HBV Genotype Predicts HBeAg Seroconversion on Tenofovir

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http://www.hivandhepatitis.com/2011_conference/easl2011/docs/0412_2010_c.html

HIV and Hepatitis.com Coverage of the

46th Annual Meeting of the European

Association for the Study of the Liver

March 30 - April 3, 2011, Berlin, Germany

HBV Genotype Predicts HBeAg Seroconversion on Tenofovir

SUMMARY: Chronic hepatitis B patients with HBV genotype A and lower HBsAg levels

at baseline were more likely to experience HBeAg seroconversion during treatment

with tenofovir (Viread), researchers reported at EASL 2011.

By Liz Highleyman

Effectiveness of treatment for chronic hepatitis B virus (HBV) infection is

assessed in various ways, including decreased HBV DNA viral load, normalization

of ALT liver enzyme levels, and hepatitis B " e " antigen (HBeAg) and hepatitis B

surface antigen (HBsAg) seroconversion and loss.

In a poster presentation at the European Association for the Study of the

Liver's International Liver Congress (EASL 2011) this month in Berlin,

Heathcote and colleagues described a study looking at factors that predict HBeAg

seroconversion among people on long-term tenofovir treatment.

The analysis included 259 participants in the pivotal Gilead Study 103 who were

HBeAg positive at baseline. About 70% were men and about one-third were Asian.

More than half had advanced fibrosis or cirrhosis. HBV genotypes A, B, C, D were

all well represented.

Participants were randomly assigned to take tenofovir or adefovir (Hepsera) for

48 weeks. After the randomized phase, all patients could take open-label

tenofovir and were followed through 192 weeks (about 4 years); the ongoing study

will continue through week 384. Based on the study protocol, patients with HBeAg

seroconversion continued on treatment until they achieved either HBsAg loss or

seroconversion

Briefly, the main study results showed that 70% of patients treated with

tenofovir through week 192 maintained undetectable HBV DNA, about 80% had normal

ALT levels, and they experienced increasing HBeAg and HBsAg loss over time.

Results

Overall, 104 patients (40%) experienced at least 1 episode of HBeAg

seroconversion during 192 weeks of treatment:

72 who stayed on tenofovir the whole time;

32 who switched from adefovir to tenofovir.

The mean time to the first HBeAg seroconversion was 69 weeks.

The proportion of patients with HBeAg seroconversion who also achieved HBsAg

loss increased over time.

People with all HBV genotypes experienced HBeAg seroconversion, but this was

more likely in people with genotype A:

Genotype D vs A: odds ratio 0.28, or 72% less likely;

Genotype C vs A: odds ratio 0.18;

Genotype B vs A: odds ratio 0.15.

In a multivariate analysis, HBV genotype and baseline HBsAg level were

significantly associated with HBeAg seroconversion.

There were no significant associations, however, between HBeAg seroconversion

and other baseline characteristics including race/ethnicity, sex, HBV viral

load, ALT level, or Knodell necroinflammatory score.

" In Study 103, HBeAg seroconversion was found in all major genotypes, " the

investigators concluded. In a multivariate model of baseline factors, they

added, only genotype and lower baseline HBsAg levels were " significantly

predictive " of HBeAg seroconversion.

Investigator affiliations: Patient Clinical Research, Toronto Western Research

Institute, Toronto Western Hospital, Toronto, ON, Canada; Department of

Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover,

Hannover, Germany; Service d'Hépato-Gastroentérologie, Hôpital Claude Huriez

2ème Étage Est, Lille, France; Gilead Sciences Inc., City, CA.

4/12/11

Reference

J Heathcote, M Manns, P Mathurin, et al. Baseline genotype and HBsAg were found

to have significant association with HBeAg seroconversion following up to 4

years of tenofovir disoproxil fumarate treatment. 46th Annual Meeting of the

European Association for the Study of the Liver (EASL 2011). Berlin. March

30-April 3. Abstract 592.

