TY  - JOUR
A1  - Heidrich, Benjamin
A1  - Wiegand, Steffen B.
A1  - Buggisch, Peter
A1  - Hinrichsen, Holger
A1  - Link, Ralph
A1  - Möller, Bernd
A1  - Böker, Klaus H. W.
A1  - Teuber, Gerlinde
A1  - Klinker, Hartwig
A1  - Zehnter, Elmar
A1  - Naumann, Uwe
A1  - Busch, Heiner W.
A1  - Maasoumy, Benjamin
A1  - Baum, Undine
A1  - Hardtke, Svenja
A1  - Manns, Michael P.
A1  - Wedemeyer, Heiner
A1  - Petersen, Jörg
A1  - Cornberg, Markus
T1  - Treatment of Naive Patients with Chronic Hepatitis C Genotypes 2 and 3 with Pegylated Interferon Alpha and Ribavirin in a Real World Setting: Relevance for the New Era of DAA
JF  - PLOS ONE
N2  - Evidence based clinical guidelines are implemented to treat patients efficiently that include efficacy, tolerability but also health economic considerations. This is of particular relevance to the new direct acting antiviral agents that have revolutionized treatment of chronic hepatitis C. For hepatitis C genotypes 2/3 interferon free treatment is already available with sofosbuvir plus ribavirin. However, treatment with sofosbuvir-based regimens is 10-20 times more expensive compared to pegylated interferon alfa and ribavirin (PegIFN/RBV). It has to be discussed if PegIFN/RBV is still an option for easy to treat patients. We assessed the treatment of patients with chronic hepatitis C genotypes 2/3 with PegIFN/RBV in a real world setting according to the latest German guidelines. Overall, 1006 patients were recruited into a prospective patient registry with 959 having started treatment. The intention-to-treat analysis showed poor SVR (GT2 61%, GT3 47%) while patients with adherence had excellent SVR in the per protocol analysis (GT2 96%, GT3 90%). According to guidelines, 283 patients were candidates for shorter treatment duration, namely a treatment of 16 weeks (baseline HCV-RNA <800.000 IU/mL, no cirrhosis and RVR). However, 65% of these easy to treat patients have been treated longer than recommended that resulted in higher costs but not higher SVR rates. In conclusion, treatment with PegIFN/RBV in a real world setting can be highly effective yet similar effective than PegIFN +/- sofosbuvir/RBV in well-selected naive G2/3 patients. Full adherence to guidelines could be further improved, because it would be important in the new era with DAA, especially to safe resources.
KW  - peginterferon alpha-2B
KW  - HCV genotype-2
KW  - sofosbuvir
KW  - infection
KW  - epidemology
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115149
SN  - 1932-6203
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Epe, Bernd
A1  - Häring, Martin
A1  - Ramaiah, Danaboyina
A1  - Stopper, Helga
A1  - Abou-Elzahab, Mohamed M.
A1  - Adam, Waldemar
A1  - Saha-Möller, Chantu R.
T1  - DNA damage induced by furocoumarin hydroperoxides plus UV (360 nm)
N2  - Wben irradiated at 360 nm, furocoumarins with a hydroperoxide group in a side chain effciently give rise to a type of DNA damage that can best be explained by a photoinduced generation of hydroxyl radicals from the excited pbotosensitizers. The observed DNA damage profiles, i.e. the ratios of single-strand breaks, sites of base loss (AP sites) and base modifications sensitive to fonnamidopyrimidine-DNA glycosylase (FPG protein) and endonuclease m, are similar to the DNA damage profile produced by hydroxyl radicals generated by lonizing radiation or by xanthine and xanthine oxidase in the presence of Fe(III)-EDTA. No such damage is observed with the corresponding furocoumarin alcohols or in the absence of near-UV radiation. The damage caused by the photo-excited hydroperoxides is not influenced by superoxide dismutase (SOD) or catalase or by D2O as solvent. The presence of t-butanol, however, reduces both the formation of single-strand breaks and of base odifications sensitive to FPG protein. The cytotoxicity caused by one of the hydroperoxides in L5178Y mome lymphoma cells is found to be dependent on the near-UV irradiation and to be much higher than that of the corresponding alcohol. Therefore the new type of photoinduced damage occurs inside cells. Intercalating photosensitizers with an attached hydroperoxide group might represent a novel and versatile class of DNA damaging agents, e.g. for phototherapy.
