Background: The purpose of the present paper was to investigate the efficacy of vitamin E in children with immunotolerant-phase chronic hepatitis B virus (CHB) infection.Methods: Fifty-eight immunotolerant children were prospectively and randomly recruited into two groups. Group 1 (study group) included 30 patients who received vitamin E at a dose of 100 mg/day throughout 3 months; group 2 (control group) contained 28 patients who did not receive any medication. Comparison of serological, virologic, and biochemical response ratios were done at the end of the therapy and after 6 months of vitamin E discontinuation.Results: Mean alanine transaminase (ALT) values in group 1 at the beginning of the therapy, 3 months after the therapy initiation and 6 months after discontinuation were 30.4 +/- 7.3 IU/L, 31.3 +/- 7.8 IU/L and 32.1 +/- 8.5 IU/L, respectively. The mean hepatitis B virus (HBV)-DNA load of group 1 at onset, and at the third and ninth months of the treatment were 3106 +/- 718 pg/mL, 3530 +/- 137 pg/mL and 3364 +/- 1246 pg/mL, respectively. These changes in both ALT and HBV-DNA values did not reach significant levels (P > 0.05). In group 2, mean ALT values at the beginning of therapy, and at the third and ninth months were 28.0 +/- 1.8 IU/L, 34.6 +/- 8.1 IU/L, and 34.1 +/- 7.0 IU/L, respectively (P > 0.05), and mean viral load of HBV-DNA was 4227 +/- 1435 pg/mL, 3368 +/- 2673 pg/mL, and 3018 +/- 2814 pg/mL, respectively (P > 0.05). There was no statistically significant difference between group 1 and group 2 at the third and ninth months in the mean ALT values and viral load of HBV-DNA (P > 0.05). Hepatitis B s antigen and hepatitis B e antigen clearance or hepatitis B s antibody and hepatitis B e antibody seroconversion were not observed in either group.Conclusion: As a first study investigating the effect of vitamin E in children with immunotolerant CHB infection, no beneficial effect could be demonstrated. Different immunomodulator protocols should be considered for future investigations.

Background. Our aim was to determine the prognostic factors effective in the response to steroid treatment and relapse frequency. Patients and Methods. In this study, we evaluated 84 children with idiopathic nephrotic syndrome followed-up from 1997–2002. The variables were analyzed with respect to medical history, physical examination, laboratory findings, response to treatment, and factors associated with remissions and relapses. Our study group consisted of 62 children with minimal change nephrotic syndrome (MCNS), 11 children with focal segmental glomerulosclerosis (FSGS), and 11 children with diffuse mesangial proliferation (DMP). Results. According to response to steroids; 57.1% were steroid-sensitive with infrequent relapses, 22.6% were steroid-dependent with frequent relapses, and 20.2% were steroid-non-responders. Significantly high non-responder ratios to steroids were found in children with initial hypertension and hematuria (p < 0.05). Although patients older than six years were found to be associated with steroid non-response (p < 0.05), the number of relapses were found to be increased with an increasing number of infections (p < 0.05). The time period for the first relapse was found to be statistically correlated with relapse numbers of the first 6 (p = 0.001) and 12 (p = 0.01) months. Conclusion. The time span between initial presentation and remission and the number of infections were significant for relapse frequency. The existence of hematuria and hypertension and age greater than 6 years at initial presentation were associated with steroid non-responsiveness. The likelihood of developing resistance to the treatment should be emphasized early to the parents of patients bearing these risk factors, and hence the possible disappointment in the family should be prevented.

To the Editor: We read the article by Verrotti et al with interest.1 They reported no significant correlation between insulinemia and serum valproic acid concentrations in obese and nonobese patients throughout the study. Weight gain has been recognized as a common adverse effect of valproic acid that leads to discontinuation in some patients, but its incidence and correlates have rarely been studied. Researchers have studied different risk factors for valproic acid–induced obesity, such as insulin, leptin, and insulin resistance. But risk factors for excessive weight gain in epileptic children treated with valproic acid have not yet been established. We want to report our controversial study results concerned with weight gain and valproate in epileptic children. We analyzed the records retrospectively and interviewed 56 children (38 boys, 18 girls), ranging in age at the start of therapy from 6 months to 12 years, attending an epilepsy clinic on valproic acid monotherapy for primary generalized epilepsy followed up over a median of 15.6 ± 8.2 months (range 6–40). Weight and height were recorded before treatment and at the time of follow-up: body mass index and weight and height for ages were converted to a Z-score. Putative risk factors included sex, age at the beginning of therapy, duration of follow-up, mental retardation, family history of obesity, and dose of valproic acid. Changes in weight Z-score and body mass index were not significantly correlated with initial weight Z-score and initial body mass index, 10, 16.5 ± 2.1, and 12, 16.8 ± 1.5, respectively, and not with age at start of therapy, duration of follow-up, sex, mental retardation, family history of obesity, or dose of valproic acid. Although most of the previous studies have supported the idea that valproic acid could cause excessive weight gain in epileptic children, weight gain was not evident in our study. However, we think that it has also been considered if these children had any other risk factors for obesity. If children had excessive weight gain during the valproic acid therapy, valproic acid would have been investigated together with other risk factors for obesity.

