Symptoms and Response to Interferon plus Ribavirin in Children with Chronic Hepatitis C

By Liz Highleyman

Compared with adults, chronic hepatitis C virus (HCV) infection in children has not been extensively studied and remains poorly understood. Two studies presented at the Digestive Disease Week (DDW) 2008 conference last week in San Diego looked at natural history and response to treatment of hepatitis C in pediatric patients.

Symptoms and Liver Disease Progression

In the first presentation, researchers described the symptomatic and physiologic presentation of pediatric patients evaluated for hepatitis C.

As background, they noted that children with hepatitis C are believed to remain asymptomatic for many years, with significant liver disease not occurring until 20-40 years after infection. Thus, treatment is often delayed due to the lack of perceived severity of disease.

In this retrospective cohort study, 62 pediatric patients were identified by diagnosis codes at an initial outpatient visit between 2000 and 2005. Demographic characteristics (age, sex, and race) and physiologic indicators (ALT, AST, GGTP, and liver biopsy results) were collected. Just over half (53%) were female; the age range was 3 months to 19 years. Most (61%) were white, 15% were black, 11% were Hispanic, and 5% were Asian.

Results

• Almost 60% of patients presented with clinical symptoms including fatigue (n=15), joint or abdominal pain (n=13), bruising or bleeding (n=6), and recurrent infections (n=2).

• 50% had abnormal ALT or AST, and 18% had abnormal GGTP.

• 4.8 % were coinfected with HIV.

• 6.5% had evidence of liver cirrhosis.

• Of the 35 children who underwent liver biopsies, 57% had some degree of fibrosis, 80% had inflammatory changes, and 8.6% had evidence of steatosis.

• All children with steatosis or cirrhosis reported symptoms.

• Boys were significantly more likely than girls to have symptoms (72.4% vs 46.9%).

• Non-white children were 6 times more likely than whites to have fibrosis.

• Children with symptoms were significantly older than those without symptoms (median 13 vs 9 years).

• For every 1 year older, the risk having symptoms increased by 14%.

• There was no significant relationship between symptom status and ALT or AST levels.

"Although this is a retrospective study with a limited sample size, this data shows that pediatric patients with HCV have potentially significant symptoms and physiologic liver changes related to HCV," the researchers concluded.

Therefore, they continued, "it is important to not delay proper evaluation and treatment of children with HCV as they may have liver disease and suffer from significant symptoms. Furthermore, it may be more important than generally thought to develop safe and effective pediatric protocols."

Response to Interferon plus Ribavirin

In the second study, researchers looked at long-term response in children with hepatitis C treated with interferon plus ribavirin.

It adults, sustained virological response (SVR), or undetectable HCV RNA 24 weeks after completion of therapy, predicts long-term clearance (> 5 years), and is widely considered to be a "cure." However, it is not known whether this also holds true for pediatric patients.

In the present study, the investigators aimed to confirm long-term HCV clearance in children treated with conventional (non-pegylated) interferon plus ribavirin. The analysis included 97 participants in 2 pediatric clinical trials (56 sustained responders and 41 non-responders) who completed at least 24 weeks of follow-up.

Participants were assessed annually for up to 5 years for clinical evidence of liver disease progression and virological evidence of HCV relapse. The 56 sustained responders were followed for a mean of 261 weeks and the 41 non-responders for a mean of 238 weeks. 82% of sustained responders and 71% of non-responders completed 3 years of follow-up; 75% and 63%, respectively, completed 5 years of follow-up

Results

• 1 sustained responder relapsed during the 5-year follow-up, at year 1.

• This patient had HCV genotype 1a and had a baseline HCV RNA level of 31,000,000 copies/mL before receiving 48 weeks of treatment.

• The same genotype was detected upon relapse (suggesting true relapse rather than reinfection).

• The Kaplan-Meier estimate for continued sustained response at 5 years was 98%.

• Of the 56 sustained responders with normal ALT at the end of the initial 24-week follow-up period, 54 (96%) maintained normal levels throughout the 5-year follow-up (1 had missing data).

• The only sustained responder with elevated ALT during the 5-year follow-up had levels less than 3 × the upper limit of normal.

• None of the children experienced clinical progression of liver disease and no deaths occurred.

• Serious adverse events were reported for 5 patients; all were considered unlikely to be related to interferon/ribavirin.

Conclusion

"SVR 24 weeks following therapy with [interferon plus ribavirin] in pediatric patients predicts long-term clearance of HCV," the researchers concluded.

They added that these results confirm those of prior research in adult patients, and "suggest that successful treatment (SVR) of HCV infection with [interferon plus ribavirin] leads to a clinical cure in both adults and children."

5/23/08

References

WA Henderson, CM Hadigan, JJ Feld, and others. Symptomatic and physiologic presentations in a cohort of pediatric patients with hepatitis C. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract S1944.

D Kelly, B Haber, RP Gonzalez-Peralta, and others. Clearance of HCV in children at 5-year follow-up is predicted by sustained virologic response at 24 weeks post treatment with interferon alfa-2b plus ribavirin. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract S1004.