Hepatitis C virus infection in children in the era of directacting antiviral

Hepatitis C virus(HCV) infection remains an important global health problem with chronic infection affecting approximately 11 million children worldwide. The emergence of direct-acting antiviral(DAA) therapies and the development of non-invasive methods for the determination of liver fibrosis will significantly improve the management of paediatric patients with chronic HCV infection in subsequent years. For paediatric patients, a new era of highly effective DAA agents is beginning, and the first results of available clinical trials are very promising. In this era, the identification and monitoring of patients continues to be an important issue. The availability of non-invasive serological and imaging methods to measure hepatic fibrosis enables the identification of patients with significant or advanced liver fibrosis stages. This article summarizes the current data on the epidemiology and progress of research aimed to evaluate the new therapies and non-invasive methods for liver injury in paediatric patients with chronic hepatitis C.

Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

AIM To investigate the impact of IL28 B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODS We enrolled 52 children(between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B(CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1(rs1131476), OAS2(rs1293747),OAS3(rs2072136), OASL(rs10849829) and IL28B(rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus(HBV) DNA level < 2000 IU/m L and normalization of ALT activity(< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response(PR) and a complete response(CR) upon measurement at the 24-wk posttreatment follow-up. RESULTS The PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response(partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown(P < 0.05). The allele association analysis revealed that only the IL-28 B rs12979860(C vs T) and IL28 B rs12980275(A vs G) markers significantly affected the achievement of PR(P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28 B rs12980275 was significantly associated with PR(AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28 B rs12979860 was present only in the no-CR group(P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the noCR group(P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype(P = 0.0002 and P = 0.001, respectively), but no association with IL28 B haplotype was observed.CONCLUSION IL28 B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.

Psychometric Evaluation of the Japanese Wijma Delivery Expectancy/Experience Questionnaire Version B

The Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ) is a widely accepted approach to measuring fear of childbirth and is available in two versions: antenatal (version A) and postnatal (version B). The aim of this study was to develop the Japanese W-DEQ version B and confirm its validity and reliability among Japanese women. A self-administered questionnaire incorporating the translated Japanese W-DEQ (JW-DEQ) version B and the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS) was distributed to Japanese mothers at two days postpartum. Of the 246 women recruited, 231 who completed the questionnaire at two days postpartum were analyzed. An exploratory factor analysis of the JW-DEQ version B revealed four factors: fear, lack of positive anticipation, isolation and riskiness. The JW-DEQ version B exhibited a positive correlation with the HADS anxiety subscale (r = 0.34, p α value derived from the total 33 items was 0.95. This study provides evidence of the factorial, concurrent validity and the internal consistency of the JW-DEQ version B. However, a further study involving participants from different demographic groups will be required.

Factors influencing the failure of interferon-free therapy for chronic hepatitis C:Data from the Polish EpiTer-2 cohort study

BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine learning algorithm(random forest).Coinfection with HBV(including patients with on-treatment reactivation of HBV infection)or HIV,extrahepatic manifestations,and renal failure did not significantly affect the treatment efficacy.CONCLUSION In patients with advanced liver disease,individualized therapy(testing for resistance-associated variants and response-guided treatment)should be considered to maximize the chance of achieving SVR.

What's new in hepatitis C virus infections in children?

The number of hepatitis C virus(HCV) infection cases is relatively low in children. This low number may be connected with the lack of screening tests and the asymptomatic course of infection. Currently,mother-toinfant transmission is the most common cause of HCV infection amongst children in developed countries. It is important to introduce routine screening tests for HCV in pregnant women. The risk of vertical transmission of HCV is estimated at approximately 5%(3%-10%). Currently,we do not have HCV transmission prevention methods. Some factors could potentially be eliminated by elective caesarean section. Currently,the method of prevention of perinatal HCV infection is the early identification and effective treatment of infections in young women in the preconception period. We describe genetic tests(IL-28 B single nucleotide polymorphisms) to identify children with an increased chance of spontaneous clearance or sustained virologic response achievement and vitamin D level as a potential predictor of treatment response in children. It is also important to develop non-invasive tests that can predict liver fibrosis. The existence of differences in the mechanisms leading to liver injury between children and adults creates new perspectives of action to reduce liver disease progression in children in the early years of life.

评价γ干扰素释放试验在结核病诊断中的临界值

背景:土耳其伊斯坦布尔胸部疾病中心。目的:通过降低结核菌素皮试(TST)、QuantiFERON-TB Gold(QFT)和G T-SPOT.TB (T-SPOT)试验的临界值,可能会提高基于γ干扰素检测试验在诊断结核上的准确性。设计:对100例未进行过治疗的培养阳性空洞型结核病人及47例健康志愿者进行对照研究,从而评估在不同临界值时,TST、QFT、T-SPOT试验的诊断效力差异。结果:各试验的敏感性分别为:TST 70%, QFT 78%,T-SPOT 83.5%,特异性分别为TST 35%,QFT 89.4%,T-SPOT 84.8%,QFT和T- SPOT的特异性都明显高于FST(P值都<0.001),但QFT和T-SPOT特异性相近(P= 0.05)。受试者工作特征曲线分析表明,当QFT临界值为0.818IU/ml时,特异性最高,敏感性没有明显降低,而降低QFT和T-SPOT的临界值时,也提高了试验的敏感性,特异性却明显降低。结论:降低TST、QFT、T-SPOT的临界值可以增加相应试验的敏感性,但只有QFT的特异性能够保持不变。

Outdoor air pollution and the onset and exacerbation of asthma

Exposure to outdoor air pollution has been consistently associated with asthma.In this study,we reviewed the epidemiological studies published within the last 5 years on the association between outdoor air pollution and exacerbation and onset of asthma.A large number of studies have been published within the last 5 years.Short-term exposure to outdoor air pollution is associated with exacerbation of pre-existing asthma,manifested as worsening of symptoms and increasing of asthma-related emergency room visits and hospital admissions.Furthermore,increasing evidence suggests that long-term exposure to outdoor air pollution can result in onset of asthma.Children are more susceptible to outdoor air pollution.Future studies should be conducted to explore the mechanisms underlying the association between air pollutants and onset of asthma,including gene involvement.In addition,disentangling the effect of a mixture of air pollutants and identifying the key components of air pollution will complete the existing evidence.More importantly,a better understanding is required on the future impact of air pollution on asthma under a changing climate.