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 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.

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.

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 investigate the curative effect of antiviral therapy and related factors influencing the curative affect in children with immune-tolerant phase chronic hepatitis B. Methods: From May 2014 to April 2015, 46 children with chronic hepatitis B, aged 1 to 16 years with immune-tolerant phase were enrolled as the treatment group. All cases in the treated group either received interferon alpha (3-5 MIU/m², once daily) in lamivudine combination (if HBV DNA decreased < 2 log₁₀) or repeatedly received interferon-alpha alone (if HBV DNA decreased >2 log₁₀) for 12 weeks. Interferon was discontinued at 72 weeks and followed-up period was continued with lamivudine for 24 weeks. At the same time, data of 23 cases of untreated children with immune-tolerant phase chronic hepatitis B were collected as the control group. The treatment group and the control group were divided into two age groups: 1-7 years old and 7-15 years old. Data measurements were compared using t-test, analysis of variance and single factor analysis methods, and the count data were analyzed by χ ² test. Multiple logistic regression analysis was used to analyze the effects of different factors on response. Results: (1) There were 22 cases aged 1-7 years in the treatment group (47.8%) and 12 cases aged 1-7 years in the control group (52.2%). The cases of mother-to-child transmission (MTCT) in treatment and control group were 34 (73.9%) and 17 (73.9%), while children with normal baseline ALT in the treatment and control group were 18 (39.1%) and 10 (43.5%). (2) At the end of follow-up, 15 cases in the treatment group (32.6%) had HBeAg serological conversion. Among them, nine (19.6%) cases had HBsAg clearance or HB-Ag seroconversion with anti-HBs, and one (2.2%) case had HBsAg clearance, but both HBeAg and anti-HBe were positive. In the control group, one case had HBV DNA lower than the lower limit of detection level, and one case had HBeAg seroconversion without HBsAg clearance. (3) At the end of follow-up, the seroconversion rates of HBeAg in patients aged 1 to 7 years and patients aged 7 to 15 years were 45.5% and 20.8%, respectively (P = 0.078) and the clearance rates of HBsAg were 36.4% and 8.3% (P = 0.023). The serum conversion rates of normal and abnormal baseline alanine aminotransferase levels were 5.6% and 50.0% (P = 0.005), and the clearance rates of HBsAg were 5.6% and 32.1% (P = 0.077), respectively. There was no statistically significant difference in gender, mother-to-child transmission, HBV DNA genotyping and baseline HBsAg level in antiviral efficacy among children (P > 0.05). (4) HBsAg and HBeAg clearance occurred in 100% of patients at the end of follow-up who had HBsAg < 3 000 IU/ml at 24 weeks of treatment. (5) Multivariate logistic regression analysis showed that serum HBeAg conversion rate had relation with non-MTCT transmission and abnormal baseline alanine aminotransferase. Furthermore, HBsAg clearance rate was associated with the age of children. Conclusion Sequential combination of interferon and lamivudine with a prolonged course can improve the HBV DNA negative conversion rate, HBeAg seroconversion rate, HBsAg loss rate and mild ALT abnormalities at baseline in children under the age of 7 years with immune-tolerant phase chronic hepatitis B.