Autoantibodies in children with chronic hepatitis B infection and the influence of interferon alpha.
OBJECTIVE
One of the serious side effects of interferon-a (IFN) is the possible induction of autoimmunity. However, data concerning children with chronic hepatitis B (HBV) infection is limited with conflicting results. The aim of this study was to evaluate the frequency of autoantibody positivity in children with chronic HBV infection and to assess whether IFN treatment has any influence on exacerbation of serological or clinical parameters of autoimmunity.


METHODS
61 children (32 female, mean age 7.5+/-3.8 years) were evaluated in two groups. Group I (29 patients) received 5 x 106 U/m2 IFN-a and group II (32 patients) 10 x 106 U/m2 IFN-a three times per week for six months. Autoantibody levels (anti-TPO, anti-Tg, AMA, ASMA, LKM-1, ANA, ds-DNA) and Ig G, A and M were analyzed before and after IFN treatment and 12 months after completion of therapy.


RESULTS
No significant difference in autoimmune antibody positivity rate was observed between the two groups when compared at the beginning of the study and at the end of IFN treatment separately. SMA positivity rate was shown to significantly increase in group I after treatment was completed (p<0.05). None of the patients positive for autoantibodies showed further laboratory or clinical signs of autoimmunity. Thyroid hormones were within normal range in patients positive for anti-thyroid antibodies; however, thyrotropin-releasing hormone (TRH) stimulation test revealed subclinical hypothyroidism. All antibodies disappeared 12 months after completion of therapy. Overall, autoantibody positivity, pre- and posttreatment, were 16.3% and 54%, respectively (p<0.05). Age, sex, hepatitis activity index (HAI) score, HBV load and the dose of IFN had no influence on autoantibody formation. Complete and sustained response rates were similar in children with and without autoantibody.


CONCLUSIONS
Autoantibody formation may occur in children with chronic HBV infection. IFN treatment leads to significant autoantibody formation, but this causes no organ dysfunction except for antithyroid antibodies associated with subclinical hypothyroidism. These results suggest that neither the presence of autoantibodies in choronic hepatitis B nor their development during IFN therapy is associated with severe autoimmune disorders in children with chronic HBV infection.
Kansu
Aydan
A
School of Medicine, Department of Pediatrics, Division of Gastroenterology, Ankara University, Ankara, Turkey.
Kuloğlu
Zarife
Z
Demirçeken
Fulya
F
Girgin
Nurten
N
D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D019562:Viral Load
D000998:Antiviral Agents; D001323:Autoantibodies; D007136:Immunoglobulins; D016898:Interferon-alpha; C060729:anti-liver kidney microsome antibody; D000410:Alanine Transaminase