Post-transfusion chronic hepatitis C in children

Two hundred and twenty-six patients who received blood products for open-heart surgery in childhood were screened by a second-generation enzyme-linked immunosorbent assay and with surrogate markers for hepatitis C virus (HCV) infection, such as alanine aminotransferase (ALT). Twenty-two (14%) of the 161 recipients who received blood products before 1989 and none of the subjects who had received blood products after 1990 (the year that the blood bank began to screen for HCV antibody) were HCV seropositive. Virologic and histologic studies showed that 10 (45%) of 24 seropositive patients had persistent hepatitis C virus infection, many with ongoing hepatitis. The remaining 12 seropositive patients with absent HCV RNA had normal ALT levels, indicating resolved hepatitis C infection. Enrolment in screening is important to detect chronic hepatitis C in children who received blood products prior to screening of blood donors for HCV antibody.     

Efficacy of interferons in treating children with chronic hepatitis C

Twenty-two children with chronic hepatitis serologically positive for hepatitis C virus (HCV) were treated with interferon-α (IFN-α). Liver biopsy showed chronic active hepatitis in 13 and chronic persistent hepatitis in 9 patients. A sustained clearance of HCV was observed in 8/22 children 12 months after the administration of IFN-α for 26 weeks, associated with normalization of HCV core antibody. Of these eight patients six had HCV genotype III and two HCV genotype II or IV. Hepatitis relapsed in seven other patients after completion of IFN-α with an increase in HCV core antibody titre, five with HCV genotype II, and two with HCV genotype III or IV. A second course of IFN-α suppressed the reactivation of HCV in all seven patients. Three of seven responders who relapsed after the first course remained negative for HCV RNA 12 months after their second course of IFN-α. However, the remaining four patients with HCV genotype II again relapsed after completing their second course of IFN-α. Seven children with the HCV genotype II resistant to IFN, including 8 weeks of IFN-β administration, and showed no significant reduction in HCV core antibody titre. Conclusion The genotype of HCV (III) and a reduction in the core antibody titre appear to be useful parameters for predicting the response to IFN-α therapy. Received: 12 September 1996 and in revised form: 28 January 1997 / Accepted: 11 February 1997     

Treatment of chronic hepatitis C in children

Since the discovery of hepatitis C virus (HCV) in 1989, significant advances have been made in our understanding of this important viral pathogen. Children at risk for HCV infection include recipients of potentially contaminated blood products and organ transplants, and infants born to HCV-infected mothers. Chronic HCV infection is usually asymptomatic in children but active hepatitis, cirrhosis and hepatocellular carcinoma can occur. The development of treatment strategies for chronic hepatitis C in children has directly evolved from clinical trials in adults. Sustained virologic response, defined by undetectable HCV RNA in serum 24 wk after completion of treatment, occurs in approximately 36% of children treated with conventional interferon alone and in about 50% of those given conventional interferon in combination with ribavirin. Pegylated interferon-based treatment regimens are better than those based on conventional interferon in adults but little is known about pegylated interferon in children. Factors associated with a favorable response to antiviral therapy in children are similar to those in adults and include infection with HCV genotype 2 or 3 and low pretreatment serum HCV RNA levels. Treatment related adverse events in children include 'flu-like' syndrome, fatigue, anorexia, weight loss, depression, anemia, leukopenia and thrombocytopenia.     

