Antiviral Therapy In Children Research Articles

Influenza and acute viral infection prevention in children with recurrent respiratory pathology

Introduction. Despite numerous scientific works devoted to the problem of acute respiratory diseases, its relevance does not decrease throughout the world, since serious complications with an unfavorable prognosis are possible.Aim. To evaluate the effectiveness of preventive antiviral therapy in children with recurrent respiratory pathology.Materials and methods. Under observation were 43 children (average age 7.43 ± 3.05 years) with recurrent respiratory pathology, who underwent health treatment in the summer period once for 14 days. The main group consisted of 22 children who were prescribed the antiviral therapy as a monotherapy for prophylactic use. The comparison group included 21 patients who underwent preventive treatment using nasopharyngeal irrigation with local antiseptic chemicals. The observation period was 3 months after prophylactic treatment.Results and discussion. After preventive treatment, the total number of episodes of ARI during the observation period in the main group in relation to the comparison group was according to nosologies: acute pharyngitis (p = 0.0317), exacerbation of chronic tonsillitis (p = 0.0137), acute rhinitis (p = 0.0692), rhinosinusitis (p = 0.0429). In the main group, during the observation period, when episodes of upper respiratory tract diseases occurred, antibacterial drugs were prescribed statistically significantly less frequently (p = 0.0296). After the preventive course, compared with the initial data, there was a decline in the number of cases of upper respiratory tract diseases per child on average per quarter. Thus, in the main group, a more pronounced significant difference was revealed in all nosological forms (acute rhinitis, rhinosinusitis p = 0.0081, acute pharyngitis p = 0.0129, tonsillopharyngitis p = 0.0384). In the comparison group – respectively: p = 0.0426; 0.0387; 0.0439.Conclusions. Carrying out preventive treatment as monotherapy in children with recurrent respiratory pathology demonstrated high effectiveness (86.37%) of the antiviral therapy.

Efficacy and Safety of Antiviral Therapy for Immune-tolerant Hepatitis B Viral Infection in Children: A Systematic Review and Meta-analysis.

Chronic hepatitis B virus (HBV) infection burden in children remains a pressing public health concern. Whether antiviral therapy should be administered to children with HBV in the immune-tolerant phase remains controversial. We performed a meta-analysis to evaluate antiviral therapy efficacy and safety in children with immune-tolerant hepatitis B (ITHB). A search was conducted in multiple databases (PubMed, Embase, Cochrane, Web of Science, CBM, CNKI and Wanfang Data) to identify clinical trials examining antiviral therapy efficacy and safety in children (1-18 years) with ITHB viral infection from inception to February 2023. Outcomes were calculated separately for controlled and single-arm studies. Nine trials (442 patients), including 2 randomized controlled trials (RCTs), 3 non-RCTs and 4 single-arm studies, were included in this meta-analysis. In the RCTs, antiviral therapy group exhibited greater rates of HBsAg loss [risk ratio (RR) = 6.11, 95% confidence interval (CI): 1.67-22.31, P Z-test = 0.006], HBsAg serologic response (RR = 5.29, 95% CI: 1.47-19.07, P Z-test = 0.011) and HBeAg loss (RR = 3.00, 95% CI: 1.35-6.66, P Z-test = 0.007) compared with the control group at the end of follow-up. In single-arm studies, the pooled incidences of HBsAg loss, HBeAg loss and HBsAg seroconversion were 24% (95% CI: -0.1% to 48%), 24% (95% CI: -0.1% to 48%) and 24% (95% CI: -5% to 52%), respectively. Current evidence suggests the effectiveness of antiviral therapy in children with HBV infection in the immune-tolerant stage, with few serious adverse events. Due to the limited quality and number of included studies, more high-quality studies are required to validate our findings.

