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Randomized Controlled Trial
. 2015 May;60(5):1457-64.
doi: 10.1007/s10620-014-3486-7. Epub 2014 Dec 23.

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

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Free PMC article
Randomized Controlled Trial

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

Maria Buti et al. Dig Dis Sci. .
Free PMC article

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.

Trial registration: ClinicalTrials.gov NCT00116805 NCT00117676.

Figures

Fig. 1
Fig. 1
Patient disposition at year 7
Fig. 2
Fig. 2
Disposition at year 7 (week 336) of patients who experienced confirmed HBsAg loss. aCompleted through year 7. bOne patient experienced seroreversion, restarted on treatment, and seroconverted again

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