IL28B SNP rs12979860 is the Critical Predictor for Sustained Viral Response in Chinese Children Aged 1 to 6 Years with Chronic Hepatitis C.

Clinical data on children with chronic hepatitis C (CHC) remain extremely limited. This study investigated sustained virologic response (SVR) to alfa-interferon 2b plus RBV treatment in children aged 1-6 years with unsafe injection-acquired CHC. 154 children with CHC aged 1 to 6 years were enrolled, 101 of them were male (65.6%) and 53 were female (34.4%), and they were treated with alfa-interferon at a dose of 1-5 MIU/m2 3 times weekly plus oral RBV (15 mg/kg/day) for 48 weeks. 57(39.3 %) of them were genotype 1b, 73(50.3%) were genotypes 2a, 15(10.3%) were undecided type. SVR was achieved in 53 of 57(93.0%) patients with genotype 1b, in 72 (98.6%) of 73 with genotype 2a, 15(100.0%) of 15 with undecided type. There was no significant statistical difference in SVR between male and female (98.0% vs 94.3%, p=0.340), genotype 2a and those with genotype 1b(98.6% vs 93.0%, p=0.160), ALT>40U/L group and ALT≤40U/L group(96.7% vs 96.8%, p=1.000), AST>40U/L group and AST≤40U/L group(95.9% vs 98.2%, p=0.654) as well as lower baseline viral load group (<6×105 IU/ml) and higher baseline viral load group(≥6×105 IU/ml)(97.3% vs 95.3%, p=0.916). Leucopenia, neutropenia, hemoglobin concentration decrease, fever, platelet count decrease and rash were 8.4%, 69.5%, 24.0%, 50.6%, 1.9% and 4.5%, respectively. And only 12(7.8%) individuals developed thyroid autoantibodies. The SVR was higher in patients with IL-28B genotype C/C than C/T (99.0% vs 80%, p=0.002). Compared with HCV viral genotype, ALT level and baseline viral load, IL-28B rs12979860 is more suitable for predicting antiviral efficacy in children with CHC. It is inappropriate to take the increase of ALT level as an essential indicator for antiviral treatment in children aged 1-6 years.

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

BACKGROUND AND OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Association of Hepatitis C Virus Infection and Interleukin-28B Gene Polymorphism in Chinese Children.

OBJECTIVE: To preliminarily explore the association of rs12979860 and rs8099917 SNPs with chronic HCV infection in Chinese Han children. METHODS: Chronic HCV infection patients (n=277; 1-17 years old, 4.5 years old in average) and healthy subjects (n=150, children; 2-17 years old, 5.2 years old in average) were recruited and tested by PCR combining direct sequencing. The differences between the rs12979860 and rs8099917 genotypes in patients and healthy subjects were compared. RESULTS: The genetic variations at rs12979860 and rs8099917 in chronic hepatitis C (CHC) children and healthy subjects did not differ significantly. The frequency of spontaneous clearance in CHC children was higher (47%), which is related to the genetic variations. The histological changes of patients were more significant compared to their clinical and biochemical indices, but they did not correlate with the genetic mutations at rs12979860 and rs8099917 significantly. CONCLUSION: The rs12979860 and rs8099917 SNPs are independent factors predicting the spontaneous clearance of Chinese CHC children patients. The correlation between diseases outcomes are in need of further study.

[A clinical study on leucogen tablets therapy efficacy during PEG-alpha interferon and alpha-interferon in chronic hepatitis B].

OBJECTIVE: To discuss the efficacy of Leucogen tablets treatment lessen the hematological reaction and raise the efficacy therapy of interferon in chronic hepatitis B treated with PEG-alpha interferon and alpha interferon. METHODS: A total of 395 patients with HBeAg-positive chronic hepatitis B (CHB) inpatients from January 2002 to February 2011. Group: All the patients were assigned to A or B according as during the treatment added Leucogen tablets or not. RESULTS: (1) All of 35.9% patients had neutrophil counts decrease under 1 x 10(9)/L, A group had 29.6%, B had 42.8% patients, P = 0.01; neutrophil counts < or = 0.75 x 10(9)/L A group had 12.6% ,B group had 26.4%, P = 0.02; neutrophil counts < or = 0. 5 x 10(9)/L A group had 4.8%, B group had 16.4%, P = 0.04. (2) A group had 8.2% patients interferon-alpha dose decreased, all the patient finished the period of therapy. B group had 23.3% patients interferon-alpha dose decreased, 2.1% of patients had paused. A group had 40.3% of patients interferon-alpha beyond conventional dose, B group had only 5.2%. (3) All of 9.8% patients had hematoblast decrease under 100 x 10(9)/L, A group had 8.7%, B had 11.1% patients; hematoblast < or = 80 x 10(9)/L A group had 5.3%, B group had 7.9%; hematoblast < or = 50 x 10(9)/L A group had 1.0%, B group had 2.6%. A group had the trend of reducing hematoblast decrease. (4) At the end of therapy A group had 67.4% patients HBVDNA < 100IU/ml, 54.3% e antigen negative, 40.7% e antigen conversed; B group had 53.9%, 41.2%, 26.9%, P was respectively 0.02, 0.01, 0.01. CONCLUSION: Leucogen tablets treatment and prevention interferon-alpha-related neutrophil counts hematological reaction in CHB treated with alpha-interferon, and had the trend of reducing interferon-alpha-related hematoblast decrease, farther improved the efficacy of alpha-interferon treatment CHB.

