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 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.     

Efficacy of vitamin E in children with immunotolerant-phase chronic hepatitis B infection

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.     

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.     

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.     

Prolonged interferon alpha treatment in children with chronic hepatitis B

Interferon alpha has been used widely to treat hepatitis B virus infection in children. However, the overall initial response rates have been < 50% and several strategies have been attempted to improve this. The aim of this study was to evaluate the safety and efficacy of prolonged interferon alpha treatment in children who did not respond to a previous course of interferon alpha treatment. Twenty-seven children with chronic hepatitis B who had not responded to a 6-month course of interferon alpha 2a (5 MU/m2 body surface) thrice weekly subcutaneously continued to receive interferon alpha at the same dosage for another 6 months without a rest phase. The children were followed for 6 months after completing 12 months of therapy. All of them had HBsAg, HBV-DNA and HBeAg tested on completion of the first course. Six of the 27 (22.2%) cleared both HBV-DNA and HBeAg after completion of therapy and all six had a sustained response. Pre-treatment predictive factors were not significantly associated with treatment response. No adverse effect of interferon was seen during follow-up. We conclude that prolonged interferon treatment is well tolerated and leads to additional benefit.     

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.     

Comparison of standard and high dosage recombinant interferon alpha 2b for treatment of children with chronic hepatitis B infection

BACKGROUND: Interferon is currently the most useful therapeutic agent for chronic viral hepatitis. The aim of this study was to compare the efficacy of standard and high dosages of interferon in children with chronic hepatitis B virus (HBV) infection. METHODS: Thirty children with chronic hepatitis B infection were randomly assigned to receive 5 million units/m2 body surface area (Group I) or 10 million units/m2 body surface area (Group II) recombinant interferon alpha 2b three times weekly for 6 months. Patients were followed for at least 6 months (range, 6 to 18; median, 9 months) after the end of therapy, by physical and serologic examination every 3 months. RESULTS: Clearance of HBV DNA occurred in 4 (27%) patients from Group I and 9 (60%) patients from Group II at the end of therapy. Hepatitis B e antigen (HbeAg) clearance was 7% (1 patient) and 53% (8 patients) in the two groups, respectively (P < 0.05). HBV DNA was undetectable in 40 and 60% of the children at the 12th month of randomization in Groups I and II, respectively. HBeAg/antibody to HBeAg seroconversion was found in 33% (5 patients) who received standard dosage and 60% (9 patients) in the high dosage group. Sustained complete response (normal alanine aminotransferase, negative HBeAg and HBV DNA at 12th month) was obtained in 5 and 9 patients respectively from groups I and II (P > 0.05). Only mean baseline serum alanine amino-transferase concentrations were predictive of response to interferon. CONCLUSIONS: A 6-month course of interferon alpha 2b in children with chronic HBV disease was well-tolerated by most patients. Sustained suppression of HBV was obtained in 60% of patients with high dosage interferon and in 33% of the patients receiving standard dosage. Although these results were not statistically significant, studies with more patients are needed to ascertain whether high dosage improves the response rate.     

The comparison of antibody response to different hepatitis b vaccines with and without pre-S2 antigen in children with cancer

Children with cancer are at an increased risk of hepatitis B infection and chronic liver disease. Since hepatitis B vaccines containing pre-S2 antigen has been recently reported as being more efficient in providing immunization in healthy individuals, the authors compared antibody response to pre-S2-containing vaccine with no-pre-S2-containing hepatitis B vaccine, when given in double doses to 100 children receiving chemotherapy. Patients, aged 1 to 16 years with negative HBV serology, were vaccinated with 2 different types of HBV vaccines between 1997 and 1999. Group 1 received Gen Hevac B containing pre-S2 (n = 41) in a dose of 20 microg for patients younger than 10 years old and 40 microg for older patients. Group 2 was vaccinated at the same dose with hepatitis B vaccines not containing pre-S2 antigen. All vaccinations were repeated at 0, 1, and 6 months. Serum samples were drawn for determination of anti-HBs titers at 1, 3, 6, and 8 months. After the third dose of vaccine, the seroconversion rate was 72% in group 1 and 62% in group 2. The anti-HBs levels were higher in the group receiving pre-S2-containing hepatitis B vaccine. However, the difference between groups was not statistically significant (p > .05). The administration of pre-S2-containing hepatitis B vaccines may give a better seroconversion and higher antibody response to vaccination in children with cancer. But a further large-scale study is needed to confirm this finding.     

