1Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong. Electronic address: firstname.lastname@example.org.
2Queen Mary Hospital, University of Hong Kong, Hong Kong.
3Alice Ho Miu Ling Nethersole Hospital, Hong Kong.
4Chan, Sing Private Practice, Flushing, NY.
5Texas Liver Institute, San Antonio, TX.
6National Cheng Kung University Hospital, Tainan, Taiwan.
7Hôpital Claude Huriez, Lille, France.
8Gilead Sciences, Inc., Foster City, CA.
9Heritage Medical Research Clinic, University of Calgary, Calgary, Canada.
10Auckland General Hospital, University of Auckland, Auckland, New Zealand.
& aims: Little is known about the benefit of antiviral therapy for hepatitis B e antigen (HBeAg)-positive patients with high viral load and normal levels of alanine aminotransferase (ALT). We evaluated the effects of single and combination therapies in immune-tolerant patients with chronic hepatitis B.
In a double-blind study, nucleos(t)ide-naïve patients with high levels of hepatitis B virus (HBV) DNA who were positive for HBeAg and had normal levels of ALT were randomly assigned to groups given either oral tenofovir disoproxil fumarate (TDF, 300 mg) and placebo (n=64) or a combination of TDF (300 mg) and emtricitabine (200 mg, n=62) for 192 weeks. The primary endpoint was proportion of patients with serum levels of HBV DNA <69 IU/mL at week 192.
The study population (mean age, 33 y; 89% Asian) was predominantly infected with HBV genotypes B and C (93%), 99% HBeAg positive, with a mean baseline level of HBV DNA of 8.41 log10 IU/mL. At week 192, 55% of patients (35/64) in the TDF+placebo group and 76% of patients (47/62) in the TDF+emtricitabine group had levels of HBV DNA <69 IU/mL (P=.016). No patients were found to have viral resistance to therapy. HBeAg seroconversion occurred in 3 patients (5%), all in the TDF+placebo group; no patient had loss of hepatitis B surface antigen. In multivariate analysis, female sex (odds ratio, 7.05; P=.002) and TDF+emtricitabine treatment (odds ratio, 3.9; P=.01) were associated with a favorable response. Both regimens were well tolerated.
In HBeAg-positive patients with chronic HBV infection, high viral loads, normal levels of ALT, and therapy with the combination of TDF and emtricitabine provided better viral suppression than TDF alone, although rates of HBeAg seroconversion and HBsAg loss were low.