Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study

Yıl: 2016 Cilt: 33 Sayı: 1 Sayfa Aralığı: 18 - 26 Metin Dili: İngilizce İndeks Tarihi: 29-07-2022

Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study

Öz:
Background: Before the introduction of direct-acting antivirals in the treatment of chronic hepatitis C patients, the combination of peginterferon alpha and ribavirin was the standard therapy. Observational studies that in-vestigated sustained virological response (SVR) rates by these drugs yielded different outcomes. Aims: The goal of the study was to demonstrate real life data concerning SVR rate achieved by peginterferon al-pha plus ribavirin in patients who were treatment-naïve. Study Design: A multicenter, retrospective observa-tional study.Methods: The study was conducted retrospectively on 1214 treatment naïve-patients, being treated with pegin-terferon alpha-2a or 2b plus ribavirin in respect of the current guidelines between 2005 and 2013. The patients' data were collected from 22 centers via a standard form, which has been prepared for this study. The data includ-ed demographic and clinical characteristics (gender, age, body weight, initial Hepatitis C virus RNA (HCV RNA) level, disease staging) as well as course of treatment (du-ration of treatment, outcomes, discontinuations and ad-verse events). Renal insufficiency, decompensated liver disease, history of transplantation, immunosuppressive therapy or autoimmune liver disease were exclusion criteria for the study. Treatment efficacy was assessed according to the patient's demographic characteristics, baseline viral load, genotype, and fibrosis scores. Results: The mean age of the patients was 50.74 (±0.64) years. Most of them were infected with genotype 1 (91.8%). SVR was achieved in 761 (62.7%) patients. SVR rate was 59.1% in genotype 1, 89.4% in genotype 2, 93.8% in genotype 3, and 33.3% in genotype 4 pa-tients. Patients with lower viral load yielded higher SVR (65.8% vs. 58.4%, p=0.09). SVR rates according to his-tologic severity were found to be 69.3%, 66.3%, 59.9%, 47.3%, and 45.5% in patients with fibrosis stage 0, 1, 2, 3 and 4, respectively. The predictors of SVR were male gender, genotype 2/3, age less than 45 years, low fibrosis stage, low baseline viral load and presence of early viro-logical response. SVR rates to each peginterferon were found to be similar in genotype 1/4 although SVR rates were found to be higher for peginterferon alpha-2b in patients with genotype 2/3. The number of patients who failed to complete treatment due to adverse effects was 33 (2.7%). The number of patients failed to complete treatment due to adverse effects was 33 (2.7%).Conclusion: Our findings showed that the rate of SVR to dual therapy was higher in treatment-naïve Turkish pa-tients than that reported in randomized controlled trials. Also peginterferon alpha-2a and alpha-2b were found to be similar in terms of SVR in genotype 1 patients.
Anahtar Kelime:

Konular: Cerrahi
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • Alter MJ. The epidemiology of acute and chronic hepatitis C. Clin Liver Dis 1997;1:559-68, vi-vii.
  • Balik I, Tosun S, Tabak F, Saltoglu N, Ormeci N, Sencan I, et al. Investigation of viral hepatitis epidemiology by a touring/travel- ling team [Turkish Viral Hepatitis Society Bus Project]. APASL Brisbane: Hepatology International; 2014. p. 1-405.
  • Dayan S, Tekin A, Tekin R, Dal T, Hosoglu S, Yazgan UC, et al. HBsAg, anti-HCV, anti-HIV 1/2 and syphilis seroprevalence in healthy volunteer blood donors in southeastern Anatolia. J Infect Dev Ctries 2013;7:665-9.
  • Freeman AJ, Dore GJ, Law MG, Thorpe M, Von Overbeck J, Lloyd AR, et al. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology 2001;34:809-16.
  • Sangiovanni A, Del Ninno E, Fasani P, De Fazio C, Ronchi G, Romeo R, et al. Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastro- enterology 2004;126:1005-14.
