Chronic hepatitis B. Treatment in childhood with alpha-interferon]

BACKGROUND: In adults several trials of successful therapy for chronic hepatitis B using alpha-interferon with rates of seroconversion from HBeAg to anti-HBe of 30-40% have been reported. Despite the experiences in children are limited, alpha-interferon seems to be a promising drug in this age group as well. We report on our results in the treatment of chronic hepatitis B virus carrier using the recombination interferon alpha-2b. METHODS: 24 children aged 0.6-16 years with chronic active or chronic persistent hepatitis B were included in the study. 12 children received 9 million units of alpha-interferon/m2 body surface area three times a week during four months. 12 control patients were not treated. The follow-up period was 9-12 months after the beginning of therapy. HBsAg, anti-HBs, anti-HBe and Hepatitis-B-Virus-DNA were assessed during this time on a regular basis. RESULTS: Only seroconversion of HBe-Ag to anti-HBe was considered as response to interferon treatment. During the follow-up period anti-HBe could be detected in 5 (41.6%) of the treated and in one (8.3%) of the untreated children. In one case additional seroconversion of HBsAg to anti-HBs due to virus elimination was observed. In all children a marked reduction of viral replication could be shown. 9 patients cleared Hepatitis-B-Virus-DNA at least for one time during therapy. Alpha-interferon was well tolerated and no severe side effects were observed. CONCLUSION: Our results demonstrate that alpha-interferon can be successfully applied to a considerable number of children with chronic hepatitis B. In patients responding to alpha-interferon usually serum transaminases become normal and infectivity of the disease is markedly reduced. alpha-Interferon treatment should be primarily recommended for children with chronic active inflammation.     

Treatment results of chronic hepatitis B in children: a retrospective study

In this retrospective study, we aimed to share our experience with different treatment modalities for chronic hepatitis B in a series of children. The study included 126 children (mean: 9.5 +/- 3.8 years). Normalization of alanine aminotransferase (ALT), loss of hepatitis B virus (HBV)-DNA and hepatitis B e antigen (HBeAg), and development of antibody to HBeAg (anti-HBe) altogether at the end of the treatment was considered as end of therapy response (ETR). Seroconversion ongoing one year after the cessation of therapy was considered as sustained response. Of the total children, 90 (71.4%) were treated, whereas the remaining were just followed-up. High-dose interferon (IFN)-alpha (10 MU/m2) alone, standard-dose IFN-alpha (6 MU/m2) plus lamivudine (4 mg/kg/d), high-dose IFN-alpha plus lamivudine, or lamivudine alone was used, IFN-alpha thrice weekly for six months, and lamivudine daily for one year. Of children who had completed their treatment, 34 (37.8%) achieved ETR. Sustained response rate was 36.7%. Response rates were different in the different treatment groups (p: 0.01). The highest response rate was observed in those who received standard-dose IFN-alpha plus lamivudine treatment (61.5%). Of children without treatment, one (2.8%) had anti-HBe seroconversion. Standard-dose IFN-alpha plus lamivudine treatment was found superior to the other treatment modalities. Predictors of ETR were similar to those found in previous studies.     

Efficacy of combined interferon alpha and long-term lamivudine therapy in children with chronic hepatitis B

The aim of this study was to evaluate the efficacy of interferon alpha (IFN-alpha) and long-term lamivudine therapy in children with chronic hepatitis B and to determine the optimal duration of lamivudine therapy. Thirty-eight HBeAg-positive children simultaneously received IFN-alpha2a 5 MU/m2 to 10 MU/m2 for six months and lamivudine (4 mg/kg/day). Lamivudine was administered until anti-HBe seroconversion and was continued for six months in responders. During the five-year study period, we evaluated the efficacy of treatment, occurrence of YMDD mutants and adverse effects. During the study period, alanine aminotransferase (ALT) normalization, clearance of hepatitis B virus (HBV) DNA, HBeAg/anti-HBeAb, HBsAg/anti-HBsAb seroconversion, and histological response were noted in 27 (71.1%), 14 (36.8%), 13 (34.2%), 2 (5.2%) and 10 (47.9%) patients, respectively. Complete response was determined in 34.2% (13/38), and in 69.2% of these responders, response was achieved within 18 months. Breakthrough and YMDD mutant rates were 65.8% and 55.2%, respectively. Breakthrough time was a median 24 months and was associated with low baseline ALT level (p < 0.01). In conclusion, although lamivudine was used for a longer period, the response rate was not higher than in previous reports. We suggest that 18 months' duration of lamivudine treatment is sufficient for combination therapy.     