KW  - DNS-Schädigung
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86870
ER  - 
TY  - JOUR
A1  - Hartmann, Sylvia
A1  - Plütschow, Annette
A1  - Mottok, Anja
A1  - Bernd, Heinz‐Wolfram
A1  - Feller, Alfred C.
A1  - Ott, German
A1  - Cogliatti, Sergio
A1  - Fend, Falko
A1  - Quintanilla‐Martinez, Leticia
A1  - Stein, Harald
A1  - Klapper, Wolfram
A1  - Möller, Peter
A1  - Rosenwald, Andreas
A1  - Engert, Andreas
A1  - Hansmann, Martin‐Leo
A1  - Eichenauer, Dennis A.
T1  - The time to relapse correlates with the histopathological growth pattern in nodular lymphocyte predominant Hodgkin lymphoma
JF  - American Journal of Hematology
N2  - Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) can present with different histopathological growth patterns. The impact of these histopathological growth patterns on relapse characteristics is unknown. We therefore analyzed paired biopsies obtained at initial diagnosis and relapse from 33 NLPHL patients who had received first‐line treatment within German Hodgkin Study Group (GHSG) trial protocols, and from a second cohort of 41 relapsed NLPHL patients who had been treated outside GHSG studies. Among the 33 GHSG patients, 21 patients presented with a typical growth pattern at initial diagnosis, whereas 12 patients had a variant histology. The histopathological growth patterns at initial diagnosis and at relapse were consistent in 67% of cases. A variant histology at initial diagnosis was associated with a shorter median time to lymphoma recurrence (2.8 vs 5.2 years; P = .0219). A similar tendency towards a shorter median time to lymphoma recurrence was observed for patients presenting with a variant histology at relapse, irrespective of the growth pattern at initial diagnosis. Results obtained from the 41 NLPHL patients who had been treated outside GHSG studies were comparable (median time to lymphoma recurrence for variant histology vs typical growth pattern at initial diagnosis: 1.5 vs 7.0 years). In conclusion, the histopathological growth pattern remains consistent at relapse in the majority of NLPHL cases, and has major impact on the time of relapse.
KW  - Hodgkin lymphoma
KW  - relapse
KW  - growth patterns
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212594
VL  - 94
IS  - 11
SP  - 1208
EP  - 1213
ER  - 
TY  - JOUR
A1  - Heidrich, Benjamin
A1  - Cordes, Hans-Jörg
A1  - Klinker, Hartwig
A1  - Möller, Bernd
A1  - Naumann, Uwe
A1  - Rössle, Martin
A1  - Kraus, Michael R.
A1  - Böker, Klaus H.
A1  - Roggel, Christoph
A1  - Schuchmann, Marcus
A1  - Stoehr, Albrecht
A1  - Trein, Andreas
A1  - Hardtke, Svenja
A1  - Gonnermann, Andrea
A1  - Koch, Armin
A1  - Wedemeyer, Heiner
A1  - Manns, Michael P.
A1  - Cornberg, Markus
T1  - Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial
JF  - PLoS ONE
N2  - Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 \(\mu\)g/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68% [55%; 81%] in Group A and 57% [43%; 71%] in Group B achieved SVR (p=0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70%) was not met. In conclusion, approximately 23% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group.
KW  - chronic hepatitis C
KW  - peginterferon alpha-2b
KW  - infection
KW  - sofosbuvir
KW  - therapy
KW  - HCV genotype 2
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151811
VL  - 10
IS  - 6
ER  -