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.     

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.     

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.     

Interferon-alpha and lamivudine combination therapy of children with chronic hepatitis b infection who were interferon-alpha nonresponders

Greater than one-half of children with chronic hepatitis B infection are nonresponders to interferon-alpha (IFN-alpha). The aim of this study was to investigate the efficacy of lamivudine (LMV) and IFN-alpha combination therapy in these children. Nineteen children were given LMV alone for 3 months; then IFN-alpha was added to LMV for 6 months. Virologic response was achieved in seven (36.8%) patients. LMV and IFN-alpha combination therapy may represent an effective treatment option.     

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.     

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.     

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.     

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.     

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.     

Tolerance of interferon-alpha therapy in children with chronic hepatitis B

OBJECTIVE: To assess the side-effects of interferon-alpha (IFN-alpha) therapy in children with chronic hepatitis B. METHODS: This prospective study was performed on one hundred children by interviewing the patients and their parents; clinical examinations and laboratory investigations were performed during and after therapy. RESULTS: The most frequent side-effects of IFN-alpha therapy were fever, flu-like symptoms, and headaches. Lowering of the mean haemoglobin level, leukocyte and platelet count was significant, but transient during INF-alpha treatment. No increase in autoantibody titres or significant alterations in thyroid function was observed. Twelve months after treatment, hepatitis Be antigen (HBeAg) elimination and alanine aminotransferase (ALT) normalization was achieved in 46% of the children; HBeAg and hepatatis B surface antigen (HBsAg) elimination, together with ALT normalization, was achieved in 14% of the cases. CONCLUSION: The side-effects of the IFN-alpha therapy in children such as fever, flu-like symptoms and bone marrow suppression are common, but transient and mild.     

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.     

Hepatitis B in children: complexities in management

Chronic hepatitis B virus (HBV) infection by definition is persistence of hepatitis B surface antigen (HBsAg) in the serum for > or =6 months. The risk of developing chronic HBV infection ranges from 90% in neonates to <5% in immunocompetent adults. HBV acquired by perinatal infection has a prolonged immune-tolerant phase, characterized by the presence of hepatitis Be antigen (HBeAg), high HBV-DNA and normal alanine aminotransferase (ALT) levels. Efficient and multi-specific helper and cytotoxic T-cell response is essential for controlling HBV infection. Chronic HBV infection is characterized by a state of HBV-specific T-cell hyporesponsiveness. The goal of therapy in chronic HBV infection is to eliminate or significantly suppress HBV replication and prevent the progression of liver disease to cirrhosis with the potential development of liver failure or hepatocellular carcinoma (HCC). In adults, drugs currently licensed for treatment of HBV infection: are interferon-alpha (IFN-alpha), lamivudine (LMV) and adefovir dipivoxil (ADV), the first two are also licensed to use in children. IFN-alpha has the advantage of having a more durable response, fixed duration of treatment and lack of resistant mutants. The disadvantages of IFN-alpha include need for thrice-weekly injections, higher cost and more side-effects compared with the nucleoside analogues. Nucleoside analogues can be given orally and used in decompensated cirrhosis and transplant recipients. ADV and newer drugs like tenefovir can successfully treat mutants produced after prolonged LMV therapy. Current protocols exclude children with immunotolerant HBV. Periodic screening with liver ultrasound scan and alpha-fetoprotein (AFP) in all children with chronic HBV infection is recommended. The severe shortage of cadaveric donor organs has led to the use of marginal (including anti-HBc-positive) cadaveric donor livers in selected transplant candidates with high medical urgency; 5-10% of all liver transplants are because of HBV. Using hepatitis B immunoglobulin and nucleoside analogues has made the outcome following liver transplantation for hepatitis B, comparable with, if not slightly better, than that in patients with other diagnoses. Future treatments should be based on the restoration of HBV-specific T-cell responses to levels similar to that seen in subjects controlling HBV.     

