Peginterferon (PegIFN) has shown promising results in the treatment of chronic hepatitis B (CHB). This study aimed to evaluate the effects of PegIFN α-2b on growth and thyroid function in young children with CHB.

A retrospective study was performed by extracting clinical data from children with CHB who received PegIFN α-2b monotherapy at the Public Health Clinical Center of Chengdu between June 2017 and December 2020. Mean, SD, independent samples t test and 1-way repeated analysis of variance were used to evaluate relevant data.

A total of 62 children were included in this study. Overall, significant differences were observed in the weight-for-age z score (WAZ), height-for-age z score (HAZ) and body mass index-for-age z score (BAZ) at different time points ( P < 0.001). WAZ, HAZ and BAZ were not affected by PegIFN α-2b at 24 weeks of treatment (all P > 0.05). WAZ, HAZ and BAZ at the end of treatment and 48 weeks after treatment; WAZ at 96 weeks after treatment were lower than baseline levels (all P < 0.05). No statistical differences were found in HAZ and BAZ at 96 weeks after treatment compared with baseline. Thyroid dysfunction developed in 17.7% of children during the treatment. Thyroid dysfunction was transient and had no effect on growth.

PegIFN α-2b has inhibitory effects on growth and can increase the incidence of thyroid dysfunction in young children with CHB. These effects are generally reversible with the cessation of therapy, although WAZ had not returned to baseline after 96 weeks of observation.

Hepatitis B e antigen (HBeAg) loss is a key event in the natural history of chronic hepatitis B virus infection. The rate and determinants of HBeAg loss depend upon cohort characteristics at baseline. Few studies have examined the age-dependent rate, and none have examined the effect of patient sex and ethnicity on the age-dependant rate. The study of age-dependent rates requires the identification and long-term follow-up of a pediatric cohort. We have studied the age-dependent rate of HBeAg loss, and the rate of HBeAg loss measured from baseline, in a multi-ethnic cohort of 454 pediatric patients. During observation, HBeAg loss was observed in 121/303 (39.9%) HBeAg-positive patients. The rate of HBeAg loss was greater in the second versus the first and third decades of life. The age-related rate of HBeAg loss was clearly affected by patient sex and ethnicity, with earlier loss observed for males and for White versus both South Asian and Chinese ethnicities. When measured from baseline, Chinese patients had a slower rate of HBeAg loss in comparison with White patients. In multivariate analysis of HBeAg loss during prolonged follow-up, male sex, older age, and White ethnicity were associated with HBeAg loss, but antiviral treatment was not.

Achievement of a 'clinical cure' in chronic hepatitis B (CHB) implies sustained virological suppression and immunological control over the infection, which is the ideal treatment goal according to domestic and international CHB management guidelines. Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens. These regimens incorporate either nucleos(t)ide analogs, immunomodulatory agents such as pegylated interferon α, or a strategic combination of both, sequentially or concurrently administered. Despite these advancements in the clinical handling of hepatitis B, achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes. These include, but are not limited to, the emergence of antiviral resistance, incomplete immune recovery, and the persistence of covalently closed circular DNA. Moreover, the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure. This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.

Interferon therapy, used in the treatment of chronic hepatitis B (CHB), is one of the means by which patients can achieve a functional cure. Pegylated interferon is currently used in the treatment of CHB. There are two main types of pegylated interferon: α-2b and α-2a.

This study explored the efficacy, safety, and predictors of treatment response for α-2b plus entecavir among children in a real-world setting.

The study included 76 patients aged 3-18 years, all of whom were treated with interferon α-2b plus entecavir. The mean duration of treatment was 401.99 days, and 31.6% (24/76) of patients achieved HBsAg clearance. Competing risk model analyses showed that children with baseline HBsAg <1500 IU/mL (subdistribution hazard ratio [sHR]=2.643, P=0.022) and a higher baseline alanine aminotransferase (ALT) level (sHR=1.005, P=0.000) had a higher probability of achieving HBsAg clearance during treatment. Conversely, children with a higher hepatitis B virus loading level (sHR=0.835, P=0.043) and age ≥10 years (sHR=0.243, P=0.002) had a lower probability of achieving HBsAg clearance during treatment. A decrease of >1 log10 in HBsAg level (sHR=3.479, P=0.001) at 12 weeks of treatment was associated with a higher probability of achieving surface antigen clearance.

These results indicated that interferon plus entecavir therapy is a promising means of achieving HBsAg clearance in children with CHB. Moreover, HBsAg, ALT, virus loading, and age are indicators of treatment success probability.