2167. Use and Timing of Antiviral Therapy for Influenza in Hospitalized U.S. Children, 2016–2020

Abstract Background According to the 2018 Infectious Diseases Society of America (IDSA) clinical practice guidelines and Centers for Disease Control and Prevention (CDC) guidance, clinicians should start antiviral treatment as soon as possible for children who are hospitalized with suspected or confirmed influenza. We assessed the use of influenza-specific antiviral therapy in children hospitalized with symptoms of acute respiratory illness and laboratory-confirmed influenza. Methods We conducted active, population-based surveillance of children hospitalized with fever and/or respiratory symptoms (12/01/2016–02/28/2020) at the seven U.S. medical centers that comprise the CDC New Vaccine Surveillance Network. We excluded children who did not undergo clinical testing (by rapid antigen testing or nucleic acid amplification test [NAAT]) or research testing (by NAAT) for influenza, those who presented out of influenza season (site- and season-specific), and those whose date of antiviral therapy or whether antiviral therapy was given was unknown. We assessed the use of influenza-specific antiviral therapy in this cohort and defined timely antiviral therapy as administration within 2 days of hospitalization. Results Of 11,275 eligible children, 1,149 (10.2%) tested positive for influenza by clinical and/or research assays (Table 1). Overall, 154 influenza cases (13.4%) were detected by clinical testing only, 428 (37.2%) by research testing only, and 567 (49.3%) by both. During their influenza-associated hospitalization, 620 children (54.0%) received influenza-specific antivirals, and therapy was timely in 572 cases (92.3%). Of those who tested positive clinically, 445/721 (61.7%) received timely antiviral therapy, 38 (5.3%) received delayed antiviral therapy, and 238 (33.0%) received no antiviral therapy. Oseltamivir was the antiviral used in all treated cases. The distribution of antiviral-treated cases varied by race and Hispanic origin and study site, but not by age at presentation or influenza season (Figure 1). Table 1 Demographic characteristics of 1,149 children with influenza enrolled in the New Vaccine Surveillance Network over four influenza seasons between December 1, 2016, and February 28, 2020. Figure 1Proportions of children with influenza enrolled in the New Vaccine Surveillance Network who received timely, delayed, or no antiviral therapy by age at presentation, race and Hispanic origin, study site, and influenza season (N=1,149). Conclusion Although antiviral therapy is recommended for all influenza-associated hospitalizations in children, antiviral prescribing remains suboptimal. Further studies would help identify and address barriers to antiviral therapy in children with influenza. Disclosures John Williams, MD, GlaxoSmithKline: Advisor/Consultant|Quidel: Advisor/Consultant Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support Mary A. Staat, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Cepheid: Grant/Research Support|National Institute of Health: Grant/Research Support|Uptodate: Royalties Geoffrey A. Weinberg, MD, Merck & Co.: Honoraria|Merck & Co.: Honoraria for composing and reviewing textbook chapters, Merck Manual of Therapeutics Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support|Moderna: DSMB|Pfizer: DSMB Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation.

Frequent alanine aminotransferase flares and promising antiviral therapy efficacy during the preschool age: An opportunity to achieve HBsAg loss in children with mother-to-child transmitted hepatitis B.

Alanine aminotransferase (ALT) flare remains one of the determinants of initiating antiviral therapy in children with chronic hepatitis B (CHB). Insufficient data exist regarding children with CHB attributed to mother-to-child transmission. This study aimed to assess the occurrence of spontaneous ALT flares and identify factors affecting therapy-induced hepatitis B surface antigen (HBsAg) loss in the flare cohort. We retrospectively included untreated children with mother-to-child transmitted CHB. The primary outcomes were spontaneous ALT flares and therapy-induced HBsAg loss. Among 83 untreated children, 73.5% (61/83) experienced spontaneous ALT flares during the median follow-up of 14.6months (range, 0.1-177.1months), with 54.1% of the first ALT flares and 44.3% of ALT peaks occurring within 6 years of age. Thirty-six of 61 children with ALT flares received antiviral therapy, nine (25.0%) of whom achieved therapy-induced HBsAg loss with a median duration of 19.3months (range, 6.5-56.2months). The age of initiation of antiviral therapy was the sole predictor of therapy-induced HBsAg loss (HR=0.544, 95% CI 0.353-0.838, p=0.006). The restricted cubic spline showed a negative relationship between the age of initiation of antiviral therapy and HBsAg loss and identified that 6.2 years of age discriminated children with therapy-induced HBsAg loss. Kaplan-Meier estimations suggested a higher probability of HBsAg loss in children who started antiviral therapy before 6.2 years old (p=0.03). In conclusion, asymptomatic ALT flares were frequent in preschool-aged children with mother-to-child transmitted CHB, and early initiation of antiviral therapy showed promising effects in those children with ALT flares.

