Efficacy and safety of tenofovir disoproxil fumarate in Asian-Americans with chronic hepatitis B in community settings

Calvin Q Pan, Huy Trinh, Alan Yao, Ho Bae, Lillian Lou, Sing Chan, Study 123 Group, Calvin Q Pan, Huy Trinh, Alan Yao, Ho Bae, Lillian Lou, Sing Chan, Study 123 Group

Abstract

Background and aims: Chronic hepatitis B (CHB) disproportionately affects the Asian-American population in the USA. Tenofovir disoproxil fumarate (TDF) has demonstrated potent antiviral activity in clinical trials, but data in Asian-Americans from community studies are lacking.

Methods: Adult Asian-American patients with CHB from private medical and community-based practices were prospectively enrolled and treated with open-label TDF 300 mg once daily in a single-arm study for 48 weeks. After Week 48, patients had the option to transition to commercially available CHB therapy. The primary efficacy endpoint was hepatitis B virus (HBV) DNA <400 copies/mL at Week 48. Secondary endpoints were safety and tolerability, serologic and biochemical responses, liver fibrosis by FibroTest, and the development of drug-resistant mutations.

Results: Of the 90 patients enrolled, 53 (58%) were hepatitis B e antigen (HBeAg)-positive at baseline. At Week 48, 74 patients (82% overall; 70% HBeAg-positive and 100% HBeAg-negative) had HBV DNA <400 copies/mL. Six (12%) HBeAg-positive patients achieved HBeAg loss/seroconversion. The percentage of patients with alanine aminotransferase in the normal range increased from 26% at baseline to 66% at Week 48. The percentage of patients with F0 (no or minimal) fibrosis by FibroTest increased from 48% to 51%, and those with F4 (severe) fibrosis decreased from 4% to 1%. No resistance to TDF developed. Treatment was well tolerated. Most adverse events were mild in severity and considered unrelated to study drug.

Conclusions: TDF is effective and well tolerated in Asian-American CHB patients in community clinic-based settings, consistent with larger registration trials. Improvement in liver fibrosis was seen in a proportion of patients. No resistance to TDF developed through 48 weeks of treatment.

Trial registration: Clinicaltrial.gov identifier NCT00736190.

Conflict of interest statement

Competing Interests: We have the following interests. This study was sponsored by Gilead, the employer of LL at the time of the study. Lillian Lou is employed by Nexus Development. CQP has acted as a consultant or speaker for Gilead Sciences, Genentech, Vertex, Onyx, BMS, and Merck, and has received grants from Gilead Sciences, Roche, BMS, and Vertex. HT has acted as a speaker and advisory board member, and has received research grants from Gilead Sciences and BMS, and owns stock in Gilead Sciences. AY has acted as a speaker for Gilead Sciences and BMS. HB hs acted as a speaker for Gilead Sciences, BMS, and Genentech. SC has acted as a speaker for Gilead Sciences, and owns no more than $20K worth of Gilead stock. Tenofovir disoproxil fumarate is a product of Gilead Sciences. There are no further patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1. Disposition of study patients.
Figure 1. Disposition of study patients.
Figure 2. Efficacy of tenofovir in Asian-Americans.
Figure 2. Efficacy of tenofovir in Asian-Americans.
(A) Proportion of HBeAg-positive and HBeAg-negative patients with HBV DNA <400 copies/mL by treatment week; (B) Mean change from baseline in HBV DNA in HBeAg-positive and HBeAg-negative patients by treatment week; (C) Fibrotest score categories at baseline and Week 48 in HBeAg-positive and HBeAg-negative patients. HBeAg, hepatitis B ‘e’ antigen; LLOQ, lower limit of quantitation.
Figure 3. Mean change from baseline in…
Figure 3. Mean change from baseline in serum creatinine level (A) and clearance rate (B) in HBeAg-positive and HBeAg-negative patients by treatment week.
HBeAg, hepatitis B ‘e’ antigen.

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