Microalbuminuria in chronic hepatitis B infection

We examined for microalbuminuria in patients with hepatitis B virus (HBV) infection, and the effect of antiviral treatment. Group I consisted of 38 patients who were inactive HbsAg carriers; group II included 21 HBeAg positive patients with chronic HBV infection who responded to antiviral treatment at 6 months; group III consisted of 24 patients with chronic HBV infection who did not respond to treatment at the end of 6 months; and group IV consisted of healthy controls. Initial level of microalbuminuria was significantly higher in group II compared to the levels measured at 3, 6, and 9 months (P<0.001). Although, there was a significant difference in microalbuminuria at initial and 3 months between group I and group II (P<0.001), no differences were found at 6 and 9 months. There was no significant difference betweeen group II and group III in terms of urine microalbuminuria at the beginning of the study, but statistically significant differences were determined at 3, 6, and 9 months (P<0.001). The measurement of microalbuminuria may indicate a preclinical renal damage, associated with chronic HBV infection. It may also be used to determine the response to treatment with interferon and lamivudine in children with HBV infection.     

Interferon treatment for chronic hepatitis B: enhanced response in children 5 years old or younger

OBJECTIVE: To test the hypothesis that there is an improved response to interferon in children with chronic hepatitis B (HBV) who are < or =5 years of age. STUDY DESIGN: Retrospective chart review of 22 consecutive children with chronic HBV (ages 17 months to 17 years; median, 83.9 months; 14 male, 8 female) treated with interferon-alpha2b. RESULTS: Ten patients (48%) responded to treatment [HBeAg (-), Anti-HBe (+), HBV DNA (-), HBsAg (+) and normal alanine aminotransferase/aspartate aminotransferase (ALT/AST) at 6 months after treatment], and 5 seroconverted HBsAg [above plus HBsAg negative and anti-HBs (+)]. Seven of 9 patients (78%) < or =5 years of age responded (5 cleared HBsAg). Three of 13 patients (23%) >5 years of age responded. Patient age at treatment was significantly lower in responders (63 +/- 70 months) versus nonresponders (104 +/- 55 months, P =.005). AST, ALT, and HBV DNA at the start of treatment were not different between responders and nonresponders or between patients < or =5 and >5 years old. CONCLUSIONS: Interferon treatment may be more effective in younger children with chronic hepatitis B.     

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.     

Characteristics and outcome of acute infection with hepatitis B virus in children with cancer.

After an outbreak of hepatitis B virus (HBV) infection in a unit of pediatric oncology, the clinical outcome and HBV markers were followed in 1 child with chronic and 10 children with acute HBV infection for 12 months. Four children had acute hepatitis with jaundice whereas 7 of the infections were subclinical. Ten children had antecedent malignancies and 1 had aplastic anemia. Four patients died of causes unrelated to the hepatitis after periods of 2, 4, 8 and 10 months. All 3 children who were not immunosuppressed at the time of contracting the HBV infection quickly turned negative for hepatitis B surface antigen (HBsAg), whereas only 2 of 8 patients who were immunosuppressed by chemotherapy eventually became HBsAg-negative. The latter 8 patients were also hepatitis B e antigen (HBeAg)-positive. Two of them quickly cleared HBeAg, but 6 remained HBeAg-positive throughout the follow-up. In 6 of 9 patients HBsAg was also detected in saliva. These results suggest that children who are receiving anticancer chemotherapy have an increased risk of remaining HBeAg-positive and secreting HBsAg and possibly HBV in their saliva, which makes them particularly infective.     

