Bursa Uludağ Üniversitesi Tıp Fakültesi Hastanesi’nde 2016-2018 yılları arasında direkt etkili antiviral tedavi alan kronik hepatit C hastalarının retrospektif irdelenmesi
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Date
2019
Authors
Şimşek, Sümeyra
Journal Title
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Publisher
Bursa Uludağ Üniversitesi
Abstract
Kronik hepatit C (KHC) enfeksiyonunun tedavisinde uzun yıllar pegile interferon (Peg-IFN) ve ribavirin (RBV) kullanılmıştır. Günümüzde yeni geliştirilen direkt etkili antiviral (DEA) ajanlar ile KHC tedavisinde %95'i aşan kalıcı virolojik yanıt oranlarına ulaşılmıştır. Bu çalışma ile, paritaprevir/ritonavir/ombitasvir±dasabuvir (PTV/RTV/OBV±DSV) veya sofosbuvir±ledipasvir (SOF±LDP)’in RBV’le veya RBV’siz verilen tedavi kombinasyonlarını alan olgularda tedavi etkinliği ve güvenliğinin saptanması amaçlanmıştır. 2016-2018 yılları arasında Bursa Uludağ Üniversitesi Tıp Fakültesi Hastanesi Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı ve Gastroenteroloji Bilim Dalı’nda KHC tanısı ile takip edilen, PTV/RTV/OBV±DSV veya SOF±LDP’in RBV’le veya RBV’siz verilen tedavi kombinasyonlarını alan olgular çalışmaya dahil edildi. Olguların demogrofik verileri; tedavi öncesi, sırasında ve sonrasında biyokimyasal ve moleküler parametreleri ile ilaç yan etkilerine bakıldı. Tedavi rejimleri ve hasta genotiplerine göre tedavi bitiminden 12 hafta sonraki HCV-RNA yanıtları (KVY12) ile 24 hafta sonraki HCV-RNA yanıtları (KVY24) karşılaştırıldı. Çalışmaya toplam 223 olgu (94 kadın, 129 erkek) dahil edildi. Olguların yaşlarının median değeri 62±14 (20-84) yıl idi. Hepatosellüler kanseri olan 19, karaciğer nakli olan 14, kronik böbrek yetmezliği olan 18, böbrek nakli olan 3 olgu mevcut idi. Olguların 173'ü (%77,6) genotip 1-1b, 19’u (%8,5) genotip 1, 17’si (%7,6) genotip 3, 9'u (%4) genotip 1-1a, 4’ü (%1,8) genotip 4 ve 1’i (0,4) genotip 2 idi. DEA tedavi öncesinde Peg-IFN±RBV±Proteaz inhibitörü deneyimi olan 103 (%46) olgu mevcutken, 120 (%54) olgu naif idi. Olguların 63’ü (%28) sirotik, 160’ı (%72) ise nonsirotik idi. 116 (%52) olguya SOF±LDP±RBV rejimi; 107 (%48) olguya PTV/RTV/OBV±DSV±RBV rejimi verildiği saptandı. KVY12, 161 olgunun 153’ünde (%94,4) elde edildi. Sekiz (%4,9) olguda KVY12 saptanmadı. Tedavi sırasında genotip 1-1b, naif kompanse sirotik olan bir olguda PTV/RTV/OBV±DSV rejimi ile alevlenme viii görülürken, tedavisini düzenli kullanmayan, genotip 1-1b, naif nonsirotik olan bir olguda ise SOF/LDP rejimi ile tedaviye yanıtsızlık görüldü. Genotip 1-1b, naif nonsirotik olan bir olguda ise PTV/RTV/OBV±DSV rejimi ile KVY12 mevcut iken 24. haftada bakılan HCV-RNA pozitif olarak saptandı. Genotip 1-1b olan olgularda diğer genotiplere göre KVY daha yüksek saptandı (p=0,009). Tüm genotip ve tedavi gruplarında cinsiyet, yaş, siroz ve tedavi deneyimi ile KVY12 arasında anlamlı bir ilişki saptanmadı (sırasıyla p=0,486; p=0,985; p=0,232; p=0,737). Olguların 34’ünde (%15) yan etki gözlendi. En sık görülen yan etki halsizlik (%8), ikinci sıklıkta kaşıntı ve karın ağrısı (%2) idi. Yan etkiler nedeniyle sadece %1,3 olguda tedavinin kesildiği görüldü. KHC’de yeni geliştirilen DEA tedavileriyle özellikle genotip 1-1b hastalarda diğer genotiplere göre KVY12 oranlarının daha yüksek olduğu gözlendi. Tedavide kullanılan PTV/RTV/OBV±DSV ve SOF±LDP etkin ve güvenilir olup yüksek KVY oranlarına sahiptir.
