Browsing by Author "Dinh, Phillip"
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Publication 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 (tdf) therapy and the risk of hepatocellular carcinoma(Elsevier, 2013-04) Kim, W. R.; Berg, Thomas; Loomba, Rohit; Schall, Raul Aguilar; Dinh, Phillip; Yee, Leland J.; Martins, Eduardo B.; Flaherty, John F.; Buti, Maria; Marcellin, P.; Gürel, Selim; Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı.Item 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 Randomized comparison of tenofovir disoproxil fumarate vs emtricitabine and tenofovir disoproxil fumarate in patients with lamivudine-resistant chronic hepatitis b(W B Saunders Co-Elsevier Inc, 2014-04-01) Fung, Scott; Kwan, Peter; Fabri, Milotka; Horban, Andrzej; Pelemis, Mijomir; Hann, Hie-Won; Gürel, Selim; Caruntu, Florin A.; Flaherty, John F.; Massetto, Benedetta; Dinh, Phillip; Corsa, Amoreena; Subramanian, G. Mani; McHutchison, John G.; Husa, Petr; Gane, Edward; GÜREL, SELİM; Uludag Üniversitesi/Tıp Fakültesi.; HLH-8209-2023BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) is active against lamivudine-resistant hepatitis B virus (HBV) infection, but data to support its clinical efficacy in this setting are limited.METHODS: In a prospective, double-blind, 96-week trial, patients were randomly assigned (1:1) to groups given TDF (300 mg, n = 141) or a combination of emtricitabine (FTC, 200 mg; n 139) and TDF (300 mg, FTC/TDF). Patients were hepatitis B e antigen (HBeAg) - positive or HBeAg-negative, with levels of HBV DNA >= 3 log10 IU/mL and lamivudine resistance mutations (HBV polymerase or reverse transcriptase amino acid substitutions rtM204I/V +/- rtL180M by INNO-LiPA Multi-DR v3; Innogenetics, Inc, Alpharetta, GA). The primary end point was proportion with HBV DNA <69 IU/mL (Roche COBAS Taqman assay; Roche Molecular Systems, Inc, Pleasanton, CA).RESULTS: Patient groups were well matched for demographic and disease characteristics, including region (60% from Europe), HBV genotype (45% genotype D), HBeAg status (47% HBeAg-positive), and duration of lamivudine treatment (mean, 3.8 years). At week 96 of treatment, 89.4% of patients in the TDF group and 86.3% in the FTC/TDF group had levels of HBV DNA <69 IU/mL (P = .43). HBeAg loss and seroconversion did not differ between groups; only 1 patient (0.7%) in the FTC/TDF group lost hepatitis B surface antigen. Treatment was well tolerated; confirmed renal events (creatinine increase of >= 0.5 mg/dL [>44 umol/L], creatinine clearance <50 mL/min, or level of PO4 <2 mg/dL [<0.65 mmol/L]) were generally mild and infrequent (<1%). Small reductions (<2%) in mean bone mineral density of hip and spine were detected by dual-energy x-ray absorptiometry in both groups. No TDF resistance developed through 96 weeks of treatment.CONCLUSIONS: TDF alone is safe and effective for treatment of patients with lamivudine-resistant, chronic HBV infection. Clinical Trials.gov No, NCT00737568.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-8209-2023