  • Veldt BJ, Heathcote EJ, Wedemeyer H, Reichen J, Hofmann WP, Zeuzem S, et al. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fi- brosis. Ann Intern Med 2007;147:677-84.
  • Miyake Y, Iwasaki Y, Yamamoto K. Meta-analysis: reduced incidence of hepatocellular carcinoma in patients not respond- ing to interferon therapy of chronic hepatitis C. Int J Cancer 2010;127:989-96.
  • Strader DB, Wright T, Thomas DL, Seeff LB; American Asso- ciation for the Study of Liver D. Diagnosis, management, and treatment of hepatitis C. Hepatology 2004;39:1147-71.
  • Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiff- man M, Reindollar R, et al. Peginterferon alfa-2b plus ribavi- rin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958-65.
  • Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gon- cales FL Jr., et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975-82.
  • Buruk CK, Bayramoglu G, Reis A, Kaklikkaya N, Tosun I, Aydin F. Determination of hepatitis C virus genotypes among hepatitis C patients in Eastern Black Sea Region, Turkey. Mik- robiyol Bul 2013;47:650-7.
  • Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment- induced viral clearance. Nature 2009;461:399-401.
  • Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, et al; PEGASYS International Study Group. Pegin- terferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and riba- virin dose. Ann Int Med 2004;140:346-55.
  • Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996;24:289-93.
  • Intraobserver and interobserver variations in liver biopsy interpre- tation in patients with chronic hepatitis C. The French METAVIR Cooperative Study Group. Hepatology 1994;20:15-20.
  • Ozer B, Serin E, Yilmaz U, Gumurdulu Y, Saygili OB, Kayas- elcuk F, et al. Clinicopathologic features and risk factors for he- patocellular carcinoma: results from a single center in southern Turkey. Turk J Gastroenterol 2003;14:85-90.
  • Alacacioglu A, Somali I, Simsek I, Astarcioglu I, Ozkan M, Camci C, et al. Epidemiology and survival of hepatocellular carcinoma in Turkey: outcome of multicenter study. Jpn J Clin Oncol 2008;38:683-8.
  • Uzunalimoglu O, Yurdaydin C, Cetinkaya H, Bozkaya H, Sahin T, Colakoglu S, et al. Risk factors for hepatocellular carcinoma in Turkey. Dig Dis Sci 2001;46:1022-8.
  • Swain MG, Lai MY, Shiffman ML, Cooksley WG, Zeuzem S, Dieterich DT, et al. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa- 2a and ribavirin. Gastroenterology 2010;139:1593-601.
  • Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, et al. Interleukin-28B polymorphism improves viral kinet- ics and is the strongest pretreatment predictor of sustained viro- logic response in genotype 1 hepatitis C virus. Gastroenterology 2010;139:120-9.e18.
  • Park SH, Park CK, Lee JW, Kim YS, Jeong SH, Kim YS, et al. Efficacy and tolerability of peginterferon alpha plus ribavirin in the routine daily treatment of chronic hepatitis C patients in Ko- rea: a multi-center, retrospective observational study. Gut Liver 2012;6:98-106.
  • Ridruejo E, Adrover R, Cocozzella D, Fernandez N, Reggiardo MV. Efficacy, tolerability and safety in the treatment of chronic hepatitis C with combination of PEG-Interferon - Ribavirin in daily practice. Ann Hepatol 2010;9:46-51.
  • Borroni G, Andreoletti M, Casiraghi MA, Ceriani R, Guerzoni P, Omazzi B, et al. Effectiveness of pegylated interferon/ribavi- rin combination in 'real world' patients with chronic hepatitis C virus infection. Aliment Pharmacol Ther 2008;27:790-7.
  • Bourliere M, Ouzan D, Rosenheim M, Doffoel M, Marcellin P, Pawlotsky JM, et al. Pegylated interferon-alpha2a plus ribavirin for chronic hepatitis C in a real-life setting: the Hepatys French cohort (2003-2007). Antivir Ther 2012;17:101-10.
