Research Article
Türkiye’de kronik Hepatit C Genotip 1 hastalarında direkt-etkili oral antiviral tedavinin gerçek yaşamda etkinliği ve güvenliği
Abstract
Amaç: Bu çalışmanın amacı, Türkiye'de ve dünyada kronik hepatit C
virüsünün (HCV) en yaygın şekli olan genotip 1 hastalarında kullanılan
paritaprevir / ritonavir, ombitasvir, dasabuvir (PrOD) ± ribavirin (RBV) ve
ledipasvir / sofosbuvir (LDV / SOF) ± RBV kombinasyon rejimlerinin gerçek
yaşamda etkinliğini ve güvenirliğini araştırmakdı.
Yöntem: Haziran 2016 ile Ekim 2017 yılları arasında, PrOD ± RBV veya LDV
/ SOF ± RBV tedavi rejimleri alan toplam 81 HCV genotipi 1 hasta dahil edildi.
Hastalar demografik, klinik ve virolojik verileri, kalıcı virolojik yanıt (KVY)
ve ayrıntılı yan etkiler değerlendirildi.
Bulgular: 81 HCV hastası, 35 (%
43.2) erkek, 46 (% 56.8) kadın olup ortalama yaş 62 idi. Hastalar Türkiye'de en
sık görülen genotip olan genotip 1 ve alt genotipler % 12.3 genotip 1a ve %
87.7 genotip 1b idi. Kronik HCV genotip 1 hastalarının KVY oranı 79 (% 96.4),
PrOD ± RBV hastalarında % 98.2 ve SOF / LDV ± RBV'de % 96 idi. Ayrıntılı yan
etki 46 (% 56.8) hastada bildirildi. Hastalarda en sık görülen yan etkiler; 18
(% 22.2) kaşıntı, 17 yorgunluk (% 21) ve 16 (% 19.8) baş ağrısı idi.
Sonuç: Bu
çalışmada bölgemizdeki tek bir merkezden elde edilen gerçek yaşam verilerine
göre, kronik HCV genotip 1 hastalarında direkt etkili oral viral tedavi
rejimleri ile yüksek KVY 12 yanıtı elde edildi ve mükemmel tolere edildiği
görüldü.
References
- 1. Lingala S, Ghany MG. Natural History of Hepatitis C. Gastroenterol Clin North Am 2015; 44: 717-34.
- 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, et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study. Clin Microbiol Infect 2015;21(11):1020-26.
- 4. Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015; 61: 77-87.
- 5. Gürbüz Y, Tülek NE, Tütüncü EE, et al. Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study, Balkan Medikal J 2016; 33: 18-26.
- 6. Backus LI, Boothroyd DB, Philips BR, et al. A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. Clin Gastroenterol Hepatol 2011; 9: 509-16.
- 7. McHutchison JG, Lawitz EJ, Shiffman ML, et al. IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med, 2009; 361: 580-93.
- 8. Lawitz EJ, Membreno FE. Response-guided therapy in patients with genotype 1 hepatitis C virus: current status and future prospects. J Gastroenterol Hepatol 2014; 29: 1574-8.
- 9. Ahmed H , Abushouk AI, Menshawya A, et al. Safety and Efficacy of Ombitasvir/ Paritaprevir/ Ritonavir and Dasabuvir with or without Ribavirin for Treatment of Hepatitis C Virus Genotype 1: A Systematic Review and Meta-analysis. Clin Drug Investig 2017; 37: 1009-23.
- 10. Flisiak R, Łucejko M, Mazur W, et al. Effectiveness and safety of ledipasvir /sofosbuvir ± ribavirin in the treatment of HCV infection: The real-world HARVEST study. Adv Med Sci 2017; 62: 387-92.
- 11. Tao T, Jiang X, Chen Y, Song Y. Efficacy and Safety of Ledipasvir/Sofosbuvir with and without Ribavirin in Patients with Chronic Hepatitis C Virus Genotype 1 Infection: a meta-analysis. Int J Infect Dis 2017; 55: 56-71.
- 12. Gürbüz Y, Tülek NE, Tobacci EE, et al. Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. Balkan Med. J, 2016; 33: 18-26.
- 13. Ferenci P, Bernstein D, Lalezari J, et al. PEARL-III Study; PEARL-IV Study. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med, 2014; 370: 1983-92.
- 14. Poordad F, Hezode C, Trinh R, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med, 2014; 370: 1973-82.
- 15. Afdhal N, Zeuzem S, Kwo P, et al. ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 2014; 370: 1889-98.
- 16. Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, et al. ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.N Engl J Med 2014; 370: 1483-93.
- 17. Welzel TM, Hinrichsen H, Sarrazin C, et al, Real-world experience with the all-oral, interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic hepatitis C virus infection in the German Hepatitis C Registry. J Viral Hepat 2017; 24: 840-49.