The long-term benefits of interferon-α (IFN-α) treatment in children with chronic hepatitis B (CHB) remain unclear. We conducted a retrospective and real-world study to evaluate the safety and long-term clearance rates of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in CHB children who received IFN-α monotherapy for 72 weeks and were with 13-year follow-up visit. Participants treated with IFN-α (n = 316) were more likely to become HBeAg negatve (39.87% vs. 27.37%; p < .05) and HBsAg negative (11.08% vs. 3.16%; p < .05) by the end of the treatment period than untreated participants (n = 95). Treated participants also had higher cumulative rates of HBeAg loss (74.13% vs. 59.27%; p < .05) and HBsAg loss (46.95 vs. 33.11%; p < 0.05) than untreated participants in parallel by the end of 13-year follow-up. In particular, the cumulative rate of HBsAg loss was higher in treated children aged 1-7 years than in those aged 8-17 years (71.40% vs. 39.0%; p < .01). Children who were HBeAg-negative at the end of IFN-α treatment or who had serum alanine aminotransferase levels of ≥80 IU/L at baseline were likely to have higher cumulative HBsAg loss rates. Accordingly, HBeAg loss at 72 weeks was positively associated with the cumulative HBsAg loss rate in untreated children. There were no serious adverse events of IFN-α therapy for the treated patients throughout the study period. Overall, IFN-α therapy was effective in obtaining higher long-term cumulative rates of HBeAg and HBsAg loss in children with HBeAg-positive immune-active CHB, especially among those aged 1-7 years.

To eliminate viral hepatitis by 2030, the World Health Organization (WHO) launched the first global health sector strategy on viral hepatitis, with particular focus given to hepatitis B and C in 2016. To achieve the reduction of mortality in children, it is indispensable to know which children should be treated and how to treat them.

In this article, the authors review the antiviral treatment of children with chronic hepatitis B virus (HBV) infection including antivirals available for children with chronic HBV infection.

The approvals of nucleos(t)ide analogues (NAs) and pegylated interferon (PEG-IFN) for children have lowered a hurdle to the initiation of antiviral treatment in children. The international guidelines use nearly the same criteria of antiviral treatment for children with chronic HBV infection, but the WHO guidelines provide a cautious stance on the antiviral treatment of children. Not only PEG-IFN but also NAs with a high genetic barrier to drug resistance should be the first-line treatment for children. In settings with limited medical resources, NAs can be the first-line treatment for children. Although the concept of an 'immune-tolerant phase' is challenged, evidence is not sufficient to recommend the treatment of HBeAg-positive immune-tolerant children.

Interferon-alpha (IFN-α) is currently the preferred antiviral treatment for children with chronic hepatitis B (CHB) aged >1-year-old. However, the evidence regarding the exact efficacy and safety in the real world is not sufficient. This study aimed to investigate the efficacy of IFN-α therapy in children with CHB and to provide a theoretical basis for practically identifying ideal antiviral therapies for CHB children.Clinical manifestations, baseline characteristics, related laboratory tests, and adverse events were retrospectively analyzed in children with CHB who visited the Children's Hospital of Fudan University, were treated with IFN-α and were followed up from January 2003 to October 2018.A total of 18 immune-active patients without advanced fibrosis were enrolled, and their average age at the start of treatment was 4.45 ± 2.75 years old. IFN α-2b was administered subcutaneously by body surface area (BSA) category, based on 3 MU/m, for a median 48 weeks. Before treatment, the alanine aminotransferase (ALT) range was 81 to 409 U/L (median 158 U/L). The median hepatitis B virus (HBV)-DNA load was 9.89 × 10 IU/mL, and the HBV-DNA load varied from 3.10 × 10 to 4.56 × 10 IU/mL. The ALT levels of 17 children became normal at an average of 12 weeks during treatment, and those of 1 child became normal at 6 weeks after IFN-α withdrawal. Sixteen (88.9%, 16/18) children became HBV-DNA negative (<10 IU/mL) at an average of 24 weeks during treatment, while 1 became negative at 96 weeks after IFN-α withdrawal and 1 remained HBV-DNA positive. HBV e antigen (HBeAg) seroconversion occurred in 13 of 14 (92.9%, 13/14) HBeAg-positive patients at an average of 12 weeks during treatment. HBV s antigen (HBsAg) loss or seroconversion occurred in 4 (22.2%, 4/18) patients at an average of 21 weeks during treatment. Only mild flu-like symptoms and transient neutropenia appeared in some children at the early treatment stage. No severe abnormal results were observed in other laboratory parameters.The antiviral monotherapy of 48 weeks of IFN-α was well tolerated and good responded, which was associated with higher rates of HBeAg seroconversion and HBsAg clearance in the children in this study than in previously reported adults and pediatric patients.

Hepatitis B virus (HBV) infection is an important public health problem in Canada. In keeping with evolving evidence and understanding of HBV pathogenesis, the Canadian Association for the Study of Liver Disease periodically publishes HBV management guidelines. The goals of the 2018 guidelines are to (1) highlight the public health impact of HBV infection in Canada and the need to improve diagnosis and linkage to care, (2) recommend current best-practice guidelines for treatment of HBV, (3) summarize the key HBV laboratory diagnostic tests, and (4) review evidence on HBV management in special patient populations and include more detail on management of HBV in pediatric populations. An overview of novel HBV tests and therapies for HBV in development is provided to highlight the recent advances in HBV clinical research. The aim and scope of these guidelines are to serve as an up-to-date, comprehensive resource for Canadian health care providers in the management of HBV infection.

