Browsing by Author "Dalekos, George N."
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Item Anti-HDV immunoglobulin M testing in hepatitis delta revisited: Correlations with disease activity and response to pegylated interferon-alpha 2a treatment(Int Medical, 2012) Mederacke, Ingmar; Yurdaydın, Cihan; Dalekos, George N.; Bremer, Birgit; Erhardt, Andreas; Çakaloğlu, Yılmaz; Yalçın, Kendal; Zeuzem, Stefan; Zachou, Kalliopi; Bozkaya, Hakan; Dienes, Hans Peter; Manns, Michael P.; Wedemeyer, Heiner; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi/Gastroenteroloji Anabilim Dalı.; 7003706434Background: The role of anti-HDV immunoglobulin M (IgM) testing in patients receiving pegylated interferon-alpha therapy for hepatitis delta is unknown. We performed anti-HDV IgM testing in a well defined cohort of HDVinfected patients who were treated with pegylated interferon-alpha 2a plus adefovir, or either drug alone. Methods: Sera from 33 HDV-RNA-positive patients from the international HIDIT-1 trial were available for anti-HDV IgM testing (ETI-DELTA-IGMK-2 assay, DiaSorin, Saluggia, Italy) before therapy, at treatment weeks 24 and 48, and at 24 weeks after the end of treatment. Results: Anti-HDV IgM tested positive in 31 out of the 33 patients (94%) prior to treatment. HDV IgM levels correlated with histological inflammatory activity (r= 0.51, P<0.01) and were higher in patients with alanine aminotransferase and gamma-glutamyl transpeptidase levels above the median (P<0.05). Quantitative anti-HDV IgM values declined in patients responding to antiviral therapy, however anti-HDV IgM remained positive after treatment in the majority of virological responders. Conclusions: We suggest that anti-HDV IgM testing might give additional useful information to determine disease activity in hepatitis delta and to predict treatment response to antiviral therapy with type I interferons. However, determination of anti-HDV IgM can not substitute HDV RNA testing, which remains the primary virological marker for response to therapy.Item Association between level of hepatitis d virus RNA at week 24 of pegylated interferon therapy and outcome(Elsevier, 2015-12) Keskin, Onur; Wedemeyer, Heiner; Tüzün, Ali; Zachou, Kalliopi; Deda, Xheni; Dalekos, George N.; Heidrich, Benjamin; Pehlivan, Selcen; Zeuzem, Stefan; Yalçın, Kendal; Tabak, Fehmi; İdilman, Ramazan; Bozkaya, Hakan; Manns, Michael; Yurdaydın, Cihan; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi/Gastroenteroloji Anabilim Dalı.; 7003706434BACKGROUND & AIMS: Interferon is the only effective treatment for chronic hepatitis D virus (HDV) infection. No rules have been set for stopping treatment based on viral kinetics. We analyzed data from an international study of hepatitis D treatment to identify factors associated with outcomes of pegylated interferon treatment, with and without adefovir. METHODS: We analyzed data from the Hep-Net-International Delta Hepatitis Intervention Trial on 50 patients with compensated liver disease who tested positive for anti-HDV and HDV RNA. Subjects received pegylated interferon alpha 2a, with adefovir or placebo, or only adefovir, for 48 weeks. Twenty-four weeks after treatment ended, 41 patients were evaluated for levels of HDV RNA and DNA, liver enzymes, and hepatitis B surface antigen (HBsAg); liver biopsy specimens were analyzed for fibrosis. Response to therapy was defined as end-of-treatment response or post-treatment week 24 virologic response. In both cases virologic response was associated with undetectable HDV RNA levels. Patients with less than a 1 log decrease in HDV RNA at the end of treatment were considered null responders. RESULTS: Based on univariate and multivariate analysis, the level of HDV RNA at week 24 of treatment was associated more strongly with response to therapy than other factors analyzed. The level of HBsAg at week 24 of treatment was associated with a response to therapy only in univariate analysis. Lack of HDV RNA at week 24 of treatment, or end of treatment, identified