V.
Rijckborst from Erasmus University Medical Center in Rotterdam
and colleagues investigated the association between early serum
HBsAg levels after starting therapy and sustained response in
HBeAg negative chronic hepatitis B patients treated with pegylated
interferon alfa-2a (Pegasys).
Pegylated
interferon leads to sustained response in only a minority of
HBeAg negative patients and adverse side effects are common,
so it is useful to identify individuals who are likely to benefit
early during the course of treatment, the researchers noted
as background.
The
present analysis included 107 HBeAg negative hepatitis B patients
who participated in an international clinical trial and were
randomly assigned to receive either 180 mcg/week pegylated interferon
alfa-2a monotherapy or pegylated interferon plus 1000-1200 mg/day
ribavirin for 48 weeks.
HBsAg
levels were measured at baseline, during treatment (weeks 4,
8, 12, 24, 36, and 48), and during follow-up (weeks 60 and 72).
Sustained response was defined as HBV DNA < 10,000 copies/mL
and normal alanine aminotransferase (ALT) 24 weeks after completion
of therapy. After sustained response rates were determined,
data from the pegylated interferon monotherapy and combination
therapy arms were merged for further analysis.
Results
 |
Sustained
response rates were statistically similar in the pegylated
interferon monotherapy and combination therapy arms (26%
vs 19%, respectively). |
|
Sustained
responders experienced larger and faster decreases in serum
HBsAg levels, compared with only modest declines among non-responders
(1.5 vs < 0.5 log IU/mL, respectively, at week 72). |
|
HBsAg
declines were apparent by week 8 in sustained responders,
but not until week 12-24 in non-responders. |
|
Serum
HBV DNA levels also declined more in sustained responders
compared with non-responders. |
|
After
completing therapy, HBV viral load levels returned to baseline
in non-responders, but remained suppressed in sustained
responders. |
|
Decreases
in HBsAg alone were of only limited value in predicting
likelihood of sustained response. |
|
Sustained
response was best predicted by a combination of decreases
in HBsAg and HBV DNA. |
|
None
of the 20 patients who had no decrease in serum HBsAg at
week 12 and less than a 2 log decline in HBV DNA achieved
sustained response (negative predictive value 100%). |
|
Participants
who experienced either no HBsAg decline at week 12 but HBV
DNA loss 2 logs, or evidence of HBsAg decline but viral
load decrease < 2 logs, had intermediate sustained response
rates of approximately 25%. |
|
In
contrast, among participants with decreased HBsAg at week
12 and at least a 2 log decline in HBV viral load, the sustained
response rate reached 39%. |
"At
week 12 of peginterferon alfa-2a treatment for HBeAg negative
chronic hepatitis B a solid stopping rule was established using
a combination of declines in serum HBV DNA and HBsAg level from
baseline," the investigators concluded.
"Quantitative
serum HBsAg in combination with HBV DNA enables on-treatment
adjustment of peginterferon therapy" in HBeAg negative
chronic hepatitis B patients, they added.
Gastroenterology
and Hepatology & Epidemiology and Biostatistics, Erasmus
MC University Medical Center, Rotterdam, Netherlands; Gastroenterohepatology,
Istanbul University Medical School, Istanbul, Turkey; Gastroenterology
and Hepatology, Medical University of Vienna, Vienna, Austria;
Infectious Diseases, Istanbul University Cerrahpasa Medical
School, Istanbul, Turkey; Gastroenterology, Turkiye Yuksek lhtisas
Hospital, Ankara, Turkey; Infectious Diseases, Hepatology and
Acquired Immune Deficiences, Medical University Wroclaw, Wroclaw,
Poland; Gastroenterology, Ege University Faculty of Medicine,
Izmir, Turkey; Infectious Diseases and Hepatology, Medical University
of Bialystok, Bialystok, Poland; Virology, Erasmus MC University
Medical Center, Rotterdam, Netherlands.
4/27/10
Reference
V
Rijckborst, BE Hansen, Y Cakaloglu, and others. Early prediction
of sustained response to peginterferon alfa-2a in HBeAg-negative
patients: the role of on-treatment HBsAg and HBV DNA levels.
45th Annual Meeting of the European Association for the Study
of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010.
(Abstract
8).