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.     

Natural History of Hepatitis B Virus Carriers Born to Hepatitis B Virus Carrier Mothers

Ninety-five infants born to hepatitis B virus (HBV) carrier women were followed without hepatitis B immune globulin injections over five months. Twenty-one infants (22%) became HBV carriers. These 21 HBV carrier children were followed and the mean follow-up period is six years and nine months. Eighteen mothers (85.7%) of these HBV carrier children were HBeAg positive in perinatal period. One was both HBeAg and anti-HBe negative and the status of the other two was unknown. The mean appearance time of HBsAg is 2.0 ± 1.2 months. Nine carrier children (42.9%) became HBeAg negative in the observation period. In seven cases (33.3%), seroconversion from HBeAg to anti-HBe was observed. In six of seven seroconverted cases, liver dysfunction was observed from the HBeAg positive phase and the liver function normalized within one year after the appearance of anti-HBe except in one case. The mean values of AST (Aspartate aminotransferase or SGOT) and ALT (Alanine aminotransferase or SGPT) of the seroconverted group during the whole observation period were significantly higher than those of the persistent HBeAg positive group. The HBeAg positive rate decreases year by year and inversely the anti-HBe positive rate increases. At 8 years old, the former rate is 55.6%, and the latter rate is 33.3%. The mean annual disappearance rate of HBeAg under eight years is 10.1 ± 5.8% and the mean annual appearance rate of anti-HBe under eight years is 6.1 ± 5.8%. The higher the mean annual disappearance rate of HBeAg, the lower the positive rate of HBeAg in pregnant women. This may contribute to the decrease in the appearance of new HBV carriers.     

Hepatitis B und C im Kindesalter

The development of new medications and therapy regimes has expanded the therapy of hepatitis B and C during the last years. In childhood therapy of chronic hepatitis B is indicated during the high viral phase if transaminase levels are increased on several occasions or if liver fibrosis above grade 2 is present or if social conditions necessitate hepatitis B virus suppression. Treatment with α-interferon is the therapy of choice and leads to seroconversion of anti-HBe in 26–38% of patients. In non-responders or contraindications against the use of interferon lamivudin can be used. After a period of 12 months these therapies lead to seroconversion of anti-HBe in 20–25% of patients and subsequently to the loss of HBeAg and a dramatic decrease of HBV-DNA and mostly also transaminases. Nowadays, therapy with nucleoside and nucleotide analogues should be given until seroconversion to anti-HBe has been achieved but in most cases this involves a long term therapy lasting several years. Therefore, exact knowledge of the characteristics of the currently available nucleosides is crucial. Chronic hepatitis C can be cured in 50–90% of children through combined treatment with alpha-interferon and ribavirin. If treatment is unsuccessful the therapy can be repeated. Medications such as protease and polymerase inhibitors are currently being tested in clinical studies on adults and in some years could be an extension to the clinical therapy.     

Effects of Short-Term Prednisolone Therapy (So-Called Steroid Rebound Therapy) in Children With HBeAg-Positive Chronic Hepatitis B

We have studied the effect of short-term prednisolone therapy on seroconversion from HBeAg to anti-HBe, transaminase levels and hepatitis B virus markers in twelve children with HBeAg-positive chronic hepatitis B. They were followed up for more than two years after the discontinuation of prednisolone. On discontinuation, 11 of the children (91.6%) showed disappearance of HBeAg. In eight of them (66.6%), seroconversion from HBeAg to anti-HBe occurred, concurrently with a gradual fall in serum transaminase level. The seronegative reaction occurred within two to 11 months, and seroconversion occurred within five to 15 months after withdrawal of prednisolone. Transaminase activities fell to normal and have remained normal during two to three years in all 11 patients, with disappearance of HBeAg. Hepatitis B virus-DNA polymerase activities were markedly elevated during prednisolone treatment, and then gradually declined along with or before seroconversion from HBeAg to anti-HBe. The patients seroconverted from HBeAg to anti-HBe showed DNA polymerase negativity throughtout the period of observation. It is thought that rapid withdrawal of prednisolone in children with HBsAg- and HBeAg-positive chronic hepatitis will result in a reduction or elimination of HB virus. In our follow-up study, HBsAg disappeared in only one patient. No severe symptoms were encountered during the period of this short-term steroid therapy.     