Efficacy and safety of peginterferon-alpha2b and ribavirin combination therapy in children with chronic hepatitis C infection

BACKGROUND: Interferon (IFN)-alpha2b plus ribavirin is approved for treatment of hepatitis C in children; however, little is known about efficacy and tolerability of pegylated IFN (PEG-IFN)-alpha2b in this population. The objective of this study was to test the efficacy and safety of PEG-IFN-alpha2b plus ribavirin in children with chronic hepatitis C. METHODS: Thirty children 3-16 years of age who had detectable hepatitis C virus (HCV) RNA for >or=3 years after exposure and elevated alanine aminotransferase values received PEG-IFN-alpha2b 1.0 microg/kg/wk plus ribavirin 15 mg/kg/d for 24 weeks (genotype 2/3) or 48 weeks (genotype 1/4). The primary endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA (<50 IU/mL) at week 24 of follow-up. RESULTS: SVR was achieved in 50% of patients (3/3 genotype 3; 12/27 genotype 1/4). At week 12, 52% of patients were HCV RNA negative and 72% had a >2 log10 decrease in viral load, compared with baseline; 87% and 71% of these patients, respectively, attained an SVR. Therapy was discontinued in 3 patients as a result of adverse events. No patient required ribavirin dose reduction; PEG-IFN-alpha2b dose was reduced in 23% of patients to manage neutropenia. CONCLUSIONS: Combination therapy with PEG-IFN-alpha2b and ribavirin treatment was effective in children with chronic hepatitis C. Virologic status at week 12 identified future responders and nonresponders. PEG-IFN-alpha2b and ribavirin were reasonably well tolerated, with no unexpected or permanent adverse effects. Further studies are needed to identify the optimum treatment regimen for this patient population.     

Hemostatic changes in children with acute lymphoblastic leukemia treated according to two different L-asparaginase schedules

Hemostatic changes in 20 children with acute lymphoblastic leukemia (ALL) who were induced with L-asparaginase (L-asp), vincristine (VCR), and prednisone (PDN) (Group A) were prospectively evaluated. These data were compared with those of a previous group of ALL patients who received L-asp as a single agent during consolidation (Group B). In Group A patients, mean plasma antithrombin activity decreased in the first 2 weeks, though not significantly. Relative to pretreatment values, mean fibrinogen concentration diminished particularly by week 3 (p less than 0.001). Activated partial thromboplastin time (APTT) decreased in the last week as well as after cessation of therapy with L-asp (p less than 0.05). Mean platelet count increased significantly by week 3 (p less than 0.05). Thromboelastograms performed in seven patients confirmed the tendency for thrombosis evidenced by a decreased APTT. Patients in Group B (L-asp alone during consolidation) had decreased concentrations of fibrinogen, AT, and Factors IX and X after L-asp therapy. APTT was prolonged. Our data demonstrate that the tendency for thrombosis is the predominant manifestation of L-asp induced coagulopathy, when the drug is associated with VCR and PDN. Thus the risk/benefit ratio for the use of L-asp early in induction in children with low risk ALL needs to be further evaluated.     

THE COMPARISON OF ANTIBODY RESPONSE TO DIFFERENT HEPATITIS B VACCINES WITH AND WITHOUT pre-S2 ANTIGEN IN CHILDREN WITH CANCER

Children with cancer are at an increased risk of hepatitis B infection and chronic liver disease. Since hepatitis B vaccines containing pre-S2 antigen has been recently reported as being more efficient in providing immunization in healthy individuals, the authors compared antibody response to pre-S2-containing vaccine with no-pre-S2-containing hepatitis B vaccine, when given in double doses to 100 children receiving chemotherapy. Patients, aged 1 to 16 years with negative HBV serology, were vaccinated with 2 different types of HBV vaccines between 1997 and 1999. Group 1 received Gen Hevac B containing pre-S2 ( n = 41) in a dose of 20 &#119 g for patients younger than 10 years old and 40 &#119 g for older patients. Group 2 was vaccinated at the same dose with hepatitis B vaccines not containing pre-S2 antigen. All vaccinations were repeated at 0, 1, and 6 months. Serum samples were drawn for determination of anti-HBs titers at 1, 3, 6, and 8 months. After the third dose of vaccine, the seroconversion rate was 72% in group 1 and 62% in group 2. The anti-HBs levels were higher in the group receiving pre-S2-containing hepatitis B vaccine. However, the difference between groups was not statistically significant ( p > .05). The administration of pre-S2-containing hepatitis B vaccines may give a better seroconversion and higher antibody response to vaccination in children with cancer. But a further large-scale study is needed to confirm this finding.     