Virologic and clinical characteristics of HBV genotypes/subgenotypes in 487 Chinese pediatric patients with CHB.

BACKGROUND: The association of hepatitis B virus (HBV) genotypes/subgenotypes with clinical characteristics is increasingly recognized. However, the virologic and clinical features of HBV genotypes/subgenotypes in pediatric patients remain largely unknown. METHODS: Four hundred and eighty-seven pediatric inpatients with CHB were investigated, including 217 nucleos(t)ide analog-experienced patients. HBV genotypes/subgenotypes and reverse transcriptase (RT) mutations were determined by direct sequencing. The stage of fibrosis and degree of inflammatory activity were evaluated by the Metavir score system. RESULTS: Among 487 enrolled pediatric patients, HBV genotype C2 and B2 were the most two prevalent (73.7% and 21.1%). Comparing with HBV/B2 infected patients, no significant difference was observed in the incidence rate and mutant patterns of lamivudine- or adefovir-resistant mutations in HBV/C2 infected patients (P > 0.05). Importantly, we found that the degree of hepatic inflammation degree, fibrosis stage and ALT level were significantly higher in HBV/C2-infected HBeAg positive patients than it was in HBV/B2-infected ones. CONCLUSIONS: The pediatric patients with HBV/C2 infection might be more susceptible to develop severe liver pathogenesis.

[Efficacy and safety of ademetionine for treatment of drug-induced liver disease in children].

OBJECTIVE: To investigate the efficacy and safety of ademetionine for treatment of cholestatic or mixed-type drug-induced liver disease (DILD) in children. METHODS: The children with DILD were divided into the treated group and control group. Yinzhihuang Granule was orally administered and Compound Glycyrrhizin Injection intravenously given in patients of both groups. Those patients in the treated group were additionally treated with intravenous infusion of 250-1000 mg ademetionine for 28 d. The incidence of pruritus and adverse effects as well as biochemical parameters in all the patients and compared between the 2 groups. For statistical analysis, Chi2 test was used for between-group comparison and t test for processing the data. RESULTS: 1) Before treatment, severe pruritus was found in 17 and 16 children in the treated and control group, respectively. Two weeks after the treatment, the symptom was significantly relieved in 14 and 3 patients in the treated and control group, respectively (Chi2 = 4.52, P < 0.05). 2) As for comparisons between the 2 groups, a P value of 0.0014 for AST level was found 4 weeks, 0.045 and 0.007 for disappearance and recovery rate of jaundice, 0.0014 and 0.0006 for decrease in TBA level and 0.0003 for gammaGT level 2 and 4 weeks after the treatment. CONCLUSION: Intravenous administration of ademetionine is safe in children with DILD and it can effectively alleviate pruritus, promote the recovery of various biochemical parameters and fasten liver functional recovery in these children. Therefore, ademetionine can be widely used for treatment of intrahepatic cholestasis in children.

[The level of TNF-alpha secretion of PBMC in patients with chronic hepatitis C and nonalcoholic fatty liver].

OBJECTIVE: To study the roles of TNF-alpha secretion of PBMC in patients with chronic hepatitis C and Nonalcoholic fatty liver. METHODS: The level of TNF-alpha 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-alpha 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-alpha in group with chronic hepatitis C and Nonalcoholic fatty liver also notably increased. CONCLUSION: It suggested TNF-alpha takes important roles in the infection course of chronic hepatitis C with Nonalcoholic fatty liver.

[Relation of viral genotypes to clinical features in children with chronic hepatitis B].

