Browsing by Author "Akarca, Ulus S."
Now showing 1 - 10 of 10
- Results Per Page
- Sort Options
Publication 96 weeks of pegylated-interferon- alpha-2α plus tenofovir or placebo for the treatment of hepatitis delta: The hidit-2 study(Wiley-blackwell, 2013-10-01) Wedemeyer, Heiner; Yurdaydin, Cihan; Ernst, Stefanie; Caruntu, Florin A.; Curescu, Manuela G.; Yalcin, Kendal; Akarca, Ulus S.; Zeuzem, Stefan; Erhardt, Andreas; Lueth, Stefan; Papatheodoridis, George; Keskin, Onur; Port, Kerstin; Celen, Mustafa K.; Stift, Judith; Heidrich, Benjamin; Mederacke, Ingmar; Hardtke, Svenja; Koch, Armin; Dienes, Hans P.; Manns, Michael P.; Gürel, Selim; GÜREL, SELİM; Bursa Uludağ Üniversitesi/Tıp Fakültesi; HLH-8209-2023Publication A transient early hbv-dna increase during peg-ifnα therapy of hepatitis d indicates loss of infected cells and is associated with hdv-rna and hbsag reduction(Wiley, 2020-12-12) Anastasiou, Olympia E.; Yurdaydin, Cihan; Maasoumy, Benjamin; Hardtke, Svenja; Caruntu, Florin Alexandru; Curescu, Manuela G.; Yalcin, Kendal; Akarca, Ulus S.; Zeuzem, Stefan; Erhardt, Andreas; Luth, Stefan; Papatheodoridis, George, V; Radu, Monica; Liebig, Stephanie; Bantel, Heike; Bremer, Birgit; Manns, Michael P.; Cornberg, Markus; Wedemeyer, Heiner; Gürel, Selim; GÜREL, SELİM; Bursa Uludağ Üniversitesi/Tıp Fakültesi; HLH-8209-2023HBV-DNA levels are low or even undetectable in the majority HDV-infected patients. The impact of PEG-IFN alpha on HBV-DNA kinetics in HDV-infected patients has not been studied in detail. We analysed data of a prospective treatment trial where 120 HDV-RNA-positive patients were randomized to receive PEG-IFN alpha-2a plus tenofovir-disoproxil-fumarate (PEG-IFN alpha/TDF, n = 59) or placebo (PEG-IFN alpha/PBO; n = 61) for 96 weeks. At week 96, HBV-DNA was still quantifiable in 71% of PEG-IFN alpha/PBO-treated patients but also in 76% of PEG-IFN alpha/TDF-treated patients, despite low HBV-DNA baseline values. Surprisingly, a transient HBV-DNA increase between weeks 12 and 36 was observed in 12 in PEG-IFN alpha/TDF-treated and 12 PEG-IFN alpha/PBO-treated patients. This increase was positively associated with HBsAg loss [(P = 0.049, odds ratio (OR) 5.1] and HDV-RNA suppression (P = 0.007, OR 4.1) at week 96. Biochemical markers of cell death (M30 and ALT) were higher during the HBV-DNA peak but no distinct systemic immune pattern could be observed by screening 91 soluble inflammatory markers. In conclusion, an early increase in HBV-DNA during PEG-IFN alpha-2a therapy occurred in more than 20% of patients, even in TDF-treated patients. This transient HBV-DNA rise may indicate PEG-IFN alpha-induced cell death and lead to long-term HDV-RNA suppression and HBsAg loss.Publication Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real-world chronic hepatitis C patients cohort(Wiley, 2019-06-01) İdilman, Ramazan; Demir, Mehmet; Aladağ, Murat; Erol, Cihan; Çavuş, Bilger; İliaz, Raim; Köklü, Hayrettin; Çakaloğlu, Yılmaz; Şahin, Memduh; Ersöz, Galip; Köksal, İftihar; Karasu, Zeki; Özgenel, Meriç; Turan, İlker; Gündüz, Feyza; Ataseven, Hüseyin; Akdoğan, Meral; Kıyıcı, Murat; Köksal, Aydın Şeref; Akhan, Sila; Günsar, Fülya; Tabak, Fehmi; Kaymakoglu, Sabahattin; Akarca, Ulus S.; Akarsu, Mesut; Alkim, Hüseyin; Araz, Filiz; Ateş, Fehmi; Aygen, Bilgehan; Balık, İsmail; Barut, Hüseyin S.; Baysal, Birol; Bolat, Aylin; Çelik, İlhami; Coşgun, Süleyman; Ensaroglu, Fatih; Gökcan, Hale; Gürel, Selim; Gürsoy, Şebnem; İnkaya, Ahmet Çağan; Kamilli, Cemil; Kav, Taylan; Kuruüzüm, Ziya; Önder, Fatih O.; Örmeci, Necati; Özbakır, Ömer; Özenirler, Seren; Özer, Birol; Özkan, Hasan; Poturoğlu, Şule; Senates, Ebubekir; Şimşek, Halis; Toka, Bilal; Ünal, Hakan; Yaras, Serkan; Yıldırım, Abdullah E.; Yıldırım, Beytullah; Yılmaz, Bülent; Yılmaz, Hasan; Yozgat, Ahmet; Yurdaydın, Cihan; Early Access Program EAP Study