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- 19. Shin HP, Burman B, Kozarek RA, et al. Real-World Single-Center Experience with Sofosbuvir-Based Regimens for the Treatment of Chronic Hepatitis C Genotype 1 Patients. Gut Liver 2017; 11: 711-20.
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- 21. Calleja JL, Crespo J, Rincón D, et al. Spanish Group for the Study of the Use of Direct-acting Drugs Hepatitis C Collaborating Group. Effectiveness, safety and clinical outcomes of direct-acting antiviral therapy in HCV genotype 1 infection: Results from a Spanish real-world cohort. J Hepatol 2017; 66: 1138-48.
- 22. Su F, Best LA, Green PK, Berry K, Ioannou GN. Direct-acting antivirals are effective for chronic hepatitis C treatment in elderly patients: a real-world study of 17 487 patients. Eur J Gastroenterol Hepatol 2017; 29: 686-93.
- 23. Rong L, Dahari H, Ribeiro RM, Perelson AS. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med 2010; 2: 30-32.
- 24. Sarrazin C, Dvory-Sobol H, Svarovskaia ES, et al. Prevalence of Resistance-Associated Substitutions in HCV NS5A, NS5B, or NS3 and Outcomes of Treatment With Ledipasvir and Sofosbuvir. Gastroenterology 2016; 151: 501-12.
- 25. Miyase S, Haraoka K, Ouchida Y, Morishita Y, Fujiyama S. Randomized trial of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin for chronic hepatitis C in Japanese patients. J Gastroenterol 2012; 47: 1014-21.
- 26. Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370: 1594-603.
- 27. Alqahtani SA, Afdhal N, Zeuzem S, et al. Safety and tolerability of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic hepatitis C virus genotype 1 infection: Analysis of phase III ION trials Hepatology 2015; 62: 25-30.
- 28. Mendizabal M, Haddad L, Gallardo PE, et al. Ombitasvir/paritaprevir/ritonavir/ dasabuvir ± ribavirin is safe and effective in HCV-infected patients in a real-life cohort from Latin America. J Med Virol, 2017; 89: 1590-96.
- 29. Terrault NA, Zeuzem S, Bisceglie D, et al. HCV-TARGET Study Group Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response. Gastroenterology 2016; 151: 1131-40.
The real-world efficacy and safety of direct-acting oral antiviral treatment in chronic Hepatitis C Genotype 1 patients in Turkey
Abstract
Objective: The
aim of this study was to investigate the real-world efficacy and safety in
Turkey of the paritaprevir/ritonavir, ombitasvir, dasabuvir (PrOD) ± ribavirin
(RBV) and ledipasvir/sofosbuvir (LDV/SOF) ± RBV combination regimens used for
chronic hepatits C virus (HCV) genotype 1 patients, which is the most common
form of this disease seen both in Turkey and worldwide.
Method: The
study included a total of 81 HCV genotype 1 patients receiving PrOD ± RBV or
LDV/SOF ± RBV treatment regimens between June 2016 and October 2017. The
patients were evaluated in respect of demographic, clinical and virological
data, sustained virologic response (SVR) and detailed adverse events (AE).
Results: The
81 HCV patients comprised 35 (43.2%) males and 46 (56.8%) females with a mean
age of 62 years. All the patients were genotype 1, which is the most commonly
seen genotype in Turkey, and the sub-genotypes were HCV genotype 1a in 12.3%
and genotype 1b in 87.7%. The SVR12 rate of all the chronic HCV genotype 1
patients was 79 (96.4%), 98.2% in the PrOD ± RBV patients and 96% in SOF/LDV ±
RBV. AEs were reported in 46 (56.8%) of the total patient group. The most
common AEs were pruritus in 18 (22.2%) patients, fatigue in 17 (21%) and
headache in 16 (19.8%).
Conclusions: According
to the real-world data obtained in this study from a single centre in our
region, a high rate of SVR12 response was obtained direct-acting oral viral
treatment regimens in patients with chronic HCV genotype 1 and there was seen
to be excellent tolerability.
References
- 1. Lingala S, Ghany MG. Natural History of Hepatitis C. Gastroenterol Clin North Am 2015; 44: 717-34.
- 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, et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study. Clin Microbiol Infect 2015;21(11):1020-26.
- 4. Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015; 61: 77-87.
- 5. Gürbüz Y, Tülek NE, Tütüncü EE, et al. Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study, Balkan Medikal J 2016; 33: 18-26.
- 6. Backus LI, Boothroyd DB, Philips BR, et al. A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. Clin Gastroenterol Hepatol 2011; 9: 509-16.
- 7. McHutchison JG, Lawitz EJ, Shiffman ML, et al. IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med, 2009; 361: 580-93.
- 8. Lawitz EJ, Membreno FE. Response-guided therapy in patients with genotype 1 hepatitis C virus: current status and future prospects. J Gastroenterol Hepatol 2014; 29: 1574-8.