OBJECTIVE: To investigate the relation of HBV genotypes to clincal features in children with chronic hepatitis B. METHODS: The genotypes of serum HBV DNA from 404 children with chronic hepatitis B were determined by PCR using type-specific primers. RESULTS: For the 404 children, genotype B in 99 (24.5%), genotype C in 285 (70.5%). For the 75 children from south part of China, 29 were of genotype B (38.7%) and 44 of genotype C (58.7%). For the 329 children from north part of China, 70 were of genotype B (21.3%) and 241 of genotype C (73.3%). There were significant differences between the children from south part and those from north part of China in genotype B and C (P = 0.002). Genotype B and C were not significantly correlated to gender, age and mother-to-fetus transmission. There was no marked difference in liver injury severity (P = 0.4796), serum HBeAg positivity, HBVDNA level, inflammatory degree of liver tissue (P = 0.209) and liver fibrosis( P = 0.177) between the children with genotype B and those with genotype C. CONCLUSION: In children with HBV infection, genotype C accounts for 70.5% and genotype B for 24.5%. The genotypes are of regional difference in children with HBV infeciton. There are replication and liver pathological change between genotype B and genotype C.

[Level of the cytokine secreted by periferal blood mononuclear cells in patients with chronic hepatitis C before antiviral therapy].

OBJECTIVE: To study the immune state of patients with chronic hepatitis C before antiviral therapy by detecting the levels of the cytokines interleukin (IL)-2, IL-4, IL-10, IL-12, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha secretion by periferal blood mononuclear cells (PBMC). METHODS: The level of the cytokine secreted by PBMC in patients with chronic hepatitis C after culturing for 72 hours in vitro was detected by ELISA. RESULTS: (1) Compared with the cytokine level of normal controls, the level of IFN-gamma, TNF-alpha, and IL-10 of patients with chronic hepatitis C significantly increased (P < 0.05) while IL-2, IL-4, and IL-12 were not detected in the culture supernatant of PBMC from both normal control and patients with chronic hepatitis C. (2) There was no statistically significant difference in secretion of the cytokines among patients with different severity of the disease. CONCLUSION: PMBCs from patients with chronic hepatitis C tend to secret Th2 type cytokines. Restoring the imbalance of TH1/TH2 may help to clear the hepatitis C virus.

[Clinical study on adverse reactions of peginterferon alfa-2a in treatment of chronic hepatitis in adults and children].

OBJECTIVE: To investigate the scope and degree of short-term adverse reactions of peginterferon alfa-2a in treatment of chronic hepatitis in adults and children to provide basis for anti-viral treatment in clinical practice. METHODS: A prospective study was conducted in adults and children with chronic hepatitis treated with peginterferon alfa-2a. Meanwhile, the reactions in the patients were recorded with a table designed by ourselves and statistically analyzed. RESULTS: The short-term adverse reactions included increase in body temperature and aching pain in joints and muscles. The increase in body temperature was the major reaction and accounted for 54.11%. The increase in body temperature began to appear in 47.6% of the patients. The body temperature was 37.3 degrees C-38.9 degrees C in most of the patients and mediate and low increase was found in 85.4% of the patients, which was decreased to 70% in the 4th week. However, the percentage of patients with high temperature was increased from 14.5% in the 1st week to 30% in the 4th week. The increase of body temperature began to appear in 9-12 h and 3-5 h after injection of peginterferon alfa-2a in the 1st and later, respectively. The duration of fever was 3-4 h in most of the patients. It appeared once in 1 week after the rejection in most of the patients. For management of fever, cooling with medication was conducted in 45.5 % of the patients. CONCLUSION: The short-term adverse reactions in patients with chronic hepatitis treated with peginterferon alfa-2a include the increase in body temperature etc. The severity of the adverse reactions gradually reduces with continuation of the treatment. Of the adverse reactions, the increase in body temperature is the major (47.6%) and others only account for 1%-16.9%. The increase in body temperature is mainly transient and no management is needed in 50% of the patients. Since the "ladder-type" dose-adding method is used for administration of peginterferon alfa-2a in this group of patients, the adverse reactions are low in number and mild in degree.

[Peripheral blood T cell subsets and TH1/TH2 cytokines secretion in children with chronic hepatitis C virus infection].