Virus genotype 1b and long-term response to interferon alpha monotherapy in children with chronic hepatitis C

Interferon alpha (IFN-) remains the basic modality in the treatment of chronic hepatitis C in children, but the effects of therapy are still unsatisfactory. The aim of this study was to evaluate parameters linked to IFN- response within a 2-year period. Human C virus (HCV) infected children (n=34) were subdivided into IFN-treated (n=20) and IFN-untreated (n=14 control) groups. The IFN-treated group received a dosage 3 MU of IFN- three times a week for 24 weeks. Liver biopsy was performed in all IFN-treated children and the HCV genotype was determined before the start of the study. Patients were sequentially screened for alanine transaminase (ALT) activity and tested for the presence of HCV-RNA in serum. All patients had either mild persistent or moderate active hepatitis, which was diagnosed from the liver biopsy. In the IFN-treated group ALT normalisation was observed by the end of treatment in 9/20 patients, but after 6 months 10 patients (50%) had sustained ALT normalisation and in 4 of them the virus was eliminated. They continued to show these features up to the end of the observation period (2 years). Eighteen out of 24 children tested had 1b genotype of virus. Out of 10 responders, all patients who were clear of HCV had the 1b genotype. The median age of responders (6.0, range 3.8–16) was significantly lower than non-responders (14.0, range 4–15) In the control group none of the children were clear of HCV-RNA. Conclusion: The negative predictive effect of HCV genotype 1b in the course of IFN- treatment may be not valid in children and other features have to be taken into account in the assessment of the efficacy of therapy.Abbreviations HCV human C virus - RNA ribonucleic acid - PCR polymerase chain reaction - ALT alanine aminotransferase - RBC red blood cells - HBsAg hepatitis B surface antigen - ELISA enzyme linked immunosorbent assay - CMV cytomegaly virus - IFN interferon - MU mega units - ETR end of treatment response - SR ALT sustained biochemical (ALT) response - HAI histological activity index - R responders - NR non-responders - U/l units per litter - CPH chronic persistent hepatitis - CAH chronic active hepatitis - APC antigen presenting cells - MHC major histocompatibility complex - ALL acute lymphoblastic leukaemia - CML chronic myelogenous leukaemia     

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.     

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.     

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.     

The effect of early treatment in children with chronic hepatitis

BACKGROUND: The aim of this study was to compare the efficacy of interferon alpha (IFN) or IFN and ribavirin (IFN+RIB) combination therapy in children with chronic hepatitis C (CHC). Most children were infected during treatment for pediatric malignancies. PATIENTS AND METHODS: We reviewed the charts of 20 patients (11 boys and 9 girls) aged 10.6 +/- 3.7 years with CHC who were treated between 1995 and 2001. Seven patients diagnosed with CHC before 1998 were treated with 3 million units of IFN three times weekly for 6 to 12 months. Thirteen children diagnosed after 1998 were treated with 3 million units of IFN three times weekly plus 15 mg/kg of ribavirin daily for 6 months (IFN+RIB). RESULTS: Demographic and clinical characteristics were not different between the two treatment groups. A sustained complete response defined as serum alanine aminotransferase normalization and hepatitis C virus RNA clearance at 6 and 12 months after termination of treatment occurred in three of seven children (43%) treated with IFN monotherapy compared with 7 of 12 children (54%) in the group treated with IFN+RIB combination therapy (not significant). The only difference between responders and nonresponders was the duration of infection before the initiation of therapy, which was significantly shorter in responders (1 +/- 0.3 vs. 5.6 +/- 2.2; P = 0.001). CONCLUSIONS: In this small cohort of children with CHC, early initiation of antiviral treatment was associated with a sustained response rate independent of treatment type. Regular follow-up of children at risk of acquiring hepatitis C virus infection should assist in the early diagnosis. Early initiation of antiviral treatment may improve the rate of sustained response.     

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.