Antiviral Agents ; administration & dosage ; therapeutic use ; Child ; Drug Therapy, Combination ; Hepatitis B, Chronic ; drug therapy ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Lamivudine ; administration & dosage ; therapeutic use ; Nucleosides ; administration & dosage ; therapeutic use ; Polyethylene Glycols ; administration & dosage ; therapeutic use

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.

Children with hepatitis C virus RNA positive were considered to start antiviral treatment.Alpha interferon or pegylated interferon plus ribavirin in children achieved satisfactory sustain virology response.Although there were many adverse events,some can be relieved by communicating with the guardian,bringing care to the patient and giving treatment.Clinical trials in children with hepatitis C by the direct-acting antiviral agents were in progress,safety and efficacy have no differences with the adult.There were still lots of work to do in view of the particularity of children.

For children with chronic hepatitis B (CHB), the antiviral therapy should be started in the immune active phase. There are two categories of antiviral drugs used for CHB: interferons (IFNs) and nucleos(t)ide analogues (NAs). In this paper, the current status of antiviral therapy of CHB in children is reviewed. It is pointed out that IFNs are the drug of first choice in antiviral therapy for children with CHB, and the individualized treatment and management of adverse events need to be considered. Some NAs can be given to those special children who cannot accept IFNs. However, there is a high risk of relapse after drug withdrawal. And the subsequent treatment will be seriously affected once the drug resistance is developed. It needs further investigation to improve the efficacy of antiviral therapy and reduce the adverse events and the drug resistance in the future.

Objective To study the roles of TNF-α secretion of PBMC in patients with chronic hepatitis C and Nonalcoholic fatty liver. Methods The level of TNF-α secretion of PBMC in patients with chronic hepatitis C and Nonalcoholic fatty liver was detected by ELISA after culturing for 72 hours in vitro, as well as patients with chronic hepatitis C and the normal control. Results (1) Compared with the normal control, the level of TNF-α in group with chronic hepatitis C and in group with chronic hepatitis C and Nonalcoholic fatty liver notably increased. (2) Compared with the group with chronic hepatitis C, the level of TNF-α in group with chronic hepatitis C and Nonalcoholic fatty liver also notably increased. Conclusion It suggested TNF-α takes important roles in the infection course of chronic hepatitis C with Nonalcoholic fatty liver.

Drug-induced liver injury (DILI) is a common disease in children with non-infectious liver di-seases, but there is no specific diagnostic method.Genetic-metabolic liver disease is a rare disease with low social recognition and requiring special examination to be diagnosed.The clinical manifestations of the 2 diseases are similar and complex, so it is easy to misdiagnose genetic-metabolic liver disease as DILI.In clinical practice, it is necessary to raise the awareness of excluding genetic-metabolic liver diseases in the diagnosis of DILI, so as to avoid misdiagnosis.

Objective Retrospectively study of the effects of interferon-α therapy on height and weight of children with chronic hepatitis B (CHB).Methods Total of 116 hospitalized cases of CHB children in Adolescent Liver Centre, 302 Military Hospital of China from January 2010 to December 2011 were respectively studied.Heights and weights of all the subjects at baseline, 24 weeks, 48 weeks, 72 weeks and 96 weeks of treatment, and 24 weeks, 48 weeks and 96 weeks of follow-up were measured.The weight Z score (WAZ), height Z score (HAZ) and body mass index (BMI) Z score of subjects with hepatic fibrosis (S) <3 and S≥3 were compared.The differences of HAZ and WAZ between baseline and treatment or follow-up in groups of subjects aged 1-6 years and 6-16 years were also compared.T test or rank sum test was used for comparison between groups.Results Among the study of all 116 patients studied, median baseline values of HAZ, WAZ and BMI Z score were 0.76, 0.38 and-0.04, respectively.For patients with hepatic fibrosis S<3, the median HAZ and WAZ were 0.83 and 0.32, respectively.For patients with hepatic fibrosis S≥3, the median HAZ and WAZ were 0.52 and 0.15, respectively.The differences were not statistically significant (both P>0.05).At 48 weeks of treatment, the median HAZ was 0.50, and the median WAZ was 0.20;after a follow-up period of 24 weeks, the median HAZ was-0.32, and the median WAZ was-0.18;after a follow-up period of 48 weeks, the median HAZ was 0.09 and the median WAZ was 0.06.All the above median values of HAZ and WAZ were significantly different from those at baseline (all P<0.05).The difference of HAZ at baseline and 96 weeks of treatment in group aged 6-16 years was significantly different from that in group aged 1-6 years (-0.74±0.69 vs-0.53±0.35, t=1.85, P<0.05).Also, the difference of WAZ at baseline and 96 weeks of treatment in group aged 6-16 years was significantly different from that in group aged 1-6 years (-0.69±0.41 vs-0.17±0.75, t=3.74, P<0.05).The difference of HAZ at baseline and 96 weeks after treatment in group aged 6-16 years was significantly different from that in groups aged 1-6 years (-1.12±0.81 vs-0.05±0.69, t=2.06, P=0.022).Conclusions Interferon-α treatment for children with chronic hepatitis B does have influence on their height and weight, which restores to some degree after the treatment finished.Physicians should pay more attention to the influence of interferon-α treatment on height and weight in children aged 6-16 years.