OBJECTIVE: To determine the cellular immunological abnormalities in children with chronic hepatitis C virus infection. METHODS: (1) The quantity of the peripheral blood T cell subsets in 16 children with chronic hepatitis C virus infection and 10 healthy blood donors was detected by FACS. (2) The levels of the TH1/TH2 cytokines secretion of PBMC in patients and healthy blood donors were detected by ELISA. RESULTS: (1) Compared with normal controls, there was no significant difference in the percentage of CD4+ cells. The percentage of CD8+ cells was significantly higher than that of controls (P < 0.05). The percentage of CD3+ cells was higher and the ratio of CD4+/CD8+ cells was lower, but the difference was not significant (P > 0.05). (2) Compared with the cytokine level of normal control, the levels of IFN-gamma, IL-10 and TNF-alpha notably increased (P < 0.01) while IL-2, IL-4, and IL-12 were not detected in the culture supernatant of PBMCs from both normal control and patients. CONCLUSION: There is an imbalance in peripheral blood T cell subsets and disturbance in cellular immunity in children with chronic hepatitis C virus infection, which may be associated with HCV persistent infection.

[Analysis on prognostic factors of liver failure in children].

OBJECTIVE: To analyze the prognostic factors of liver failure in children. METHODS: The clinical data of 105 children with liver failure treated in the No. 302 Hospital in the past 17 years were retrospectively analyzed. The related factors were analysed by EXCELL 2000 and STATA 7.0, multivariate statistical analysis was performed by Logistic regression. RESULTS: (1) A total of 72 children died and the mortality was 68.6%. (2) Univariate statistical analysis showed that the factors significantly correlated with death were age, clinical type and stage of liver failure, decrease in prothrombin activity (PTA) and albumin (AIB) level, increase in serum level of total bilirubin (TBIL), appearance of deviation of TBIL and ALT, complications and hepatic encephalopathy. There was no significant difference between boys and girls. (3) There was no significant difference among etiological diagnoses such as HBV infection, Wilson's disease, and unknown pathogeny. (4) Multivariate statistical analysis showed that PTA (P = 0.000) and TBIL (P = 0.029) were independent risk factors of mortality of the children. CONCLUSION: The prognosis of liver failure in children is poor and mortality is high. PTA and TBIL might be useful for indicating prompt diagnosis and treatment to improve survival rate of the children with liver failure.

[An open-label pilot study evaluating the efficacy and safety of peginterferon alfa-2a combined with ribavirin in children with chronic hepatitis C].

OBJECTIVE: To evaluate the efficacy and safety of peginterferon alfa-2a plus ribavirin in the treatment of children with chronic hepatitis C (CHC) in China. METHODS: Totally 54 children with CHC were treated with peginterferon alfa-2a plus ribavirin from July 2003 to July 2004. The dose of peginterferon alfa-2a was 104 microg.(m2)-1 per week. An inductive treatment with interferon 1-3 MIU q.o.d for a week was given before peginterferon for the reduction of possible side effects. Initially 1/3 to 1/2 dose of ribavirin was given and then the was gradually increased to an ideal level of 15-20 mg.kg(-1).d(-1). RESULTS: The mean age of the patients was 11.3 years. Twenty three patients (42.6%) had received interferon plus ribavirin but the disease relapsed or did not respond to the treatment. The HCV of 70.8 percent of patients was genotype 1 and 14.8 percent of patients had a high viral load (>/=10(-6)/L). After 3-month treatment, 87.5% (42/48) and 8.3% (4/48) of the patients became HCV RNA negative or the viral load reduced by >/= 2 log, respectively, and only 8.3% (4/48) of the patients failed to respond. After 6-month treatment, 87.9% (29/33) and 6.1% (2/33) of the patients became HCV RNA negative or had a >/= 2 log reduction of HCV RNA, respectively, and only 6.1% (2/33) failed to respond. The adverse events were the typical of those reported in the treatment with interferon and ribavirin. Pyrexia occurred in 48.1% of patients, fatigue in 46.3%, decreased appetite in 9.3%, and skin rash in 3.7%. The absolute neutrophil counts of 51 patients (94.4%) were reduced to

[Study on treatment effectiveness and safety in children with chronic hepatitis B or C using bicyclo tablets].

BACKGROUND: To evaluate treatment effectiveness and safety of bicyclo tablets in children with chronic hepatitis B or C. METHODS: A randomized controlled trial was conducted in 148 children with chronic hepatitis B or C for evaluating safety, tolerability, and efficacy of treatment with bicyclo tablets or Hugan tablets. Children in therapy group were treated with bicyclo tablets and control group treated with Hugan tablets. RESULTS: (1) ALT and AST level decreased more prominently in therapy group than in control group (P<0.01). (2) Bicyclo was more effective than Hugan tablets (P<0.01). (3) Symptoms were ameliorated more prominently in bicyclo group than in control group (P<0.01). (4) Both groups had no significant adverse events. CONCLUSION: Satisfactory therapeutic effect and safety were obtained with bicyclo tablets in children with chronic hepatitis B or C.

Pathological changes and clinical manifestations of 1020 children with liver diseases confirmed by biopsy.

