Therapeutic vaccination in the immunotolerant phase of children with chronic hepatitis B infection

AIM: Hepatitis B virus (HBV) infection is a major global health concern and is the most common cause of chronic liver disease worldwide. Our aim was to investigate the efficacy of specific HBV vaccination as active immunotherapy in treating chronic hepatitis B (CHB) infection during the immunotolerant phase of children with normal aminotransferase values and high viral load. MATERIALS AND METHODS: Seventy-four patients never vaccinated before were randomly and prospectively recruited into two groups. Group 1 included 43 patients vaccinated with three standard injections of the GenHevac B vaccine at 30-day intervals. Group 2 contained 31 patients who did not receive any medication or vaccination (control group). Postvaccination serologic and virologic evaluation was performed 6 months after the first injection and at the end of the 12th month. Response to therapy was defined as loss of HBV DNA in serum and hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg), development of hepatitis B e antibody (anti-HBe). RESULTS: The mean baseline alanine aminotransferase (ALT) value in Group 1 was 33.0 +/- 9.6 IU/l, 34.6 +/- 13.9 IU/l at 6 months after first injection and 34.3 +/- 17.1 IU/l at end of 12 months (P > 0.05). In Group 1 the HBV DNA load at the start of immunization was 3571 +/- 1292 pg/ml; this value was 3220 +/- 1217 pg/ml at the 6th month and 2931 +/- 1292 pg/ml at the 12th month (P > 0.05). In Group 2 the mean ALT values at the beginning of therapy and at the 6th and 12th months were 32.6 +/- 7.8, 32.3 +/- 8.0 and 30.3 +/- 7.3 IU/l, respectively (P > 0.05), and the mean viral load HBV DNA values were 3909 +/- 1378, 3546 +/- 869 and 3106 +/- 718 pg/ml, respectively (P > 0.05). There was no statistically significant difference between Group 1 and Group 2 at the end of the 6th and 12th months in the mean ALT values and mean viral load of HBV DNA (P > 0.05). Except for one patient in each group, hepatitis B surface antigen and HBeAg clearance or hepatitis B surface antibody and anti-HBe seroconversion were not observed during follow-up (P > 0.05). CONCLUSION: In this multicentered study comparison of vaccinated and unvaccinated groups of immunotolerant children with CHB infection showed no difference in the clearance of HBV DNA or seroconversion from HBeAg to anti-HBe. Different immunization protocols should be considered for future investigations in the immunotolerant phase of children with CHB infection.     

Comparison of treatments of chronic hepatitis B in children with lamivudine and α-interferon combination and α-interferon alone

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.     

Therapeutic efficacy of sequential and simultaneous treatments with interferon-α and lamivudine in children with chronic hepatitis B

BACKGROUND: Interferon (IFN)-alpha and lamivudine (LAM), a nucleoside analog, are frequently used drugs for the treatment of chronic hepatitis B (CHB), and their combined therapy has been shown to be effective. The purpose of the present study was to examine the therapeutic efficacy of sequential and simultaneous combination therapies of IFN-alpha and LAM in children with CHB. METHODS: A total of 45 children with CHB, whose antibody status was positive for hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), and HBV-DNA at least for 6 months; who had alanine aminotransferase (ALT) levels 1.5-fold higher than normal and hepatic activity index scores higher than 6, were allocated to two groups. The first group included 24 children who were given standard dose IFN-alpha (5 MU/m(2) s.c., thrice weekly) for 6 months, followed by LAM (4 mg/kg per day per oral, maximum 100 mg/day) for an additional 6 months (sequential therapy group). The second group included 21 children who were given IFN-alpha and LAM therapy simultaneously for 6 months and who continued with LAM alone for another 6 months (simultaneous therapy group). Partial response was defined as normalization of ALT and eradication of HBV-DNA. Complete response was defined as normalization of ALT, eradication of HBV-DNA and e seroconversion. Non-responders were defined as having positive HBV-DNA and abnormal ALT levels. Sustained response was defined as absence of HBsAg and presence of hepatitis B surface antibody (anti-HBs). RESULTS: The mean age of the sequential therapy group was 12.7 +/- 4.1 years, and 16 (66.7%) of the patients were male. The mean age of the simultaneous therapy group was 14.8 +/- 4.6 years, and 15 (71.4%) were male. In the first group, 13 patients (54.2%) were non-responders; partial response was observed in five patients (20.8%), and complete response was seen in six patients (25%). Despite the occurrence of e seroconversion, normalization of ALT was not achieved in one case. In the second group, which consisted of 21 patients, 11 subjects (52.4%) were non-responders; partial response was observed in one case (4.8%), and complete response was seen in seven (33.3%). Sustained response was found in two patients (9.5%). There were no significant differences between the groups (P > 0.05). CONCLUSION: When the therapeutic efficiency of two different treatment regimens applied for 1 year was evaluated in childhood CHB therapy, it was remarkable that there was a sustained response and a higher complete response in group 2, although there was no considerable difference between the therapy results of both groups.     

