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, Jenny 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., Foster 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.