The natural history of chronic hepatitis B is complex including immune-tolerant phase,immune clearance phase,inactive carrier phase and reactivation phase,among these phases,it has not yet reached a consensus on the definition of the immune-tolerant phase,because its key immune features are not entirely sure.However,the current diagnostic criteria of this phase require normal alanine aminotransferase (ALT) levels,positive hepatitis B s antigen and e antigen,high serum hepatitis B virus DNA (HBV-DNA),and slight or normal inflammation of liver histology.Antiviral therapy in this phase is currently not recommended in all guidelines,but in recent years,antiviral treatment of immune-tolerant children achieved efficacy in several study.Nonetheless before new findings are published,it would be important to closely and regular monitor serum ALT and HBV-DNA in the immune-tolerant children.

OBJECTIVETo explore the pathological and clinical characteristics of children with liver diseases by retrospective study on clinical and liver biopsy pathological data of children with liver diseases.

METHODThis retrospective analysis was performed at Beijing No. 302 Hospital among 3 932 children with liver diseases who visited the hospital from January 2001 to December 2012. The kinds of diseases were compared with the results of 1983-2000.

RESULT(1) Liver biopsy was successful in 99.72% (3 932/3 943) of cases of 2001-2012 group, complications occurred in 31 children only. (2) Of the 3 932 cases, 2 647 (67.32%) had hepatitis , non-hepatotropic viral hepatitis and non viral liver disease were seen in 365 cases (9.28%), and 920 cases (23.4%), respectively. Among 2 647 cases with viral hepatitis, 2 115 were hepatitis B (79.90%), 521 hepatitis C (19.69%), 7 were hepatitis A (0.26%) and 4 hepatitis E (0.15%), respectively. (3) In 2001-2012 group, the degrees of inflammatory activity (>G2) of liver were seen in 9.57% (202/2 111) patients with hepatitis B, while 23.57% (132/560) in 1983-2000 group. There was significant difference between the two groups (χ(2)=80.36, P=0.00 ). (4) Significant difference was observed in the rate of non viral liver disease between 2001-2012 group (23.40%, 920/3 932) and 1983-2000 group (9.61%, 98/1 020) (χ(2)=93.46, P=0.00). In 2001-2012 group, including 46 kinds of diseases, which were significantly higher than those of 1983-2000 group (18 kinds). In 2000-2012, the main causes of diseases were liver degeneration (18.26%, 168/920), drug-induced liver injury (13.59%, 125/920), fatty liver (8.80%, 81/920) and liver glycogen accumulation disease (8.70%, 80/920). While in 1983-2000 group, the main causes were liver degeneration (20.41%, 20/98), fatty liver (16.33%, 16/98), glycogen storage disease (10.20%, 10/98) and myopathy (9.18%, 9/98).

CONCLUSIONLiver biopsy in children is safe and feasible. Hepatitis B virus was ranked first in children with liver diseases in 2001-2012 group. The kinds of non viral hepatic disorders had changed and extended.

Adolescent ; Biopsy, Needle ; Child ; Child, Preschool ; Female ; Hepatitis B ; pathology ; Hepatitis, Viral, Human ; pathology ; Hepatolenticular Degeneration ; epidemiology ; pathology ; Humans ; Infant ; Liver ; pathology ; Liver Diseases ; pathology ; Liver Function Tests ; Male ; Retrospective Studies

Objective:To evaluate the efficacy and safety of direct antiviral drugs based on sofosbuvir in the treatment of chronic hepatitis C in children.Methods:Data of children diagnosed with chronic hepatitis C from May 2017 to December 2019 and received sofosbuvir (SOF, body weight ≥ 17 kg 200 mg/d, <17 kg 150 mg/d)/ledipasvir (LDV, body mass ≥ 17 kg 45 mg/d, <17 kg 33.75 mg/d) or velpatasvir (VEL, body weight ≥ 17 kg 50 mg/d), were collected. The patients were treated with ribavirin (RBV, 15 mg/kg·d) for 12 weeks and followed up for 12 weeks. The main outcome measures were sustained virological response (SVR) at 12 weeks follow-up after drug discontinuation, and the occurrence of adverse events during the treatment period was observed to evaluate the safety of the drug.Results:HCV RNA turned negative in 10 of the 13 children (76.92%), within 2 weeks after antiviral treatment, in 2 cases (15.38%) HCV RNA turned negative in 2-4 weeks, in 1 case (7.69%) RBV was added when HCV RNA did not turn negative in 8 weeks, but turned negative at 10 weeks. At 12 and 24 weeks after discontinuation of antiviral drugs (SVR12), HCV RNA continued to be negative, and at 24 weeks (SVR24), it was also negative. Adverse reactions: headache occurred in 2 cases (15.38%), fatigue in 3 cases (23.08%), no serious adverse reactions occurred in any of the patients.Conclusions:The efficacy and safety of direct antiviral drugs based on SOF in the treatment of children with chronic hepatitis C were good.