Combined lamivudine/interferon-alpha treatment in "immunotolerant" children perinatally infected with hepatitis B: a pilot study

OBJECTIVE: To investigate whether combining the antiviral effect of lamivudine with the immune-boosting action of interferon-alpha (IFN-alpha) is effective in treating hepatitis B virus (HBV) "immunotolerant" children. STUDY DESIGN: Twenty-three children (8 boys; mean age, 10 years) infected during the first year of life (17 Asian, 21 with normal aminotransferase levels, 15 with HBV-DNA >1000 pg/mL by hybridization and all with mild histologic changes) were treated with lamivudine (3 mg/kg) for 8 weeks alone and then lamivudine (3 mg/kg) and IFN-alpha (5 MU/m(2), 3 times weekly) in combination for 10 months. RESULTS: Seventy-eight percent became HBV-DNA negative at the end of treatment, 5 (22%) seroconverted to anti-HBe, 4 (17%) of whom achieved complete viral control, becoming persistently HBsAg negative and anti-HBs positive. None had YMDD mutations. The viral status of the patients has not changed after a median follow-up of 40 months (range, 36 to 48). CONCLUSIONS: This pilot study suggests that lamivudine pretreatment followed by a combination of lamivudine and IFN-alpha can induce complete viral control in HBV immunotolerant children, hitherto considered poor responders.     

哮喘患儿血清IL 12 TGFβ1 与IgE 水平变化的研究

目的：检测哮喘患儿不同病期的白细胞介素12 ( IL-12) 、转化生长因子β1 ( TGFβ1 ) 与免疫球蛋白E( IgE) 水平变化的规律,并探讨不同病期IL-12,TGFβ1水平与IgE水平的相关性,据此阐述它们在哮喘中的临床意义。方法：采用ELISA 方法检测85例哮喘患儿及30例正常儿童的血清IL-12,TGFβ1与总IgE 水平。结果：哮喘组血清IL-12,TGFβ1水平明显低于对照组,而IgE 水平则哮喘组明显高于对照组,且发作期IL-12,TGFβ1 水平（28.42±10.73 ng/L,40.25±11.73 pg/mL）明显低于缓解期（40.42±15.26 ng/L,65.41±22.38 pg/mL）,差异有显著性 (P< 0. 01),缓解期血清IL-12,TGFβ1 水平明显低于对照组（67.42±20.58 ng/L,178.54±90.56 pg/mL）,差异有显著性(P<0.01),发作期血清IgE 水平（280.35±80.54 IU/mL）明显高于缓解期（145.67±51.25 IU/mL）, 差异有显著性(P< 0.01), 缓解期血清IgE 水平明显高于对照组（53.61±13.32 IU/mL）, 差异有显著性(P<0.01),哮喘患儿血清IL-12,TGFβ1水平与IgE呈负相关(P< 0.01)。结论：哮喘患儿存在IL-12,TGFβ1及IgE 水平失衡,提示IL-12,TGFβ1 在哮喘的发病中起着重要作用,检测它们的水平可为哮喘的诊断及判断病情提供依据。     

Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study

AIM: To determine whether supplemental oral vitamin E is effective in lowering serum aminotransferase and alkaline phosphatase levels in children with nonalcoholic steatohepatitis (NASH) associated with obesity. STUDY DESIGN: Open-label pilot study enrolling all children <16 years old with chronically elevated serum aminotransferase (alanine aminotransferase and aspartate aminotransferase) levels for greater than 3 months, who demonstrated a diffusely echogenic liver on ultrasonography, had no demonstrable reason for abnormal serum chemistry values other than obesity, and therefore were diagnosed to have NASH. Patients were prescribed oral vitamin E between 400 and 1200 IU per day. Serum chemistry values were monitored monthly during treatment. RESULTS: Eleven subjects with a mean age of 12.4 years were enrolled; treated patients were followed up for 4 to 10 months. The body mass index did not change significantly before and after treatment (32.8 +/- 3.8 kg/m(2) vs 32.5 +/- 4.4 kg/m(2), respectively). Serum alanine aminotransferase decreased from 175 +/- 106 IU/L to 40 +/- 26 IU/L (P <.001, paired Student t test), serum aspartate aminotransferase decreased from 104 +/- 61 IU/L to 33 +/- 11 IU/L (P <.002), and alkaline phosphatase decreased from 279 +/- 42 IU/L to 202 +/- 66 IU/L (P <.003) during treatment. Serum aminotransferase levels remained normal during treatment but returned to abnormal in those electing to stop treatment. Serum alpha-tocopherol levels were within the normal range before the commencement of therapy and increased significantly with supplementation. The liver remained diffusely echogenic during therapy, at the time serum aminotransferase levels were reduced. CONCLUSIONS: Daily oral vitamin E administration normalized serum aminotransferase and alkaline phosphatase levels in children with NASH. Obese children with NASH should be encouraged to lose weight as part of a comprehensive weight reduction program and to consider taking supplemental alpha-tocopherol.     

乙型肝炎病毒母婴传播影响因素探讨

目的：探讨乙型肝炎病毒(HBV)母婴传播的影响因素,寻求降低婴儿HBV感染率的方法。方法：HBV携带及慢性乙型肝炎孕妇共635例,分别比较不同血HBV DNA滴度,不同分娩方式（剖宫产或自然分娩）,以及不同肝功能状态孕妇所生婴儿出生时及3月龄时HBV的感染率。新生儿生后12 h内肌注乙肝免疫球蛋白200 U 及重组酵母乙肝疫苗10 μg;生后即刻显示血清HBV感染存在者,14 d时再肌注乙肝免疫球蛋白200 U。结果：孕妇高滴度组（HBV DNA>105拷贝/mL）所生新生儿出生时（14.4% vs 4.1%,P<0.01）与3月龄时（4.7% vs 0,P<0.01）HBV感染率均高于低滴度组（HBV DNA ≤105拷贝/mL）。两组新生儿3月龄时HBV感染率均低于出生时（P<0.05）。自然分娩的孕妇其婴儿出生时HBV感染率明显高于剖宫产组（P<0.01）,但3月龄时,两组感染率接近。HBV携带孕妇所生婴儿出生时HBV感染率明显高于慢性乙型肝炎孕妇所生婴儿（P<0.01）,但3月龄时两组婴儿HBV感染率亦接近。结论：孕妇血清HBV DNA水平与新生儿HBV宫内感染密切相关,故降低孕妇血清HBV DNA水平可能成为减少新生儿HBV感染的一种有效途径。在乙肝免疫球蛋白及重组酵母乙肝疫苗的双重保护下,孕妇的分娩方式与肝功能状态对HBV母婴传播无影响。     

d-Alpha-tocopheryl polyethylene glycol-1000 succinate enhances the absorption of vitamin D in chronic cholestatic liver disease of infancy and childhood.

Rickets and osteopenia, common problems in chronic childhood cholestasis, have been attributed to vitamin D malabsorption leading to reduced serum levels of 25(OH)-vitamin D. d-alpha-Tocopheryl polyethylene glycol-1000 succinate (TPGS), a water-soluble form of vitamin E, forms micelles at low concentration. We evaluated the potential role of TPGS in enhancing vitamin D absorption in eight children (aged 5 mo to 19 y) with severe chronic cholestasis (three extrahepatic biliary atresia, three nonsyndromic intrahepatic cholestasis, and two Alagille syndrome). To evaluate vitamin D absorption, the subjects received vitamin D3 1000 IU/kg (maximum dose of 50,000 IU); they then received the same dose of vitamin D3 mixed with TPGS (25 IU/kg). Serial serum vitamin D3 levels and areas under the curve were measured. All patients had enhanced absorption of vitamin D when it was administered in a mixture with TPGS. Mean area under the curve for serum vitamin D3 was 403.0 +/- 83.1 nmol x h/L (155.6 +/- 32.1 ng x h/mL), with a mean rise above baseline of 13.5 +/- 1.8 nmol/L (5.2 +/- 0.7 ng/mL) with vitamin D/TPGS compared with no rise when vitamin D was given alone (both p less than 0.001). Seven patients have been followed for at least 3 mo while receiving the vitamin D/TPGS combination. Those with initially low serum 25(OH)-vitamin D levels (less than 37.5 nmol/L or 15 ng/mL) had normalization (range 37.5-146 nmol/L) within 1 mo, whereas those with initially normal levels remained normal. While the patients were receiving vitamin D/TPGS, serum vitamin E to total lipid ratio either normalized or remained normal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of interferon-α2b treatment in children with chronic hepatitis B who have previously undergone therapy for cancer

