Seven-Year Efficacy and Safety of Treatment with Tenofovir Disoproxil Fumarate for Chronic Hepatitis B Virus Infection

Abstract

BackgroundLong-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).AimWe assessed the efficacy, safety, and resistance of TDF for up to 7 years (336 weeks) in HBeAg-positive and HBeAg-negative CHB patients.MethodsPatients 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).ResultsOf 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).ConclusionsLong-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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10620-014-3486-7) contains supplementary material, which is available to authorized users.

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…In addition, studies using sensitive markers of glomerular and tubular kidney function and of bone mineral density have also reported chronic tubular damage and decline of eGFR and bone mineral density in TDF treated patients. 70,[79][80][81][82][83][84][85][86][87] Therefore, it seems appropriate for now to monitor all CHB patients treated with TDF therapy for adverse renal effects with serum creatinine (eGFR) and serum phosphate levels. Moreover, CHB patients at high renal risk undergoing any NA therapy should be monitored with serum creatinine (eGFR) levels.…”

Treatment for hepatitis B in patients with drug resistance

“…At present, no typical TDF-resistant mutations have been described, even after 7 years of antiviral treatment (21). However, TDF shares some structural similarities to ADV, raising the concern of potential cross-resistance between both drugs.…”

A comparison between entecavir and tenofovir in chronic hepatitis B in the clinical practice: a single-center experience

“…I dati estrapolati dagli studi clinici registrativi [15][16][17] e dagli studi di real life [24][25][26][27][28] sui singoli farmaci mostrano tassi di risposta virologica, resistenza e tollerabilità simili fra ETV e TDF. Anche il rischio di nefrotossicità associata a TDF, emerso durante la sorveglianza post-marketing dei pazienti HIV-positivi trattati con TDF [29], appare molto basso nei pazienti con CHB [23,30], sebbene recentemente siano stati riportati 3 casi di sindrome di Fanconi in pazienti con CHB trattati con TDF [31,32]; lo stesso vale per la riduzione della densità minerale ossea [30]. Tuttavia, pochi studi hanno messo direttamente a confronto ETV con TDF.…”

“…Fra i NUC, entecavir (ETV) e tenofovir disoproxil fumarato (TDF) si distinguono per la potenza e l'elevata barriera genetica contro lo sviluppo di resistenze [15][16][17][18][19][20][21][22][23], per cui sono raccomandati come farmaci di prima linea nel trattamento della CHB [1,[11][12][13]. Sebbene l'efficacia e la sicurezza a lungo termine di ognuno sia stata valutata da studi clinici su larga scala [15][16][17][18][19][20][21][22][23][24][25][26][27][28], i dati comparativi fra i due farmaci sono molto limitati.…”