Although the introduction of hepatitis B vaccine has been contributing to the reduction in the prevalence of hepatitis B virus (HBV) carriers worldwide, the treatment of children with chronic HBV infection is a challenge to be addressed. HBeAg seroconversion, which induces low replication of HBV, is widely accepted as the first goal of antiviral treatment in children with chronic hepatitis B. However, spontaneous HBeAg seroconversion is highly expected in children with chronic HBV infection. Therefore, the identification of children who need antiviral treatment to induce HBeAg seroconversion is essential in the management of chronic HBV infection. Guidelines and experts' opinion show how to identify children who should be treated and how to treat them. If decompensated cirrhosis is absent, interferon-alpha is the first-line antiviral treatment. Nucleos(t)ide analogues (NAs), such as lamivudine, adefovir, entecavir and tenofovir, are also available for the treatment of children, although the approval age differs among them. If decompensated cirrhosis is present, NAs are the first-line antivirals. When the emergence of drug-resistant HBV variants is taken into consideration, entecavir (approved for age 2 years or older) and tenofovir (age 12 years or older), which have high genetic barriers, will play a central role in the treatment of HBV infection. However, the optimal duration of NA treatment and adverse events of long-term NA treatment remain unclear in children. In resource-constrained countries and regions, the financial burden of visiting hospitals, receiving routine blood examination and purchasing antiviral drugs is heavy. Moreover, there is no clear evidence that the induction of HBeAg seroconversion by antiviral treatment prevents the progression of liver disease to cirrhosis and hepatocellular carcinoma in children with chronic HBV infection. It is thus imperative to clarify the clinical impact of antiviral treatment in children with HBV infection.

Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

For two decades, hepatitis B vaccine has been integrated into national routine childhood vaccination programs in almost all countries. The prevalence of HBsAg has decreased in children worldwide. However, there are children who miss the benefit of hepatitis B vaccine in some regions and countries. Long-term follow-up studies have revealed the clinical outcomes of chronic hepatitis B virus infection in children. A small percentage of chronically infected children develop liver cirrhosis and hepatocellular carcinoma. However, it is controversial who should be treated and when antiviral treatment should be initiated in children. Compared with adult studies, the data are insufficient to evaluate the pathogenesis of hepatitis B infection and the efficacy of antiviral treatment in childhood. New antiviral drugs have been approved for children and adults. Also, oral antiviral drugs are administered to pregnant women to reduce the hepatitis B virus mother-to-child transmission rate.

The development of effective nucleos(t)ide analogs (NAs) against hepatitis B virus (HBV) has improved the outcome of patients with chronic hepatitis B (CHB). This review updates issues related to the management of CHB patients included in special populations. Entecavir (ETV) and tenofovir (TDF) represent the currently recommended first-line NAs in patients with HBV decompensated cirrhosis. The combination of HBV immunoglobulin (usually for a finite duration) and NA is considered the standard of care for prophylaxis against HBV recurrence after liver transplantation. TDF is the best choice for hemodialysis patients and in patients with chronic kidney disease with nucleoside resistance. ETV and telbivudine are the preferred options in naïve renal transplant recipients and with low viremia levels, respectively. All hepatitis B surface antigen (HBsAg)-positive candidates should be treated with NAs before renal transplantation to achieve undetectable HBV DNA at the time of transplantation. Conventional interferon or NAs can also be used in children, on the basis of well-established therapeutic indication. Pregnant women at high risk of perinatal transmission could be treated with lamivudine, telbivudine or TDF in the last trimester of pregnancy. HBsAg-positive patients under immunosuppression should receive NA pre-emptively (regardless of HBV DNA levels) up to 12 mo after its cessation. In HBsAg negative, anti-HBc positive patients under immunosuppression, further studies are needed to form a final conclusion; however, it seems that anti-HBV prophylaxis is justified in such patients with hematological diseases and/or for those receiving rituximab-containing regimens, regardless of their anti-HBs or serum HBV DNA status.

Hepatitis B e antigen (HBeAg) seroconversion is an important event in patients with chronic hepatitis B virus (HBV) infection. This study aimed to clarify the outcome of long-term follow-up of chronic HBV infection and the factors affecting HBeAg seroconversion in children in Japan.

Patients who were first examined at our institution between 1980 and 2012, who were <20 years of age at the time of this initial visit, and who were positive for hepatitis B surface antigen for at least 6 months were identified retrospectively. Sex, age at diagnosis, HBV genotype, maximum serum alanine aminotransferase (ALT) level, occurrence of hepatitis flare-ups (yes/no), and transmission route were evaluated to identify the predictors of HBeAg seroconversion.

A total of 205 children with chronic HBV were enrolled. Among them, 192 were positive for HBeAg upon diagnosis of chronic HBV infection. Out of this group, 95 (49%) achieved HBeAg seroconversion and 43 (21%) received treatment during the follow-up period. Only the maximum serum ALT level was significantly associated with the achievement of HBeAg seroconversion by multivariate analysis (P < 0.05). Kaplan-Meier analysis showed that the median times to HBeAg seroconversion (50% achievement of HBeAg seroconversion) of the treated and untreated children were 10.2 and 12.0 years, respectively. The cumulative proportion of HBeAg seroconversion was significantly higher in the treated children than in the untreated children (P = 0.02).

A higher serum ALT level was a predictor for HBeAg seroconversion. Antiviral treatment could accelerate the achievement of HBeAg seroconversion in HBV-infected children.

Effective management of children with chronic hepatitis B is still an unresolved issue.

To assess the outcome of different therapeutic regimens among children with HBeAg-positive chronic hepatitis B.

Electronic database searches identified clinical trials that completed specific periods of treatment and follow-up. Sustained response rates were defined by the loss of HBV DNA and HBeAg, and by the normalization of liver enzymes. The loss of HBsAg and seroconversion to anti-HBs were also listed.

