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.

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.