Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA.
OBJECTIVE
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. We evaluated the effects of single and combination therapies in immune-tolerant patients with chronic hepatitis B.


METHODS
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 alanine aminotransferase 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 end point was proportion of patients with serum levels of HBV DNA <69 IU/mL at week 192.


RESULTS
The study population (mean age was 33 years; 89% were Asian) was predominantly infected with HBV genotypes B and C (93%), 99% were HBeAg positive with a mean baseline level of HBV DNA of 8.41 log10 IU/mL. At week 192, 55% of patients (35 of 64) in the TDF+placebo group and 76% of patients (47 of 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.


CONCLUSIONS
In HBeAg-positive patients with chronic HBV infection, high viral loads, normal levels of alanine aminotransferase, and therapy with the combination of TDF and emtricitabine provided better viral suppression than TDF alone, although rates of HBeAg seroconversion and hepatitis B surface antigen loss were low.
Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong. Electronic address: hlychan@cuhk.edu.hk.
Henry L Y
HL
Chan
Queen Mary Hospital, University of Hong Kong, Hong Kong.
Chi Kuen
CK
Chan
Alice Ho Miu Ling Nethersole Hospital, Hong Kong.
Aric Josun
AJ
Hui
Chan, Sing Private Practice, Flushing, New York.
Sing
S
Chan
Texas Liver Institute, San Antonio, TX.
Fred
F
Poordad
National Cheng Kung University Hospital, Tainan, Taiwan.
Ting-Tsung
TT
Chang
Hôpital Claude Huriez, Lille, France.
Philippe
P
Mathurin
Gilead Sciences, Inc., Foster City, California.
John F
JF
Flaherty
Gilead Sciences, Inc., Foster City, California.
Lanjia
L
Lin
Gilead Sciences, Inc., Foster City, California.
Amy
A
Corsa
Gilead Sciences, Inc., Foster City, California.
Anuj
A
Gaggar
Gilead Sciences, Inc., Foster City, California.
G Mani
GM
Subramanian
Gilead Sciences, Inc., Foster City, California.
John G
JG
McHutchison
George
G
Lau
Heritage Medical Research Clinic, University of Calgary, Calgary, Ontario, Canada.
Sam
S
Lee
Auckland General Hospital, University of Auckland, Auckland, New Zealand.
Edward J
EJ
Gane
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010757:Phosphorous Acids / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
C574165:9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine; D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D010757:Phosphorous Acids; D003841:Deoxycytidine; D000410:Alanine Transaminase; D000068679:Emtricitabine; D000225:Adenine
Combination Therapy; FTC; HBsAg; Immune Tolerant