Efficacy of primary hepatitis B immunization in children with acute lymphoblastic leukemia

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) carry a high risk of hepatitis B virus (HIV) infection. The present study was conducted to see if prior routine hepatitis B vaccine received as a part of national immunization program could prevent HBV infection in these children. METHODOLOGY: Ninety-six children with ALL were screened for HBV. Children were divided into three groups according to their initial HBV serology; previously vaccinated children (Group I) (n=34) previously unvaccinated and seronegative children (Group II) (n=56),and unvaccinated but HBsAg negative and anti-HBs positive children (group III) (n=6). Sixty-seven of 96 (69.7%) children received vaccination. The schedule was initiated during the third month of maintenance therapy and each course consisted of three doses given at one month interval. RESULTS: Anti-HBs seroconversion following the first course of three doses of hepatitis B vaccination in group I, II and III was 57%, 33% and 100%, respectively. It increased to 97% in Group I, 62.5% in Group II, 100% in Group III. HBsAg positivity was found in 11 children (11.5%) and all of them developed chronic hepatitis B. Ten of them were in Group II whereas only one child was in Group I (P<0.04). CONCLUSION: This data reveals that routine HBV vaccination within the national immunization program plays an important role in decreasing subsequent hepatitis B infection in children with ALL.     

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.     

High-dose interferon results in high HBsAg seroclearance in children with chronic hepatitis B infection

Clinical trials for chronic hepatitis B (HBV) infection in children have shown usefulness of interferon alpha 2b (IFN-alpha) in eliminating HBV replication and in improving liver histology. Although it is not the ultimate goal of the interferon treatment for chronic HBV infection, it has been suggested in adults that HBsAg clearance decreases the likelihood of development of hepatocellular carcinoma, and prolongs the survival. HBV DNA clearance has been shown to be higher with higher doses of interferon in children, but it was rarely associated with HbsAg clearance. Ten MU/m2 was tried in 46 children who had biopsy-proven chronic HBV infection. They received IFN-alpha subcutaneously three times/week for six months. The treatment regimen was completed in 41 children and the second liver hiopsy was carried out one year after the end of the treatment in 30 of 41 patients. With this schedule, 15 (36.6%) children showed persistent loss of HBV DNA 12 months after the cessation of the treatment, 20 (48.7%) lost HBeAg, and eight (19.5%) developed anti-HBs antibody with loss of HBsAg. A significant improvement in liver histology was obtained in children with HBV DNA clearance. Serum ALT levels normalized in all HBeAg seroconverters. These findings suggested that the 10 MU/m2 IFN-alpha treatment was well tolerated and resulted in a high rate of HbsAg clearance in addition to HBV DNA clearance in a group of chidren with chronic HBV infection.     

Lamivudine treatment for chronic hepatitis B infection in children unresponsive to interferon

BACKGROUND/AIMS: Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. This prospective open study reports the results of lamivudine treatment in children with chronic hepatitis B infection who did not respond to previous interferon treatment. PATIENTS AND METHODS: Lamivudine, 3 mg/kg/day (maximum, 100 mg/day), was given for 52 weeks to 20 children and adolescents, ages 8.5 to 19 years, with chronic hepatitis B infection who had been treated with interferon 2 to 5 years earlier. We evaluated virologic and biochemical responses, the occurrence of YMDD mutants and adverse effects. RESULTS: All children were HBV DNA+, hepatitis B e antigen (HBeAg) /anti-hepatitis B e antibody- at start of treatment. At the end of 1 year, HBV DNA declined by 95% in all patients, and 8 of 18 (44%) had sustained undetectable HBV DNA by hybridization assay. Median pretreatment alanine aminotransferase (ALT) x1.5 upper limit of normal decreased to ALT x0.9 upper limit of normal after 1 year. One child became HBeAg-negative. YMDD mutants were detected in 11 of 17 (65%) children after 1 year of lamivudine treatment. Among children with YMDD mutant variants, 54% maintained normal ALT values and 45% had undetectable HBV DNA by hybridization assay. No adverse effects were observed. CONCLUSIONS: Children with chronic hepatitis B infection treated with lamivudine after failure of interferon therapy had decreased HBV replication and improved ALT values. However, lamivudine treatment resulted in an exceptionally high rate of lamivudine-resistant mutants and low HBeAg seroconversion rate.     

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.     