Hearing Loss in Congenital CMV Disease Post-Ganciclovir

Source: Lanzieri TM, Caviness AC, Blum P, et al. Progressive, long-term hearing loss in congenital CMV disease after ganciclovir therapy. J Pediatric Infect Dis Soc. 2021;piab095. doi:10.1093/jpids/piab095Investigators from the CDC, Atlanta, GA, and Baylor College of Medicine, Houston, TX, conducted a study to assess long-term hearing outcomes in children with symptomatic congenital cytomegalovirus (CMV) infection, and the impact of ganciclovir therapy on hearing loss. For the study, they analyzed data from children born 1983–2005 who were enrolled in the Congenital CMV Longitudinal Study. All study participants had CMV infection detected in urine samples in the first 3 weeks of life and had microcephaly, chorioretinitis, neurologic abnormalities or evidence of reticuloendothelial system involvement (eg, petechiae/purpura). Study children had longitudinal assessments of hearing with auditory brainstem response testing and behavioral audiometry; those with hearing thresholds >20 dB were classified as having sensorineural hearing loss (SNHL). SNHL was defined as congenital if diagnosed in the first month of life. Study children were placed into 3 groups: Group A included patients who had been enrolled in a clinical trial and received ganciclovir; group B included children with SNHL, microcephaly and/or chorioretinitis but who were untreated; and group C comprised those without any of these findings who also were not treated with ganciclovir. The primary study outcome was long-term assessment of hearing loss among children in these 3 groups.Data were analyzed on 76 children; 17 (22%) in group A, 27 (36%) in group B, and 32 (42%) in group C. Among the 17 children in group A, 16 had microcephaly, chorioretinitis, or congenital SNHL; median duration of ganciclovir treatment in these patients was 40 days. Overall, the most common findings in study patients when they were neonates were purpura/petechiae (82% of those in group A, 78% in group B, and 63% in group C); 71% and 70%, respectively, of those in groups A and B had microcephaly. Congenital SNHL was diagnosed in 65% of patients in group A and 56% for those in group B, although hearing was not assessed in the first month of life in all study participants. The median age at last hearing assessment was 13 years for children in groups A and C and 11 years for those in group B. At that time, 16 (94%) patients in group A, 24 (89%) children in group B, and 16 (50%) group C patients had SNHL. SNHL was categorized as severe (>70 dB) in 12 (71%), 16 (59%), and 7 (22%) children, respectively, in groups A, B, and C.The authors conclude that most children in this study with congenital CMV infection developed substantial SNHL with or without ganciclovir treatment.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The current investigators provide long-term hearing outcomes for infants born 1983–2005 who were enrolled in the Congenital CMV Longitudinal Study. Participants were selected based on having severe disease as newborns.1,2 Not surprisingly, most developed substantial SNHL. As previously discussed, symptomatic congenital CMV infection at birth is a risk factor for SNHL. (See AAP Grand Rounds. 2019;42[5]:57.)3 Many infants also had microcephaly and/or head CT scan findings suggesting tissue destruction or dysplastic growth, which also are associated with an increased risk of SNHL.4 The results of early clinical trials of intravenous ganciclovir1,2 had suggested short-term stabilization or improvement in hearing at 6 months but were not borne out by the current investigation.With the introduction of oral valganciclovir, a phase III, randomized, placebo-controlled clinical trial, conducted during 2008– 2011, evaluated 6 weeks versus 6 months of therapy with valganciclovir.5 There was modest improvement in hearing and developmental outcomes at 12 and 24 months. Based on this trial, the AAP currently recommends 6 months of oral valganciclovir for infants with moderately to severely symptomatic congenital CMV infection who can start treatment in the first month of life.6 The current authors state that their findings cannot be extrapolated to infants who receive current standard of care therapy. Infants receiving valganciclovir are being followed to determine their long-term hearing outcomes.Another area that is not addressed is the role of valganciclovir for infants with congenital CMV infection who have isolated SNHL. The 2017 consensus guidelines do not routinely recommend valganciclovir for these infants based on insufficient evidence. Pasternak et al reported that 12 months of antiviral therapy for infants with congenital CMV infection and isolated SNHL led to improved hearing, but their study did not include a control group.(See AAP Grand Rounds. 2018;40[5]:55.)8Infants with congenital CMV infection are at risk for SNHL despite receipt of antiviral therapy. These infants deserve close audiology follow-up.The apparent lack of major benefit of antiviral therapy in children with symptomatic congenital CMV infection underscores the need for prevention. Neither CMV-IGIV nor investigational vaccines have yet proven efficacious.6