Pegylated interferon (Peg-IFN) and ribavirin (RBV) have been used for many years in the treatment of chronic hepatitis C (CHC) infection. Recently, CHC has led to the development of new direct acting antiviral agents (DAA) and the achievement of sustained virologic response (SVR) in excess of 95%. The aim of our study is to investigate the efficacy and safety of the treatment regimens for CHC with paritaprevir/ritonavir/ ombitasvir±dasabuvir (PTV/RTV/OBV±DSV) and sofosbuvir±ledipasvir (SOF±LDP) with or without RBV, in our clinic. Patients who get PTV/RTV/OBV±DSV or SOF±LDP treatments in the Department of Infectious Diseases and Gastroenterology of Bursa Uludağ University Medical Faculty between in the years of 2016-2018 were included in our study. Demographic datas of the cases; biochemical and molecular parameters before, during and after the treatment and drug side effects were examined. 12 and 24 weeks after the treatments finalized, treatment responses were compared according to treatment regimens and HCV genotypes. A total of 223 cases (94 female, 129 male) were included in the study. The median age of the patients was 62±14 (20-84) years. There were 19 patients with hepatocellular cancer, 14 patients with liver transplantation, 18 patients with chronic renal failure and 3 patients with kidney transplantation. 173 (77,6%) of the cases were genotype 1-1b, 19 (8,5%) genotype 1, 17 (7,6%) genotype 3, 9 (4%) genotype 1-1a, 4 (1,8%) were genotype 4 and 1 (0,4) were genotype 2. There were 103 (46%) cases with Peg-IFN±RBV±Protease Inhibitor experiences prior to DAA treatment and 120 x (54%) cases were naive. 63 (28%) of the cases were cirrhotic and 160 (72%) were nonsirotic. 116 (52%) cases got SOF±LDP±RBV regimen; PTV/RTV/OBV±DSV±RBV regimen was given to 107 (48%) patients. 12 weeks after treatment HCV-RNA was negative in 153 (94,4%) of 161 patients. In 8 (4,9%) patients, there was no sustained virologic response (SVR12) on the 12th week. One naive patient with genotype 1-1b which also had compensated cirrhosis showed exacerbation with PTV/RTV/OBV±DSV regimen during the treatment, also, there was no respend to treatment in a naive, genotype 1-1b paient who didn’t use the medications regularly. One naive, nonsirotic patient with genotype 1-1b was HCV-RNA positive at the 24th week with PTV/RTV/OBV±DSV regimen. Patients with genotype 1-1b were found to have higher SVR12 rates than the other genotypes (p = 0,009). There was no significant corelations for SVR12 between sex, age, cirrhosis, treatment experience in all genotypes and treatment groups (p = 0,486; p = 0,985; p = 0,232; p = 0,737 respectively). Side effects were seen in 34 (15%) of the cases. The most common side effect was weakness (8%), secondly itchiness and abdominal pain (2%). Only 1,3% patients were discontinued the treatment because of the side effects. We find that SVR12 rates were higher in patients with genotype 1-1b than other genotypes with DAA treatments for CHC. PTV/RTV/OBV±DSV and SOF±LDP are effective and reliable, and have high rates of SVR12.