Our searches found 20 eligible articles (1112 enrolled patients, 2-18 years old). Interferon-alpha therapy showed significantly higher sustained response rate and loss of HBsAg than no therapy (Odd's ratio 3.0, 95% confidence interval 1.6-5.4; and 2.3, 1.1-11.3, respectively). The sustained response rate was not significantly different between interferon and interferon plus lamivudine, or plus prednisone, or plus hepatitis B vaccine; this rate was significantly higher for interferon compared with combined interferon plus levamisole or vitamin E.

Interferon-alpha is still the most effective treatment option for children with HBeAg-positive chronic hepatitis B. Randomized trials are warranted for further comparing interferon to newer antiviral agents in terms of efficacy, safety, emergence of mutant variants, and cost/benefit ratio.

The spectrum of chronic hepatitis B infection in children ranges from asymptomatic carriage with minimal disease, to progression to cirrhosis and risk of hepatocellular carcinoma in adulthood. Identifying those who will benefit from treatment is a challenge. Interferon-based therapies have limited efficacy, while prolonged use of nucleos(t)ide analogues may promote resistance. New antiviral agents have improved barriers to resistance, but long-term outcome is not yet known. Untreated infection, however, may in some, lead to natural seroconversion and reduce risk of further disease. Hepatitis B e antigen-positive infection is the most common scenario in chronically infected children, with e antigen-negative hepatitis rarely encountered. This paper reviews the clinical guidelines published in 2013 by the National Institute for Health and Care Excellence (NICE) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), and focuses on the guidance for treatment in e antigen-positive children. The most significant difference is the lower threshold for starting treatment recommended by NICE guidelines. The need for regular evaluation of each child, in the light of new evidence and new drugs as they emerge, must remain the focus of each clinician involved in the care of children with hepatitis B virus infection.

Although a rather benign course of chronic hepatitis B virus (HBV) infection during childhood has been described, 3-5% and 0.01-0.03% of chronic carriers develop cirrhosis or hepatocellular carcinoma before adulthood. Considering the whole lifetime, the risk of hepatocellular carcinoma rises to 9-24% and the incidence of cirrhosis to 2-3% per year. The aim of this article is to review the current knowledge regarding the natural history and treatment of chronic hepatitis B in children and to focus on critical aspects and unresolved questions in the management of childhood HBV infection. A literature search was carried out on MEDLINE, EMBASE, and Web of Science for articles published in English in peer-reviewed journals from January 1980 to February 2013. The search terms used included "Hepatitis B virus infection," "children," "HBV," "interferon," "lamivudine," "adefovir," "entecavir," and "tenofovir." Articles resulting from these searches and relevant references cited in the articles retrieved were reviewed. The current goals of therapy are to suppress viral replication, reduce liver inflammation, and reverse liver fibrosis. Therapeutic options for children are currently limited, and the risk for viral resistance to current and future therapies is a particular concern. Based on the data available at this time, it is the consensus of the panel that it is not appropriate to treat children in the immune-tolerant phase or in the inactive carrier state. For children in the immune-active or reactivation phases, liver histology can help guide treatment decisions. Outside of clinical trials, interferon is the agent of choice in most cases; currently, available nucleoside analogs are secondary therapies.

The spontaneous seroconversion rate of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) virus infection in children is lower than that in adults. However, few studies have investigated the rate of transition from the immune-tolerant to the early immune-clearance phase in children.

From February 2000 to August 2011, we enrolled 133 children aged <18 years who had visited the Department of Pediatrics, Kyungpook National University Hospital. All subjects were in the immune-tolerant phase of HBeAg-positive CHB virus infection. The estimated transition rate into the early immune-clearance phase was calculated using the Kaplan-Meier method.

Among the 133 enrolled pediatric CHB virus infection patients in the HBeAg-positive immune-tolerant phase, only 21 children (15.8%) had converted to the early immune-clearance phase. The average age at entry into active hepatitis was 10.6±4.8 years. The incidence of transition from the immune-tolerant to the early immune-clearance phase in these children was 1.7 episodes/100 patient-years. When analyzed by age, the estimated transition rate was 4.6%, 7.1%, and 28.0% for patients aged <6, 6-12, >12 years, respectively.

In children with CHB virus infection, the estimated rate of entry into the early immune-clearance phase was 28.0% for patients aged 12-18 years, which was significantly higher than that observed for children aged <12 years (11.7%; p=0.001).

There has been a dramatic increase in treatment options for both chronic hepatitis B (CHB) and chronic hepatitis C (CHC) infection in adults over the past 5-10 years, resulting in standardized regimes for initial treatment, relapsers and even infection in the setting of recurrence post-liver transplantation. These regimes have resulted in the halting of the disease progression, reduction in the risk of hepatocellular carcinoma and removal of these infections as a contraindication for liver transplantation. However, treatment in children must be considered carefully in the context of the natural history of these infections and host factors, particularly the immunological mileu, which may affect response to therapy. The as yet unknown long-term effects of medications must also be balanced with the probability of significant life-long morbidity or mortality from chronic hepatitis and its complications. Furthermore, the development of drug resistance, particularly in the case of CHB, has significant implications for the pediatric patient who may exhaust effective therapeutic options at a relatively young age. For these reasons, initiation of therapy must be based on sound criteria. Based on the current data, we recommend that therapy should be offered to children with CHB who have an elevation in alanine aminotransferase (>2-3 x upper limit of normal) for more than 6 months. Therapy with interferon-alpha should be offered in the majority of cases with the aim of immune clearance as measured by early antigen seroconversion. By contrast, treatment indication for CHC in children remains controversial. If used, combination therapy with pegylated interferon and ribavirin is likely to produce the highest rates of sustained viral response.

