Browsing by Author "Flisiak, Robert"
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Item Efficacy and safety of tenofovir alafenamide (TAF) at 96 weeks in chronic HBV (CHB) patients with risk factors for use of tenofovir disoproxil fumarate (TDF)(Wiley, 2017-10) Buti, Maria; Stepanova, Tatjana; Celen, Mustafa K.; Flisiak, Robert; Ryder, Stephen D.; Streinu, Adrian Cercel; Flaherty, John F.; Gaggar, Anu; Suri, Vithika; Mo, Shuyuan; Subramanian, Mani; Nurmukhametova, Elena; Zoulim, Fabien; Andreone, Pietro; Marcellin, Patrick; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi/Dahiliye Anabilim Dalı/Gastroenteroloji Bilim Dalı.; HLH-8209-2023Publication Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate(Elsevier, 2014-07-11) Marcellin, Patrick; Buti, Maria; Krastev, Zahari; de Man, Robert A.; Zeuzem, Stefan; Lou, Lillian; Gaggar, Anuj; Flaherty, John F.; Massetto, Benedetta; Lin, Lanjia; Dinh, Phillip; Subramanian, G. Mani; McHutchison, John G.; Flisiak, Robert; Gürel, Selim; Dusheiko, Geoffrey M.; Heathcote, E. Jenny; GÜREL, SELİM; Uludag Üniversitesi/Tıp Fakültesi.; HLH-8209-2023Background & Aims: In a study of 266 chronic hepatitis B e antigen (HBeAg)-positive patients, 23 experienced hepatitis B surface antigen (HBsAg) loss with up to 5 years of tenofovir disoproxil fumarate (TDF) treatment. HBsAg kinetics in patients with and without HBsAg loss and predictors of HBsAg loss were evaluated.Methods: HBsAg levels were quantified every 12 weeks. A multivariable regression analysis, involving prespecified baseline characteristics and on-treatment response parameters, was performed; a stepwise procedure identified independent predictors of HBsAg loss.Results: Among patients with HBsAg loss, 14 (61%), 1 (4%), 0 and 7 (30%) were genotypes A through D, respectively; 1 (4%) was genotype F. HBsAg loss was preceded by viral suppression (HBV DNA < 29 IU/ml; n = 23) and HBeAg loss (n = 19). Among treated patients the strongest independent predictors of HBsAg loss were Caucasian race with genotype A/D and 64 years of infection (HR = 14.3, 95% confidence interval [CI] 4.7-43.4; p < 0.0001) and an HBsAg decline of >= 1 log(10) IU/ml at week 24 (HR = 13.7, 95% CI 5.6-33.7; p < 0.0001). Among TDF-treated patients, a reduction in HBsAg level of >= 1-log(10) by week 12 or 24 had a positive predictive value of 35%-45%, respectively, and a negative predictive value of 94%-97%, respectively.Conclusions: HBsAg loss in HBeAg-positive patients receiving TDF involves a chronology of virologic and serologic responses; patients with HBV genotypes A or D and a rapid early decline in HBsAg are more likely to lose HBsAg.Item Long term tenofovir disoproxil fumarate for chronic hepatitis B infection is associated with sustained virological, biochemical and serological responses with no detectable resistance(Wiley, 2014-11) Chan, Alain; Marcellin, Patrick; Tsai, Naoky; Flisiak, Robert; Petersen, Jorg; Kotzev, Iskren; Flaherty, John; Gaggar, Anuj; Kitrinos, Kathryn; Mchutchison, John; George, Jacob; Buti, Maria; Gane, Edward; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi.; HLH-8209-2023Publication Long term treatment with tenofovir disoproxil fumarate for chronic hepatitis b infection is safe and well tolerated and associated with durable virologic response with no detectable resistance: 8 year results from two phase 3 trials(Wiley, 2014-01-01) Marcellin, Patrick; Gane, Edward J.; Flisiak, Robert; Trinh, Huy N.; Petersen, Joerg; Gürel, Selim; Kaita, Kelly D.; Kotzev, Iskren A.; Tsai, Naoky; Flaherty, John F.; Schall, Raul E. Aguilar; Kitrinos, Kathryn