Changes in hepatitis Be antigen/antibody system in children with chronic hepatitis B virus infection

The long-term changes in the HBeAg/anti-HBe system were examined in 55 children with chronic type B hepatitis (52 patients) or cirrhosis (three patients) during a follow-up period of two to 10 years. At the time of presentation, positive reactions to HBeAg were seen in 46 children, and to anti-HBe in nine. Spontaneous seroconversion from HBeAg to anti-HBe occurred in 13 of 38 patients (average annual rate 16%), mainly those with acute onset of hepatitis B or with features of active liver disease at presentation and with a focal distribution pattern of hepatitis B core antigen in the liver. Normalization of transaminase activity and disappearance of histologic features of activity were the rule in patients in whom seroconversion occurred, but the exception in those who maintained persistently HBeAg-positivity. In contrast to the favorable evolution of illness observed in children showing anti-HBe seroconversion, three of nine patients who had anti-HBe-positive reactions at presentation were found to have liver cirrhosis, and a fourth patient had features of active hepatitis throughout the observation period. Because delta antigen was detected in the liver in two of these patients, it is conceivable that etiologic cofactors could have influenced their course of chronic hepatitis.     

IgM antibody to hepatitis B core antigen in children with chronic type B hepatitis

IgM antibody to hepatitis B core antigen (anti-HBc IgM) was investigated by an antibody-capture radioimmunoassay (serum dilution 14000) in serum samples from 31 untreated children with chronic hepatitis B who were followed prospectively for 1–7 years. At the start, all patients were positive for hepatitis B e antigen (HBeAg), and anti-HBc IgM was detected in 23 cases, including 15 out of 16 with chronic active hepatitis and 7 out of 14 with chronic persistent hepatitis. A significant positive correlation was found between anti-HBc IgM levels and severity of liver damage (P<0.05), while an inverse relationship was found between anti-HBc IgM levels and distribution of hepatitis B core (HBcAg) antigen in the liver as detected by immunofluorescence. In fact 75% of anti-HBc IgM positive patients showed a focal HBcAg pattern (less than 40% positive nuclei), whereas 87% of antibody negative cases exhibited a diffuse HBcAg expression (more than 60% stained nuclei). During follow-up, seroconversion from HBeAg to anti-HBe with subsequent remission of liver disease occurred in 82% of patients presenting with detectable levels of anti-HBc, including three out of seven cases with chronic persistent hepatitis, but in none of the cases that were initially negative (P<0.01). These results indicate that during the natural course of chronic hepatitis B in children, anti-HBc IgM levels in serum reflect the degree of host immune response to infected hepatocytes. The close correlation between anti-HBc IgM seropositivity and seroconversion from HBeAg to anti-HBe suggests that anti HBc IgM may have a prognostic value during the follow-up of children with chronic HBeAg positive hepatitis B.Abbreviations anti-HBc IgM IgM antibody to hepatitis B core antigen - HBeAg hepatitis B antigen - HBcAg hepatitis B core antigen - HBV hepatitis B virus - ALT alanine aminotransferase - CAH chronic active hepatitis - CPH chronic persistent hepatitis     

Chronic hepatitis B infection: long term comparison of children receiving interferon alpha and untreated controls