Recombinant interferon-alpha-2A with or without steroid pretreatment in children with chronic hepatitis B

Interferon is the most promising therapeutic agent for the treatment of chronic viral hepatitis. The results of studies suggest that corticosteroid pretreatment may improve the response rate. Twenty-nine children with chronic hepatitis B (CHB) were randomly assigned to receive recombinant interferon alpha (rIFN-alpha) alone (Group 1.5 million units/m2 body surface, 3 times a week for 24 weeks) or to receive oral prednisone (Group 2.2 mg/kg/day for 3 weeks, discontinued by tapering the dose within 1 week) followed by rIFN-alpha (same dose as above). Tests for liver function and hepatitis B virus (HBV) markers including HBV-DNA were done periodically. Overall, 10 patients (34.5%) cleared hepatitis Be antigen and 13 (44.8%) HBV-DNA. Anti-HBe seroconversion was observed in nine patients (31%). Only three patients (10.3%) cleared hepatitis B surface antigen and seroconverted to anti-HBs. No response was obtained in 11 patients (37.9%). There was no statistically significant difference between the two treatment groups regarding response rate. Baseline transaminases levels and HBV-DNA concentrations were predictive parameters for HBeAg clearance. It is concluded that prednisone pretreatment does not have a beneficial effect in children with CHB.     

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.     

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.     

IFN-γ+874基因单核苷酸多态性与宫内HBV感染易感性关系的研究

目的　研究宫内乙型肝炎病毒 (HBV)感染患儿的干扰素γ(IFN γ) 874单核苷酸多态性 (SNP)与宫内HBV感染易感性的关系 ,探讨宫内HBV感染的遗传易感因素。方法　母亲为HBV携带者 ,新生儿出生后按程序使用乙肝疫苗或乙肝疫苗联合乙肝免疫球蛋白进行免疫。出生时外周静脉血HBsAg和 (或 )HBV DNA阳性并持续阳性 6个月以上者为宫内HBV感染组 ,共 4 6例。出生时及以后随访中未曾出现过HBsAg或HBV DNA阳性 ,1岁时抗HBs达保护滴度以上者为正常免疫组 ,共73例。用ABIPrism770 0高通量荧光PCR系统对IFN γ 874SNP进行测定。结果　宫内HBV感染组IFN γ 874AA、AT和TT基因型分布频率分别为 6 7 4 %、19 6 %和 13 0 % ;正常免疫组AA、AT和TT基因型分布频率分别为 4 5 2 %、30 1%和 2 4 7%。两组IFN γ 874基因型的分布频率差异有显著性 (χ2=5 10 2 ,P <0 0 5 )。宫内HBV感染儿童IFN γ 874AA基因型占优势。结论IFN γ 874基因多态性与宫内HBV感染有关 ,提示IFN γ 874基因多态性可能在决定个体宫内HBV感染遗传易感性方面有一定意义     

Clinical importance of hepatitis B virus DNA detection in serum of children with chronic hepatitis B]

206 sera from 172 children with chronic hepatitis B infection were tested for HBV DNA by dot blot hybridization. 111 were positive and 95 negative for HBV DNA. 103 (78.6%) of the positive patients had HBeAg and 5 (7.7%) anti-HBe. In 60 (92.3%) of the anti-HBe positive sera no HBV DNA could be detected. Children with elevated liver enzymes had HBV DNA in 80.1%, whereas in 71.6% of the chronic HBsAg carriers with normal liver enzymes no HBV DNA was found. In 87 of the 95 dot blot negative patients polymerase chain reaction was performed. 73 (83.9%) children of this group were HBV DNA positive. All HBeAg positive patients and those with elevated aminotransferases had HBV DNA in their serum. 56 anti-HBe-positive HBsAg carriers were also positive; 14 were negative for HBV DNA. Our results demonstrate that viral sequences can be found in all HBeAg positive and in most of the anti-HBe positive children. Patients with ongoing virus replication have to be considered infectious and recommendation for vaccination of close relatives of these patients must be stressed.     

