Browsing by Author "Bremer, Birgit"
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Publication A novel non-invasive fibrosis score based on cytokines and clinical parameters for the use in chronic hepatitis delta(Wiley-blackwell, 2013-10-01) Heidrich, Benjamin; Wranke, Anika; Yurdaydin, Cihan; Stift, Judith; Caruntu, Florin A.; Curescu, Manuela G.; Yalcin, Kendal; Zeuzem, Stefan; Erhardt, Andreas; Lueth, Stefan; Papatheodoridis, George V.; Bremer, Birgit; Grabowski, Jan; Kirschner, Janina; Port, Kerstin; Cornberg, Markus; Christine, Falk; Dienes, Hans Peter; Hardtke, Svenja; Manns, Michael P.; Wedemeyer, Heiner; Gurel, 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 Anti-HDV IgM as a marker of disease activity in hepatitis delta(Public Library Science, 2014-07-29) Wranke, Anika; Heidrich, Benjamin; Ernst, Stefanie; Serrano, Beatriz Calle; Caruntu, Florin Alexandru; Curescu, Manuela Gabriela; Yalcin, Kendal; Gürel, Selim; Zeuzem, Stefan; Erhardt, Andreas; Lueth, Stefan; Papatheodoridis, George V.; Bremer, Birgit; Stift, Judith; Grabowski, Jan; Kirschner, Janina; Port, Kerstin; Cornberg, Markus; Falk, Christine S.; Dienes, Hans-Peter; Hardtke, Svenja; Manns, Michael P.; Yurdaydin, Cihan; Wedemeyer, Heiner; HIDIT-2 Study Grp; GÜREL, SELİM; Uludağ Üniversitesi/Tıp Fakültesi.; HLH-8209-2023Background: Hepatitis delta frequently leads to liver cirrhosis and hepatic decompensation. As treatment options are limited, there is a need for biomarkers to determine disease activity and to predict the risk of disease progression. We hypothesized that anti-HDV IgM could represent such a marker.Methods: Samples of 120 HDV-infected patients recruited in an international multicenter treatment trial (HIDIT-2) were studied. Anti-HDV IgM testing was performed using ETI-DELTA-IGMK-2-assay (DiaSorin). In addition, fifty cytokines, chemokines and angiogenetic factors were measured using multiplex technology (Bio-Plex System). A second independent cohort of 78 patients was studied for the development of liver-related clinical endpoints (decompensation, HCC, liver transplantation or death; median follow up of 3.0 years, range 0.6-12).Results: Anti-HDV IgM serum levels were negative in 18 (15%), low (OD<0.5) in 76 (63%), and high in 26 (22%) patients of the HIDIT-2 cohort. Anti-HDV IgM were significantly associated with histological inflammatory (p<0.01) and biochemical disease activity (ALT, AST p<0.01). HDV replication was independent from anti-HDV IgM, however, low HBV-DNA levels were observed in groups with higher anti-HDV IgM levels (p<0.01). While high IP-10 (CXCL10) levels were seen in greater groups of anti-HDV IgM levels, various other antiviral cytokines were negatively associated with anti-HDV IgM. Associations between anti-HDV IgM and ALT, AST, HBV-DNA were confirmed in the independent cohort. Clinical endpoints occurred in 26 anti-HDV IgM positive patients (39%) but in only one anti-HDV IgM negative individual (9%; p = 0.05).Conclusions: Serum anti-HDV IgM is a robust, easy-to-apply and relatively cheap marker to determine disease activity in hepatitis delta which has prognostic implications. High anti-HDV IgM levels may indicate an activated interferon system but exhausted antiviral immunity.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.Publication Anti-hdv-igm levels as a marker of disease activity and response to pegylated interferon-α based therapy in hepatitis delta(Wiley-blackwell, 2013-10-01) Wranke, Anika; Yurdaydin, Cihan; Heidrich, Benjamin; Ernst, Stefanie; Koch, Armin; Serrano, Beatriz Calle; Caruntu, Florin A.; Curescu, Manuela G.; Yalçın, Kendal; Zeuzem, Stefan; Erhardt, Andreas; Lueth, Stefan; Papatheodoridis, George V.; Bremer, Birgit; Stift, Judith; Kirschner, Janina; Port, Kerstin; Cornberg, Markus; Dienes, Hans P.; Hardtke, Svenja; Manns, Michael P.; Wedemeyer, Heiner; Gurel, Selim; GÜREL, SELİM; Bursa Uludağ Üniversitesi/Tıp Fakültesi; HLH-8209-2023Item Anti-hdv-igm testing in hepatitis delta revisited: Correlations with disease activity and response to pegylated interferon alfa-2a treatment(Elsevier, 2010) Mederacke, Ingmar; Yurdaydın, Cihan; Bremer, Birgit; Çakaloğlu, Yılmaz; Erhardt, A.; Yalçın, Kendal; Zachou, Kalliopi; Heidrich, Benjamin; Dalekos, Georgios N.; Dienes, Hans P.; Manns, M. P.; Wedemeyer, Heiner; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı.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 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-8209-2023