At present, therapy of children with chronic hepatitis B and C is still based on few drugs, all burdened by a series of side-effects, unsatisfactory serum conversion rates, and/or drug-resistance. Moreover, selection of subjects to treat with conventional therapies is not univocal, especially during the pediatric age when the disease course is often mild with significant spontaneous seroconversion rate. Our review deals with pros and cons points when a physician decides to design a drug therapy for a child with chronic viral hepatitis, and different possible therapeutic opportunities.

A literature search was performed through PubMed. The newest articles, reviews, systematic reviews, and guidelines were included in this review.

The management of children with viral hepatitis is still controversial over whom and when to treat and the use of drug(s). Novel therapeutic strategies have been evaluated only in clinical and preclinical trials involving, for instance, "therapeutic" vaccines. The data on safety and effectiveness of new drugs are also reviewed.

The results of reported studies confirmed that at least some of the new drugs, with greater efficacy and/or minor side-effects, will be used clinically.

Hepatitis B virus (HBV) infection is a worldwide health problem, which can cause acute liver failure, acute hepatitis, chronic hepatitis, liver cirrhosis, and liver cancer. It is most prevalent in Asia, Africa, Southern Europe, and Latin America. Approximately 2 billion people in the world have been infected by HBV, with more than 350 million as chronic carriers. Implementation of the HBV vaccine led to a significant reduction in viral transmission in many areas of the world; however, it remains highly endemic in many developing countries. The main source of infection in childhood is via perinatal transmission or horizontal transmission during preschool years. The majority of children with chronic hepatitis B (CHB) infection are asymptomatic; however, they may develop progressive disease and are at increased risk of advanced liver disease or liver cancer before their third decade. All children with chronic HBV infection should be regularly monitored for disease progression. The goal of therapy for children with CHB is to arrest disease progression and reduce the risk of developing cirrhosis and cancer. The available medications have a low success rate because of immunotolerance in the child and the development of viral resistance to standard therapy. Therefore, case selection and determination of the best time to commence treatment are essential to increase treatment efficacy and reduce the risk of viral resistance.

We aimed to evaluate the therapeutic efficacy of pegylated interferon alpha-2a 180μg as a treatment for hepatitis B 'e' antigen (HBeAg)-positive genotype D chronic hepatitis B patients.

Thirty patients attending the outpatient clinic at the National Hepatology and Tropical Medicine Research Institute were treated with peg.interferon alpha-2a (180μg) weekly for a period of 48 weeks. Pre-enrolment assessment was performed through biochemical, serological and quantitative HBV DNA testing. Liver biopsy was performed in all patients. Evaluation was done at weeks 12, 24 and 48 of treatment by liver enzymes, complete blood count (CBC), HBeAg/HBeAb and quantitative HBV DNA testing.

At the end of 48 weeks of treatment only three cases (10%) of the study population showed HBeAg seroconversion and an undetectable HBV DNA level. None of responders exhibited hepatitis B surface antigen (HbsAg) loss. There were five (16.7%) primary non-responders, four (13.3%) relapsers, four (13.3%) cases flared at week 12, and 14 (46.6%) cases who were non-responders. No specific predictors of response could be identified among patients.

One year of peg. interferon alpha-2a 180μg weekly led to HBeAg seroconversion and an undetectable HBV DNA level in 10% of cases. Considering the privilege of a finite duration of treatment, tailoring of treatment and proper patient selection is of great importance in considering this therapy as a first line of treatment among HBeAg-positive chronic HBV Egyptian patients.

Whereas e-seroconversion represents the loss of hepatitis B e-antigen (HBeAg) followed by gain of antibody to HBeAg (anti-HBe), 'inactive chronic infection' extends this concept to include e-seroconversion with decreased serum viral load and biochemical remission. These events must be well-characterized before treatment outcomes can be evaluated. We examined the rates of e-seroconversion and achievement of inactive chronic infection among children with chronic HBV infection. Children who were HBsAg positive >6 months were identified retrospectively between 1983 and 2008 from the Hospital for Sick Children Liver Clinic. Inactive chronic infection was defined as loss of HBeAg, serum ALT ≤40 IU/mL, and HBV DNA <10(6 ) IU/mL. Both e-seroconversion and achievement of inactive chronic infection were characterized using survival analysis. The effect of transmission route, treatment, age at diagnosis, ethnicity, gender and baseline ALT on these rates was evaluated with univariate and multiple regression. Of 252 HBeAg-positive cases, 59.9% had HBV-infected mothers, 77% were Asian, and 33 received interferon-α. Untreated children were younger at last follow-up (mean 14.5 vs 17.6 years), had lower ALT (median 60 vs 116 IU/mL) and had shorter follow-up (6.6 vs 9.1 years, all P < 0.002) compared to treated children. Crude e-seroconversion rate was 41.7% over 0.5-19.1 years of follow-up, and this was not affected by transmission route (P = 0.93), gender (P = 0.62) nor treatment (P = 0.08). 49% achieved inactive chronic infection by age 19 years. Being non-Asian, age at diagnosis<3 years, and ALT ≥40 IU/mL were associated with a higher rate of e-seroconversion and achieving inactive chronic infection (P < 0.0001). Almost 50% of children achieved inactive chronic infection by early adulthood.