Pegylated interferon (Peg-IFN) and ribavirin (RBV) have been used for many years in the treatment of chronic hepatitis C (CHC) infection. Recently, CHC has led to the development of new direct acting antiviral agents (DAA) and the achievement of sustained virologic response (SVR) in excess of 95%. The aim of our study is to investigate the efficacy and safety of the treatment regimens for CHC with paritaprevir/ritonavir/ ombitasvir±dasabuvir (PTV/RTV/OBV±DSV) and sofosbuvir±ledipasvir (SOF±LDP) with or without RBV, in our clinic. Patients who get PTV/RTV/OBV±DSV or SOF±LDP treatments in the Department of Infectious Diseases and Gastroenterology of Bursa Uludağ University Medical Faculty between in the years of 2016-2018 were included in our study. Demographic datas of the cases; biochemical and molecular parameters before, during and after the treatment and drug side effects were examined. 12 and 24 weeks after the treatments finalized, treatment responses were compared according to treatment regimens and HCV genotypes. A total of 223 cases (94 female, 129 male) were included in the study. The median age of the patients was 62±14 (20-84) years. There were 19 patients with hepatocellular cancer, 14 patients with liver transplantation, 18 patients with chronic renal failure and 3 patients with kidney transplantation. 173 (77,6%) of the cases were genotype 1-1b, 19 (8,5%) genotype 1, 17 (7,6%) genotype 3, 9 (4%) genotype 1-1a, 4 (1,8%) were genotype 4 and 1 (0,4) were genotype 2. There were 103 (46%) cases with Peg-IFN±RBV±Protease Inhibitor experiences prior to DAA treatment and 120 x (54%) cases were naive. 63 (28%) of the cases were cirrhotic and 160 (72%) were nonsirotic. 116 (52%) cases got SOF±LDP±RBV regimen; PTV/RTV/OBV±DSV±RBV regimen was given to 107 (48%) patients. 12 weeks after treatment HCV-RNA was negative in 153 (94,4%) of 161 patients. In 8 (4,9%) patients, there was no sustained virologic response (SVR12) on the 12th week. One naive patient with genotype 1-1b which also had compensated cirrhosis showed exacerbation with PTV/RTV/OBV±DSV regimen during the treatment, also, there was no respend to treatment in a naive, genotype 1-1b paient who didn’t use the medications regularly. One naive, nonsirotic patient with genotype 1-1b was HCV-RNA positive at the 24th week with PTV/RTV/OBV±DSV regimen. Patients with genotype 1-1b were found to have higher SVR12 rates than the other genotypes (p = 0,009). There was no significant corelations for SVR12 between sex, age, cirrhosis, treatment experience in all genotypes and treatment groups (p = 0,486; p = 0,985; p = 0,232; p = 0,737 respectively). Side effects were seen in 34 (15%) of the cases. The most common side effect was weakness (8%), secondly itchiness and abdominal pain (2%). Only 1,3% patients were discontinued the treatment because of the side effects. We find that SVR12 rates were higher in patients with genotype 1-1b than other genotypes with DAA treatments for CHC. PTV/RTV/OBV±DSV and SOF±LDP are effective and reliable, and have high rates of SVR12.
Description
Keywords
Kronik hepatit C enfeksiyonu, Paritaprevir/ ritonavir/ ombitasvir+dasabuvir, Ledipasvir/sofosbuvir, Kalıcı virolojik yanıt, Chronic hepatitis C, Sustained virologic respons, Ledipasvir/sofosbuvir, Paritaprevir/ritonavir/ombitasvir+dasabuvir
Citation
Şimşek, S. (2019). Bursa Uludağ Üniversitesi Tıp Fakültesi Hastanesi’nde 2016-2018 yılları arasında direkt etkili antiviral tedavi alan kronik hepatit C hastalarının retrospektif irdelenmesi. Yayınlanmamış tıpta uzmanlık tezi. Bursa Uludağ Üniversitesi Tıp Fakültesi.