  • Yenice N, Mehtap O, Gumrah M, Arican N. The efficacy of pe- gylated interferon alpha 2a or 2b plus ribavirin in chronic hepa- titis C patients. Turk J Gastroenterol 2006;17:94-8.
  • Dogan UB, Akin MS, Yalaki S. Sustained virological response based on the week 4 response in hepatitis C virus genotype 1 patients treated with peginterferons alpha-2a and alpha-2b, plus ribavirin. Eur J Gastroenterol Hepatol 2013;25:1317-20.
  • Kau A, Vermehren J, Sarrazin C. Treatment predictors of a sustained virologic response in hepatitis B and C. J Hepatol 2008;49:634-51.
  • D'Souza R, Sabin CA, Foster GR. Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy. Am J Gastroenterol 2005;100:1509-15.
  • Cua IH, Hui JM, Kench JG, George J. Genotype-specific inter- actions of insulin resistance, steatosis, and fibrosis in chronic hepatitis C. Hepatology 2008;48:723-31.
  • Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology 2005;128:636-41.
  • Dai CY, Huang JF, Hsieh MY, Hou NJ, Lin ZY, Chen SC, et al. Insulin resistance predicts response to peginterferon-alpha/ ribavirin combination therapy in chronic hepatitis C patients. J Hepatol 2009;50:712-8.
  • Ferenci P, Fried MW, Shiffman ML, Smith CI, Marinos G, Gon- cales FL Jr, et al. Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin. J Hepatol 2005;43:425-33.
  • Ghany MG, Strader DB, Thomas DL, Seeff LB; American As- sociation for the Study of Liver D. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009;49:1335-74.
  • European Association for the Study of the L. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2011;55:245-64.
  • Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di Costan- zo GG, Lanza AG, et al. Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection. Gastroenterology 2010;138:116-22.
  • Rumi MG, Aghemo A, Prati GM, D'Ambrosio R, Donato MF, Soffredini R, et al. Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferon-alpha2b plus ribavirin in chronic hepatitis C. Gastroenterology 2010;138:108-15.
  • Awad T, Thorlund K, Hauser G, Stimac D, Mabrouk M, Gluud C. Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepa- titis C: systematic review of randomized trials. Hepatology 2010;51:1176-84.
  • McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 2009;361:580-93.
  • Jin YJ, Lee JW, Lee JI, Park SH, Park CK, Kim YS, et al. Mul- ticenter comparison of PEG-IFN alpha2a or alpha2b plus ribavi- rin for treatment-naive HCV patient in Korean population. BMC Gastroenterol 2013;13:74.
  • Dogan UB, Atabay A, Akin MS, Yalaki S. The comparison of the efficacy of pegylated interferon alpha-2a and alpha-2b in chronic hepatitis C patients with genotype 1. Eur J Gastroen- terol Hepatol 2013;25:1082-5.
  • Hauser G, Awad T, Brok J, Thorlund K, Stimac D, Mabrouk M, et al. Peginterferon plus ribavirin versus interferon plus ribavirin for chronic hepatitis C. Cochrane Database Syst Rev 2014;2:CD005441.
  • Fried MW. Side effects of therapy of hepatitis C and their man- agement. Hepatology 2002;36:S237-44.
APA Gürbüz Y, TÜLEK N, Tutuncu E, KORUK S, AYGEN B, Demirturk N, KINIKLI S, Kaya A, YILDIRMAK T, süer k, KORKMAZ F, URAL O, AKHAN S, GÜNAL Ö, TUNA N, köse ş, GÖNEN İ, ÖRMEN B, Turker N, Saltoglu N, Batirel A, TUNCER G, BULUT C, SIRMATEL F, ÜLÇAY A, KARAGÖZ E, TOSUN D, ŞENER A, AYNİOĞLU A, SARGIN ALTUNOK E (2016). Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. , 18 - 26.
