By
Liz Highleyman
Pietro
Lampertico and colleagues from Italy assessed the influence
of treatment duration on response rates among hepatitis B "e"
antigen (HBeAg) negative chronic hepatitis B patients with genotype
D virus.
Treatment with pegylated interferon for 1 year leads to long-term
virological response in a proportion of HBeAg negative chronic
hepatitis B patients, but genotype D has been shown to be less
responsive to interferon compared with genotypes A, B, or
C, the researchers noted as background.
Prior research showed that an extended duration of therapy with
conventional interferon led to improved response rates, and
the present study aimed to determine whether the same would
be true for pegylated interferon.
The analysis included 127 Italian hepatitis B patients who were
randomly allocated to receive 3 regimens:
 |
180
mcg/week pegylated
interferon alfa-2a (Pegasys) for 48 weeks; |
|
180
mcg/week pegylated interferon for 48 weeks, followed by
a lower dose of 135 mcg/week for an additional 48 weeks
(total 96 weeks); |
|
180
mcg/week pegylated interferon plus 100 mg/day lamivudine
(Epivir-HBV) for 48 weeks, followed by the lower dose
for an additional 48 weeks. |
About
70% of study participants were men and the average age was 45
years. Almost all (94%) had HBV genotype D, ALT was elevated
(median 95 IU/mL), the median baseline HBV viral load level
was about 6 logs, and 12% had liver cirrhosis.
Results
|
In
an intent-to-treat analysis, virological response rates
at the end of treatment were similar in patients treated
for 48 and 96 weeks (59% vs 67%, respectively; not a statistically
significant difference). |
|
Rates
were also statistically similar at 6 months post-treatment
(22% vs 29%, respectively). |
|
Patients
in the 48 week group, however, were more likely to experience
viral relapse after 6 months. |
|
After
1 year of post-treatment follow-up, participants treated
for 48 weeks had a significantly lower sustained virological
response rate than those treated for 96 weeks (12% vs 29%,
respectively; P = 0.03). |
|
ALT
normalization rates at the end of treatment were similar
in the 48 week and 96 week groups (29% vs 31%, respectively). |
|
No
patients in the 48 week group experienced hepatitis B surface
antigen (HBsAg) clearance, while in the 96 week group 2%
did at the end of treatment and 6% did so during 1 year
of follow-up. |
|
At
the end of treatment, 4% of participants in the 48 week
group and 8% in the 96 week group had HBsAg <
10 IU/mL, but after 1 year of follow-up the respective rates
diverged to 0 and 10%, respectively. |
|
Treatment
discontinuation rates were similar regardless of duration. |
|
Extended
duration pegylated interferon was well-tolerated, with no
observed increase in adverse events or safety issues. |
|
Adding
lamivudine to extended duration pegylated interferon did
not improve treatment response rates. |
|
Combination
pegylated interferon/lamivudine was also well-tolerated
overall, but was associated with more serious adverse events. |
Based
on these findings, the investigators concluded, "In HBeAg
negative genotype D patients with chronic hepatitis B, 2 year
treatment with pegylated interferon alfa-2a was safe and improved
significantly the rates of post-treatment virological and serological
response."
First Division Gastroenterology, IRCCS Fondazione Policlinico,
Milan; Liver Unit, Cardarelli Hospital, Naples; Infectious Disease
Unit, SS Anna and Sebastiano Hospital, Caserta; Clinic of Infectious
Disease, Universita di Bari, Bari; Gastroenterology and Hepatology
Unit, Universita di Palermo, Palermo; Department of Surgical
and Gastroenterological Sciences, Universita di Padova, Padova;
Medical Science Department, Universita di Cagliari, Cagliari;
Department of Internal Medicine, IRCCS Fondazione Policlinico,
Universita di Studi di Milano, Milan; Unit of Infectious Diseases
and Hepatology, Azienda Ospedaliera di Parma, Parm; Biostatistics
Unit of Quintiles, Milan, 11Roche, Monza, Italy.
5/7/10
Reference
P Lampertico, M Vigano, G Di Costanzo, and others. Extended
(2 years) treatment with peginterferon alfa-2a [40kd] improves
sustained response rates in genotype D patients with HBeAg negative
chronic hepatitis B. 45th Annual Meeting of the European Association
for the Study of the Liver (EASL 2010). Vienna, Austria. April
14-18, 2010. (Abstract
98).