Interferon-alpha treatment of chronic hepatitis B in childhood: a consensus advice based on experience in European children.

BACKGROUND: The efficacy of interferon (IFN) in children with chronic hepatitis B has been evaluated in randomized controlled trials over the past decade, but recommendations for treatment based on this experience have not been published yet. The purpose of this workshop, held in Madrid in October 1997, was to provide pediatricians with guidelines for practical use of IFN in hepatitis B. METHODS: Eighteen European pediatricians and hepatologists agreed to report and discuss their experience on 1,122 treated children, 40% of whom were considered responders. RESULTS: Agreement was obtained on the following main items: 1) rationale for treatment is to accelerate hepatitis B early antigen (HBeAg) clearance in a subgroup of patients; 2) candidates for treatment are children with HBeAg and HBV DNA positivity, with low-intermediate HBV DNA levels and abnormal alanine aminotransferase values, aged 2 years or more; 3) IFN is contraindicated in children with decompensated liver disease, cytopenia, severe renal or cardiac disorders, and autoimmune disease; 4) the standard treatment regimen is 5 mU/m2 thrice weekly for 6 months. Retreatment in nonresponders is not indicated. CONCLUSIONS: A consensus was obtained on the use of IFN in children with hepatitis B, based on its short-term efficacy. The long-term clinical and virological effects of the drug, however, remain to be evaluated.     

Hepatitis B virus DNA in liver tissue of chronic HBsAg carriers in childhood and its relationship to other viral markers.

The aim of the study was to examine the state of hepatitis B virus (HBV) DNA in liver tissue of 103 children with chronic hepatitis B aged 0.5-18 years to detect free and integrated viral sequences by Southern blot hybridization. HBV DNA was found in 74 patients. Seventy-two were seropositive for hepatitis B e antigen (HBeAg) and two had anti-HBe antibodies. Integrated sequences could be demonstrated in two children. One of them had only integrated HBV DNA and was anti-HBe seropositive. The other one presented both free and integrated viral sequences and developed seroconversion from HBeAg to anti-HBe 5 months after biopsy. In 29 hepatitis B surface antigen (HBsAg) carriers, no HBV DNA could be detected in the liver. Ten were HBeAg and 19 anti-HBe seropositive. HBV DNA in serum was found in 65 of the 74 Southern blot-positive and only in two cases of the Southern blot-negative patients. In conclusion, most of the HBeAg-positive children had free HBV DNA in their liver tissue and all patients with anti-HBe except one were negative. According to our results, HBV DNA integration into the liver cell genome can occur at an early stage of chronic disease but is not a frequent event.     

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.     

Cytomegalovirus hepatitis and ganciclovir treatment in immunocompetent children

Ganciclovir treatment in children with cytomegalovirus (CMV) infection is still controversial and only indicated in selected cases. The aim of thi study was to evaluate clinical and demographic features of CMV hepatitis in immunocompetent children and to determine the effect of ganciclovir treatment in these patients retrospectively. The study was carried out in a group o 29 children with CMV hepatitis. All the patients were investigated for signs of infection, inborn errors of metabolism, genetic diseases, extrahepatic biliary atresia and other causes of hepatitis. Two patients with congenital CMV infection and two patients with biliary atresia were excluded from the study group. The patients included in the study were divided into two groups: non-cholestatic hepatitis (n=16) as Group I and cholestatic hepatitis (n=9) as Group II. Four (25%) patients in the non-cholestatic group and four (44.4 in the cholestatic group were treated with ganciclovir for a median of 21 days. The mean age was 9.6+/- 10.9 months (median age 6 months) in Group I, while cholestatic hepatitis patients in Group II were significantly younger, with a mean age of 2.7+/-0.9 months (p<0.01). The most prominent symptoms at admission were diarrhea and vomiting (25%) in Group I. In Group I, all cases (100%) and in Group II, three of four cases (75%) treated with ganciclovir had recovery from acute CMV hepatitis. In the non-cholestatic group, no relapses were observed while one patient in the cholestatic group relapsed and progressed into chronic liver disease. Patients who received supportive treatment showed a marked decrease in GGT, ALT, AST and bilirubin levels spontaneously and no relapses of hepatitis were observed in at least one year of follow-up. Although ganciclovir therapy is not indicated particularly in immunocompetent cases, since most were self-limited infections, in case of progressive and persistent hepatitis, such as in our cases, ganciclovir was a treatment option; no side effect due to ganciclovir therapy was observed in our cases. Although ganciclovir seems to be effective in progressive CMV hepatitis, multicenter randomized studies in a large study group are necessar to determine the efficacy and indications for ganciclovir treatment.     