Spontaneous remission of chronic hepatitis C in children

The clinical course of 48 children with chronic hepatitis C (33 boys, 15 girls; mean age: 12.2 years) was monitored for more than 3 years to clarify its natural course. All patients were positive for the second-generation antibody to hepatitis C virus (anti-HCV) and for serum hepatitis C virus (HCV) RNA. All but one patient had a history of blood transfusion. Serum levels of alanine aminotransferase (ALT) had been abnormal for more than 1.5 years. Spontaneous remission defined as a biochemical remission lasting more than 1 year in association with the disappearance of serum HCV RNA, occurred in 4 (8.3%), however, in 25%, HCV RNA was still detectable in the liver even after its disappearance from serum. In this patient, the level of antibody to HCV core antigen (anti-HCV core) did not decrease significantly and serum HCV RNA eventually reappeared. The serum titre of HCV RNA in the 4 children with spontaneous remission was lower than in the remaining 44 children. Spontaneous remission may occur in children with chronic hepatitis C in whom the serum titre of HCV RNA is low and serum level of anti-HCV core decreases significantly. Assessment of the intrahepatic HCV RNA is necessary to confirm complete remission. Conclusion A low serum titre of HCV RNA and a significant decrease in the serum titre of anti-HCV core were associated with spontaneous remission in children with chronic hepatitis C. Intrahepatic HCV RNA assessment is necessary to confirm complete remission. Received: 9 April 1996 and in revised form: 8 April 1997 / Accepted: 15 April 1997     

Hepatitis C virus antibodies in a long-term follow-up of beta-thalassaemic children with acute and chronic non-A non-B hepatitis

The presence of antibodies toward hepatitis C virus (HCV) was examined in 78 polytransfused betathalassaemic children. The anti-HCV status was correlated with acute and chronic non-A non-B (NANB) hepatitis that developed during a follow up of about 13 years. Anti-HCV was present in 83.3% of children with acute NANB hepatitis and in 82.9% of those with chronic NANB hepatitis. The percentage of chronic evolution was 56.7% for acute anti-HCV positive NANB hepatitis and 50.0% for anti-HCV negative NANB hepatitis. The long-term persistence of anti-HCV antibodies did not correlate with chronic evolution of liver infection in thalassaemic patients. Histological features of chronic hepatitis showed little or no difference between HCV associated or non-associated liver disease. The multifactorial liver injury in beta-thalassaemic children explains the high prevalence of cirrhosis (about 30%) observed in these patients with NANB hepatitis. On the other hand, independent of liver disease, some patients never seroconverted during the follow up in spite of the high number of transfusions suggesting the existence of non-responders.     

Management of chronic hepatitis B and C virus infections

Hepatitis B and C virus (HBV and HCV) infections present an important health problem causing significant morbidity and mortality on a worldwide scale. The younger the subjects infected, the higher the risk predisposing to progression towards chronic infection. Treatment of chronic HBV and HCV infections is aimed at reducing hepatic inflammation and thus improving the symptoms, decreasing the likelihood of long-term sequelae such as hepatocellular carcinoma, and increasing the survival rate. Interferon accelerates the spontaneous course of chronic HBV infection in children with greater disease activity and lower levels of replication. There is limited information on the use of lamivudine and its long-term benefit in children with chronic HBV infection. The response of combination therapy with IFN and ribavirin in children with chronic HCV infection is still under investigation. The long-term clinical and virological effects of various drugs used in chronic HBV and HCV infections on children remain to be evaluated.     

Antenatal hepatitis C virus screening and management of infected women and their children: policies in Europe

A postal survey of 31 European centres was conducted to document current practices regarding screening and management of hepatitis C virus (HCV)-infected pregnant women and their children. Antenatal HCV prevalence was low. Universal antenatal screening programmes were in place in ten centres, selective screening occurred in ten other centres, two did not specify the type of policy, and there was no screening programme in nine centres. Numbers of HCV-infected children were low. Breastfeeding was recommended for infants of infected mothers in ten centres, discouraged in ten centres, in three centres women were merely informed of the risks, and there were no guidelines in eight centres. Polymerase chain reaction was available in all centres. In 17 centres children born to HCV-infected women were seen every 3 months for at least the 1st year. Conclusion The optimum antenatal hepatitis C virus screening approach and the appropriateness of breastfeeding recommendations are unclear and this survey highlights the lack of uniformity in current practice. Received: 15 January 1999 / Accepted: 10 March 1999     