To study the incidence of relapse and natural history on stopping antiviral therapy in children with chronic hepatitis B

To study the incidence of relapse and natural history on stopping antiviral therapy in children with chronic hepatitis B

Correlation of qAnti-HBc with antiviral efficacy in children with chronic hepatitis B and exploration of its possible immune mechanism

Objective: To compare the baseline difference in the quantitative hepatitis B core antibody levels (qAnti-HBc) between non-response and response group in children with HBeAg-positive chronic hepatitis B (CHB) who received antiviral therapy, and further explore the proportion and functional activity of CD8 + memory T lymphocyte subsets with different qAnti-HBC levels in peripheral blood of children. Methods: The baseline anti-HBc quantification (qAnti-HBc) levels of 85 children with HBeAg-positive CHB who visited the Department of Infectious Diseases, Children's Hospital of Chongqing Medical University from June 2018 to December 2020 were detected retrospectively. The relationship between the baseline qAnti-HBc level and HBeAg serological response in 37 children who received antiviral therapy was analyzed. The proportion of CD8(+) memory T lymphocyte subsets and the secretion levels of interferon (IFN) γ, and tumor necrosis factor (TNF) α in peripheral blood of 59 children at baseline were detected by flow cytometry. The relationship between qAnti-HBc level and the proportion and functional activity of CD8(+) memory T lymphocyte subsets was analyzed. Pearson's Chi-square test was used to compare the count data. Mann-Whitney U test or Kruskal-Wallis test was used to compare measurement data between two or more groups, and Spearman's rank correlation analysis was used for the correlation between continuous variables. Results: Among 37 children who received entecavir (ETV, 21/37 cases) or pegylated interferon (Peg-IFN, 16/37 cases), 18 cases had developed HBeAg seroconversion (10/ 21 cases in the ETV group, 8/16 cases in the Peg-IFN group). The baseline qAnti-HBc level was significantly higher in the response group [4.71 (4.64~4.81) log(10)IU/ml] than the non-response group children [4.54 (4.45~4.64) log(10)IU/ml, Z = -3.316, P = 0.001]. The proportion of CD8(+) Tem, CD38(+)CD8(+) Tem, CD38(+)CD8(+) Temra cells and the levels of IFNγ and TNFα secreted by CD8(+) T lymphocytes were significantly higher in the high-qAnti-HBc group than the low-qAnti-HBc group (P < 0.05). The proportion of CD8(+) Tem, CD38(+)CD8(+) Tem and CD38(+)CD8(+) Temra cells was significantly higher in ALT > 1× upper limit of normal value (ULN) group than ALT≤1×ULN group (P < 0.05). However, there were no significant differences in the levels of IFNγ and TNFα secreted by CD8(+) T lymphocytes between the two groups (P > 0.05). Spearman's correlation analysis showed that qAnti-HBc was positively correlated with the proportion of CD8(+) Tem, CD38(+)CD8(+) Tem, CD38(+)CD8(+) Temra cells and the level of IFNγ secreted by CD8(+)T lymphocytes (P < 0.05). Additionally, ALT was only positively correlated with the proportion of CD38(+)CD8(+) TEM and CD38(+) CD8(+) Temra cells (P < 0.05). Conclusion: Raised baseline qAnti-HBc level is related to the HBeAg serological response to antiviral therapy in children with CHB. Peripheral blood effector CD8+ T lymphocytes of CHB children with higher qAnti-HBc show stronger phenotype and functional activation characteristics, which may shed some light on the underlying immune mechanism related to antiviral therapy efficacy in children with CHB.

Clinical follow-up of children with immune-tolerant chronic hepatitis B receiving antiviral therapy

Objective To investigate the long-term clinical benefits of antiviral therapy in children with immune-tolerant chronic hepatitis B. Methods Long-term follow-up was performed for 46 children with immune-tolerant chronic hepatitis B who were enrolled in the treatment group of the previous randomized controlled trial, and clinical evaluation was performed at weeks 108, 120, 132, 144, 168, and 192 after the trial started. Results All 46 patients completed the follow-up. From week 96 (after the clinical trial started) to week 192 (when the follow-up ended), another 3 patients achieved serum HBV DNA clearance, another 7 patients achieved serum HBeAg clearance, another 6 patients achieved HBeAg seroconversion, and another 3 patients achieved HBsAg seroconversion, while there was no change in the number of patients who achieved serum HBsAg clearance, with a total number of 37 (80.4%), 22 (47.8%), 21 (45.7%), 10(21.7%), and 10(21.7%), respectively. Among these patients, 9(19.6%) did not achieve HBV DNA clearance and they all had virologic breakthrough after drug withdrawal. Conclusion Further large-sample clinical trials are needed to investigate antiviral therapy for children with immune-tolerant chronic hepatitis B.

