Interferon: a meta-analysis of published studies in pediatric chronic hepatitis B.
Perinatally infected Asian children respond poorly to interferon (IFN) therapy. In contrast, IFN therapy seems to be more effective in Caucasian children who presumably acquired HBV infection later in life. We reviewed seven controlled studies of IFN treatment in children with chronic hepatitis B living in western countries (216 treated, and 200 untreated children). Before treatment all patients were HBeAg and HBV-DNA +ve, with a biopsy proven chronic hepatitis B. Ages ranged 1 to 16 years (mean age 7 years). Most patients were Caucasian. Protocols which have been adopted may schematically be divided into protocols which have used high doses of IFN (7.5 to 10 MU/sqm/TIW), and protocols which have used low doses of IFN (3 to 6 MU/sqm/TIW), with a short (3 to 6 months) or a long duration of treatment (12 months). The percentage of treated patients who, at the end of treatment, lost HBV-DNA (that in most studies corresponded also to HBeAg serum conversion) averages 20 to 58% (mean 35.5%) that is much higher than that observed in controls (range 8-17%; mean 11.4%). A better trend is probably observed only in patients who received the treatment for a longer period of time. At the end of treatment, low percentages of patients lost BsAg (range 0-4%; mean 1.1%): again higher doses tend to be more effective than lower doses. In some studies IFN has been shown to significantly accelerate the termination of viral replication. Data on longer term outcome of IFN treatment in Caucasian children are scarce and confirm results obtained at short and at medium-term FU either in horizontally either in perinatally infected children. Results from few randomized controlled trials of interferon therapy with prednisone priming in Chinese and Caucasian children were comparable to results obtained without prednisone. In one study steroid priming did not potentiate the effect of IFN, however it existed a tendency of prednisone to improve HBeAg clearance in patients with normal aspartate aminotransferase, and alanine aminotransferase activity lesser than 100 u/l. In most studies, factors positively influencing response rates of IFN treatment are represented by severe inflammation in the basal liver biopsy, high basal levels of serum transaminase, low basal levels of serum HBV-DNA. Vertical transmission may be considered a factor adversely affecting the response to IFN treatment both in Chinese and Caucasian population. In general in most controlled studies, the majority of responders have shown a significant reduction in hepatic inflammation and transaminase normalization. Children have a low risk of developing severe IFN-induced side effects. Adverse reactions and worsening of health-related quality of life were tolerable and did not seem to be a limiting factor for IFN therapy in young candidates.
Vajro
P
P
Department of Pediatrics, University of Naples Federico II, Italy.
Migliaro
F
F
Fontanella
A
A
Orso
G
G
D000998:Antiviral Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018849:Controlled Clinical Trials as Topic; D004279:DNA, Viral / Q000032:analysis*; D004334:Drug Administration Schedule; D005260:Female; D006513:Hepatitis B e Antigens / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007372:Interferons / Q000008:administration & dosage*; D007558:Italy; D008297:Male; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D007372:Interferons