Interferon for chronic hepatitis C in patients cured of malignancy

Six patients with chronic hepatitis C who were cured of malignancy were treated with recombinant interferon-alpha at the dose of 4 MU/m² for 12 months; the post-treatment follow up period was 12 months. Therapy was stopped within 6 months in three patients because of persistently abnormal alanine aminotransferase levels. In the remaining three patients, a complete normalization of alanine amnotransferase levels was obtained during treatment but it was not maintained after the end of interferon therapy. In addition, no patient cleared hepatitis C virus ribonucleic acid in serum. These results suggest that recombinant interferon is not effective in patients with chronic hepatitis C who were cured of a previous malignancy.     

Diagnosis and management of paediatric hepatitis C virus infection

Hepatitis C virus (HCV) infection in children is uncommon and there are few guidelines indicating optimal management. It is estimated that 125-250 children are infected vertically with HCV in Australia each year and very few of these children are diagnosed and followed medically. Without accurate diagnosis and follow up, these children cannot be offered optimal care, and are at risk of presenting in adult life with significant liver pathology and long-term sequelae.     

Shift in the buoyant density of hepatitis C virus particles in infants infected by mother-to-infant transmission

BACKGROUND: Hepatitis C virus (HCV) particles in sera can be divided into two classes: low-density free particles and high-density immune complex particles. Previous studies have revealed that the clinical progression of HCV infection is closely associated with the occurrence of the former class, rather than the latter, in an experimental chimpanzee model and in HCV-infected adult cases. METHODS: To verify this concept in infantile cases, we prospectively analysed HCV particle populations, fractionated according to buoyant density, in serum samples from five infants infected by mother-to-infant transmission. RESULTS: In all five cases, HCV particles were predominantly high density at the age of one month. In four of five cases, low-density HCV particles became predominant in association with a decrease in maternally transmitted antibody levels. In one case, in which high serum levels of alanine aminotransferase persisted, low-density particles were predominant between the ages of 3 and 9 months, in three consecutive samples. In other cases, in which infants were asymptomatic or had transient hepatitis, low-density HCV particles were predominant at only one sampling point or not at all throughout the follow-up period. CONCLUSIONS: Maternal antibody transmitted via the placenta reacts with the HCV particles in infants infected through vertical transmission. A decrease in maternal antibody levels results in an increase in low-density free virions. It is suggested that low-density particles play an important role in liver inflammation.     

Seroprevalence of hepatitis B, hepatitis C and human immunodeficiency virus antibodies among multitransfused thalassaemic children in Shiraz, Iran

OBJECTIVE: To evaluate the rate of seropositivity to hepatitis B and C and human immunodeficiency virus (HIV) infections among children with beta-thalassaemia major receiving multiple transfusions in Shiraz, Iran, compared with healthy controls. METHODOLOGY: The study was performed during 1999-2000 on multitransfused children with beta-thalassaemia major registered by the Shiraz Thalassaemia Society. Hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies (Ab) and HIV Ab were checked using a second-generation enzyme-linked immunosorbent assay (ELISA). Positive tests were confirmed by western blots. Healthy blood donors were used for the control group. RESULTS: Hepatitis B surface antigen, anti-HCV Ab and HIV Ab were positive in four of 755 (0.53%, 95% confidence interval (CI)=0.17-1.3), 73 of 466 (15.7%; 95% CI=12.6-19.2) and none of 466 patients tested, respectively. Positive sera for HBsAg, anti-HCV Ab and HIV Ab were found in 85 (1.07%), 47 (0.59%) and 27 (0.34%) of 7879 control children, respectively. The rate of anti-HCV Ab was significantly higher in patients than in the control group (P < 0.0001). In patients, the rate of positive anti-HCV Ab was significantly higher than the rate for positive HBsAg (P < 0.0001). CONCLUSION: It is concluded that HCV is the current major problem in multitransfused children with thalassaemia major and more careful pretransfusion screening of blood for anti-HCV must be introduced in our blood banks.     

