Quality
of Life for Children on Hepatitis C Treatment
SUMMARY
Children treated with pegylated interferon plus ribavirin
or placebo experienced some worsening of physical symptoms
after starting therapy, but most had no clinically significant
changes in quality of life or emotional and cognitive functioning
by the end of treatment. |
By
James Learned
Recent
data indicate that children and adolescents with chronic
hepatitis C virus (HCV) infection respond as well or better
than adults to HCV treatment. Hepatitis C disease progression
tends to be more benign in children compared with adults; however,
almost 30% of children with chronic hepatitis C experience symptomatic
progression, which can lead to cirrhosis
and hepatocellular
carcinoma later in their lives.
Many
studies have examined quality of life (QOL) and psychological
and cognitive effects of chronic HCV infection before and during
treatment in adults, but little is known about these factors in
children.
Recognizing
that few studies address this issue -- and that somewhat contradictory
findings have been published -- James Rodrigue from Beth Israel
Deaconess Medical Center and colleagues set out to measure QOL,
behavioral adaptation, depression, anxiety, and cognitive functioning
in children undergoing interferon-based hepatitis C treatment,
all of which are pertinent to childhood development.
The
primary goals of the study included:
 |
Achieving
a better understanding of QOL and these other factors to help
clinicians inform patients and their parents/guardians about
possible side effects of treatment; |
|
Identifying
the negative ramifications of chronic HCV infection and its
treatment to facilitate the development and implementation
of therapeutic and pharmacological interventions aimed at
lessening unfavorable effects in children. |
As
described in the May
2011 issue of Hepatology, researchers mined data from
Peds-C, a prospective, multi-site, randomized study of 114 participants
ages 5 to 18, all with chronic HCV infection; none of the participants
had undergone hepatitis C treatment before.
Approximately
half of the children (55) received once-weekly pegylated interferon
alfa-2a (Pegasys) plus 15 mg/kg daily ribavirin, while the other
half (59) received pegylated interferon plus placebo. Participants
with undetectable HCV viral load at 24 weeks continued treatment
for the full 48-week course. Participants in the pegylated interferon/ribavirin
arm whose viral load was still detectable at week 24 were considered
non-responders and treatment was discontinued. Children with detectable
viral load at week 24 in the placebo arm were also considered
non-responders and were offered open-label pegylated interferon
plus ribavirin for 48 weeks.
Measures
of QOL, behavioral/emotional functioning, and cognitive functioning
were evaluated before starting treatment, at 24 and 48 weeks during
treatment, 6 months after treatment, and at 2 subsequent annual
visits. QOL and functioning were assessed based on various questionnaires
and checklists, most of which were completed by a parent or guardian.
Assessments included measures of the child's functional status,
well-being, self-esteem, family impact, behavioral problems, emotional
control, and mental health including anxiety and depression, among
others.
The
114 participants had a median age of 10.7 years; 75% were white,
45% were female, and 75% had HCV genotype 1. All were treatment-naive.
Other exclusion criteria included decompensated liver disease,
serious depression, and a history of other severe illness. There
were no significant differences between the 2 study arms in terms
of sociodemographic or medical characteristics.
Results
 |
After
6 months of treatment, average physical QOL scores declined
significantly compared to baseline in both the pegylated interferon/ribavirin
and pegylated interferon/placebo arms, although scores remained
within the average range. |
|
Overall,
there was statistically significant worsening of bodily pain
and general health at 24 weeks compared to baseline. |
|
However,
there were no significant changes in behavioral/emotional
or cognitive functioning at 24 weeks. |
|
Three
children (5%) taking pegylated interferon/ribavirin -- but
none of those taking pegylated interferon/placebo -- had significant
increases in depression symptoms at 24 weeks. |
|
A
majority of children who remained on treatment for the full
48 weeks in both the pegylated interferon/ribavirin and pegylated
interferon/placebo arms experienced no clinically significant
changes in QOL, behavior, depression, or cognitive functioning
at the end of treatment or during follow-up. |
|
Although
7 children (17%) who remained on treatment for 48 weeks experienced
clinical decline in physical QOL, 5 of them returned to baseline
QOL by the end of treatment or 6 months later. |
|
Scores
on all outcome measures did not differ significantly from
baseline for any of the children who completed 48 weeks of
treatment in either arm at the 1-year and 2-year follow-up
evaluations. |
|
Age,
race, sex, route of HCV transmission, and baseline alanine
aminotransferase (ALT) were not significantly associated with
participants' QOL or other psychosocial outcomes at any time
during the study. |
The
researchers described several limitations of their study. They
presented data based primarily on parent or guardian input rather
than from the children themselves, and acknowledged that "Such
reports can be biased for many different reasons and, therefore,
may not accurately capture the true functional status of the child."
Although
the sample size was large compared to other published studies,
the number of children who remained on their assigned treatment
through the full 48 weeks was relatively small, and this may have
limited the ability to detect small changes in QOL or functioning
over time. Finally, the authors did not assess QOL and the other
psychosocial outcomes until 24 weeks after treatment initiation.
It is possible, they wrote, "that changes in these parameters
occurred in the early stages of treatment and subsequently recovered
by the time of our 24-week assessment."
Compared
with adults, they suggested, children appear have less severe
HCV disease, fewer medical and psychiatric problems, and more
stable social support. These factors may account for the stability
in quality of life and fewer problematic behavioral/emotional
issues.
Based
on their findings, the researchers concluded, "Previously,
we reported that pretreatment scores for this HCV pediatric cohort
were comparable to that of healthy children, and now we provide
evidence that this remains largely unchanged after 48 weeks of
peginterferon with ribavirin (or placebo) treatment and for 2
years after cessation of therapy."
"[F]or
the few children who experienced clinically significant changes
in QOL and behavioral/emotional functioning, almost all of them
returned to healthy baseline levels by the end of treatment or
by the 6-month follow-up assessment," they continued. "As
the first randomized pediatric study to examine the QOL, psychological
functioning, and cognitive impact of both peginterferon alone
and with ribavirin, these findings have important clinical implications."
Investigator
affiliations: Beth Israel Deaconess Medical Center, Boston, MA;
Children's Hospital Medical Center, Cincinnati, OH; Children's
Hospital of Philadelphia, Philadelphia, PA; Children's Hospital
Boston, Boston, MA; George Washington University, Washington,
DC; James Whitcomb Riley Hospital for Children, Indianapolis,
IN; Children's Hospital and Regional Medical Center, Seattle,
Washington; University of Colorado Denver School of Medicine,
Children's Hospital, Aurora, CO; University of California, San
Francisco, CA; Columbia University, New York, NY; Johns Hopkins
University School of Medicine, Baltimore, MD; Division of Digestive
Diseases and Nutrition, National Institute of Diabetes and Digestive
and Kidney Diseases, Bethesda, MD; University of Massachusetts
Medical School, Worcester, MA; University of Florida College of
Medicine and Shands Children's Hospital, Gainesville, FL.
5/24/11
Reference
James
R. Rodrigue, William Balistreri, Barbara Haber, et al. Peginterferon
With or Without Ribavirin Has Minimal Effect on Quality of Life,
Behavioral/Emotional, and Cognitive Outcomes in Children. Hepatology
53(5): 1468-1475 (abstract).
May 2011