Serum zinc status in chronic hepatitis B and its relationship to liver histology and treatment results

BACKGROUND: It is known that cytotoxic T lymphocytes are responsible for viral clearance in chronic hepatitis B (HBV) infection. Zinc deficiency affects development of acquired immunity by preventing certain functions of T lymphocytes. We investigated the serum zinc levels and the relationship to liver histopathology and response to interferon alpha (IFN-alpha) and lamivudine combination therapy in 28 children with chronic HBV infection. METHODS: A course of IFN-alpha was injected as 5 million U/m2 subcutaneously, thrice a week for 6 months and lamivudine 4 mg/kg per day orally, for 1 year. Normalization of alanine aminotransferase (ALT), loss of HBV DNA, hepatitis B e antigen (HBeAg) seroconversion altogether was considered as end of therapy response (ETR). RESULTS: The ETR was achieved in eight (30.7%) patients. Serum zinc concentrations of 20 healthy children and patients was not significantly different (P>0.05). While pretreatment serum ALT, zinc, histological activity index (HAI) and portal inflammation scores were statistically higher in children who had ETR (P<0.005, P<0.05, P<0.05 and P<0.05, respectively), pretreatment serum HBV DNA was lower (P<0.005). Serum zinc level was correlated with HAI and portal inflammation scores (P<0.01 and P<0.01). CONCLUSION: This study showed the relationship of serum zinc status to liver histopathology and to the ETR and may be a preliminary study leading new studies focusing on zinc status in patients with chronic HBV infection.     

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.     

Clinical significance of TT virus infection in children with chronic hepatitis B

BACKGROUND: The pathogenic role of TT virus (TTV) is not clear in patients with chronic hepatitis B. The aims of the present study were to determine the frequency of TTV positivity in serum and saliva samples and the possible role of TTV in children with chronic hepatitis B. METHODS: Sera and saliva from 29 healthy children and 25 children with chronic hepatitis B were tested for TTV-DNA by means of real-time polymerase chain reaction (PCR). RESULTS: Fifty-two percent (13/25) of the serum samples and 32% (8/25) of the saliva samples were positive for TTV-DNA in children with chronic hepatitis B. In healthy non-transfused children, TTV-DNA was detected in 58% (17/29) of the serum samples and 41% (12/29) of the saliva samples. Six (46%) of 13 children with chronic hepatitis and 10 (59%) of 17 healthy children had TTV-DNA positivity both in serum and saliva samples. Two serum samples were negative for TTV-DNA while the saliva samples were positive for TTV-DNA in chronic hepatitis B and control groups. Mean age, sex, serum alanine aminotransferase levels, hepatitis B virus (HBV)-DNA values were similar in TTV-positive and -negative children with chronic hepatitis B. However, total histologic activity index (HAI), periportal necrosis and portal inflammation scores were significantly higher in children with HBV-DNA and TTV-DNA viremia (P = 0.013, P = 0.008, P = 0.015, respectively). CONCLUSIONS: Because total HAI, periportal necrosis and portal inflammation scores were higher in children with TTV coinfection, TTV infection may contribute to the progression of liver damage in children with chronic hepatitis B.     

Immunogenicity of recombinant hepatitis B vaccine in urban black children from Ga-Rankuwa, Bophuthatswana, South Africa.

Many areas in Southern Africa have a relatively high endemicity for hepatitis B for which the only effective medical measure is vaccination. The aim of this study was to evaluate the antibody response to a recombinant hepatitis B vaccine (Engerix B; Smith Kline-Beecham) in a black urban population, with the use of the recommended regimen and a low dose, short course. One hundred eleven children seronegative for hepatitis B virus (5 to 19 years old) were randomized to receive one of the two vaccination schedules (20 micrograms at zero, 1 and 6 months or 2 micrograms at zero, 1 and 2 months). Antibody to hepatitis B surface antigen was determined 6 to 8 weeks after the last dose by radioimmunoassay (Ausab; Abbott Laboratories). The recommended schedule gave a seroconversion rate of 100% with a geometric mean titer of 585.9 mIU/ml. The low dose, short course schedule produced a seroconversion rate of 63.8% and a geometric mean titer of 73.8 mIU/ml. In the 5- to 9-year-old individuals, however, 71.6% seroconverted (geometric mean titer 114.2 mIU/ml). For cost reasons further investigations on low dose regimens are indicated.     

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     

Lamivudine and interferon-alpha combination treatment of childhood patients with chronic hepatitis B infection

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.     

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.     

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.