Peginterferon Alfa-2a (40KD) Plus Lamivudine or Entecavir in Children With Immune-Tolerant Chronic Hepatitis B.

Treatment guidelines for chronic hepatitis B (CHB) do not recommend antiviral therapy for patients in the immune-tolerant phase of the disease, which generally occurs in children who acquire hepatitis B virus (HBV) vertically and may last for decades. On the basis of promising results of a pilot study, we conducted a randomized, controlled, multicenter study to evaluate the efficacy and safety of antiviral therapy in children and adolescents with immune-tolerant CHB. Fifty-nine children aged 3 to <18 years hepatitis B e antigen-positive with an HBV DNA titer >20,000 IU/mL and persistently normal alanine aminotransferase levels were randomized to 56 weeks of antiviral therapy with an oral nucleoside analogue [entecavir or lamivudine], combined with subcutaneous peginterferon alfa-2a from week 8, or 80 weeks of untreated observation. The primary efficacy outcome was hepatitis B surface antigen loss 24 weeks post-treatment in the antiviral therapy group or at the end of observation in the control group. Enrollment was terminated after the results of two similar studies showed that similar antiviral regimens were ineffective in children and adults with immune-tolerant CHB. At 24 weeks post-treatment, 1 of 26 patients in the antiviral treatment group experienced HBsAg loss (vs none of 33 patients in the control group). No serious treatment-related adverse events were reported, and no patients discontinued treatment because of adverse events. The antiviral regimen evaluated in this trial had an acceptable tolerability profile, but was ineffective in children and adolescents with immune-tolerant CHB.

Features of the course and therapy of HIV infection in children at different stages of the disease

Purpose of the study . Analysis of clinical and laboratory features of the course of HIV infection and antiviral therapy in children at different stages of the disease. Materials and methods. Under supervision in the department of motherhood and childhood there were 90 children with HIV infection, which were divided into 3 groups: 1st group – 35 people. with a diagnosis of HIV infection in the first 2 months of life, group 2 – 25 people. with a diagnosis at the age of 6-12 months and the 3rd group (30 people) with a diagnosis of HIV infection over the age of 2 years. Statistical processing of the research results was carried out using the software package Statistica for Windows (version 8.0). Research results. Early detection of HIV infection and the beginning of antiretroviral therapy (ARVT) led to the absence of clinical manifestations of the disease, low levels of HIV RNA in the blood and normal levels of CD4 lymphocytes, which persisted for 3 years of observation. The detection of HIV infection and the start of ART in the first 6–12 months of life of children was characterized by clinical symptoms up to CNS damage, high levels of HIV RNA in the blood, moderate decrease in CD4 lymphocytes, with normalization after 3–6 months of treatment and after 3 years of observation. Late diagnosis of HIV infection in children – over 2 years of age is characterized by severe forms of the disease with secondary manifestations – AIDS in 20,0% of cases, low rates of CD4 lymphocytes, damage to the central nervous system with the formation of spastic diplegia, and slow recovery of immunity. The use of the drug Viferon, rectal suppositories in the combined treatment of EBV-mononucleosis and a generalized form of CMV infection allows the early treatment of the main symptoms of herpes virus infections and normalization of laboratory parameters. Conclusion Our prospective study showed that mother-tochild transmission of HIV was realized due to the absence of the first stage of chemoprophylaxis (during pregnancy), and was also aggravated in 9 cases (10,0%) by breastfeeding. The severity of the clinical manifestations of HIV infection, the levels of CD4-lymphocytes and HIV RNA in the blood directly depend on the period of detection and the initiation of ART in children. The inclusion of human recombinant interferon alpha-2b with antioxidants (Viferon rectal suppositories) in the etiopathogenetic therapy of comorbid herpes virus diseases (EBV-mononucleosis, a generalized form of CMV infection) is effective and safe.

Coronavirus disease 2019 in children: Characteristics, antimicrobial treatment, and outcomes.

