination of Hepatitis C virus genotype and HCV infection transmission routes in Cukurova University Medical Faculty Hospital

Abstract

Objective: Determination of the genotype is critical in process of treatment and detection of cronic liver diease caused HIV infection. In this study, we examined blood samples of patients which have been sent to the Central Laboratory of Çukurova University Medical Faculty Hospital for HCV genotyping and the distrubition and transmission routes of HCV genotypes in our region have been determined by examining patients file records. Methods: Between January 2015 and August 2016, HCV genotypes of 119 HCV-RNA COBAS AmpliPrep / COBAS TaqMan HCV real-time PCR, Roche Diagnostics, Germany the results of 119 patients who were identified as positive for HCV genotype were examined respectively from the record in Central Laboratory of Çukurova University Medical Faculty Hospital. The demographic data of patients were obtained from the hospital electronic information system and patient files. “Sacace HCV Genotype Plus Real TM” kit was used for HCV genotyping which can detect genotype 1a, 1b, 2, 3, 4, 5a, 6 by real-time PCR method. Results: In the study of 119 patients, genotype 1 was detected in 71,4% 12.6% genotype 1a, 58.8% genotype 1b , genotype 3 in 16.8%, genotype 2 in 7.6%, genotype4 in 3.4%. Genotype 5 5a 0.8% which has not been reported previously in Adana, was determined in a Syrian female patient. 45.0% of patients who were infected with genotype 3 and 33.3% of patients with genotype 2 infection were intravenous drug users IVDUs ; and young men 83.3% constituted the majority of this patient group. In addition, genotype 3 infection was detected in 4 patients who were have a risk for being IVDU with psychiatric disorders and suicide attempt. The distrubition of HCV genotypes in 11 Syrian patients nearly completed medical interventions was 63.6% genotype 1a, 27.3% genotype 4 and 9.1% genotype 5a respectively. Conclusion: Epidemiology of HCV infection has varried in Turkey in recent years. Although medical interventions are the main risk factor and genotype 1b infection prevalence is 85-90% in our country, genotype 1b infection prevalence has been decreasing in recent years. The incidence of other genotypes are increasing, and previously undetected genotype 5 infection has been determined in Syrian immigrants in our country. Genotype 2 and genotype 3 infections which are associated with intravenous drug use have been increased in southern Turkey, such as Adana. Although transmission risk of HCV infection with medical interventions has decreased with increasing infection control measurement practice, the increasing number of IVDUs will be important in the HCV infection transmission in the future

Keywords

• HCV genotypes, risk factors, intravenous drug use, genotype 5 infection

Kaynakça

1. Ishii S, Koziel MJ. Immune responses during acute and chronic infection with hepatitis C virus. Clin Immunol, 2008; 128(2): 133-47.
2. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol, 2014; 61: 45-57.
3. Tozun N, Ozdogan O, Cakaloglu Y, Idilman R, Karasu Z, Akarca U, et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a field-work TURHEP study. Clin Microbiol Infect, 2015; 21(11): 1020-6.
4. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology, 2014; 59(1): 318-27.
5. Simmonds P. Genetic diversity and evolution of hepatitis C virus-15 years on. J Gen Virol, 2004; 85: 3173–88.
6. Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis, 2005; 5(9): 558-67.
7. Epidemiology of hepatitis C in Turkey. Excerpt based on presentations of S Erensoy and H Abacıoğlu at “Burden and Prevention of Viral Hepatitis in Turkey” meeting. Viral Hepatitis, 2010; 18: 8-9.
8. Yıldırım B, Tahan V, Ozaras R, Aytekin H, Mert A, Tabak F, et al. Hepatitis C Virus Risk Factors in the Turkish Community. Digestive Diseases and Sciences, 2005; 50(12): 2352-5.