[Guest guest]

http://www.hivandhepatitis.com/2011_conference/easl2011/docs/0412_2010_c.html

HIV and Hepatitis.com Coverage of the

46th Annual Meeting of the European

Association for the Study of the Liver

March 30 - April 3, 2011, Berlin, Germany

HBV Genotype Predicts HBeAg Seroconversion on Tenofovir

SUMMARY: Chronic hepatitis B patients with HBV genotype A and lower HBsAg levels

at baseline were more likely to experience HBeAg seroconversion during treatment

with tenofovir (Viread), researchers reported at EASL 2011.

By Liz Highleyman

Effectiveness of treatment for chronic hepatitis B virus (HBV) infection is

assessed in various ways, including decreased HBV DNA viral load, normalization

of ALT liver enzyme levels, and hepatitis B " e " antigen (HBeAg) and hepatitis B

surface antigen (HBsAg) seroconversion and loss.

In a poster presentation at the European Association for the Study of the

Liver's International Liver Congress (EASL 2011) this month in Berlin,

Heathcote and colleagues described a study looking at factors that predict HBeAg

seroconversion among people on long-term tenofovir treatment.

The analysis included 259 participants in the pivotal Gilead Study 103 who were

HBeAg positive at baseline. About 70% were men and about one-third were Asian.

More than half had advanced fibrosis or cirrhosis. HBV genotypes A, B, C, D were

all well represented.

Participants were randomly assigned to take tenofovir or adefovir (Hepsera) for

48 weeks. After the randomized phase, all patients could take open-label

tenofovir and were followed through 192 weeks (about 4 years); the ongoing study

will continue through week 384. Based on the study protocol, patients with HBeAg

seroconversion continued on treatment until they achieved either HBsAg loss or

seroconversion

Briefly, the main study results showed that 70% of patients treated with

tenofovir through week 192 maintained undetectable HBV DNA, about 80% had normal

ALT levels, and they experienced increasing HBeAg and HBsAg loss over time.

Results

Overall, 104 patients (40%) experienced at least 1 episode of HBeAg

seroconversion during 192 weeks of treatment:

72 who stayed on tenofovir the whole time;

32 who switched from adefovir to tenofovir.

The mean time to the first HBeAg seroconversion was 69 weeks.

The proportion of patients with HBeAg seroconversion who also achieved HBsAg

loss increased over time.

People with all HBV genotypes experienced HBeAg seroconversion, but this was

more likely in people with genotype A:

Genotype D vs A: odds ratio 0.28, or 72% less likely;

Genotype C vs A: odds ratio 0.18;

Genotype B vs A: odds ratio 0.15.

In a multivariate analysis, HBV genotype and baseline HBsAg level were

significantly associated with HBeAg seroconversion.

There were no significant associations, however, between HBeAg seroconversion

and other baseline characteristics including race/ethnicity, sex, HBV viral

load, ALT level, or Knodell necroinflammatory score.

" In Study 103, HBeAg seroconversion was found in all major genotypes, " the

investigators concluded. In a multivariate model of baseline factors, they

added, only genotype and lower baseline HBsAg levels were " significantly

predictive " of HBeAg seroconversion.

Investigator affiliations: Patient Clinical Research, Toronto Western Research

Institute, Toronto Western Hospital, Toronto, ON, Canada; Department of

Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover,

Hannover, Germany; Service d'Hépato-Gastroentérologie, Hôpital Claude Huriez

2ème Étage Est, Lille, France; Gilead Sciences Inc., City, CA.

4/12/11

Reference

J Heathcote, M Manns, P Mathurin, et al. Baseline genotype and HBsAg were found

to have significant association with HBeAg seroconversion following up to 4

years of tenofovir disoproxil fumarate treatment. 46th Annual Meeting of the

European Association for the Study of the Liver (EASL 2011). Berlin. March

30-April 3. Abstract 592.