responders with positive predicted values of 71% and 100%, respectively. At 24 weeks after treatment, a decrease in HDV RNA level of less than 1 log, combined with no decrease in HBsAg level, identified null responders with a positive predictive value of 83%. A decrease in HDV RNA level of more than 2 log at week 24 of treatment identified null responders with a negative predictive value of 95%. CONCLUSIONS: Based on an analysis of data from a large clinical trial, the level of HDV RNA at week 24 of treatment with pegylated interferon, with or without adefovir for 48 weeks, can identify patients who will test negative for HDV RNA 24 weeks after the end of treatment. This information can be used to help physicians manage patients receiving therapy for chronic hepatitis D.Publication Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis(Wiley, 2021-11-28) Efe, Cumali; Lammert, Craig; Taşcılar, Koray; Dhanasekaran, Renumathy; Ebik, Berat; Higuera-de la Tijera, Fatima; Çalışkan, Ali R.; Peralta, Mirta; Gerussi, Alessio; Massoumi, Hatef; Catana, Andreea M.; Purnak, Tuğrul; Rigamonti, Cristina; Aldana, Andres J. G.; Khakoo, Nidah; Nazal, Leyla; Frager, Shalom; Demir, Nurhan; Irak, Kader; Melekoğlu-Ellik, Zeynep; Kaçmaz, Hüseyin; Balaban, Yasemin; Atay, Kadri; Eren, Fatih; Alvares-da-Silva, Mario R.; Cristoferi, Laura; Urzua, Alvaro; Eskazan, Tuğçe; Magro, Bianca; Snijders, Romee; Barutcu, Sezgin; Lytvyak, Ellina; Zazueta, Godolfino M.; Demirezer-Bolat, Aylin; Aydın, Mesut; Heurgue-Berlot, Alexandra; De Martin, Eleonora; Ekin, Nazım; Yıldırım, Sümeyra; Yavuz, Ahmet; Bıyık, Murat; Narro, Graciela C.; Kıyıcı, Murat; Akyıldız, Murat; Kahramanoğlu-Aksoy, Evrim; Vincent, Maria; Carr, Rotonya M.; Günşar, Fulya; Reyes, Eira C.; Harputluoğlu, Murat; Aloman, Costica; Gatselis, Nikolaos K.; Ustundağ, Yücel; Brahm, Javier; Vargas, Nataly C. E.; Güzelbulut, Fatih; Garcia, Sandro R.; Aguirre, Jonathan; Anders, Margarita; Ratusnu, Natalia; Hatemi, İbrahim; Mendizabal, Manuel; Floreani, Annarosa; Fagiuoli, Stefano; Silva, Marcelo; Idılman, Ramazan; Satapathy, Sanjaya K.; Silveira, Marina; Drenth, Joost P. H.; Dalekos, George N.; Assis, David N.; Bjornsson, Einar; Boyer, James L.; Yoshida, Eric M.; Invernizzi, Pietro; Levy, Cynthia; Montano-Loza, Aldo J.; Schiano, Thomas D.; Ridruejo, Ezequiel; Wahlin, Staffan; KIYICI, MURAT; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Gastroenteroloji Anabilim Dalı.; FHW-0015-2022Background We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.Item Efficacy of pegylated interferon-based treatment in patients with cirrhosis due to chronic delta hepatitis: Comparison with non-cirrhotic patients(Wiley, 2009-10) Yurdaydın, Cihan; Kobacam, Gökhan; Cakaloğlu, Yılmaz; Erhardt, Andreas; Değertekin, Halil; Zeuzem, Stefan; Dalekos, George N.; Bozkaya, Hakan; Dienes, Hans P.; Manns, Michael P.; Wedemeyer, Heiner; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı/Gastroenteroloji Bilimdalı.Publication Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta(Lippincott Williams & Wilkins, 2014-07-01) Heidrich, Benjamin; Yurdaydin, Cihan; Kabacam, Gokhan; Ratsch, Boris A.; Zachou, Kalliopi; Bremer, Birgit; Dalekos, George N.; Erhardt, Andreas; Tabak, Fehmi; Yalçın, Kendal; Gürel, Selim; Zeuzem, Stefan; Cornberg, Markus; Bock, C. -Thomas; Manns, Michael P.; Wedemeyer, Heiner; GÜREL, SELİM; Uludağ Üniversitesi/Tıp Fakültesi/Gastroenteroloji Anabilim Dalı.; HLH-8209-2023Interferon alpha is the only treatment option for hepatitis delta virus (HDV). Trials investigating the efficacy of pegylated interferon alpha (PEG-IFNa) showed HDV RNA negativity rates of 25-30% 24 weeks after therapy. However, the clinical and virological long-term outcome of HDV-infected patients treated with PEG-IFNa is unknown. We performed a retrospective-prospective follow-up of 77 patients treated for 48 weeks with either PEG-alfa-2a and adefovir (ADV) or either drug alone in the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-1) trial. Long-term follow-up data were available