The guideline on the management of chronic hepatitis B (CHB) was first developed in 2004 and revised in 2007 by the Korean Association for the Study of the Liver (KASL). Since then there have been many developments, including the introduction of new antiviral agents and the publications of many novel research results from both Korea and other countries. In particular, a large amount of knowledge on antiviral resistance--which is a serious issue in Korea--has accumulated, which has led to new strategies being suggested. This prompted the new guideline discussed herein to be developed based on recent evidence and expert opinion.

The main targets of this guideline comprise patients who are newly diagnosed with CHB and those who are followed or treated for known CHB. This guideline is also intended to provide guidance for the management of patients under the following special circumstances: malignancy, transplantation, dialysis, coinfection with other viruses, pregnancy, and children.

Hepatitis B virus (HBV) infection may lead to acute or chronic hepatitis, cirrhosis and hepatocellular carcinoma. The incidence rate of paediatric hepatitis B is 0.2/100,000 to 1.8/100,000 in Canada. Hepatitis B virus infection is acquired largely through mother-to-infant (vertical) or community-based (horizontal) transmission in early childhood, whereas older children are susceptible to HBV infection through exposure to contaminated blood during intravenous drug use or through sexual transmission. Immigrants from endemic areas and some Native Canadian populations are also at a higher risk for HBV infection. Infection with HBV may manifest in three forms: acute self-limited hepatitis, chronic hepatitis or massive hepatic necrosis causing acute liver failure. The identification of HBV infection and the characterization of the disease relies on serological and virological tests. The course of chronic hepatitis B may be classified into three phases: an immunotolerant phase, an active phase and an inactive phase. Current treatment options include interferon-alpha and lamivudine for individuals with elevated serum alanine aminotransferase levels and markers of persistent viral replication. Children with chronic hepatitis B require regular monitoring and age-appropriate lifestyle counselling. Paediatricians are well-positioned to promote vaccination and encourage testing of those who are at risk for hepatitis B. With effective universal vaccination against hepatitis B, this infection could be essentially eliminated in Canada.

There has been much progress in antiviral therapy for chronic hepatitis B; however, antiviral therapy for hepatitis B in special populations is still very challenging. Here, we review antiviral therapy for hepatitis B in special populations, including children and pregnant patients, patients with hepatitis-B-related cirrhosis, patients with acute hepatitis B and chronic hepatitis B surface antigen carriers who receive immunosuppressive or cytotoxic therapy. Major advances have been made in antiviral therapy for hepatitis B in these special populations because of recent increasing availability of oral nucleoside/nucleotide analogues that are well-tolerated and highly effective; however, the findings are mostly based on small uncontrolled short-term studies. More well-designed clinical studies on antiviral therapy for hepatitis B in these special populations are urgently needed to obtain more evidence-based high-quality data.

Hepatitis B is the most common chronic viral infection of the liver. Chronic hepatitis B is estimated to affect at least 350 million people worldwide and is the leading cause of death from liver disease. There have been dramatic developments both in the diagnostic field and in drug treatment of chronic hepatitis B. Today, chronic hepatitis B is a well manageable disease in the vast majority of cases and the main challenge remains the detection of affected patients at an early enough disease stage to prevent end-stage liver disease and its complications. The rapid pace of drug development mandated an update of the Austrian guidelines on the treatment of hepatitis B, which after 1994 and 1998 were now dating back to 2005 in their third version. All chapters from the 3. consensus statement from 2005 were renewed except for the chapter on liver biopsy, which is still valid in its 2005-version. In particular, virologic parameters take now center stage for treatment decisions, HBV-genotyping is now being considered for the choice of treatment, and the oral first line treatment for chronic hepatitis B has been changed. Overall this consensus statement accounts for the major advances in the management of hepatitis B and significantly changes clinical management of patients with hepatitis B in Austria.

Viral hepatitis poses important problems for children. In preschoolers, hepatitis A virus (HAV) infection frequently causes acute liver failure. Vaccinating toddlers against HAV in countries with high endemicity is expected to decrease mortality. HAV vaccine demonstrates efficacy (comparable to immunoglobulin) as post-exposure prophylaxis. A recently developed vaccine against hepatitis E virus (HEV) may benefit fetal health, because pregnant women are most prone to acute liver failure as a result of HEV. Hepatitis B vaccine continues to demonstrate value and versatility for preventing serious liver disease. With chronic infection, undetectable levels of serum HBV DNA complement e-seroconversion as the preferred outcome measure; suppressed viral load correlates with long-term complications better than HBeAg status. Among Taiwanese children, low pretreatment HBV DNA (<2 x 10(8) copies/ml) strongly predicted response to interferon-alpha. Future paediatric studies must incorporate HBV DNA levels. The rationale for routine treatment of immunotolerant hepatitis B during childhood remains uncertain. Any treatment of chronic hepatitis B in childhood requires consideration of the risks and benefits. Childhood hepatitis C virus (HCV) infection results mainly from mother-to-infant transmission. Babies of HCV-infected women should be tested for serum HCV RNA at 1 month of age. If negative, confirmatory anti-HCV antibody testing may be performed between 12 and 15 months of age. Children with chronic hepatitis C may develop progressive fibrosis/cirrhosis, particularly in the setting of obesity and insulin resistance. Treatment of children chronically infected with genotype 2 or 3 is highly successful: combination therapy of pegylated interferon-alpha and ribavirin is well tolerated and superior to pegylated interferon-alpha alone.

