D or delta virus is a defective pathogen that can only replicate
in the presence of hepatitis
B virus (HBV). When the 2 viruses occur together, however,
they can cause more severe liver disease than HBV alone.
Treatment for hepatitis delta has not been extensively studied
and there are currently no approved therapies.
In the present analysis, Heiner Wedemeyer and fellow investigators
with the Hep-Net-International Delta Hepatitis Intervention
Trial (HIDIT) Study Group investigated the safety and efficacy
of 48 weeks of treatment with pegylated
or the 2 drugs combined.
This randomized trial included 90 participants with HDV
infection. Patients were allocated (1:1:1) to receive either
180 mcg/week pegylated interferon alfa-2a (Pegasys) plus
10 mg/day adefovir, the same dose of pegylated interferon
plus placebo, or the same dose of adefovir alone for 48
Researchers looked at efficacy end-points including normalization
of alanine aminotransferase (ALT) liver enzyme levels, clearance
of HDV RNA, and decline in hepatitis B surface antigen (HBsAg)
patients receiving pegylated interferon plus adefovir
and 2 receiving pegylated interferon alone achieved
ALT normalization at week 48, compared with none in
the adefovir monotherapy arm.
of patients taking pegylated interferon plus adefovir
and 24% taking pegylated interferon alone achieved undetectable
HDV viral load by week 48, again compared with none
taking adefovir alone.
of patients receiving pegylated interferon either alone
or in combination with adefovir experienced sustained
virological response, or undetectable HDV RNA 24 weeks
after completion treatment, compared with none taking
people in the pegylated interferon plus adefovir arm
and 2 in the pegylated interferon monotherapy group
saw a decline in HBsAg levels of more than 1 log IU/mL
from baseline to week 48, again with no responders in
the adefovir monotherapy group.
on these findings, the study authors concluded, "Treatment
with [pegylated interferon] alfa-2a for 48 weeks, with or
without adefovir, resulted in sustained HDV RNA clearance
in about one quarter of patients with HDV infection."
While adding adefovir to pegylated interferon did not increase
the rate of ALT normalization or HDV viral load clearance,
it did appear to improve the likelihood of HBsAg decline.
Investigator affiliations: Hannover Medical School, Hannover,
Germany; Heinrich Heine University, Düsseldorf, Germany;
Johann Wolfgang Goethe University, Frankfurt, Germany; Robert
Koch Institute, Berlin, Germany; University Köln, Cologne,
Germany; University of Ankara Medical School, Ankara, Turkey;
Ufuk University Medical School, Ankara, Turkey; Memorial
Hospital Istanbul, Istanbul, Turkey; University of Uludag
Medical School, Bursa, Turkey; University Larissa, Larissa,
H Wedemeyer, C Yurdaydin, GN Dalekos, and others (HIDIT
Study Group). Peginterferon plus Adefovir versus Either
Drug Alone for Hepatitis Delta. New England Journal of
Medicine 364(4): 322-331 (Abstract).
January 27, 2011