BACKGROUND: Liver biopsy plays an important role in accurate diagnosis of various liver diseases in children and liver damages caused by systemic illnesses. This study was designed to evaluate the value of liver biopsy in diagnosis of liver diseases in children and explore the relationship between their pathological changes and clinical manifestations. METHODS: One-second liver biopsy was performed in 1023 pediatric patients with liver diseases at our department from 1983 to 2000. Diagnosis of viral hepatitis was based on the diagnostic criteria formulated by the Chinese Society of Infectious and Parasitic Diseases in 1995. Inflammatory changes of the liver were graded from 0 to 4 (G0-4). RESULTS: Liver biopsy was performed successfully in 1020 patients including 135 infants and young children, of whom 90% were hospitalized patients with chronic liver diseases. Hepatitis virus was the leading cause for chronic liver diseases, among which hepatitis B was detected in 75.4% of the patients. Sixty-nine patients showed liver impairment induced by disorders relevant to that metabolism, Wilson's disease, and glycogen storage disease. Liver inflammatory injury (

[Clinical features of liver failure in children].

OBJECTIVE: To analyze the etiology, clinical and laboratory characteristics of hepatic failure in 105 children. METHODS: The clinical data of 105 children with hepatic failure treated in our hospital from January 1986 to June 2003 were retrospectively analyzed by EXCELL 2000 and t test. RESULTS: (1)Of the 105 children with hepatic failure, 9 were cases with fulminant hepatic failure, 38 with subacute hepatic failure and 58 with chronic hepatic failure. (2)Morbidity was the highest in 7-12 years old children (43/105, 41.0%) followed by infants (30/105, 28.6%). (3)CMV infection could be confirmed in 9 infants (30.0%), etiological diagnosis was not possible in 13 infants (43.3%). Etiological diagnosis could be confirmed in children over 1 year of age, which included hepatitis B (n=22, 29.3%), Wilson's disease (n=15, 20.0%), hepatitis A (n=10,13.3%). Etiology in 21 cases (28.0%) could not be confirmed. (4)Seventy-one cases (67.6%) had ascites, 34 of them (47.9%) had spontaneous peritonitis. Thirty-five cases were complicated with other infections. The commonest complication was pulmonary infection and sepsis was the next. Fifty-one cases (48.6%) had hydroelectrolyte imbalance. Forty-eight cases (46.2%) had hepatic encephalopathy, which may be subclinical in children under three years of age. (5)The incidence of hypoglycemia was 77.2%(71/92). CONCLUSION: The etiology of liver failure was related to age. CMV infection was the commonest in infants. HBV, HAV infection was the commonest in children over 1 year of age and Wilson?s disease was the next. It is necessary to prevent and manage the associated complications as early as possible such as spontaneous peritonitis, hepatic encephalopathy, hydroelectrolyte imbalance and hypoglycemia etc.

[Clinical features of hepatitis A in 1,629 children].

BACKGROUND: To investigate the clinical features of hepatitis A in 1 629 children under 14 years of age treated in our department at various periods of time. METHODS: The patients were divided into two groups: 1. Group A consisted of 883 patients treated from January 1984 to December 1990; 2. Group B consisted of 746 patients treated from January 1991 to December 2000. The clinical data of all the patients were retrospectively analyzed. RESULTS: 1. The average age was 7.17+/-3.27 and 8.78+/- 3.28 years (chi2=0.54, P>0.05) and the mean course of disease 26.25+/-16.96 and 25.65+/-12.58 days (chi2=0.29, P>0.05). 2. Double peak or multi-peak serum ALT was found in 89 patients. Four peaks of serum ALT was found in one patient. 3. HBsAg was found positive in 143 patients (8.80%). The mean course of disease was 34.40+/-25.86 and 25.20+/-15.43 days (chi2=146.5, P<0.001) in HBsAg positive and negative patients, respectively. 4. Liver puncture biopsy in 26 patients with hepatitis A showed that there was piecemeal necrosis in 2 patients. CONCLUSIONS: 1. There was no significant delay in age of children with HAV infection in 1990s. There was no marked difference in the course of disease between the patients simultaneously receiving various drugs and those receiving one or two drugs. 2. The double peak or multi-peak of serum ALT in patients with hepatitis A might be related to liver damage caused by HAV and immune mechanism. 3. The major type of virus for combined infection in patients with hepatitis A is HBV. The course of disease was prolonged with combined infection of HBV. 4. Piecemeal necrosis might be seen in the liver of a small proportion of patients with hepatitis A alone, which may not be enough to suggest chronicity.