Although the clinical course of chronic hepatitis B (CHB) is relatively mild in a majority of children, a certain proportion of patients develops chronic liver disease that finally results in serious liver injury. Reports regarding clinical outcome of infection are scarce.

The aim of this study was to assess inflammatory activity, fibrosis, and their correlation to clinical data in children with CHB before antiviral treatment.

The study included 200 children, aged 1.5-18 years (mean 7.49+/-4.01 years), with CHB hospitalized before liver biopsy between 1992 and 2003. History and clinical data were analyzed. Histopathological assessment was based on the modified Knodell system. Statistical analysis was performed, and results with P<0.05 were considered significant.

Necroinflammatory activity was found to be mild in 115 children and moderate in 44. Ninety-three children had minimal fibrosis (S1), 62 children - S2, and the remaining 8 - S3-S4. Alanine aminotransferase (ALT) activity was proportional to staging (Kruskall-Wallis test H=10.84, P=0.028) and was significantly higher in the children with staging >or=S2, P=0.0008. Spontaneous hepatitis B early antigen seroconversion occurred in 30/200 children (15%) and was related to the shorter length of infection, P=0.008.

Intensity of liver injury in children with CHB varies from minimal to marked necroinflammatory activity and fibrosis varies from none to advanced. Progression of liver fibrosis seems to be proportional to the age at infection. ALT activity appears to be higher in the children with significant (S2-S4) fibrosis. Spontaneous hepatitis B early antigen seroconversion is apparently related to the shorter length of infection and higher ALT activity.

Hepatitis B virus (HBV) infection is a worldwide problem and can cause acute liver failure, acute hepatitis, chronic hepatitis, liver cirrhosis, and liver cancer. In areas of high prevalence such as in Asia, Africa, southern Europe, and Latin America, the hepatitis B surface antigen positive rate ranges from 2% to 20%.In endemic areas, HBV infection occurs mainly during infancy and early childhood. Mother-to-infant transmission accounts for approximately half of the chronic HBV infections. In contrast to infection in adults, HBV infection during early childhood results in a much higher rate of persistent infection and long-term serious complications such as liver cirrhosis and HCC.Three phases of chronic hepatitis B have been identified: the immune-tolerant phase, the immune-active phase, and the inactive hepatitis B phase. These phases of infection are characterized by variations in viral replication, hepatic inflammation, spontaneous clearance, and response to antiviral therapy.The optimal goal of antiviral therapy for chronic HBV infection is to eradicate HBV and to prevent its related liver complications. However, due to the limited effect of available therapies in viral eradication, the goal of treatment is to reduce viral replication, to minimize liver injury, and to reduce infectivity. In this review the current recommendations for monitoring and treating chronic HBV infection in children are reviewed.

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease throughout the world, leading to cirrhosis and hepatocellular carcinoma in many individuals. Children are more likely to develop chronic HBV infection as they demonstrate greater immunotolerance to the virus, and response to therapy in children remains disappointing. Three therapeutic agents for chronic HBV infection in children have been approved in the USA, including standard IFN-alpha, lamivudine and adefovir. IFN-alpha has been the most effective ( approximately 30% hepatitis B e antigen [HBeAg] seroconversion; 10% hepatitis B surface antigen [HBsAg] seroconversion), although benefits are primarily observed in children with alanine aminotransferase levels over two-times the upper limit of normal and must be weighed against significant side effects. Studies comparing the long-term outcome of chronic hepatitis B in children treated with IFN-alpha and in untreated controls show that the rate of anti-HBeAb seroconversion tends to overlap in treated and untreated patients within a few years of follow-up, suggesting that IFN-alpha simply accelerates a spontaneous event. Lamivudine's virologic response rates mirror those of IFN-alpha (23-31% HBeAg seroconversion) with easier administration and a better safety profile but lower HBsAg seroconversion (2-3%) and high rates of drug resistance. Adefovir data show low rates of resistance and a good safety profile, but virologic response was limited to adolescent patients and was lower than that of lamivudine (16% HBeAg seroconversion; <1% HBsAg seroconversion). Entecavir and tenofovir, both approved therapies for adults with chronic HBV infection, are in trials for use in children. Future therapies will probably include these agents as well as combined therapies. Finally, watchful waiting of children is an option since current therapies are only 30% effective at best, although the long-term impact of therapy in childhood on rates of cirrhosis and hepatocellular carcinoma remains unknown.