OBJECTIVES: To investigate the virological outcome of chronic hepatitis B (CH-B) in children who received interferon alpha (IFN) compared with no treatment. METHODS: Seventy-four children with CH-B (median age, 6.1 years; 44 boys) selected from a cohort of 158 cases were included and divided into two groups: IFN-treated (n = 37) and control (n = 37). The controls were matched with the treated children by baseline alanine aminotransferase (ALT) levels, sex and age. The Kaplan-Meier method was performed to estimate the time to clearance of hepatitis B e antigen (HbeAg) and hepatitis B surface antigen (HbsAg). RESULTS: Mean duration of follow-up was comparable in two groups (5.2 +/- 3.8 years in treatment group versus 5.2 +/- 3.7 years in control group, NS). HBeAg and HBsAg loss occurred in 20 (54.1%) and three treated children versus 13 (35.1%) and one untreated children (NS), respectively. The 7-year cumulative HBeAg and HBsAg clearance rates were 47.5% and 8.9% after the first visit in the treatment group versus 33.5% and 4.0% in untreated children (NS), respectively. Elevated baseline ALT (two times upper limit of normal) had a significant effect on the long-term cumulative rate of HBeAg seroconversion in treated patients (P = 0.01) but not in the untreated group. CONCLUSIONS: These findings show that the overall long-term virological outcome does not differ significantly between IFN-treated and untreated children but that a significant benefit of treatment on the long term rate of HBeAg seroconversion is obtained in children with higher baseline ALT levels.     

Serological and histological follow up of chronic hepatitis B infection.

In order to study the clinical, serological, and morphological evolution of chronic hepatitis B virus infection in childhood, a prospective study has been carried out. A total of 90 children with a chronic infection were followed up for a mean (SD) of 3 (1.8) years. At the beginning of the study, 61 children were asymptomatic and 77 were household contacts of chronic carriers. Serologically 77 were hepatitis B e antigen (HBeAg) positive and 71 of them were positive to hepatitis B virus DNA. The mean alanine aminotransferase activities were higher among HBeAg positive patients than in antihepatitis B e (anti-HBe) positive ones. The most severe histological damage was also found among HBeAg positive patients. The annual seroconversion rate was 14%. A significant increase in the alanine aminotransferase activity was observed 13 (5.6) months before appearance of anti-HBe in the 85% of cases. Among anti-HBe positive patients, the alanine aminotransferase activities were normal in all except three (19%), two of whom had intrahepatic delta antigen. An increase in the histological activity was observed among patients who maintained HBeAg presence while an amelioration of liver damage was observed in anti-HBe carriers.     

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.     

Lamivudine treatment in maternally transmitted chronic hepatitis B virus infection patients

BACKGROUND: Lamivudine treatment in chronic carriers who acquired hepatitis B virus through maternal transmission were investigated. METHODS: A total of 29 subjects (Male:Female, 24:5; mean age, 14.7 +/- 5.6 years) who were hepatitis B e antigen (HBeAg) seropositive for >6 months, alanine aminotransferase (ALT) was >1.3 times of upper limit of normal value, and receiving a 52 week-long treatment, received open-label lamivudine (3 mg/kg per day, maximum 100 mg/day). Another 29 subjects matched for gender, age, liver function, and HBeAg status followed up before the introduction of lamivudine served as the control group. The control group did not receive any treatment and were evaluated at week 52 after the onset of abnormal ALT. Mothers of all study subjects were hepatitis B surface antigen (HBsAg) carriers. A successful treatment response at week 52 was defined as: (i) undetectable hepatitis B virus DNA by real time polymerase chain reaction; (ii) normal ALT; and (iii) HBeAg/anti-HBe seroconversion. Lamivudine-resistant YMDD mutants were checked at week 52. RESULTS: The lamivudine group did not reach a better successful treatment response rate than the control group (17 vs 10%, P = 0.44), except in patients with a baseline ALT >5 times of the upper limit of normal value. YMDD mutants developed in 34% of patients in the lamivudine group. CONCLUSION: Lamivudine treatment is effective for maternally transmitted subjects with high ALT.     

Hypercalciuria is the main renal abnormality finding in Human Immunodeficiency Virus-infected children in Venezuela