At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help pediatricians understand the conditions of COVID-19 in children. We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan Children's Hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-α nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.

CON: All Patients With Immune-Tolerated Hepatitis B Virus Do Not Need to Be Treated.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-1-reading-attar a video presentation of this article.

ARVI antiviral therapy in children in modern clinical practice

In the context of the wide range of products recommended for antiviral therapy, there is still a need for continuous evaluation of their effectiveness and safety in pediatrics. The work describes the experience of non-interventional study of the domestic drug umifenovir in the modern clinical practice. The authors studied 216 case histories of children hospitalized with acute respiratory viral infections at early stages of the disease. Against the background of the drug administration a significant reduction in the duration of all symptoms of the infectious process and the need to prescribe antibiotic therapy to patients, a reduction in the chances of complicated flu and acute respiratory viral infections, as well as a favorable safety spectrum and a high level of compliance during treatment.

Influenza and ARVI: challenges and solutions

ARVI and influenza are one of the topical problems of pediatrics, which is due to the high level of morbidity in the child population, a significant incidence of severe and complicated forms of disease, especially in young children. In the structure of infectious pathology in children, this group of diseases still retains its leading position, accounting for up to 70% of all registered cases. Almost every child annually and more than once endures ARVI or flu episodes. This group of infections causes significant economic damage both to the household budget and the national budget as a whole. In order to improve the provision of medical care for children, improve the qualifications of pediatricians and share experience of the Department of Pediatrics named after Academician G.N. Speranskiy RMACPE (Head of Department Dr. of Sci. (Med), Professor I.N. Zakharova), a scientific and practical seminar «Influenza and acute respiratory infections 2018/2019: challenges and solutions» was held. Within the framework of the event, supported by «Valenta Pharm», specialists considered a number of topical issues, including vaccine prophylaxis and treatment of ARVI and influenza, taking into account modern epidemiological, microbiological and virological data. The seminar participants paid special attention to the validity of antiviral therapy in children, in particular, such drug as Ingavirin®.

Antiviral therapy in hepatitis B virus-infected children with immune-tolerant characteristics: A pilot open-label randomized study

Chronic infection with hepatitis B virus (HBV) in children is a serious health problem worldwide. How to treat children with immune-tolerant chronic hepatitis B infection, commonly characterized by hepatitis B e antigen (HBeAg) positivity, high viral load, normal or mildly elevated alanine aminotransferase and no or minimal inflammation in liver histology, remains unresolved. This trial aims to study the benefits of antiviral therapy in children with these characteristics. This is a pilot open-label randomized controlled study. From May 2014 to April 2015, 69 treatment-naive chronically HBV-infected children, aged 1 to 16 years, who had immune-tolerant characteristics were recruited to this trial and randomly assigned, in a 2:1 ratio, to treatment group and control group. Patients in the treatment group received either interferon-α (IFN) monotherapy or consecutively received IFN monotherapy, combination therapy of IFN and lamivudine (LAM), and LAM therapy alone. All patients were observed until week 96. At baseline, epidemiological, biochemical, serological, virological and histological indices were consistent across the treatment and control groups. Of the 46 patients in the treatment group, 73.91% had undetectable serum HBV DNA, 32.61% achieved HBeAg seroconversion and 21.74% lost hepatitis B surface antigen (HBsAg) at the endpoint. No LAM resistance emerged at week 96. In the control group, only one (4.35%) patient underwent spontaneous HBeAg seroconversion and had undetectable serum HBV DNA during observation, and moreover, none developed HBsAg clearance. For all patients, no serious adverse events were observed. Antiviral treatment with a sequential combination of IFN and LAM resulted in a significant improvement in the rates of undetectable serum HBV DNA, HBeAg seroconversion and HBsAg loss in children with chronic HBV infection and immune-tolerant characteristics. There is a lack of data regarding treatment of immune-tolerant chronic hepatitis B (CHB). It remains unresolved how children with immune-tolerant CHB should be treated. This paper reports the outcomes from a pilot open-label randomized controlled trial on antiviral therapy in children with immune-tolerant characteristics. It shows that a sequential combination of interferon-α and lamivudine was beneficial.