BACKGROUND: The aim of the present study was to evaluate the efficacy of treatment with recombinant interferon (IFN)-alpha2b in 12 children with chronic hepatitis B who had previously undergone therapy for cancer. METHODS: Nine children had acute leukemias and the other three children had solid tumors. The mean (+/-SD) age of the children was 8.4+/-3.8 years (range 4-16 years). All cases were hepatitis B virus (HBV)-DNA positive and 11 were hepatitis B e antigen (HBeAg) positive. One was anti-HBe positive (mutant strain). Four cases were anti-delta IgG positive. Liver biopsy revealed chronic hepatitis B in 11 patients and cirrhosis in one patient. Interferon-alpha2b was given at a dose of 5 MU/m2 three times a week, subcutaneously, for 12 months. RESULTS: Elimination of serum HBV-DNA was obtained in three cases, but a further three patients demonstrated a marked decrease in HBV-DNA levels after therapy. Three of 11 patients seroconverted from HBeAg to anti-HBe. Alanine aminotransferase (ALT) levels returned to normal in three of nine cases in whom the ALT levels were high before treatment. At the end of therapy, the mean histologic activity index score was significantly diminished (P = 0.0039). CONCLUSIONS: In conclusion, a 12 month course of IFN-alpha2b induces some beneficial effects on virologic, biochemical and histologic indices in children with chronic hepatitis B who have previously undergone therapy for cancer.     

Oral vitamin A, E and D supplementation of pre-term newborns either breast-fed or formula-fed: a 3-month longitudinal study

BACKGROUND: In contrast to the studies of vitamin A and E status in children, adolescents and adults, information on preterm infants is scarce. In the present investigation we examined the vitamin A, D and E status of pre-term infants at birth, and verified whether, at 1 and 3 months, breast or formula feeding affected the plasma concentration of those vitamins while being supplemented with Uvesterol ADEC. PATIENTS AND METHODS: In this prospective study, 2 groups of consecutively recruited preterm newborns fed either breast milk or formula received 3000 IU of vitamin A, 5 IU of vitamin E and 1000 IU of vitamin D daily. Vitamin A and E were measured by high performance liquid chromatography and spectrophotometry. 25-hydroxyvitamin D, a surrogate marker for vitamin D status, was measured by radioimmunoassay, and retinol binding-protein concentration was measured by immunonephelometry. RESULTS: At birth, formula-fed and breast-milk fed infants had similar plasma concentrations of vitamin A (0.75 +/- 0.20 and 0.64 +/- 0.21 micromol/L, ns), 25-hydroxyvitamin D (34.4 +/- 25.6 and 47.5 +/- 26.7 nmol/L, ns) and vitamin E (9.5 +/- 3.2 and 8.4 +/- 3.3 micromol/L, ns). Vitamins A and E, and retinol binding-protein concentrations steadily increased with time in both groups of infants without attaining, at 3 months, values considered normal in term infants and in young children. At 3 months of age, concentrations of 25-hydroxyvitamin D reached values comparable to those observed in term infants. CONCLUSION: Plasma concentrations of vitamins A and E and of retinol binding-protein steadily increased during the the study without reaching full repletion values. At the conclusion of the study, the type of nutrition did not affect plasma vitamin concentrations.     

Prevention of vitamin D deficiency in adolescents and pre-adolescents. An interventional multicenter study on the biological effect of repeated doses of 100,000 IU of vitamin D3]

