Studies of the effectiveness of interferon alpha treatment for chronic hepatitis C in children.
BACKGROUND
The significance of hepatitis C infection in Poland, particularly in a pathology of the developmental age still increased. The aim of the study was the analysis of interferon alpha therapy efficacy in children with chronic C hepatitis.


METHODS
30 children (aged from 3 years to 15 years, 16 females, 14 males) were included in the study. In each patient HCV infection was confirmed by the serological, molecular (with identification of HCV genotype) and histopathological methods. The duration of observation of HCV-infected children after the diagnosis was made followed for at least 6 months. Transaminase level in each case was 50% higher than normal. The schema of interferon alpha treatment was: 3 MU 3 times a week subcutaneously for 25 weeks. Time of observation started at the beginning of the therapy and finished 1 year after the end of the treatment.


RESULTS
The analysis of the HCV genotypes showed the predominance of the genotype 1 (66.7%): subtype 1a was found in 20% patients, subtype 1b--in 43.5% children. Genotype 4 (subtype 4c4d or 4b) was confirmed in 30% patients, genotype 3 (subtype 3a) in 3.3% patients. In the histopathological picture of the liver predominated minimal or moderate inflammation activity (grading: 1--in 50%, 2--in 46.6%, 3--in 3.4%) and little fibrosis (staging: 0--in 80%, 1--in 13.3%, 2--in 6.7%). In many children mild side effects of interferon alpha therapy were observed: pseudoinfluenzal symptoms (in 46.7%), lack of appetite (in 16.7%), abdominal pain (in 10%), thrombocytopenia (in 6.7%), granulocytopenia, hair loss, irritability, itching of the skin (in 3.4%). At the end of therapy in 36.7% patients serum HCV-RNA was undetectable. The percentage of children without serum HCV-RNA decreased 6 months after the end of therapy to 20% patients and a year after the end of therapy to only 13.6% children. In children with HCV-RNA elimination was observed early reduction of ALT level. For the definition of the predictive factors of good prognosis patients were divided into 2 groups: group I (without HCV-RNA elimination at the end of the treatment) and group II (patients HCV-RNA negative a year after the end of therapy). Both group of children were similar in respect of age, disease duration and interferon alpha dosis/m2. At the beginning of the treatment mean ALT level was statistically higher in group II than in group I. IL-2 level was significant higher in group II than at the beginning, after 2 and 4 months of the therapy. There were no significant differences in IL-1 beta, IL-4 and IL-6 level between patients in group I and II. The differences in ALT activity during IFN-therapy between 2 groups of patients were statistically significant; since second month of therapy higher ALT level was observed in a group of patients without HCV-RNA elimination. In the histopathological picture of the liver a year of the end of therapy in 20% children reduction of inflammatory activity and progression of fibrosis in both group of patients was observed.


CONCLUSIONS
Because of a little efficacy, high costs, psychological load of young patients and possible following consequences of the interferon alpha therapy it is necessary to manage the further researches to find a new method of treatment of chronic C hepatitis. High ALT activity and elevated IL-2 level before treatment seems to be predictive factors of the good response to interferon alpha therapy.
Czerwionka-Szaflarska
M
M
Chair and Department of Pediatrics, Allergology and Gastroenterology, Medical University, ul. Ujejskiego 75, 85-168 Bydgoszcz, Poland.
Chrobot
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Szaflarska-Szczepanik
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D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D011044:Poland; D012367:RNA, Viral / Q000097:blood
D000998:Antiviral Agents; D016898:Interferon-alpha; D007376:Interleukin-2; D012367:RNA, Viral; D000410:Alanine Transaminase