BACKGROUND:The aim of this study was to compare the efficacy of the alpha-interferon treatment with treatment using alpha-interferon and lamivudine in combination for cases of childhood chronic hepatitis B infection. METHODS:Patients were evaluated in two groups retrospectively. In group 1, 27 patients were simultaneously given alpha-interferon 2b 10 MU/m2, 3 days a week by s.c. injection plus lamivudine 4 mg/kg a day (maximum 100 mg) for 12 months. In group 2, there were 13 patients who only received the same dosage of alpha-interferon and no lamivudine over the same period of time. RESULTS:In group 1 the initial mean value of alanine aminotransferase (ALT) was 121 +/- 66 IU/L and decreased to 27.8 +/- 11.5 IU/L; in group 2, initial mean values of ALT was 129 +/- 46 IU/L and decreased to 60 +/- 6 IU/L at the end of the twelfth month of the therapy (P < 0.05). Hepatitis B virus DNA (HBV-DNA) clearance was obtained in all group 1 patients and six of 13 patients in group 2 at the end of the therapy (P < 0.001). The rates of hepatitis B early (HBe) antigen clearance and anti-HBe seroconversion were 59 and 37% in group 1 and 46 and 30.7% in group 2 (P > 0.05). The number of patients with complete response was found to be 10 out of 27 (37%) in group 1 and four out of 13 cases (30.7%) in group 2, 6 months after the end of the therapy. There was no statistically significant difference between both groups (P > 0.05). CONCLUSION:alpha-Interferon and lamivudine combination therapy had a more beneficial effect than alpha-interferon monotherapy in normalization of ALT and clearance of HBV-DNA; however, the complete response rate at 6 months after the end of the therapy was not statistically significantly different between both groups.

To The Editors: We recently observed an unusual adverse effect in a child being treated with interferon alpha for hepatitis B disease. A 7-year-old boy was admitted with complaints of a stomachache and lack of appetite. These complaints had been ongoing for 18 months. His mother was a health worker in the central laboratory of our University Hospital and was a chronic hepatitis B virus carrier. His initial laboratory evaluation by soluble hybridization method disclosed the following results. Liver function test results were abnormal, and other test results were hepatitis B surface antigen- and hepatitis B e antigen-positive, anti-hepatitis B surface antibody- and anti- hepatitis B e antibody-negative, hepatitis B virus DNA value >2000 pg/ml. In follow-up evaluations conducted during 6-month period, similar findings continued. A liver biopsy was performed revealing an inflammatory score of 6 of 18 on the Knodell histology activity index. A 6-month treatment of interferon alpha 2b (IFN), 5 million units/m2 s.c. three times per week, was initiated. The patient was called for routine follow-up every 2 months. His family reported an increased growth of eyelashes, which they trimmed periodically with scissors. During physical examination the eyelashes were observed to be unusually long and close together. The patient did not have such symptoms or appearance before the initiation of IFN treatment. Eyelash growth was so pronounced that the child complained that it interfered with his vision. The symptom lasted throughout the treatment period. However, 2 months after the conclusion of the treatment, the patient’s eyelashes had returned to their natural state. By the end of the treatment period, the patient had remission characterized by hepatitis B e antigen/anti-hepatitis B e antibody seroconversion and alanine aminotransferase normalization (35 IU/l). Side effects of interferon therapy are widespread and limit its usage. Influenza symptoms are reported by >75% and depression by 10 to 40% of interferon users. Severe adverse effects are less common but may be life-threatening, including autoimmune diseases, thrombotic-thrombocytopenic purpura and acute renal failure. 1 Acute adverse effects, flu-like symptoms, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Subacute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. 2 Some adverse effects, such as convulsion, vertigo, abnormal thyroid function, hemolytic anemia, acute renal failure, autoimmune hepatitis, etc., are rare. 3 These adverse effects are often dose-related and necessitate the interruption or reduction in the dosage of INF alpha. To our knowledge there are three reports in the literature concerning hypertrichosis of the eyelashes as a result of interferon therapy. 4–6 In our patient no other side effect was seen other than hypertrichosis. We did not need to stop the treatment or reduce the doses of the INF alpha because of this adverse effect. The patient successfully completed the period of interferon alpha treatment and obtained complete response during follow-up in a 6-month period after therapy. We conclude that hypertrichosis of the eyelashes is a rare side effect of INF treatment found among children and is not in itself adequate cause for the reduction of interferon alpha doses. Bunyamin Dikici, M.D. Mehmet Bosnak, M.D. Abdullah Dagli, M.D. Kenan Haspolat, M.D.

BACKGROUND:The aim of our study was to compare the efficacy of combined interferon-alpha and lamivudine in children with chronic hepatitis B infection and two durations of treatment (6 and 12 months).METHODS:Combination of interferon-alpha 2b (10 MU/m2 of body surface) and lamivudine 4 mg/kg (maximum, 100 mg) were given synchronously to 30 patients for 6 months (Group 1) and to 27 patients for 12 months (Group 2). Biochemical, virologic and serologic features were compared between two groups at the end of therapy and 6 months after therapy.RESULTS:Hepatitis B e antigen clearances were 33 and 59% at the end of treatment and 37 and 56% 6 months after therapy in Groups 1 and 2, respectively (P > 0.05). Hepatitis B virus DNA clearances were 97 and 100% at the end of treatment and 97 and 96% 6 months after therapy in Groups 1 and 2, respectively (P > 0.05). In both groups normalization of alanine aminotransferase was maintained at the end of therapy and 6 months after therapy (P < 0.05). Sustained complete responses were obtained in 20 and 37% of patients at the end of therapy and 6 months after therapy, respectively (P = 0.07).CONCLUSIONS:When the combination of large dosage interferon-alpha 2b and lamivudine therapy in children was compared at the end of therapy and 6 months after therapy, normalization of alanine aminotransferase and the clearances of hepatitis B e antigen and hepatitis B surface antigen in both groups were directly proportional to the duration of treatment. However, the higher complete response rate at 12 months of combination therapy was not statistically different from that at 6 months.