Common in Patients Taking Oral Meds
Nearly half of patients taking nucleoside/nucleotide analogs
to treat hepatitis B experienced viral breakthrough over
5 years, and about 40% of these were not attributable
to drug resistance mutations.
analogs including lamivudine (Epivir-HBV),
adefovir (Hepsera), entecavir
(Tyzeka), and tenofovir (Viread)
are highly active against hepatitis
B virus (HBV), but drug resistance can emerge over time,
compromising the effectiveness of long-term therapy. This
is especially likely if agents are used one at a time and
when adherence is poor.
described in the May
2011 issue of Hepatology, Chanunta Hongthanakorn,
Anna Lok, and colleagues from the University of Michigan conducted
a study to determine the likelihood of virological breakthrough
and genotypic resistance among chronic hepatitis B patients
receiving nucleoside/nucleotide analogs in routine clinical
is an edited excerpt from a recent press release issued by
Hepatology publisher Wiley-Blackwell describing the study
and its findings.
B Virus Reemerges with Long-Term
Nucleoside Analog Treatment
breakthrough not linked to antiviral drug resistance; non-adherence
to medication likely.
April 27, 2011 -- A recently published study revealed that
virological breakthrough (VBT) is common in patients receiving
nucleoside analogs (NUCs) for chronic hepatitis B. Nearly
40% of the VBTs found were not related to antiviral drug resistance.
Details of this retrospective study are published in the May
issue of Hepatology, a journal published by Wiley-Blackwell
on behalf of the American Association for the Study of Liver
VBT is the first manifestation of antiviral drug resistance
during NUC therapy of chronic hepatitis B. NUC drugs approved
for treatment of chronic hepatitis B include lamivudine (LAM),
adefovir (ADV), entecavir (ETV), telbivudine (TBV), and tenofovir
(TDF). While the medications suppress the virus with few side
effects, they do not eradicate HBV and require long-term treatment
to provide clinical benefit. With long-term NUC therapy, studies
have shown an increasing risk of drug resistance particularly
with monotherapy regimens.
In the current study, Anna Lok, MD, and colleagues from the
University of Michigan Health System examined the incidence
of VBT and genotypic resistance (GR) in 148 patients with
chronic hepatitis B who were treated with NUCs between January
2000 and July 2010. The mean age of study participants was
45 years and 73% were male. Researchers reviewed medical records
and recorded patient demographics, hepatitis B virus (HBV)
markers, liver panel, blood counts and liver histology.
Results showed that during a mean follow-up of 38 months,
39 (26%) patients had at least 1 VBT, and upon retesting,
15 (38%) of these patients did not have a VBT and 10 had no
evidence of GR. Researchers reported the probability of VBT,
confirmed VBT [on 2 consecutive tests], and GR at five years
was 46%, 30%, and 34%, respectively. "Our analysis showed
an alarmingly high rate of VBT in clinical practice and the
only factor significantly linked to VBT was failure to achieve
undectectable HBV DNA," said Dr. Lok.
HBV DNA decreased in the 10 patients who initially experienced
a VBT, but who did not have confirmed VBT or GR, when the
same drug regimen was maintained. Nine of these patients had
undetectable HBV DNA at the most recent follow-up, a mean
of 7 months after the initial VBT. These data suggest that
non-adherence to medication may be a common cause of VBT.
"Counseling patients with chronic hepatitis B on the
importance of medication adherence, and confirming reemergence
of the virus and genetic mutations that cause resistance,
can help to avoid unnecessary changes to antiviral treatments,"
advised Dr. Lok.
Investigator affiliations: Division of Gastroenterology,
Department of Internal Medicine, University of Michigan Health
System, Ann Arbor, MI.
C Hongthanakorn, W Chotiyaputta, K Oberhelman, and others.
Virological breakthrough and resistance in patients with chronic
hepatitis B receiving nucleos(t)ide analogs in clinical practice.
Hepatology 53(5) (abstract).
Hepatitis B Virus Reemerges with Long-Term Nucleoside Analog
Treatment. Media advisory. April 27, 2011.