for 58 out of 77 patients (75%) with a median time of follow-up of 4.5 (0.5-5.5) years and a median 3 visits per patient. Patients treated with ADV alone received retreatment with PEG-IFNa (48% versus 19%; P = 0.02) more often. Hepatitis B virus surface antigen (HBsAg) became negative in six PEG-IFNa-treated patients until the end of long-term follow-up (10%). Sixteen patients tested HDV RNA-negative 6 months after PEG-IFNa treatment who were entered in the long-term follow-up study. Out of these, nine individuals tested HDV RNA-positive at least once during further long-term follow-up, with seven patients being HDV RNA-positive at the most recent visit. Clinical endpoints (liver-related death, liver transplantation, hepatic decompensation, hepatocellular carcinoma) were observed in three PEG-IFNa-treated (8%) and three ADV-treated (14%) patients during posttreatment long-term follow-up with an overall annual event rate of 2.5% (4.9% in cirrhosis). Sequencing confirmed the reappearance of pretreatment virus strains in all cases. Conclusion: Late HDV RNA relapses may occur after PEG-IFNa therapy of hepatitis delta and thus the term sustained virological response should be avoided in HDV infection. The annual posttreatment rate of clinical events in hepatitis delta patients eligible for PEG-IFNa therapy is about 2.5% and 4.9% in patients with cirrhosis.Item Peginterferon plus adefovir versus either drug alone for hepatitis delta(Massachusetts Medical Soc, 2011-01-27) Wedemeyer, Heiner; Yurdaydın, Cihan; Dalekos, George N.; Erhardt, Andreas; Çakaloğlu, Yılmaz; Değertekin, Halil; Zeuzern, Stefan; Zachou, Kalliopi; Bozkaya, Hakan; Koch, Armin; Bock, Thomas; Dienes, Hans Peter; Manns, Michael P.; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi.; 7003706434BACKGROUND Chronic infection with hepatitis B virus and hepatitis delta virus (HDV) results in the most severe form of viral hepatitis. There is no currently approved treatment. We investigated the safety and efficacy of 48 weeks of treatment with peginterferon alfa-2a plus adefovir dipivoxil, peginterferon alfa-2a alone, and adefovir dipivoxil alone. METHODS We conducted a randomized trial in which 31 patients with HDV infection received treatment with 180 mu g of peginterferon alfa-2a weekly plus 10 mg of adefovir daily, 29 received 180 mu g of peginterferon alfa-2a weekly plus placebo, and 30 received 10 mg of adefovir alone weekly for 48 weeks. Follow-up was conducted for an additional 24 weeks. Efficacy end points included clearance of HDV RNA, normalization of alanine aminotransferase levels, and a decline in levels of hepatitis B surface antigen (HBsAg). RESULTS The primary end point - normalization of alanine aminotransferase levels and clearance of HDV RNA at week 48 - was achieved in two patients in the group receiving peginterferon alfa-2a plus adefovir and two patients in the group receiving peginterferon alfa-2a plus placebo but in none of the patients in the group receiving adefovir alone. At week 48, the test for HDV RNA was negative in 23% of patients in the first group, 24% of patients in the second, and none of those in the third (P=0.006 for the comparison of the first and third groups; P=0.004 for the comparison of the second and third). The efficacy of peginterferon alfa-2a was sustained for 24 weeks after treatment, with 28% of the patients receiving peginterferon alfa-2a plus adefovir or peginterferon alfa-2a alone having negative results on HDV-RNA tests; none of the patients receiving adefovir alone had negative results. A decline in HBsAg levels of more than 1 log(10) IU per milliliter from baseline to week 48 was observed in 10 patients in the first group, 2 in the second, and none in the third (P<0.001 for the comparison of the first and third groups and P=0.01 for the comparison of the first and second). CONCLUSIONS Treatment with peginterferon alfa-2a for 48 weeks, with or without adefovir, resulted in sustained HDV RNA clearance in about one quarter of patients with HDV infection.