- 9. Ahmed H , Abushouk AI, Menshawya A, et al. Safety and Efficacy of Ombitasvir/ Paritaprevir/ Ritonavir and Dasabuvir with or without Ribavirin for Treatment of Hepatitis C Virus Genotype 1: A Systematic Review and Meta-analysis. Clin Drug Investig 2017; 37: 1009-23.
- 10. Flisiak R, Łucejko M, Mazur W, et al. Effectiveness and safety of ledipasvir /sofosbuvir ± ribavirin in the treatment of HCV infection: The real-world HARVEST study. Adv Med Sci 2017; 62: 387-92.
- 11. Tao T, Jiang X, Chen Y, Song Y. Efficacy and Safety of Ledipasvir/Sofosbuvir with and without Ribavirin in Patients with Chronic Hepatitis C Virus Genotype 1 Infection: a meta-analysis. Int J Infect Dis 2017; 55: 56-71.
- 12. Gürbüz Y, Tülek NE, Tobacci EE, et al. Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. Balkan Med. J, 2016; 33: 18-26.
- 13. Ferenci P, Bernstein D, Lalezari J, et al. PEARL-III Study; PEARL-IV Study. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med, 2014; 370: 1983-92.
- 14. Poordad F, Hezode C, Trinh R, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med, 2014; 370: 1973-82.
- 15. Afdhal N, Zeuzem S, Kwo P, et al. ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 2014; 370: 1889-98.
- 16. Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, et al. ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.N Engl J Med 2014; 370: 1483-93.
- 17. Welzel TM, Hinrichsen H, Sarrazin C, et al, Real-world experience with the all-oral, interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic hepatitis C virus infection in the German Hepatitis C Registry. J Viral Hepat 2017; 24: 840-49.
- 18. Chan HL, Tsang OT, Hui YT, et al. Real-life efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir in chronic hepatitis C patients in Hong Kong. J Gastroenterol Hepatol 2017; 32: 1230-33.
- 19. Shin HP, Burman B, Kozarek RA, et al. Real-World Single-Center Experience with Sofosbuvir-Based Regimens for the Treatment of Chronic Hepatitis C Genotype 1 Patients. Gut Liver 2017; 11: 711-20.
- 20. Backus LI, Belperio PS, Shahoumian TA, et al. Comparative effectiveness of ledipasvir/ sofosbuvir ± ribavirin vs. ombitasvir/ paritaprevir /ritonavir/dasabuvir ± ribavirin in 6961 genotype 1 patients treated in routine medical practice. Aliment Pharmacol Ther, 2016; 44: 400-10.
- 21. Calleja JL, Crespo J, Rincón D, et al. Spanish Group for the Study of the Use of Direct-acting Drugs Hepatitis C Collaborating Group. Effectiveness, safety and clinical outcomes of direct-acting antiviral therapy in HCV genotype 1 infection: Results from a Spanish real-world cohort. J Hepatol 2017; 66: 1138-48.
- 22. Su F, Best LA, Green PK, Berry K, Ioannou GN. Direct-acting antivirals are effective for chronic hepatitis C treatment in elderly patients: a real-world study of 17 487 patients. Eur J Gastroenterol Hepatol 2017; 29: 686-93.
- 23. Rong L, Dahari H, Ribeiro RM, Perelson AS. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med 2010; 2: 30-32.
- 24. Sarrazin C, Dvory-Sobol H, Svarovskaia ES, et al. Prevalence of Resistance-Associated Substitutions in HCV NS5A, NS5B, or NS3 and Outcomes of Treatment With Ledipasvir and Sofosbuvir. Gastroenterology 2016; 151: 501-12.
- 25. Miyase S, Haraoka K, Ouchida Y, Morishita Y, Fujiyama S. Randomized trial of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin for chronic hepatitis C in Japanese patients. J Gastroenterol 2012; 47: 1014-21.
- 26. Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370: 1594-603.
- 27. Alqahtani SA, Afdhal N, Zeuzem S, et al. Safety and tolerability of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic hepatitis C virus genotype 1 infection: Analysis of phase III ION trials Hepatology 2015; 62: 25-30.
- 28. Mendizabal M, Haddad L, Gallardo PE, et al. Ombitasvir/paritaprevir/ritonavir/ dasabuvir ± ribavirin is safe and effective in HCV-infected patients in a real-life cohort from Latin America. J Med Virol, 2017; 89: 1590-96.
- 29. Terrault NA, Zeuzem S, Bisceglie D, et al. HCV-TARGET Study Group Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response. Gastroenterology 2016; 151: 1131-40.
There are 29 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Medical Science Research Articles |
| Authors | |
| Publication Date | March 20, 2018 |
| Acceptance Date | February 25, 2018 |
| Published in Issue | Year 2018 |