M.; Subramanian, Mani; McHutchison, John G.; George, Jacob; Janssen, Harry L.; Buti, Maria; GÜREL, SELİM; Uludağ Üniversitesi/Tıp Fakültesi; HLH-8209-2023Item Long-term clinical outcomes in cirrhotic chronic hepatitis B patients treated with tenofovir disoproxil fumarate for up to 5 years(Springer, 2015-04) Buti, Maria; Fung, Scott; Gane, Edward; Afdhal, Nezam H.; Flisiak, Robert; Flaherty, John F.; Martins, Eduardo B.; Yee, Leland J.; Dinh, Phillip; Bornstein, Jeffrey D.; Subramanian, G. Mani; Janssen, Harry L. A.; George, Jacob; Marcellin, Patrick; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi/Gastroenteroloji Anabilim Dalı.; 7003706434Phase 3 clinical studies have shown that long-term treatment with tenofovir disoproxil fumarate (TDF) can suppress hepatitis B viral load and promote significant fibrosis regression and cirrhosis reversal in a majority of treated chronic hepatitis B (CHB) patients. This retrospective analysis investigated the impact of baseline cirrhosis status on virologic, serologic, and histologic outcomes in patients treated with TDF. Patients enrolled in studies GS-US-174-0102 and GS-US-174-0103 who had baseline liver biopsy-diagnosed cirrhosis and entered the open-label phase of the studies were included in the virologic and serologic analyses. Patients (both HBeAg positive and negative) with paired liver biopsies at baseline and 5 years (N = 348) were included in a histologic analysis. After 5 years on study, comparing patients with and without baseline cirrhosis, respectively: 99.2 and 98.0 % achieved virologic response (hepatitis B viral load < 69 IU/ml) (p = 0.686); 79.7 and 81.9 % had normal serum levels of alanine aminotransferase (p = 0.586); 4.0 and 1.2 % developed hepatocellular carcinoma (p = 0.044). In HBeAg-positive patients with and without baseline cirrhosis, HBsAg loss occurred in 14.4 and 8.3 % of patients, respectively (p = 0.188). One HBeAg-negative patient had HBsAg loss. This represents the largest analyses to date of CHB patients with sequential liver biopsies demonstrating that treatment with TDF for up to 5 years is associated with favorable virologic, serologic, and histologic outcomes, regardless of baseline cirrhosis status. Notably, histologic improvement was observed in the majority of cirrhotic and noncirrhotic patients.Publication Seven years of treatment with tenofovir df for chronic hepatitis b virus infection is safe and well tolerated and associated with sustained virological, biochemical and serological responses with no detectable resistance(Wiley-blackwell, 2013-10-01) Marcellin, Patrick; Gane, Edward J.; Tsai, Naoky; Flisiak, Robert; Petersen, Joerg; Kotzev, Iskren A.; Flaherty, John F.; Dinh, Phillip; Gaggar, Anuj; Kitrinos, Kathryn M.; Subramanian, Mani; McHutchison, John G.; George, Jacob; Buti, Maria; Gurel, Selim; GÜREL, SELİM; Bursa Uludağ Üniversitesi/Tıp Fakültesi; HLH-8209-2023Item Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis b virus ınfection(Springer, 2015-05) Tsai, Naoky; Petersen, Joerg; Flisiak, Robert; Krastev, Zahary; Schall, Raul Aguilar; Flaherty, John F.; Martins, Eduardo B.; Charuworn, Prista; Kitrinos, Kathryn M.; Subramanian, G. Mani; Gane, Edward; Marcellin, Patrick; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı/Gastroenteroloji Bilim Dalı.; 7003706434Background Long-term tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB) is associated with sustained viral suppression and regression of fibrosis and cirrhosis at year 5 (240 weeks) and no TDF resistance through 6 years (288 weeks). Aim We assessed the efficacy, safety, and