要重视儿童慢性病毒性肝炎的诊断和治疗

<正>多种病毒感染均可引起肝脏炎症,然而一般所称病毒性肝炎常仅指由嗜肝病毒感染引起者。迄今为止,有明确临床意义的嗜肝病毒包括甲型肝炎病毒(HAV)、乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)、丁型肝炎病毒(HDV)     

The burden of hepatitis C virus infection in children: estimated direct medical costs over a 10-year period

OBJECTIVE: To quantify the burden of pediatric hepatitis C virus (HCV) disease over the coming decade. STUDY DESIGN: Using national Census results and published and unpublished data, we constructed estimates of HCV prevalence, incidence, rate of vertical transmission, sustained viral response (SVR), and severe complications of infection. Using these figures, we generated a projection model for pediatric HCV outcomes, and we then performed a sensitivity analysis by altering the rates of fibrosis development and SVR. RESULTS: A prevalence of 23,048 to 42,296 pediatric patients with chronic HCV combined with 7200 new cases from vertical transmission was used for further calculations. Over the next decade, estimated screening costs were 26 million US dollars, monitoring costs ranged from 117 million US dollars to 206 million US dollars, and treatment costs ranged from 56 million US dollars to 104 million US dollars. CONCLUSIONS: To date, pediatric HCV has received relatively little attention, but it will have a significant economic impact over the next 10 years if changes in practice are not made.     

Virus genotype 1b and long-term response to interferon alpha monotherapy in children with chronic hepatitis C

Interferon alpha (IFN-) remains the basic modality in the treatment of chronic hepatitis C in children, but the effects of therapy are still unsatisfactory. The aim of this study was to evaluate parameters linked to IFN- response within a 2-year period. Human C virus (HCV) infected children (n=34) were subdivided into IFN-treated (n=20) and IFN-untreated (n=14 control) groups. The IFN-treated group received a dosage 3 MU of IFN- three times a week for 24 weeks. Liver biopsy was performed in all IFN-treated children and the HCV genotype was determined before the start of the study. Patients were sequentially screened for alanine transaminase (ALT) activity and tested for the presence of HCV-RNA in serum. All patients had either mild persistent or moderate active hepatitis, which was diagnosed from the liver biopsy. In the IFN-treated group ALT normalisation was observed by the end of treatment in 9/20 patients, but after 6 months 10 patients (50%) had sustained ALT normalisation and in 4 of them the virus was eliminated. They continued to show these features up to the end of the observation period (2 years). Eighteen out of 24 children tested had 1b genotype of virus. Out of 10 responders, all patients who were clear of HCV had the 1b genotype. The median age of responders (6.0, range 3.8–16) was significantly lower than non-responders (14.0, range 4–15) In the control group none of the children were clear of HCV-RNA. Conclusion: The negative predictive effect of HCV genotype 1b in the course of IFN- treatment may be not valid in children and other features have to be taken into account in the assessment of the efficacy of therapy.Abbreviations HCV human C virus - RNA ribonucleic acid - PCR polymerase chain reaction - ALT alanine aminotransferase - RBC red blood cells - HBsAg hepatitis B surface antigen - ELISA enzyme linked immunosorbent assay - CMV cytomegaly virus - IFN interferon - MU mega units - ETR end of treatment response - SR ALT sustained biochemical (ALT) response - HAI histological activity index - R responders - NR non-responders - U/l units per litter - CPH chronic persistent hepatitis - CAH chronic active hepatitis - APC antigen presenting cells - MHC major histocompatibility complex - ALL acute lymphoblastic leukaemia - CML chronic myelogenous leukaemia     