Study progress of antiviral therapy in children with chronic hepatitis B

The antiviral treatment for children with chronic hepatitis B virus(HBV) infection should be started in the immune active phase.Interferon(IFN) is the drug of first choice in most cases, however, the individual treatment and management of adverse effects need to be considered.Currently, Nucleos(t)ide analogues(NAs) can be used as the first choice only for those special children who can′t use IFN. Efficacy will be seriously affected once the emergence of viral resistance mutants to NAs.However, there is high risk of relapse after the NAs are discontinued.Compared with the mono therapy, the therapeutic strategy of interferon combined with NAs have obtained better effect and safety in children with chronic HBV infection. Key words: Chronic hepatitis B; Interferon; Nucleos(t)ide analogues; Treatment; Child

A retrospective study on HBsAg clearance rate after antiviral therapy in children with HBeAg-positive chronic hepatitis B aged 1-7 years

Objective: To investigate the HBsAg clearance rate after antiviral therapy in children with HBeAg-positive chronic hepatitis B (CHB) aged 1-7 years. Methods: A retrospective analysis was performed for the HBsAg clearance rate in 293 children who were hospitalized in 302 Hospital of PLA from June 2006 to December 2013, met the inclusion criteria, received antiviral therapy, and were followed up for at least 6 months after the withdrawal of antiviral therapy. The t-test or the rank sum test was applied according to the distribution of continuous data, and the chi-square test was used for comparison of categorical data. Results: The HBsAg positive rate of children's mothers was 91.1%. In the age groups of >1-≤2 years, >2-≤3 years, >3-≤4 years, >4-≤5 years, >5-≤6 years, and >6-≤7 years, the HBsAg clearance rates were 66.1%, 65.5%, 45.7%, 41.3%, 20.6%, and 27.6%, respectively. There were significant differences in HBsAg clearance rate between the age groups of >1-≤3 years and >3-≤5 years, >1-≤3 years and >5-≤7 years, and >3-≤5 years and >5-≤7 years (P = 0.001, 0.000, and 0.008). Of all children, 64.8% were boys, among whom 41.1% achieved HBsAg clearance, and 35.2% were girls, among whom 61.2% achieved HBsAg clearance; there was a significant difference in HBsAg clearance rate between boys and girls (P = 0.001). The children with pretreatment alanine aminotransferase (ALT) levels of ≤80 IU/L, > 80 IU/L, ≤200 IU/L, and > 200 IU/L had HBsAg clearance rates of 40.7%, 51.2%, 47.6%, and 49.4%, respectively; there were no significant differences in HBsAg clearance rate between the ALT ≤80 IU/L and ALT > 80 IU/L groups and the ALT ≤200 IU/L and ALT > 200 IU/L groups (P = 0.101 and 0.778). There was no significant difference in HBsAg clearance rate between the pretreatment HBV DNA load < 1×107 IU/ml and ≥1×107 IU/ml groups (54.9% vs 46.7%, P = 0.286). Of all children, 14.2% had genotype B and an HBsAg clearance rate of 57.1%, and 85% had genotype C and an HBsAg clearance rate of 39.5%; there was no significant difference in HBsAg clearance rate between the genotype B group and the genotype C group (P = 0.051). Of all children, 90.4% underwent liver biopsy, among whom 10.9% had severe liver fibrosis (F≥3) and liver cirrhosis, as well as an HBsAg clearance rate of 31%; the non-severe liver fibrosis/liver cirrhosis group had an HBsAg clearance rate of 49.2%, and there was no significant difference in HBsAg clearance rate between these two groups (P = 0.065). There was no significant difference in HBsAg clearance rate between the liver inflammation grade (G) < 2 group and the G ≥ 2 group (39.5% vs 50.9%, P = 0.084). Of all children, 58.7% received interferon antiviral therapy alone and had an HBsAg clearance rate of 48.8%, and 41.3% received interferon alone for 6 months followed by lamivudine antiviral therapy and had an HBsAg clearance rate of 47.1%; there was no significant difference between these two groups (P = 0.770). Conclusion: In children with HBeAg-positive CHB aged 1-7 years who receive antiviral therapy, HBsAg clearance rate is correlated with age and sex, and the children aged < 5 years can achieve a higher HBsAg clearance rate.

