A sustained virologic response, defined by undetectable serum HCV RNA 24 weeks after treatment cessation, is the primary objective of chronic HCV treatment. However, the virologic benefits of HCV treatment may be attenuated by negative changes along other clinical parameters that are of importance to patients and their caregivers, including QOL and psychological functioning. For instance, compromised QOL, fatigue, and depression increases the likelihood that adults will discontinue HCV treatment before realizing health benefits.(8
) Findings from the current study, however, indicate that few children experience clinically significant changes in QOL, behavior problems, depression, or cognitive functioning during or after HCV treatment. Previously, we reported that pre-treatment scores for this HCV pediatric cohort were comparable to that of healthy children (19
), and now we provide evidence that this remains largely unchanged after 48 weeks of peginterferon with ribavirin (or placebo) treatment and for two years after cessation of therapy. 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.
Overall QOL, behavior, depression, or executive function did not change for children over time, regardless of whether they received PEG 2a + RV or PEG 2a + PL. On the surface, this finding differs from both pediatric and adult studies, which have reported declines in QOL and other functional or psychological parameters during HCV treatments.(20
) For instance, while PEG 2a has fewer QOL side-effects than unmodified interferon (28
), the addition of RV has been shown to substantially impair QOL in adults.(27
) Relative to adults, children may have less severe disease, fewer medical and psychiatric co-morbidities, and more available and stable social support systems. These factors may account for the lower incidence of QOL and behavioral/emotional impairment observed in the current study.
Iorio et al.(20
) showed that the QOL of children deteriorates in the first month of interferon-alpha treatment, although QOL returned to baseline within three months of concluding treatment. We did not conduct QOL assessments during the first 6 months of treatment, so we are unable to determine whether impairments were present in our cohort during the early part of treatment. However, we did find that, for 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. It is important to note the different methodological and treatment characteristics between our study and the Iorio et al. study when evaluating these findings. For instance, in contrast to our study, the Iorio et al. study included children with different viral infections (HBV and HCV) and treated with various interferon types, schedules, and routes of administration. Also, Iorio et al. measured QOL using a modified version of the Sickness Impact Profile (SIP), which is an adult-based health status measure that has not been standardized on pediatric samples. In contrast, our patient cohort was homogeneous, children received a standardized antiviral regimen, and we used QOL instruments that have been developed and validated specifically for pediatric populations.
Findings reported herein must be considered in the context of several important study limitations. First, we present data based primarily on parent or guardian report. Such reports can be biased for many different reasons and, therefore, may not accurately capture the true functional status of the child. For instance, parents who are more stressed and worried about their child's medical status may respond different to questions about their child's functioning, compared to parents who are coping well with their child's condition. Second, while the sample size was large compared to published literature, the number of children who remained in their assigned treatment through the full 48 weeks of treatment was relatively small and this may have limited our ability to detect small changes in QOL functioning over time. Third, we did not assess QOL and the other psychosocial outcomes until 24 weeks after treatment initiation. It is possible that changes in these parameters occurred in the early stages of treatment and subsequently recovered by the time of our 24 week assessment.
In conclusion, PEG 2a + RV has been shown to be superior to PEG alone in achieving early and sustained virologic response in children and adolescents.(5
) Data from the current study show that overall QOL, behavioral/emotional functioning, and cognitive functioning are not deleteriously impacted by the inclusion of RV. Nevertheless, because some individual children may experience clinical changes over time, we recommend close monitoring of these patient-oriented outcomes for those children receiving PEG 2a, with or without RV.