In 2007, the world celebrated the 50th anniversary of the discovery of interferon (IFN) by Isaacs and Lindenmann. Subsequently, the IFN-alpha gene was cloned, fully sequenced and IFN-alpha was produced in recombinant form. Recombinant IFN-alpha is now used as the basis for treatment of chronic hepatitis C virus infection and can also be used to treat certain forms of chronic hepatitis B virus infections. IFNs have also been used in other viral infections, although with less success. The antiviral mechanisms of IFNs are reviewed in this chapter as well as the utility of IFNs in the treatment of persistent viral infections.

In pregnant women and children, the hepatitis B virus can cause acute or chronic hepatitis or liver cirrhosis. Perinatally-acquired infection causes persistent infection in 90% of cases and can be avoided through administration of the hepatitis B vaccine and specific immunoglobulin in the first day of life. Prevention of mother-to-child transmission requires screening for hepatitis B surface antigen (HBsAg) in pregnant women to identify which newborns should be immunized. In some countries this strategy is substituted by universal vaccination of neonates. In infected children, inactivation of viral replication with conversion of HBeAG-positive to anti-HBe-positive status usually occurs. If this seroconversion does not take place and necroinflammatory activity persists in the liver, the use of antiviral agents such as interferon or nucleoside and nucleotide analogs is warranted.

The short- and long-term benefits of interferon (IFN)-alpha therapy in young patients with chronic hepatitis B (CHB) acquiring infection perinatally or during early childhood have been questioned.

Twenty-one Taiwanese hepatitis B envelope antigen (HBeAg)-positive CHB patients aged 1.8-21.8 years (median 14.0 years) with alanine aminotransferase (ALT)>80 IU/L at entry were enrolled for IFN-alpha therapy. They received IFN-alpha therapy with a dose of 3 MU/m(2)/day three times a week for 24 weeks. A control group included untreated 21 CHB patients closely matched for gender, age, duration of ALT >80 IU/L and HBeAg status. All 42 patients were prospectively followed for 6.5-12.5 years after the end of therapy.

The cumulative rate of virological response [anti-HBe seroconversion and serum hepatitis B virus (HBV)-DNA <10(5) copies/ml] was not different between the IFN-treated patients and control patients at 1 year (41 vs 44%) and at 6 years (88 vs 89%) after stopping treatment. Serum hepatitis B surface antigen loss occurred in two (9.5%) treated patients and in one (4.8%) control patient. Patients with a successful treatment response (anti-HBe seroconversion, HBV-DNA <10(2) copies/ml and ALT normalization at 1 year after stopping treatment) were younger than those without a successful response (P=0.03). A lower pretreatment serum HBV-DNA level (<2 x 10(8) copies/ml) is not only a significant factor to predict successful treatment response (P=0.008) but also has a beneficial effect on the long-term cumulative rate of virological response in IFN-treated patients (P=0.021), but not in control patients. Genotype difference or emergence of a precore stop codon mutant before treatment was not predictive for HBeAg clearance.

For young CHB patients in Taiwan with infection occurring perinatally or in early childhood, the real advantage of IFN-alpha therapy was not observed. IFN-alpha therapy showed a beneficial effect on short- and long-term virological outcomes only in those with a lower pretreatment serum HBV-DNA level.

Among current treatment options for chronic hepatitis B, nucleoside/nucleotide analog therapy has better tolerability and most patients respond to the therapy, while interferon (IFN) therapy has rather severe side-effects and a lower response rate. However, nucleoside/nucleotide analog therapies have problems of the emergence of drug resistance and poor sustainability of response after discontinuation. After the first nucleoside/nucleotide analog lamivudine, adefovir and entecavir are now utilized in many countries. Adefovir has efficacy for lamivudine resistant patients and current data suggests that adding adefovir to ongoing lamivudine is better than switching to adefovir in terms of viral suppression and the occurrence of resistance. Entecavir can be the first choice for naïve patients, although cross-resistance has been known for lamivudine resistant patients and mutational screening should take place before using entecavir with such patients. Many other new nucleoside/nucleotide analogs are being developed such as telbivudine, clevudine and tenofovir; the details of each drug will be disclosed in near future.

Hepatitis B virus (HBV) infection may cause acute, fulminant, or chronic hepatitis, leading to liver cirrhosis or hepatocellular carcinoma. Despite the availability of effective vaccine, HBV infection during infancy or early childhood is common in areas of high endemicity. In these regions, mother-to-infant transmission accounts for approximately 50% of chronic infections. Although the natural history of HBV infection in adults is well characterized, little information is available in the literature regarding the natural history of HBV infection in children. Similar to infection in adults, chronic HBV infection in children can be divided into distinct phases: immune tolerant, immune clearance, and inactive carrier state. However, acute exacerbation, with reactivation of HBV replication and re-elevation of alanine aminotransferase levels after hepatitis B e antigen seroconversion, is relatively rare in children, in comparison to adults. Although several potent antiviral agents are now available for the treatment of chronic hepatitis B, experience with these agents in the pediatric setting is limited. To date, conventional interferon alpha and lamivudine are the only two antiviral agents approved to treat chronic hepatitis B in children. The rapid emergence of resistant HBV associated with long-term lamivudine therapy, as well as poor tolerability associated with conventional interferon alpha, are factors that should be considered before initiating antiviral therapy. This article reviews current knowledge regarding the natural history and treatment of chronic hepatitis B in children. Factors that affect the natural history of HBV infection in children are also reviewed.