9. Ciccozzi M, Ciccaglione A-R, Presti AL, Yalcinkaya T, Taskan ZP, Equestre M, et al. Reconstruction of the evolutionary Dynamics of the hepatitis C virus 1b epidemic in Turkey. Infect Genet Evol, 2011; 11(5): 863-8.
10. Abacıoglu YH, Davidson F, Tuncer S, Yap PL, Ustacelebi S, Yulug N, et al. The distribution of hepatitis C virus genotypes in Turkish patients. J Viral Hepat, 1995; 2: 297-301.
11. Yarkın F, Hafta A. Kronik hepatit C enfeksiyonu olan hastalarda hepatit C virüs (HCV) genotiplerinin dağılımı. Viral Hepatit Derg, 2000; 6: 164-8.
12. Bozdayi AM, Aslan N, Bozdayi G, Türkyilmaz AR, Sengezer T, Wend U, et al. Molecular epidemiology of hepatitis B, C and D viruses in Turkish patients. Arch Virol, 2004; 149 (11): 2115- 29.
13. Altuglu I, Soyler I, Ozacar T, Erensoy S. Distribution of hepatitis C virus genotypes in patients with chronic hepatitis C infection in Western Turkey. Int J Infect Dis, 2008; 12: 239-44.
14. Gökahmetoğlu S, Atalay MA, Kılınç A. Determination of the hepatitis C virus genotypes with ‘pyrosequencing’ method. Erciyes Med J, 2011; 33(2): 99-102.
15. Kirişçi O, Çalışkan A, Alkış Koçtürk S, Erdoğmuş P, Gül M. The Relationship Between Distrubution of HCV-RNA yükü and ALT-AST Levels with Genotypes of Hepatitis C Virus Infected Patients. Viral Hepatitis Journal, 2013; 19(2): 67-70.
16. Öztürk AB, Doğan ÜB, Öztürk NA, Özyazıcı G, Demir M, Akın MS ,et al. Hepatitis C virus genotypes in Adana and Antakya regions of Turkey. Turk J Med Sci, 2014; 44: 661-5.
17. Kuşçu F, Kömür S, İnal AS, Ulu AC, Kurtaran B, Taşova Y, et al. Changing Epidemiology of Chronic Hepatitis C in Adana. Viral Hepatitis Journal, 2014; 20(1): 15-18.
18. Çalışkan A, Kirişçi Ö, Özkaya E, Özden S, Tümer S, Çağlar S, et al. Distribution and Predominance of Genotype 3 in Hepatitis C Virus Carriers in the Province of Kahramanmaras, Turkey. Hepat Mon, 2015; 15(4): e25142.
19. Uçbilek E, Abaylı B, Koyuncu M, Mıdıklı D, Gözüküçük S, Akdağ A, et al. Distrubition of hepatitis C virus genotypes among intravenous drug users in Çukurova Region of Turkey. Turk J Med Sci, 2015; 46: 66-71.
20. Kayman T, Polat C, Ergör G, Abacıoğlu YH. Characterization of HCV genotype 4d infections in Kayseri, Turkey. Turk J Med Sci, 2015; 45: 547-52.
21. Kamal SM, Nasser IA. Hepatitis C virus genotype 4: what we know and what we don’t yet know. Hepatology, 2008; 47(4): 1371–83.
22. Kahraman SO. Theoretical and spatial assessment of labor migration from Turkey to MENA countries. Int J Hum Sci, 2012; 9: 1158–78.
23. Yıldırım MS, Yayla B, Cirit OS. Gaziantep Dr. Ersin Arslan Devlet Hastanesi HCV Genotip Verileri: Türkiye’de İlk Genotip 5 Tespiti mi? 2. Ulusal Klinik Mikrobiyoloji Kongresi,10-13 Kasım 2013, Antalya. Kongre Kitabı sy: 382, PS 432.
24. Antaki N, Haddad M, Kebbewar K, Abdelwahab J, Hamed O, Aaraj R, et al: Syrian Working Group for the Study of Viral Hepatitis. The unexpected discovery of a focus of hepatitis C virüs genotype 5 in a Syrian province. Epidemiol Infect, 2009; 137(1): 79–84.
25. Legrand-Abravanel F, Sandres-Sauné K, Barange K, Alric L, Moreau J, Desmorat P, et al. Hepatitis C virus genotype 5: epidemiological characteristics and sensitivity to combination therapy with interferon-alpha plus ribavirin. J Infect Dis, 2004; 189: 1397–400.
26. Delwaide J, Gerard C, Reenaers C, Vaira D, Bastens B, Bataille C, et al; Groupe Liegeois D’etudes Des Virus Hepatotropes (GLEVE). Hepatitis C virus genotype 5 in southern Belgium: epidemiological characteristics and response to therapy. Digestive Diseases and Science, 2005; 50: 2348–51.
27. Esteban JI, Sauleda S, Quer J. The Changing Epidemiology of Hepatitis C Virus Infection in Europe. J Hepatol. 2008;48(1):148-62.
28. Karaca C, Cakaloğlu Y, Demir K, Ozdil S, Kaymakoğlu S, Badur S, et al. Risk factors for the transmission of hepatitis C virus infection in the Turkish population. Dig Dis Sci, 2006; 51: 365-9.
29. Morice Y, Cantaloube JF, Beaucourt S, Barbotte L, De Gendt S, Goncales FL, et al. Molecular epidemiology of hepatitis C virus subtype 3a in injecting drug users. J Med Virol, 2006; 78(10): 1296–303.
30. Akkarathamrongsin S, Hacharoen P, Tangkijvanich P, Theamıboonlers A, Tanaka Y, Mizokami M, et al. Molecular epidemiology and genetic history of hepatitis C virus subtype 3a infection in Thailand. Intervirology, 2013; 56(5): 284–94.