Recent studies have shown a high prevalence of calcium and vitamin D deficiencies in adolescents. The aim of this present study was to follow the changes in calcium status and 25 hydroxyvitamin D (25[OH]D) and parathyroid hormone (iPTH) levels during winter in preadolescents and adolescents from four university hospitals in northern France. SUBJECTS AND METHODS: Two groups of teenagers and adolescents (range: 10-15 years) were followed from October 1996 to June 1997. They were given either 100,000 IU of vitamin D (treated group n = 33) or a placebo (control group n = 35) in October, January and April. Serum calcium, phosphate, 25(OH)D and iPTH levels were measured at inclusion and every three months thereafter. RESULTS: At inclusion, plasma or serum 25(OH)D levels were < or = 10 ng/mL in 16 subjects and < 6 ng/mL in six. In control children, no significant change in 25(OH)D occurred during the study, while plasma or serum iPTH levels increased to 34 +/- 11 pg/mL. In the treated groups, 25(OH)D levels remained > 20 ng/mL in every subject; no hypercalcemia was observed; and the mean plasma or serum iPTH level was 25 +/- 14 pg/mL at the end of the study. CONCLUSION: Teenagers presented with a high prevalence of biological vitamin D deficiency at the end of summer. The increase of iPTH during winter in the unsupplemented group suggests that this has secondary consequences on their calcium homeostasis unless they are supplemented with vitamin D. We advocate a sufficient calcium supply and a 100,000 IU vitamin D supplement given two or three times during winter to preadolescents and adolescents living in northern France.     

Comparative immunogenicity of hepatitis B vaccine administered into the ventrogluteal area and anterolateral thigh in infants

OBJECTIVE: To compare the immunological response of hepatitis B vaccine given by intramuscular injection into the anterolateral thigh and ventrogluteal site of infants up to 10 months old at initiation of vaccination. METHODS: An open, randomized study of 200 healthy infants recruited from a single practice in a small regional town in New South Wales was carried out. Infants were vaccinated with hepatitis B vaccine (Engerix-B 10 microg) using a 0 months, 1 month, 6 months regimen, with venous blood being collected from children 4-6 weeks after the last dose of vaccine for quantitative determination of hepatitis B surface antibody (anti-HBs) titre. Infants with anti-HBs titre > or = 100 m IU/mL were considered to be 'good' responders and were unlikely to acquire clinically significant hepatitis B infection. Infants with anti-HBs titre < 100 m IU/mL were considered to be 'poor' responders and were given a booster dose of Engerix-B 20 micro g; serology was repeated for anti-HBs titre 2-3 months after this injection. RESULTS: Quantitative anti-HBs titre was obtained from 177 infants: 171 4-6 weeks after the last dose of vaccine; 87 at the ventrogluteal site (46 boys, 41 girls); and 84 at the anterolateral thigh site (38 boys, 46 girls). Good antibody response (anti-HBs titre > or = 100 m IU/mL) was not significantly different for the two sites (ventrogluteal 96.6%, anterolateral thigh 93.2%), and antibody geometric mean titres (GMT) for anti-HBs were comparable for the two sites (ventrogluteal 2071.2 +/- 5.8m IU/mL, anterolateral thigh 2073.2 +/- 5.2m IU/mL). CONCLUSION: The ventrogluteal and anterolateral thigh vaccination sites in infants are immunologically comparable for hepatitis B vaccine. Presumably the variance of this study with studies of adults reflected the uniform injection of vaccine antigen into muscle tissue in infants.     

Low birth weight for gestational age and subsequent male gonadal function

OBJECTIVE: To verify whether a reduced birth weight for gestational age was associated with a testicular dysfunction in postpubertal boys.Study design: Boys born small for gestational age (SGA) (n = 25) were compared to 24 born with an appropriate weight. All subjects were postpubertal (mean age 17.5 +/- 1.3 and 17.6 +/- 2.0 years, respectively). The following clinical and endocrinologic variables were evaluated: final height, target height, body mass index, testicular volume, follicle-stimulating hormone, luteinizing hormone, testosterone, and inhibin B. RESULTS: The SGA group had reduced testicular size (16.3 +/- 2.7 mL vs 22.8 +/- 3.2 mL; P <.0001) with a lower testosterone level (3.76 +/- 1.35 ng/mL vs 4.77 +/- 1.55 ng/mL; P <.05) and a higher LH value (4.41 +/- 1.61 IU/L vs 3.44 +/- 1.29 IU/L; P <.05). Among the SGA group, 54% had a mean testicular volume >2 SD below the control mean (ie, <16 mL) and in these subjects, the inhibin B level was low (143 +/- 46 pg/mL vs 229 +/- 76 pg/mL; P <.0001). SGA patients with smaller testes had lower final height relative to target height(P <.05 vs patients with larger testes) and for the SGA group, inhibin B correlated with testicular size (P <.0001). Positive correlations also were found between the reduction of final height relative to target height and testicular volume (P <.005) and inhibin B values (P <.05). CONCLUSIONS: SGA subjects have pituitary-gonadal axis function that tends toward hypogonadism. There is a disruption of the exocrine function in subjects with smaller testicular size who failed to show a complete height catch-up growth. This study supports a link between low birth weight and lower fertility in adult males.     

