Baseline Genotype And HBsAg Were Found To Have Significant Association With HBeAg Seroconversion Following Up To 4 Years Of Tenofovir Disoproxil Fumarate Treatment

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Baseline Genotype And HBsAg Were Found To Have Significant Association With

HBeAg

Seroconversion Following Up To 4 Years Of Tenofovir Disoproxil Fumarate

Treatment

J. Heathcote1, M. Manns2, P. Mathurin3, R. Ebrahimi4, J. 4, L. Lou4, C.

Ng4

1Patient Clinical Research, Toronto Western Research Institute, Toronto Western

Hospital, Toronto, ON, Canada, 2Department of Gastroenterology, Hepatology and

Endocrinology, Medical School of Hannover,

Hannover, Germany, 3Service d'Hépato-gastroentérologie, Hôpital Claude Huriez

2ème étage Est, Lille, France, 4Gilead Sciences Inc., City, CA, USA.

Summary

• Overall, 104 HBeAg (+) patients from Study 103 experienced

at least one event of HBeAg seroconversion during the 192

weeks

• Genotype A is associated with higher HBeAg seroconversion

• In the multivariate stepwise analysis, baseline genotype and

HBsAg levels were associated with HBeAg seroconversion.

─ No association was found with other baseline characteristics

including race, gender, HBV DNA levels, ALT levels and

Knodell scores

• Proportion of HBeAg seroconverted patients with HBsAg loss

increases over time

Background

• Tenofovir disoproxil fumarate (TDF) was approved for chronic

hepatitis B (CHB) in 2008

• TDF patients treated for 192 weeks maintained undetectable

HBV DNA, normal ALT levels and experienced increasing

HBeAg and HBsAg loss

─ 68% (TDF-TDF) and 72% (ADV-TDF) of HBeAg (+) patients

with HBV DNA <400 copies/mL (ITT analysis)

─ ~80% of all patients with normal ALT

─ 41% of HBeAg (+) patients on TDF with HBeAg loss

and 29% with HBeAg seroconversion

─ 10.8% HBeAg (+) patients on TDF with HBsAg loss

OBJECTIVE

• To identify the baseline characteristics associated with HBeAg

seroconversion for HBeAg (+) patients who have been treated

with TDF for up to 4 years

METHODS

• Patients with HBeAg (+) CHB were randomized to doubleblind,

once daily TDF 300 mg or adefovir dipivoxil 10 mg

(ADV). After Week 48, eligible patients initiated open-label TDF

for 7 additional years

• Based on the study protocol, patients with HBeAg

seroconversion continued on treatment unless reaching either

HBsAg loss or HBsAg seroconversion

• A multivariate stepwise logistic regression analysis was

performed to screen for baseline factors associated with

HBeAg seroconversion

─ A p-value of 0.1 was used for entry and remaining in the

screening model

─ Signifi cance level of 0.05 was used for the fi nal model

• The Markov 2-State Model (considering a stochastic

process as opposed to one time event) refl ects HBeAg

seroconversion as a non-permanent event allowing the

estimate to account for obseved reversibility of HBeAg

status

• Special thanks to all participating investigators and patients in study

GS-US-174-0103

Poster Number

715

Results

Conclusions

• In Study 103, HBeAg seroconverison was found

in all major genotypes

• In a multivariate model of baseline factors, only

genotype and HBsAg levels were signifi cantly

predictive of HBeAg seroconversion

© 2011 Gilead Sciences, Inc. All rights reserved.

[Guest guest]

Baseline Genotype And HBsAg Were Found To Have Significant Association With

HBeAg

Seroconversion Following Up To 4 Years Of Tenofovir Disoproxil Fumarate

Treatment

J. Heathcote1, M. Manns2, P. Mathurin3, R. Ebrahimi4, J. 4, L. Lou4, C.

Ng4

1Patient Clinical Research, Toronto Western Research Institute, Toronto Western

Hospital, Toronto, ON, Canada, 2Department of Gastroenterology, Hepatology and

Endocrinology, Medical School of Hannover,

Hannover, Germany, 3Service d'Hépato-gastroentérologie, Hôpital Claude Huriez

2ème étage Est, Lille, France, 4Gilead Sciences Inc., City, CA, USA.

Summary

• Overall, 104 HBeAg (+) patients from Study 103 experienced

at least one event of HBeAg seroconversion during the 192

weeks

• Genotype A is associated with higher HBeAg seroconversion

• In the multivariate stepwise analysis, baseline genotype and

HBsAg levels were associated with HBeAg seroconversion.

─ No association was found with other baseline characteristics

including race, gender, HBV DNA levels, ALT levels and

Knodell scores

• Proportion of HBeAg seroconverted patients with HBsAg loss

increases over time

Background

• Tenofovir disoproxil fumarate (TDF) was approved for chronic

hepatitis B (CHB) in 2008

• TDF patients treated for 192 weeks maintained undetectable

HBV DNA, normal ALT levels and experienced increasing

HBeAg and HBsAg loss

─ 68% (TDF-TDF) and 72% (ADV-TDF) of HBeAg (+) patients

with HBV DNA <400 copies/mL (ITT analysis)

─ ~80% of all patients with normal ALT

─ 41% of HBeAg (+) patients on TDF with HBeAg loss

and 29% with HBeAg seroconversion

─ 10.8% HBeAg (+) patients on TDF with HBsAg loss

OBJECTIVE

• To identify the baseline characteristics associated with HBeAg

seroconversion for HBeAg (+) patients who have been treated

with TDF for up to 4 years

METHODS

• Patients with HBeAg (+) CHB were randomized to doubleblind,

once daily TDF 300 mg or adefovir dipivoxil 10 mg

(ADV). After Week 48, eligible patients initiated open-label TDF

for 7 additional years

• Based on the study protocol, patients with HBeAg

seroconversion continued on treatment unless reaching either

HBsAg loss or HBsAg seroconversion

• A multivariate stepwise logistic regression analysis was

performed to screen for baseline factors associated with

HBeAg seroconversion

─ A p-value of 0.1 was used for entry and remaining in the

screening model

─ Signifi cance level of 0.05 was used for the fi nal model

• The Markov 2-State Model (considering a stochastic

process as opposed to one time event) refl ects HBeAg

seroconversion as a non-permanent event allowing the

estimate to account for obseved reversibility of HBeAg

status

• Special thanks to all participating investigators and patients in study

GS-US-174-0103

Poster Number

715

Results

Conclusions

• In Study 103, HBeAg seroconverison was found

in all major genotypes

• In a multivariate model of baseline factors, only

genotype and HBsAg levels were signifi cantly

predictive of HBeAg seroconversion

© 2011 Gilead Sciences, Inc. All rights reserved.