Kidney involvement in children with Human Immunodeficiency Virus (HIV) infection is increasing in prevalence in parallel with the longer survival of HIV-infected patients and the side-effects of new antiretroviral drugs. However, there are only a few reports describing renal tubular disorders in HIV+ children. This is a cross-sectional, case series study evaluating kidney disease in 26 Venezuelan HIV-infected children. The study cohort consisted of 15 girls and 11 boys, with a median age of 5.9 years (25–75th percentile: 3.6–7.8), who had been treated with antiretrovirals for 2.8 ± 0.4 years, Overall, the patients were short for their age and gender (Z-height: −3.1; 25–75th percentile: −4.94 to −1.98), and 15 showed signs of mild to moderate malnutrition. All of the children had a normal estimated glomerular filtration rate (136 ± 22.6 ml/min/1.73 m²), and glomerular involvement was only observed in one patient with isolated proteinuria. None had nephromegaly. In contrast, tubular disorders were commonly found. Hypercalciuria was detected in 16 of the patients (UCa/Cr = 0.28; 25–75th percentile: 0.17–0.54 mg/mg), with five of these showing crystalluria. Eight children showed hyperchloremia, and three had frank metabolic acidosis. Kidney stones were absent in all, but one boy had bilateral medullary nephrocalcinosis. Conclusion, in Venezuelan children, HIV infection per se, or its specific treatment, was commonly associated with renal tubular dysfunction, especially hypercalciuria and acidosis, potentially leading to nephrocalcinosis and growth impairment. We recommend renal tubular evaluation during the follow-up of children with HIV infection.     

Lipid and lipoprotein profiles in children with familial hypercholesterolaemia: effects of therapy

In 71 children with familial hypercholesterolaemia the effect of dietary and/or medical treatment was evaluated. Initial total cholesterol and low density lipoprotein (LDL)-cholesterol levels were significantly lower in children who were consecutively treated by diet (Step-One-Diet) than in those who received additional medication. By dietary treatment, the median total cholesterol level (236.5 mg/dl; range 210–510 mg/dl) was reduced by 7.4% and the median LDL-cholesterol level (162 mg/dl; range 126–423 mg/dl) by 9.9%. By dietary and medical therapy, the median total cholesterol level (330 mg/dl; range 270–424 mg/dl) was reduced by 29.7% and the median LDL-cholesterol level (263 mg/dl; 192–333 mg/dl) by 25.9%. High density lipoprotein (HDL)-cholesterol and HDL 3 remained unchanged. HDL 2 showed a significant decrease of 15.6% up to 27 mg/dl (13–42 mg/dl) on medical treatment. Apolipoprotein A I levels did not change during therapy. Initial apolipoprotein B levels were significantly higher in children who were treated by diet and medication and were reduced by 28.9% by combined therapy. In 28 patients (39.4%) an excess of lipoprotein (a) was detected. Regarding the apolipoprotein E phenotype, 32.2% of the patients carried the risk gene ɛ4 in a hetero- or homozygous form. Conclusion Early dietary and/or medical treatment in hypercholesterolaemic children significantly ameliorates the lipoprotein status. The pretherapy lipoprotein status seems to prognosticate the effectiveness of therapy. Received: 16 April 1997 / Accepted in revised form: 27 May 1998     

Retreatment with higher dose interferon alpha in children with chronic hepatitis B infection.

BACKGROUND: More than 50% of children with chronic hepatitis B infection do not respond to interferon-alpha (IFN-alpha) treatment and are prone to have progressive liver disease. The best treatment modality is unknown in these children. The aim of this study was to evaluate the possible benefit of a second higher dose IFN-alpha therapy for children with chronic hepatitis B diseases who failed previous therapy. METHODS: Twenty-four children with chronic hepatitis B infection who had not responded to previous IFN-alpha treatment were enrolled into the study. All were hepatitis B virus DNA- and hepatitis B e antigen-positive for >6 months after initial treatment. They received 10 megaunits (MU)/m2 of IFN-alpha 2a three times a week for 24 weeks. Liver function tests, hepatitis B virus markers and hepatitis B virus DNA were determined regularly during treatment and follow-up. A complete response was defined as clearance of both hepatitis B virus DNA and hepatitis B e antigen (HBeAg). RESULTS: At the end of therapy 8 (33.3%) patients cleared hepatitis B virus DNA and seroconverted to anti-HBeAg. Patients were followed for an average period of 12.2 +/- 4.7 months after retreatment. During follow-up an additional 4 patients cleared hepatitis B virus DNA and seroconverted to anti-HBe, whereas one seroconverted patient became HBeAg-positive again. Thus 11 patients (45.8%) had complete response at the end of the follow-up period. Alanine aminotransferase normalized in 11 responder patients and in 5 nonresponders. Positive predictive factors were low baseline titers of hepatitis B virus DNA and elevated transaminase values (> 100 IU/l). CONCLUSIONS: IFN-alpha retreatment with a higher dose may be an alternative modality for treatment of children with chronic hepatitis B infections who failed previous IFN-alpha, especially in those with favorable predictive factors.     