Chicago Gürbüz Yunus,TÜLEK Necla Eren,Tutuncu Ediz,KORUK Süda Tekin,AYGEN Bilgehan,Demirturk Nese,KINIKLI SAMI,Kaya Ali,YILDIRMAK Taner,süer kaya,KORKMAZ Fatime,URAL Onur,AKHAN Sıla,GÜNAL Özgür,TUNA Nazan,köse şükran,GÖNEN İbak,ÖRMEN Bahar,Turker Nesrin,Saltoglu Nese,Batirel Ayse,TUNCER Günay,BULUT CEMAL,SIRMATEL FATMA,ÜLÇAY Asım,KARAGÖZ Ergenekon,TOSUN Derviş,ŞENER Alper,AYNİOĞLU Aynur,SARGIN ALTUNOK Elif Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. (2016): 18 - 26.
MLA Gürbüz Yunus,TÜLEK Necla Eren,Tutuncu Ediz,KORUK Süda Tekin,AYGEN Bilgehan,Demirturk Nese,KINIKLI SAMI,Kaya Ali,YILDIRMAK Taner,süer kaya,KORKMAZ Fatime,URAL Onur,AKHAN Sıla,GÜNAL Özgür,TUNA Nazan,köse şükran,GÖNEN İbak,ÖRMEN Bahar,Turker Nesrin,Saltoglu Nese,Batirel Ayse,TUNCER Günay,BULUT CEMAL,SIRMATEL FATMA,ÜLÇAY Asım,KARAGÖZ Ergenekon,TOSUN Derviş,ŞENER Alper,AYNİOĞLU Aynur,SARGIN ALTUNOK Elif Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. , 2016, ss.18 - 26.
AMA Gürbüz Y,TÜLEK N,Tutuncu E,KORUK S,AYGEN B,Demirturk N,KINIKLI S,Kaya A,YILDIRMAK T,süer k,KORKMAZ F,URAL O,AKHAN S,GÜNAL Ö,TUNA N,köse ş,GÖNEN İ,ÖRMEN B,Turker N,Saltoglu N,Batirel A,TUNCER G,BULUT C,SIRMATEL F,ÜLÇAY A,KARAGÖZ E,TOSUN D,ŞENER A,AYNİOĞLU A,SARGIN ALTUNOK E Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. . 2016; 18 - 26.
Vancouver Gürbüz Y,TÜLEK N,Tutuncu E,KORUK S,AYGEN B,Demirturk N,KINIKLI S,Kaya A,YILDIRMAK T,süer k,KORKMAZ F,URAL O,AKHAN S,GÜNAL Ö,TUNA N,köse ş,GÖNEN İ,ÖRMEN B,Turker N,Saltoglu N,Batirel A,TUNCER G,BULUT C,SIRMATEL F,ÜLÇAY A,KARAGÖZ E,TOSUN D,ŞENER A,AYNİOĞLU A,SARGIN ALTUNOK E Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. . 2016; 18 - 26.
IEEE Gürbüz Y,TÜLEK N,Tutuncu E,KORUK S,AYGEN B,Demirturk N,KINIKLI S,Kaya A,YILDIRMAK T,süer k,KORKMAZ F,URAL O,AKHAN S,GÜNAL Ö,TUNA N,köse ş,GÖNEN İ,ÖRMEN B,Turker N,Saltoglu N,Batirel A,TUNCER G,BULUT C,SIRMATEL F,ÜLÇAY A,KARAGÖZ E,TOSUN D,ŞENER A,AYNİOĞLU A,SARGIN ALTUNOK E "Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study." , ss.18 - 26, 2016.
ISNAD Gürbüz, Yunus vd. "Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study". (2016), 18-26.
APA Gürbüz Y, TÜLEK N, Tutuncu E, KORUK S, AYGEN B, Demirturk N, KINIKLI S, Kaya A, YILDIRMAK T, süer k, KORKMAZ F, URAL O, AKHAN S, GÜNAL Ö, TUNA N, köse ş, GÖNEN İ, ÖRMEN B, Turker N, Saltoglu N, Batirel A, TUNCER G, BULUT C, SIRMATEL F, ÜLÇAY A, KARAGÖZ E, TOSUN D, ŞENER A, AYNİOĞLU A, SARGIN ALTUNOK E (2016). Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. Balkan Medical Journal, 33(1), 18 - 26.