Grp; KIYICI, MURAT; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Gastroenteroloji Anabilim Dalı; 0000-0002-3208-6211; AAI-4213-2021The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow-up period was 22months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child-Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P<0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow-up of 6months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P=0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.Ledipasvir and sofosbuvir with or without ribavirin is an effective and tolerable treatment in hepatitis C virus-infected patients with advanced liver disease. Eradication is associated with improvements in liver function and reduces the risk of developing a new occurrence of hepatocellular carcinoma.Item Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): A randomised, placebo controlled, phase 2 trial(Elsevier, 2019-03) Wedemeyer, Heiner; Yurdaydin, Cihan; Hardtke, Svenja; Caruntu, Florin Alexandru; Curescu, Manuela G.; Yalcin, Kendal; Akarca, Ulus S.; Erhardt, Andreas; Lueth, Stefan; Papatheodoridis, George V.; Keskin, Onur; Port, Kerstin; Radu, Monica; Celen, Mustafa K.; Idilman, Ramazan; Weber, Kristina; Stift, Judith; Wittkop, Ulrike; Heidrich, Benjamin; Zeuzem, Stefan; Gürel, Selim; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı.; 7003706434Abstract Background Hepatitis D is the most severe form of chronic viral hepatitis. Treatment guidelines recommend 1 year of peginterferon alfa, which is effective in 25-30% of patients only. Whether prolonged therapy with peginterferon alfa-2a for 96 weeks and combination therapy with tenofovir disoproxil fumarate (TDF) would increase hepatitis D virus (HDV) RNA suppression is unknown. We aimed to explore whether prolonged treatment of HDV with 96 weeks of peginterferon would increase HDV RNA response rates and reduces post-treatment relapses. Methods We did two parallel, investigator-initiated, multicentre, double-blind randomised, controlled trials at 14 study sites in Germany, Greece, Romania, and Turkey. Patients with chronic HDV infection and compensated liver disease who were aged 18 years or older were eligible for inclusion. All patients were HBsAg positive for at least 7 months, anti-HDV positive for at least 3 months, and HDV-RNA positive at the local laboratory at the screening visit. Patients were ineligible if alanine aminotransferase levels were higher than ten times above the upper limit of normal and if platelet counts were lower than 90 000 per mu L, or if they had received interferon therapy or treatment with a nucleoside and nucleotide analogue within the preceding 6 months. Patients were randomly assigned by blinded stratified block randomisation (1:1) to receive 180 mu g of peginterferon alfa-2a weekly plus either TDF (300 mg once daily) or placebo for 96 weeks. The primary endpoint was the percentage of patients with undetectable HDV RNA at the end of treatment assessed by intention to treat. The trials are registered as NCT00932971 and NCT01088659. Findings Between June 24, 2009, and Feb 28, 2011, we randomly assigned 59 HDV RNA-positive patients to receive peginterferon alfa-2a plus TDF and 61 to receive peginterferon alfa-2a plus placebo, including 48 (40%) patients with cirrhosis to the two treatment groups (23 in the peginterferon alfa-2a plus TDF group and 25 in the peginterferon alfa-2a plus placebo group). The primary endpoint was achieved in 28 (48%) of 59 patients in the peginterferon alfa-2a plus TDF group and in 20 (33%) of 61 patients in the peginterferon alfa-2a plus placebo group (odds ratio 1.84, 95% CI 0.86-3.91, p=0.12). We recorded 944 adverse events (459 in the peginterferon alfa-2a plus TDF group and 485 in the peginterferon alfa-2a plus placebo group). The most common adverse events were haematological, behavioural (eg, fatigue), musculoskeletal, influenza-like syndromes, and psychiatric complaints. Interpretation Addition of TDF resulted in no significant improvement in HDV RNA response rates at the end of treatment. These findings highlight that alternative treatment options are needed for hepatitis D.Item Pegylated-Interferon-a-2a plus Tenofovir or Placebo for the treatment of hepatitis delta: First results of the HIDIT-2 study(Wiley, 2012-10) Yurdaydın, Cihan; Wedemeyer, Heiner; Caruntu, Florin A.; Curescu, Manuela G.; Yalçın, Kendal; Akarca, Ulus S.; Zeuzem, Stefan; Erhardt, Andreas; Lueth, Stefan; Papatheodoridis, George V.; Port, Kerstin; Keskin, Onur; Radu, Monica N.; Çelen, Mustafa K.; İdilman, Ramazan; Stift, Judith; Mederacke, Ingmar; Heidrich, Benjamin; Manns, Michael P.; Dienes, Hans Peter; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı.; 0000-0002-7279-2161; EYK-5719-2022Publication Real-world efficacy and safety of Ledipasvir plus Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience(Aves, 2020-10-09) Değertekin, Bülent; Demir, Mehmet; Akarca, Ulus S.; Kani, Haluk Tarık; Üçbilek, Enver; Yıldırım, Emre; Güzelbulut, Fatih; Balkan, Ayhan; Vatansever, Sezgin; Danış, Nilay; Demircan, Melek; Soylu, Aliye; Yaras, Serkan; Kartal, Aysun; Kefeli, Ayşe; Gündüz, Feyza; Yalçın, Kendal; Erarslan, Elife; Aladağ, Murat; Harputluoğlu, Murat; Özakyol, Ayşegül; Temel, Tuncer; Akarsu, Mesut; Sümer, Hale; Akın, Mete; Albayrak, Bülent; Şen, İlker; Alkim, Hüseyin; Uyanıkoğlu, Ahmet; Irak, Kader; Öztaşkın, Sinem; Uğurlu, Çağrı Burak; Güneş, Şevkican; Gürel, Selim; Nuriyev, Kenan; İnci, İsmail; Kaçar, Sabite; Dinçer, Dinç; Doğanay, Levent; Göktürk, Hüseyin Savaş; Mert, Ali; Coşar, Arif Mansur; Dursun, Hakan; Atalay, Roni; Akbulut, Sabiye; Balkan, Yasemin; Koklu, Hayrettin; Şimşek, Halis; Özdoğan, Osman; Çoban, Mehmet; Poturoğlu, Şule; Ayyıldız, Talat; Yapalı, Suna; Günşar, Fulya; Akdoğan, Meral; Özenirler, Seren; Akyıldız, Murat; Sezgin, Orhan; Özdoğan, Osman; Kaymakoğlu, Sabahattin; Besişik, Fatih; Karasu, Zeki; Idılman, Ramazan; GÜREL, SELİM; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Gastroenteroloji ve Hepatoloji Anabilim Dalı.; 0000-0002-7279-2161; HLH-8209-2023Background/Aims: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population.Material and Methods: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)+/- ribavirin (RBV) ombitasvir/paritaprevir/ritonavir +/- dasabuvir (PrOD)+/- RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed.Results: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90 +/- 54.60 U/L to 17.00 +/- 14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51 +/- 4.54 to 7.32 +/- 3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0 +/- 16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%).Conclusion: LDV/SOF or PrOD +/- RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.Item Recurrence and occurrence of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment for chronic hepatitis C in patients with advanced liver disease: Turkish multi-center early access program(Elsevier, 2018-04) İdilman, Ramazan; Demir, Mehmet; Aladağ, Murat; Kaymakoğlu, Sabahattin; Erol, Cihan; Çavuş, Bilger; İliaz, Raim; Akarca, Ulus S.; Köklü, Seyfettin; Çakaloğlu, Yılmaz; Şahin, M.; Köksal, I.; Özgenel, Meriç; Toka, Bilal; Karasu, Zeki; Ersöz, Galip; Akdoğan, Meral; Kıyıcı, Murat; Uludağ Üniversitesi/Tıp Fakültesi/Gastroenteroloji Anabilim Dalı.; AAI-4213-2021Item Residual low HDV viraemia is associated HDV RNA relapse after PEG-IFNa-based antiviral treatment of hepatitis delta: Results from the HIDIT-II study(Wiley, 2020-11-20) Bremer, Birgit; Anastasiou, Olympia E.; Hardtke, Svenja; Caruntu, Florin A.; Curescu, Manuela G.; Yalçın, Kendal; Akarca, Ulus S.; Zeuzem, Stefan; Erhardt, Andreas; Luth, Stefan; Papatheodoridis, George V.; Radu, Monica; İdilman, Ramazan; Manns, Michael