Severe osteopenia in a young boy with Kostmann's congenital neutropenia treated with granulocyte colony-stimulating factor: suggested therapeutic approach

Kostmann's syndrome is a congenital disorder that causes an impairment of myeloid differentiation in the bone marrow characterized by severe neutropenia, which can be treated with recombinant human granulocyte colony-stimulating factor (G-CSF). We present the case of a 13-year-old boy with Kostmann's syndrome who was treated with recombinant human G-CSF from age 3.5 years. His growth and development was normal, although complicated by intermittent infections. Bone mineral density (BMD) measurement revealed severe osteopenia at the spine and hips (lumbar spine BMD 0.486 g/cm(2); Z score -3.6), and he was referred to the Endocrine Service. Relevant laboratory evaluation showed a pretreatment ionized calcium level at the upper limit of normal (1.28 mmol/L; range: 1.13-1.32 mmol/L), suppressed intact parathyroid hormone (iPTH) level (12 pg/mL; range: 10-65 pg/mL), and a low 1,25-dihydroxy vitamin D level (21 pg/mL; range: 24-65 pg/mL). He had evidence of increased bone turnover evidenced by elevated urinary deoxypyridinoline (DPD) cross-links (46.9 nmol/mmol creatinine; range: 2-34 nmol/mmol creatinine) and a simultaneous increase in markers of bone formation with elevated osteocalcin level (200 ng/mL; normal: 20-80 ng/mL) and alkaline phosphatase level (236 IU/mL; normal: 38-126 IU/mL). Because of clinical concern for his skeletal health, bisphosphonate therapy with intravenous pamidronate was initiated. One month after treatment, the iPTH and DPD cross-links were in the normal range (54 pg/mL and 17.7 nmol/mmol creatinine, respectively) and the 1,25-dihydroxy vitamin D level was elevated (111 pg/mL). Four months after treatment, there was a striking increase in BMD at the lumbar spine (+30.86%), femoral necks (left, +20.02%; right, +17.98%), and total hips (left, +18.40%; right, +15.94%). Seven months after bisphosphonate therapy, his biochemical parameters showed a return toward pretreatment levels with increasing urinary DPD cross-links (28.7 nmol/mmol creatinine) and decreasing iPTH (26 pg/mL). However, the BMD continued to increase (8 months posttreatment), but the magnitude of the increment was attenuated (lumbar-spine, +4.8%; left total hip, +1.2% and right total hip +2.4%), relative to BMD at 4 months. Eight months after the initial treatment, his iPTH was suppressed at 14 pg/mL and he again received pamidronate (at a lower dose); 3 months later, he had an additional increase in BMD (lumbar spine +7.4%, left total hip +3.9%, right total hip +2.7%), relative to the previous study. We hypothesize that prolonged administration of G-CSF as treatment for Kostmann's syndrome is associated with increased bone resorption, mediated by osteoclast activation and leading to bone loss. In children, the resulting osteopenia can be successfully managed with antisreorptive bisphosphonate therapy with significant improvement in bone density. Measurements of biochemical parameters of bone turnover can be used to monitor the magnitude and duration of the therapeutic response and the need for BMD reassessment and, perhaps, retreatment.     

Evaluation of a pediatric multiple vitamin preparation for total parenteral nutrition in infants and children. I. Blood levels of water-soluble vitamins

