Quality of Life for Children on Hepatitis C Treatment

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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.

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 -- 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; Washington University, Washington, DC; 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; s 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 R. Rodrigue, 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

http://www.hivandhepatitis.com/hep_c/news/2011/0520_2011_c.html