Date: 23 Dec 2014
Seven-Year Efficacy and Safety of Treatment with Tenofovir Disoproxil Fumarate for Chronic Hepatitis B Virus Infection
Maria Buti, Naoky Tsai, Joerg Petersen, Robert Flisiak, Selim Gurel, Zahary Krastev, Raul Aguilar Schall, John F. Flaherty, Eduardo B. Martins, Prista Charuworn, Kathryn M. Kitrinos, G. Mani Subramanian, Edward Gane, Patrick Marcellin
1. Department of Hepatology, Hepatic and Digestive Diseases (CIBERehd), Hospital General Universitari Vall d’Hebron and Networked Biomedical Research Center, Pg. Vall d’Hebron, 119-129, 08035, Barcelona, Spain
2. Department of Medicine, Queens Medical Center, University of Hawaii at Manoa, 550 S. Beretania Street, POB III #405, Honolulu, HI, 96734, USA
3. Head, Liver Unit, IFI Institute at the Asklepios Klinik St. Georg Hamburg, University of Hamburg, Haus L, Lohmühlenstr. 5, 20099, Hamburg, Germany
4. Department of Infectious Diseases and Hepatology Medical, University of Białystok, 15-540, Białystok, Poland
5. Department of Gastroenterology, University of Uludag, Özlüce Mh., 16120, Bursa, 16059, Turkey
6. Department of Gastroenterology, University Hospital, St. Ivan Rilsky, 15 Akademik Ivan Geshov, 1431, Sofia, Bulgaria
7. Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA
8. Department of Gastroenterology and Hepatology, Auckland City Hospital, 2 Park Road, Auckland, 1142, New Zealand
9. Service d’Hepatologie, Hôpital Beaujon, 100 Boulevard du General Leclerc, 92110, Clichy, France
Abstract
Background
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.
641例患者最初随机,585(91.3%)进入了开放性阶段;五百八十五分之四百三十七(74.7%)仍然在研究在每年7.患者在治疗7年,99.3%维持抑制病毒(HBV DNA <69 IU / mL)中,80.0%达到血清谷丙转氨酶正常化,和HBeAg阳性患者中,154分之84(54.5%)和一百五十四分之二十五(11.8%)获得HBeAg和HBsAg消失,分别。一/ 375(0.3%)HBeAg阴性患者的HBsAg实现损失。到TDF无电阻通过7年检测。在开放标签阶段,3/4级药物相关的不良事件少见(1.0%);十(1.7%)患者血清肌酐≥0.5毫克/升以上基准抬高。骨密度无显著的变化是从今年4观察到7年(192周周336)。
结论