This study represents the first attempt to evaluate the response to the only intravenous vitamin preparation (MVI Pediatric) for infants and children receiving total parenteral nutrition. Eighteen preterm infants (group 1), 26 term infants and children receiving total parenteral nutrition for 2 to 4 weeks (group 2A), and eight infants and children receiving total parenteral nutrition for 3 to 6 months (group 2B) were studied. Term gestation infants and children up to 11 years of age received daily vitamin doses that approximated the 1974 Recommended Dietary Allowances and coincided with the 1975 American Medical Association Nutrition Advisory Group total parenteral nutrition dosage guidelines for children weighing more than 10 kg. Preterm infants received 65% of these dosages. RBC transketolase (vitamin B1), glutathione reductase (B2), and glutamic oxaloacetic transaminase (B6) activities were maintained at normal levels, and niacin levels were maintained within the reference range (7.1 +/- 0.32 micrograms/mL) in all study patients. Pantothenate, biotin, and ascorbate were maintained at reference levels in groups 2A and 2B. In group 1, ascorbic acid was increased significantly during treatment from 1.53 +/- 0.16 to 3.60 by seven days and to 2.54 +/- 0.62 by day 28 of treatment (reference normals = 0.99 +/- 0.1 mg/dL). RBC folate was maintained within the reference range of 411 +/- 76 pg/mL; however, pantothenate and biotin levels increased significantly to more than 2 SD above reference values during treatment, and vitamin B12 levels, which were above the reference range initially, were maintained at more than 2 SD above the reference range throughout treatment. The elevation in vitamin B12 was seen in both group 1 and 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lamivudine Facilitates Optimal Chemotherapy in Hepatitis B Virus-Infected Children with Hematological Malignancies: A Preliminary Report

Hepatitis B virus (HBV) reactivation is well documented in infected patients who have hematologic malignancies, precluding appropriate chemotherapy courses and, therefore, increasing the possibility of relapse of malignancies. The objective of this study was to evaluate lamivudine treatment to prevent hepatitis B reactivation in children with cancer who acquired infection with HBV and so allow completion of optimal chemotherapy. Ten children (7:3 M:F; median age: 9.8 years), undergoing chemotherapy for hematological malignancies and suffering from immunosuppressive-induced hepatitis B virus reactivation, were treated concurrently with lamivudine (3 mg/kg bw,od) for up to 18 months. All were HBsAg+ve, HBsAb?ve, HBV-DNA+ve. Serology markers (HBsAg/Ab, HBeAg/Ab, HBV-DNA) and ALT were tested 3 monthly. Histological assessments were performed pre- and 18 months post-lamivudine therapy. During lamivudine therapy chemotherapy courses were completed for all children, and none of the patients suffered reactivation of hepatitis. After a median follow-up of 10 months, remission of malignancy was maintained in 7/10 patients while 3 patients relapsed. HBeAg+ve seroconversion occurred in 4/9 HBeAg+ve children within 3 months. After 9 months of therapy, 8/10 were HBV-DNA?ve. Six out of 7 children with histological evidence of chronic hepatitis showed marked improvement post-therapy. Lamivudine therapy for up to 18 months in children receiving chemotherapy helped prevent recurrence of hepatitis B exacerbations and improved the underlying chronic hepatitis, while facilitating completion of appropriate chemotherapy regimens without compromise.     

Elevation of serum stem-cell factor in postoperative biliary atresia

BACKGROUND: Biliary atresia (BA) is one of the most common causes of neonatal cholestasis. Stem-cell factor (SCF) has been implicated in the development of fibrosis in various diseases. The objective of the present study was to examine the significant role of SCF in BA. METHODS: Fifty-seven pediatric patients with BA after Kasai operation and 30 healthy children were recruited. The mean ages of BA patients and controls were 6.1 +/- 0.6 years and 6.1 +/- 0.7 years, respectively. The patients were categorized into two groups according to their serum levels of total bilirubin (TBil < 2 mg/dL, no jaundice vs TBil > or = 2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT < 100 vs ALT > or = 100 U/L). The serum SCF levels were determined on commercially available enzyme-linked immunosorbent assay. RESULTS: The mean serum SCF level of the BA children was higher than that of normal controls (748.3 +/- 17.9 pg/mL vs 582.2 +/- 17.3 pg/mL; P < 0.001). Subsequent analysis demonstrated that the BA patients with serum ALT > or = 100 U/L had significantly greater levels of serum SCF compared to those with serum ALT < 100 U/L (796.5 +/- 22.6 pg/mL vs 694.7 +/- 25.0 pg/mL, respectively; P = 0.002). In addition, serum SCF levels were significantly elevated in the patients with portal hypertension (PH) compared with those without PH (810.0 +/- 18.8 pg/mL vs 634.1 +/- 20.1 pg/mL, P < 0.001). CONCLUSION: The current study showed that BA patients had higher serum SCF levels compared with controls. The significant elevation in SCF levels is associated with the presence of PH and the degree of hepatic injury. These findings suggest that SCF may play a part in the pathogenesis of hepatic fibrosis in BA patients after Kasai procedure.     