resistance of TDF for up to 7 years (336 weeks) in HBeAg-positive and HBeAg-negative CHB patients. Methods Patients who completed 1 year (48 weeks) of randomized treatment with TDF or adefovir dipivoxil were eligible to receive open-label TDF for a total duration of 8 years (384 weeks). Results Of 641 patients initially randomized, 585 (91.3 %) entered the open-label phase; 437/585 (74.7 %) remained on study at year 7. For patients on treatment at year 7, 99.3 % maintained viral suppression (HBV DNA < 69 IU/mL), 80.0 % achieved serum alanine aminotransferase normalization, and in HBeAg-positive patients, 84/154 (54.5 %) and 25/154 (11.8 %) achieved HBeAg and HBsAg loss, respectively. One/375 (0.3 %) HBeAg-negative patients achieved HBsAg loss. No resistance to TDF was detected through 7 years. During the open-label phase, grade 3/4 drug-related adverse events were uncommon (1.0 %); ten (1.7 %) patients had elevation of serum creatinine >= 0.5 mg/dL above baseline. No significant change in bone mineral density was observed from year 4 to year 7 (week 192 to week 336). Conclusions Long-term TDF treatment was associated with sustained virologic, biochemical, and serologic responses, without resistance. TDF treatment was well tolerated, with a low incidence of renal and bone events. These data confirm the safety and efficacy of long-term TDF for CHB.Item Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B(Elsevier, 2011-01) Heathcote, E. Jenny; Marcellin, Patrick; Buti, Maria; Gane, Edward; De Man, Robert A.; Krastev, Zahary; Germanidis, George; Lee, Samuel S.; Flisiak, Robert; Kaita, Kelly; Manns, Michael; Kotzev, Iskren; Tchernev, Konstantin; Buggisch, Peter; Weilert, Frank; Kurdas, Oya Ovunc; Shiffman, Mitchell L.; Trinh, Huy; Snow-Lampart, Andrea; Borroto, Katyna Esoda; Mondou, Elsa; Anderson, Jane; Sorbel, Jeff; Rousseau, Franck; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi/ İç Hastalıkları Anabilim Dalı.; 7003706434BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF), a nucleotide analogue and potent inhibitor of hepatitis B virus (HBV) polymerase, showed superior efficacy to adefovir dipivoxil in treatment of chronic hepatitis B through 48 weeks. We evaluated long-term efficacy and safety of TDF monotherapy in patients with chronic hepatitis B who were positive or negative for hepatitis B e antigen (HBeAg+ or HBeAg-). METHODS: After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, patients who underwent liver biopsy were eligible to continue the study on open-label TDF for 7 additional years; data presented were collected up to 3 years (week 144) from 85% of participants. Primary efficacy end points at week 144 included levels of HBV DNA and alanine aminotransferase, development of resistance mutations, and presence of HBeAg or hepatitis B surface antigen (HBsAg). RESULTS: At week 144, 87% of HBeAg- and 72% of HBeAg+ patients treated with TDF had levels of HBV DNA <400 copies/mL. Among patients who had previously received adefovir dipivoxil and then received TDF, 88% of the HBeAg- and 71% of the HBeAg+ patients had levels of HBV DNA <400 copies/mL; overall, 81% and 74%, respectively, maintained normalized levels of alanine aminotransferase and 34% had lost HBeAg. Amino acid substitutions in HBV DNA polymerase that are associated with resistance to tenofovir were not detected in any patient. Cumulatively, 8% of HBeAg+ patients lost HBsAg. TDF maintained a favorable safety profile for up to 3 years. CONCLUSIONS: TDF was safe and effective in the long-term management of HBeAg+ and HBeAg- patients with chronic hepatitis B.