Chicago Gürbüz Yunus,TÜLEK Necla Eren,Tutuncu Ediz,KORUK Süda Tekin,AYGEN Bilgehan,Demirturk Nese,KINIKLI SAMI,Kaya Ali,YILDIRMAK Taner,süer kaya,KORKMAZ Fatime,URAL Onur,AKHAN Sıla,GÜNAL Özgür,TUNA Nazan,köse şükran,GÖNEN İbak,ÖRMEN Bahar,Turker Nesrin,Saltoglu Nese,Batirel Ayse,TUNCER Günay,BULUT CEMAL,SIRMATEL FATMA,ÜLÇAY Asım,KARAGÖZ Ergenekon,TOSUN Derviş,ŞENER Alper,AYNİOĞLU Aynur,SARGIN ALTUNOK Elif Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. Balkan Medical Journal 33, no.1 (2016): 18 - 26.
MLA Gürbüz Yunus,TÜLEK Necla Eren,Tutuncu Ediz,KORUK Süda Tekin,AYGEN Bilgehan,Demirturk Nese,KINIKLI SAMI,Kaya Ali,YILDIRMAK Taner,süer kaya,KORKMAZ Fatime,URAL Onur,AKHAN Sıla,GÜNAL Özgür,TUNA Nazan,köse şükran,GÖNEN İbak,ÖRMEN Bahar,Turker Nesrin,Saltoglu Nese,Batirel Ayse,TUNCER Günay,BULUT CEMAL,SIRMATEL FATMA,ÜLÇAY Asım,KARAGÖZ Ergenekon,TOSUN Derviş,ŞENER Alper,AYNİOĞLU Aynur,SARGIN ALTUNOK Elif Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. Balkan Medical Journal, vol.33, no.1, 2016, ss.18 - 26.
AMA Gürbüz Y,TÜLEK N,Tutuncu E,KORUK S,AYGEN B,Demirturk N,KINIKLI S,Kaya A,YILDIRMAK T,süer k,KORKMAZ F,URAL O,AKHAN S,GÜNAL Ö,TUNA N,köse ş,GÖNEN İ,ÖRMEN B,Turker N,Saltoglu N,Batirel A,TUNCER G,BULUT C,SIRMATEL F,ÜLÇAY A,KARAGÖZ E,TOSUN D,ŞENER A,AYNİOĞLU A,SARGIN ALTUNOK E Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. Balkan Medical Journal. 2016; 33(1): 18 - 26.
Vancouver Gürbüz Y,TÜLEK N,Tutuncu E,KORUK S,AYGEN B,Demirturk N,KINIKLI S,Kaya A,YILDIRMAK T,süer k,KORKMAZ F,URAL O,AKHAN S,GÜNAL Ö,TUNA N,köse ş,GÖNEN İ,ÖRMEN B,Turker N,Saltoglu N,Batirel A,TUNCER G,BULUT C,SIRMATEL F,ÜLÇAY A,KARAGÖZ E,TOSUN D,ŞENER A,AYNİOĞLU A,SARGIN ALTUNOK E Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. Balkan Medical Journal. 2016; 33(1): 18 - 26.
IEEE Gürbüz Y,TÜLEK N,Tutuncu E,KORUK S,AYGEN B,Demirturk N,KINIKLI S,Kaya A,YILDIRMAK T,süer k,KORKMAZ F,URAL O,AKHAN S,GÜNAL Ö,TUNA N,köse ş,GÖNEN İ,ÖRMEN B,Turker N,Saltoglu N,Batirel A,TUNCER G,BULUT C,SIRMATEL F,ÜLÇAY A,KARAGÖZ E,TOSUN D,ŞENER A,AYNİOĞLU A,SARGIN ALTUNOK E "Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study." Balkan Medical Journal, 33, ss.18 - 26, 2016.
ISNAD Gürbüz, Yunus vd. "Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study". Balkan Medical Journal 33/1 (2016), 18-26.