Alpha interferon and lamivudine combination therapy for chronic hepatitis B in children

BACKGROUND: Lamivudine is a new alternative therapeutic agent for chronic hepatitis B, in which alpha interferon (IFN-alpha) monotherapy is not successful enough. Published reports have revealed no satisfactory data on IFN-alpha and lamivudine combination therapy in children. The aim of this study is to investigate the efficacy and safety of this combination therapy in children with chronic hepatitis B. METHODS: Children with chronic hepatitis B were given either IFN-alpha and lamuvidine (group 1, n = 47) or IFN-alpha alone (group 2, n = 30). Alpha interferon was administered as 5 million U/m2 s.c., thrice a week for 6 months and lamivudine 4 mg/kg per day p.o., maximum 100 mg, for 1 year. Clinical examination was performed; blood cell counts and serum alanine aminotransferase (ALT) and amylase were studied at each visit. At the third, sixth and twelfth month, serological markers were determined. RESULTS: End of therapy response was achieved in 19 (40.4%) patients in group 1 and in 14 (46.7%) children in group 2 (P > 0.05). In group 1, pretreatment serum ALT and hepatic activity index (HAI) were statistically higher in children who responded to therapy (P < 0.005). In group 2, mean serum ALT was higher and hepatitis B virus (HBV) DNA was lower in responders. Sustained response rate was 40.4 versus 43.3% in two groups. CONCLUSION: The response rate of IFN-alpha and lamivudine combination therapy in children with chronic hepatitis B was similar to that of IFN-alpha monotherapy. High ALT level and HAI, rather than low HBV-DNA level were found to be important predictors of response.     

Plasma homocysteine levels in children and adolescents with type 1 diabetes

OBJECTIVE: Hyperhomocysteinemia has been established as a risk factor for cardiovascular disease. The objective was to investigate total plasma homocysteine concentrations in children and adolescents with type 1 diabetes and a control group. METHOD: Twenty-seven children with type 1 diabetes and 27 subjects of an age- and sex-matched control group were recruited. Fasting samples were collected for plasma total homocysteine, serum vitamin B12, folate, and creatinine. RESULTS: Fasting total homocysteine concentrations showed no difference between patients and controls (5.6 +/- 2.9 micromol/L vs 5.7 +/- 2.2 micromol/L; p greater than 0.05). The diabetic patients had significantly higher serum folate than the healthy controls (11.4 +/- 3.3 ng/mL vs 9.4 +/- 4.1 ng/mL; P = 0.02 and higher serum B12 than the control group (282.8 +/- 119 pg/mL vs 228.5 +/- 50.9 pg/mL; P = 0.03). Total plasma homocysteine concentration correlated with age (r = 0.44, P = 0.02), weight (r = 0.56, P = 0.002), body mass index (r = 0.57, P = 0.002), folate (r = -0.48, P = 0.01), and creatinine (r = 0.41, P = 0.03) in diabetic patients. In stepwise multivariate regression model for diabetics, the independent correlates for total plasma homocysteine concentration was folate (P = 0.002). CONCLUSION: We concluded that fasting plasma total homocysteine concentrations were within normal limits in children and adolescents with type 1 diabetes who were without any clinical evidence of microvascular and macrovascular complications.     

The influence of interferon-alpha and combination interferon-alpha and lamivudine therapy on height and weight in children with chronic hepatitis B infection

AIM: To evaluate the height and weight patterns of children with chronic hepatitis B (CHB) with and without treatment. METHODS: Thirty-four patients with immunoactive CHB randomly assigned to receive interferon-alpha2a (IFN) (5 mIU/m2, 6 months, group I) or IFN (same dose and duration) plus lamivudine (4 mg/kg/day, 24 months) (group II). Fifteen immunotolerant patients (group III) were followed without any treatment. Height (Ht-SDS), weight (Wt-SDS) and growth velocity (GV-SDS) standard deviation scores were monitored for a total of 36 months. RESULTS: Ht-SDS was significantly lower in group II than in group I one year after completion of IFN treatment (p < 0.05). Wt-SDS was significantly higher in group I than the other groups two years after completion of IFN treatment (p < 0.05). In groups I and II, the percentage of children showing abnormal GV-SDS decreased once treatment was completed (p < 0.05). CONCLUSION: CHB does not have deleterious effects on height and weight. Although IFN treatment temporarily compromises weight gain and growth velocity, lamivudine does not have any additional adverse effect.