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.     

The association of elevated alanine aminotransferase and the metabolic syndrome in an overweight and obese pediatric population of multi-ethnic origin

We studied the association between alanine aminotransferase (ALT) and features of the metabolic syndrome in a cohort of overweight and obese children aged 3–18 years. An oral glucose tolerance test was performed in 443 consecutive children from an obesity out-patient clinic (median age 11.2, range 3.1–18.0 years; n = 240 boys) of multi-ethnic origin. The prevalence of the metabolic syndrome, insulin resistance, elevated ALT (>30 IU/L), and the association of ALT with (components of) the metabolic syndrome was assessed. The metabolic syndrome was present in 26.9%. Elevated ALT levels were found in 20.3%, with a higher prevalence in boys than in girls (25.8% versus 13.8%, P < 0.001). ALT was associated with the prevalence of the metabolic syndrome, insulin resistance, high triglycerides, and low HDL-cholesterol after adjustment for gender, age, and BMI. In conclusion, elevated ALT levels were highly prevalent and associated with the metabolic syndrome, insulin resistance, high triglycerides, and low HDL-cholesterol in an obese multiethnic pediatric population.     

Growth hormone treatment enhances bone mineralisation in children with chronic renal failure

Dual energy X-ray absorptiometry of the whole body and the lumbar spine was performed to study bone mineralisation before and after 1 year of recombinant human growth hormone (rhGH) treatment in ten children with chronic renal failure. At the start, median age was 7.3 years (range 2.0–8.8 years) and median glomerular filtration rate 15 ml/min per 1.73 m² (range 7–41 ml/min per 1.73 m²). Total body mineral content (TBMC), lumbar spine mineral content (LBMC), total body bone mineral density (TBMD) and lumbar spine mineral density (LBMD) improved significantly (P < 0.05) after 1 year of treatment. Bone mineral data before and after treatment were compared with two groups of controls, i.e. ten healthy children matched for age and ten healthy children matched for height. Patients' TBMC, LBMC, TBMD and LBMD data before treatment were no different from those of height-matched controls; the same was true after 1 year of treatment except for the patients' significantly better LBMD (P < 0.05). When compared with age-matched controls, patients had significantly lower baseline TBMC and LBMC levels before treatment; after treatment LBMC was no longer different. However, there were no differences in TBMD or LBMD between patients and age-matched controls at baseline or after rhGH. Conclusion Recombinant human growth hormone treatment for 1 year results in a significant increase in both growth velocity and bone mineralisation. Comparison with height-matched controls shows a similar bone mineralisation at baseline and a better bone mineral density after treatment. Received: 10 August 2000 and in revised form 10 November 2000 and 5 January 2001 /  Accepted: 8 January 2001     

Lamivudine and high-dose interferon alpha 2a combination treatment in naïve HBeAg-positive immunoactive chronic hepatitis B in children: an East Mediterranean center’s experience

Chronic hepatitis B virus infection is among the most common causes of chronic liver disease in children. The aim of this study was to document prospectively our experiences related to lamivudine and high-dose interferon-α2a combination in naïve, e antigen positive, chronic hepatitis B virus infection treatment in children. Thirty-three children diagnosed as naïve, immunoactive chronic hepatitis B were treated with lamivudine (3 mg/kg/day) and interferon-α2a (10 MU/m², thrice weekly). Initially, lamivudine was initiated three months before interferon-α for induction, and after June 2002, both drugs were started simultaneously. After interferon-α was stopped, lamivudine alone was continued for six months. HBeAg seroconversion with the normalization of serum ALT was achieved at the end of treatment and at the end of follow-up for 20/33 patients. Initial mean alanine aminotransferase, 142.9 IU/L, decreased to a mean value of 31.4. End-treatment response and sustained response rates were 66.7% (14/21) and 50% (6/12), respectively, in patients that underwent lamivudine induction before interferon-α and in patients that began to receive the two drugs simultaneously (p=0.4). Flu-like syndrome and anorexia were the most common complaints. As our conclusions, we propose that interferon-α2a plus lamivudine combination therapy is highly successful and safe in children suffering from chronic hepatitis B. Lamivudine induction before interferon does not seem to be necessary.