Predictors of virologic response to Lamivudine treatment in children with chronic hepatitis B infection

BACKGROUND: Some children with chronic hepatitis B develop advanced liver disease. Lamivudine, an oral nucleoside, is a therapeutic option. A recent large, multicenter study demonstrated that lamivudine was superior to placebo in eliciting loss of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA from serum in children (2 to 17 years) treated for 52 weeks. OBJECTIVE: To identify pretreatment factors that predict the likelihood of response to lamivudine in children with chronic hepatitis B infection. STUDY DESIGN: Data from the multicenter trial in 297 children (191 lamivudine, 96 placebo) were analyzed for the effects of baseline factors on the likelihood of responses. These responses included virologic response, defined as loss of HBeAg and HBV DNA, and HBeAg seroconversion, defined as loss of HBeAg and development of antibody to HBeAg. Univariate and multivariate analyses examined the effects of lamivudine treatment, age, gender, race, body weight, body mass index, previous interferon treatment and baseline alanine aminotransferase (ALT), histologic activity index (HAI) score and HBV DNA on the virologic responses. RESULTS: In the univariate analysis higher baseline ALT, higher HAI score and lower HBV DNA level predicted a greater likelihood of virologic responses to lamivudine. In the multivariate model only baseline ALT and HAI score were predictive of responses. There was no effect of age or ethnicity on response. CONCLUSIONS: Children with higher pretreatment ALT and HAI scores are most likely to respond to lamivudine. Age, ethnicity and other factors do not significantly influence the frequency of virologic responses in children with chronic hepatitis B infection.     

Chronic viral hepatitis B in childhood

The results of immunological studies in serum and liver tissue from 26 patients with chronic HBsAg-positive hepatitis (15 CPH, 9 CAH, 2 MinH) are presented.Determination of serum immunoglobulins showed no significant differences between the three categories of HBsAg-positive CH. AGF, ANA and AMA were not demonstrable in our patients.HBsAg and anti-HBc were demonstrated in all patients, HBeAg in 16, anti-HBe in 6 patients. 2 children had anti-HBs antibodies.Elevated DNA polymerase activity was found in 8 of 12 HBeAg-seropositive and 0 of 9 HBeAg-sero-negative patients.HBcAg was present in liver tissue from 9 of 10 HBeAg-seropositive and 1 of 9 HBeAg-seronegative children. In some cases the classification of viral antigen expression patterns according to the studies of Bianchi and Gudat did not correspond to the histological diagnosis and the presence of serum HBeAg.Studies in 51 family members of 23 children showed a high incidence of HBsAg carriers among the siblings and frequent evidence of anti-HBs in the mothers. Altogether, contact with HBV was demonstrated in 28 of the relatives studied.Abbreviations used HBV hepatitis B virus - CH chronic hepatitis - CPH chronic persistent hepatitis - CAH chronic aggressive hepatitis - MinH minimal hepatitis - HBsAg hepatitis B surface antigen - HBcAg hepatitis B core antigen - HBeAg hepatitis B e antigen - anti-HBs antibody to HBsAg - anti-HBc antibody to HBcAg - anti-HBe antibody to HBeAg - AGF anti-gamma-globulin factors - ANA antinuclear antibodies - AMA antimitochondrial antibodies - SMA smooth muscle antibodies - LMA liver membrane antibodies - DNA desoxyribonucleic acid