P.; Cornberg, Markus; Yurdaydın, Cihan; Wedemeyer, Heiner; Gürel, Selim; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları.; HLH-8209-2023; 7003706434The role of low levels of HDV-RNA during and after interferon therapy of hepatitis D is unknown. We re-analysed HDV RNA in 372 samples collected in the HIDIT-2 trial (Wedemeyer et al, Lancet Infectious Diseases 2019) with the Robogene assay (RA; Jena Analytics). Data were compared with the previously reported in-house assay (IA). We detected HDV-RNA in one-third of samples previously classified as undetectable using the highly sensitive RA. Low HDV viraemia detectable at week 48 or week 96 was associated with a high risk for post-treatment relapse, defined as HDV RNA positivity in both assays at week 120. HDV RNA relapses occurred in 10/15 (67%) patients with detectable low HDV RNA at week 48 and in 10/13 (77%) patients with low viraemia samples at week 96. In contrast, the post-treatment relapse rate was lower in patients with undetectable HDV RNA in both assays during treatment.Publication Residual low hdv viremia is associated with hdv rna relapse after peg-ifna-based antiviral treatment of hepatitis d (delta): Results from the hidit-ii study(Elsevier, 2020-08-01) Bremer, Birgit; Anastasiou, Olympia; Hardtke, Svenja; Caruntu, Florin Alexandru; Curescu, Manuela Gabriela; Yalcin, Kendal; Akarca, Ulus S.; Idilman, Ramazan; Zeuzem, Stefan; Erhardt, Andreas; Lueth, Stefan; Papatheodoridis, George; Radu, Monica; Manns, Michael P.; Cornberg, Markus; Yurdaydın, Cihan; Wedemeyer, Heiner; Gürel, Selim; GÜREL, SELİM; Bursa Uludağ Üniversitesi/Tıp Fakültesi.; HLH-8209-2023Item Ten-year follow-up of a randomized controlled clinical trial in chronic hepatitis delta(Wiley, 2020-07-24) Wranke, Anika; Hardtke, Svenja; Heidrich, Benjamin; Dalekos, George; Yalçın, Kendal; Tabak, Fehmi; Çakaloğlu, Yılmaz; Akarca, Ulus S.; Lammert, Frank; Haeussinger, Dieter; Mueller, Tobias; Woebse, Michael; Manns, Michael P.; Idilman, Ramazan; Cornberg, Markus; Wedemeyer, Heiner; Yurdaydın, Cihan; Gürel, Selim; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı.; EYK-5719-2022; 7003706434Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis. PEG-interferon alpha-2a (PEG-IFNα-2a) is the only effective treatment but its long-term clinical impact is unclear. The aim of this study was to investigate the long-term outcome after 48 weeks of pegylated interferon alpha-2a therapy. We performed a retrospective follow-up study of the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-I trial). Patients had received 48 weeks of treatment with either PEG-IFNα-2a plus adefovir dipivoxil (ADV) (Group I), PEG-IFNα-2a alone (Group II) or adefovir dipivoxil alone (Group III). Liver-related complications were defined as liver-related death, liver transplantation, liver cancer and hepatic decompensation defined as development of Child-Pugh scores B or C or an increase in Model for End-stage Liver Disease (MELD) scores of five or more points in relation to baseline values. Patients were considered for further analysis when they were retreated with PEG-IFNα-2a. Follow-up data (at least 1 visit beyond post-treatment week 24) were available for 60 patients [Group I, (n = 19), Group II (n = 20), Group III (n = 21)]. Mean time of follow-up was 8.9 (1.6 - 13.4) years. 19 patients were retreated with IFN-based therapy: 42% (n = 8) in PEG-IFNα-2a arms and 58% (n = 11) in the adefovir only arm. Clinical complications on long-term follow-up occurred in 17 patients and were associated with nonresponse to therapy and baseline cirrhosis. The annual event-free survival rate in patients with cirrhosis vs noncirrhotic patients at year 5 and 10 was 70% vs 91% and 35% vs 76%. Long-term follow-up of a large randomized clinical trial suggests that off-treatment HDV RNA response to PEG-IFNα-2a treatment leads to improved clinical long-term outcome.