心脏直视术后心肌肌钙蛋白Ⅰ的转归及其影响因素相关性分析

目的探讨心脏直视术后心肌肌钙蛋白Ⅰ(TnTi)的转归,并就其与各影响因素作相关性分析。方法收集57例中低温体外循环下行心内畸形纠治术后患儿,年龄(2.34±2.11)岁.体重(10.92±4.59)kg。按病种不同分为A组(法洛氏四联症组,n=31)和B组(室间隔缺损组,n=26)。分别测定术前、主动脉开放5min、6h、12h、24h、48h、72h7个时相点血清TnTi浓度和心功能评分(score),记录体外转流时间(TT)、主动脉阻断时间(CT)以及监护窒预后情况。结果①与术前相比,主动脉开放5min时TnTi显著升高达到峰值(P<0.01),72h后仍高于术前水平(P<0.01);A组患儿血清TnTi显著高于B组患儿,两组cTnTi峰值分别是术前的118和55倍。②患儿TT、CT、手术机械损伤部位及程度与TnTi浓度呈正相关,相关系数分别为0.51、0.51、0.35(P均<0.01)。score与TnTi浓度呈负相关,相关系数为-0.52(P<0.01)。③2.3μg／L是预估患儿术后心功能恢复以及指导临床治疗的临界值。结论TnTi是心脏直视术后评价心肌受损的可靠指标,对反映患儿术后心功能的恢复有一定参考价值。     

Alpha interferon and lamivudine combination therapy for chronic hepatitis B in children

BACKGROUND: Lamivudine is a new alternative therapeutic agent for chronic hepatitis B, in which alpha interferon (IFN-alpha) monotherapy is not successful enough. Published reports have revealed no satisfactory data on IFN-alpha and lamivudine combination therapy in children. The aim of this study is to investigate the efficacy and safety of this combination therapy in children with chronic hepatitis B. METHODS: Children with chronic hepatitis B were given either IFN-alpha and lamuvidine (group 1, n = 47) or IFN-alpha alone (group 2, n = 30). Alpha interferon was administered as 5 million U/m2 s.c., thrice a week for 6 months and lamivudine 4 mg/kg per day p.o., maximum 100 mg, for 1 year. Clinical examination was performed; blood cell counts and serum alanine aminotransferase (ALT) and amylase were studied at each visit. At the third, sixth and twelfth month, serological markers were determined. RESULTS: End of therapy response was achieved in 19 (40.4%) patients in group 1 and in 14 (46.7%) children in group 2 (P > 0.05). In group 1, pretreatment serum ALT and hepatic activity index (HAI) were statistically higher in children who responded to therapy (P < 0.005). In group 2, mean serum ALT was higher and hepatitis B virus (HBV) DNA was lower in responders. Sustained response rate was 40.4 versus 43.3% in two groups. CONCLUSION: The response rate of IFN-alpha and lamivudine combination therapy in children with chronic hepatitis B was similar to that of IFN-alpha monotherapy. High ALT level and HAI, rather than low HBV-DNA level were found to be important predictors of response.     

Growth in the first 5 years of life is unaffected in children with perinatally-acquired hepatitis C infection

OBJECTIVES: To identify the effect of vertical hepatitis C virus (HCV) infection or exposure on growth in childhood. STUDY DESIGN: Children (n=1203) born to HCV-infected mothers were followed up from birth prospectively in centers of the European Paediatric Hepatitis C virus Network. Z-scores compared height- and weight-for-age in HCV-infected and -uninfected children, adjusting for other factors using linear regression. We also quantified the effect of maternal chronic infection with HCV on childhood growth. RESULTS: There was no significant effect of vertical HCV infection on growth (height P=.223, weight P=.095) nor a significant effect of maternal chronic infection with HCV (height P=.733, weight P=.274). Prematurity and maternal injecting drug use were associated with a significant reduction in height (P < .001) and weight (P < .001) in all HCV-exposed children. CONCLUSIONS: This population of HCV exposed infants has higher rates of maternal injecting drug use and prematurity than standard populations and so there are implications for growth of these children, but this is not a direct result of HCV infection or exposure to chronic maternal HCV infection.