Toll-like receptors 7 and 8 mRNA in monocytes of Egyptian children with chronic hepatitis C infection genotype 4 as predictor to “response” interferon and ribavirin treatment

BackgroundThe contribution of the host immune response to sustained virologic response (SVR) is not clear in children with chronic hepatitis C (CHC). It is still unknown whether TLRs 7&8 expression in monocytes is related to disease progression in HCV infected children or whether it represents a protective factor in those patients who are slow disease-progressors. ObjectiveThe aim of this study was to assess the value of expression of TLRs 7&8 and TNF as a predictor for the outcome of antiviral therapy in children with CHC. Patients and methodsThis prospective study included fifty CHC children aged 5–18years. Thirty-four were males, sixteen were females who received Peg-IFN-α-2b and RBV for 48weeks. mRNA levels of TLRs 7&8 in monocytes were evaluated using real-time PCR before a 48-week treatment with Peg-IFN-α-2b and RBV. In addition, we studied tumor necrosis factor (TNF) production in monocytes using three-color immunofluorescence and flow cytometry after TLRs 7&8 ligand Resiquimod (R848) stimulation. ResultsAccording to the virological response of the treatment, the infected children were classified into sustained virological response (SVR) 72% and non-responder 28%. The study determined that mRNA levels of TLRs 7&8 were significantly high in SVR compared to non-responders. Furthermore, after stimulation with R848 the median fluorescence intensity (MFI) for TNF protein was significantly high in SVR compared to non-responders. ConclusionsTLRs 7&8 and TNF have great importance in controlling HCV infection and the responses to IFN therapy. Further research covering other stages of CHC at large numbers and at different monocytes subsets levels will be needed.

Interferon-α plus ribavirin yields 98 % sustained virologic response in children aged 1-5 years with iatrogenic chronic hepatitis C.

The clinical features and efficacies of antivirals for children with hepatitis C virus (HCV) infections that are acquired through different transmission routines are poorly understood worldwide. This study investigated the clinical characteristics of children who were infected via iatrogenic means and analyzed the efficacy of antiviral therapy in children with chronic hepatitis C (CHC). In total, 256 children with HCV infections aged 1 to 5 years were enrolled and surveyed. Interferon-α plus ribavirin was administered to 162 children with CHC for 24 or 48 weeks. The sustained virologic response (SVR) at 24 weeks post-treatment was determined. The median duration of infection was 11.5 (range 6-24) months. The median age was 2.7 years, and 64.5 % of the subjects were male. Ninety-three children (36.3 %, 93/256) exhibited spontaneous resolution of the HCV infection. The remaining 163 (63.7 %) were HCV RNA-positive and had HCV genotypes 1b and 2a, which were identified in 42 and 58 %, respectively, of the 133 tested children. Liver biopsies were performed in all HCV RNA-detectable children. A total of 23.9 % cases exhibited grade 2 activity, and 30.1 % exhibited stage 2/3 liver fibrosis. The serum HCV RNA levels were positively correlated with the aminotransferases. Of the 162 treated CHC children, 158 (97.5 %) achieved SVR. The side effects were mild, and 158 (97.5 %) of the treated patients tolerated the treatment well. This study revealed that histological liver disease can be present within 6-24 months of acquiring an HCV infection in children aged 1-5 years. Interferon-α plus ribavirin therapy is a highly effective and cost-effective means of managing children with early-stage chronic HCV infection.

Mannose-binding lectin in chronic hepatitis C in children

Objective. To investigate effect of mannose-binding lectin (MBL) genetic polymorphisms and phenotype in chronic hepatitis C and its impact on response to antiviral therapy in children. Methods. Fifty four children with chronic hepatitis C, aged 2.5–18 years were enrolled. Forty-five children were treated with interferon-α (IFN-α) alone (n = 2) or IFN-α and ribavirin (n = 43). Twenty-one children who responded to antiviral therapy were defined as sustained responders to therapy (IFN-SR). Before therapy, MBL genotypes and serum MBL levels (by ELISA) were determined. MBL genotype distribution and levels were correlated to disease characteristics and response to therapy. Results. Children with chronic hepatitis C who did not respond to antiviral therapy (IFN-NR) presented more frequently MBL2 polymorphisms, although this did not reach significance (p = 0.08). MBL levels were significantly lower in children classified as IFN-NR when compared to children defined as IFN-SR (1.623 ng/ml vs. 3.699 ng/ml), (p = 0.04). Serum activity levels of ALT and AST were higher in children with A/O MBL genotype when compared to group with A/A genotype (p < 0.05). Conclusions. Our findings suggest negative effect of MBL deficiency (defined by genotype and phenotype) on progression of chronic hepatitis C in children and response to antiviral therapy.