Decreased ratio of CD4/CD8 lymphocytes might be predictive for successful interferon alpha and lamivudine combined therapy in childhood chronic hepatitis B infection: A preliminary study.
BACKGROUND
In the development of chronic hepatitis with hepatitis B virus infection and in response to therapy, the immune status of the infected host plays a critical role. In this study, immunological variables were assessed in patients before interferon alpha and lamivudine therapy to determine if any pretreatment immunological parameter could be an indicator of response to therapy in childhood chronic hepatitis B infection.


METHODS
Forty-four patients with chronic hepatitis B virus infection, aged 9.0 +/- 3.9 years, were enrolled in the study. The pretreatment clinical features, biochemical test results, histological activity indexes and immunological parameters were evaluated. All patients received interferon alpha for 6 months and lamivudine for 52 weeks. Four patients who could not be followed up were excluded from the study. The other 40 patients have been followed for a mean period of 27.5 +/- 9.7 months after therapy discontinuation.


RESULTS
Seventeen patients showed loss of hepatitis B early antigen (HBeAg) with appearance of anti-HBe (42.5%) and six of those who responded also showed loss of hepatitis B surface antigen (HBsAg) with the presence of anti-HBs (15%). Except elevated aspartate aminotransferase levels, there was no significantly correlation between response and sex, age, pretreatment duration of disease and histological activity indexes. Pretreatment immunoglobulins (Ig), IgG subclasses, complement C3, C4 and secretory IgA levels were also not found to be significantly related to response. The evaluation of lymphocyte subsets showed that therapy responders had significantly reduced pretreatment ratios of CD4/CD8+ lymphocytes due to prominent increased percentages of CD8+ cells. The other cellular immunity parameters and some cell surface adhesion molecules were similar in both groups.


CONCLUSIONS
This study emphasizes the importance of increased pretreatment CD8+ lymphocyte percentages leading to a significant decrease in CD4/CD8 ratio in chronic hepatitis B virus infection of childhood as an immunological factor predicting response to treatment.
Genel
Ferah
F
Department of Pediatrics, Faculty of Medicine, Ege University, Bornova, Izmir, Turkey. ferahgen@yahoo.com
Unal
Faith
F
Ozgenc
Funda
F
Aksu
Guzide
G
Aydogdu
Sema
S
Kutukculer
Necil
N
Yagci
Rasit V
RV
D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000945:Antigens, Differentiation, T-Lymphocyte / Q000187:drug effects / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000187:drug effects; D002648:Child; D002669:Child Welfare; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D007223:Infant; D007229:Infant Welfare; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D016896:Treatment Outcome
D000945:Antigens, Differentiation, T-Lymphocyte; D000998:Antiviral Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D006513:Hepatitis B e Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D016898:Interferon-alpha; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase