小儿庚型肝炎的探讨

为了探讨一种新型肝炎病毒，即庚型肝炎病毒（ｈｅｐａｔｉｔｉｓＧｖｉｒｕｓ，ＨＧＶ）在小儿中的感染特点，检测了３６例肝炎患儿及１６例健康体检儿童血清中ＨＧＶ－ＲＮＡ（套式逆转录ＰＣＲ法）。结果表明，３６例肝炎中有１１例ＨＧＶ感染者，其中６例合并慢性ＨＣＶ感染（３例接受过干扰素治疗），２例合并慢性ＨＢＶ感染，２例为慢性非Ａ－Ｅ肝炎，１例合并ＨＢＶ＋ＨＡＶ感染。１６例健康儿童均阴性。ＨＧＶ感染率在血制品输入者１０例中７例阳性，在未输入者２２例中３例阳性（两者比较，Ｐ＜０．０１），在血制品使用情况不明者２０例中１例阳性。提示输入血制品是小儿ＨＧＶ感染的主要途径，但不排除还有其他途径，感染者主要为慢性肝炎患儿，干扰素的疗效有待进一步研究     

Hepatitis C and G Virus infections in polytransfused children

The prevalence of hepatitis C virus (HCV) and a newly identified hepatitis G virus (HGV) and their clinical significance were studied in 42 polytransfused Taiwanese children. Serological assays for antibodies against HCV (anti-HCV) and polymerase chain reaction for serum HCV ribonucleic acid (RNA) and HGV RNA were performed. The prevalence of anti-HCV and HGV RNA was 17% and 14%, respectively in 42 polytransfused children. Anti-HCV seropositives had a significantly higher mean age, peak serum transaminase level, and longer transfusion duration than seronegatives, while children with HGV infection usually had no or only mild hepatitis activities. The prevalence of anti-HCV dropped sharply after implementation of anti-HCV screening, however the prevalence of HGV viraemia remained unchanged. Conclusion HGV infection is not uncommon in polytransfused Taiwanese children and the virus does not cause significant hepatitis compared to HCV infection. Current blood donor screening for anti-HCV can effectively protect polytransfused children from HCV infection but the impact of additional screening for HGV markers awaits further studies. Received: 10 October 1996 and in revised form: 26 November 1996 / Accepted 26 November 1996     

High rate of maternal-infant transmission of hepatitis G virus in HIV-1 and hepatitis C virus-infected women

The prevalence of hepatitis G virus (HGV) infection was investigated in 56 mothers with both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection. Thirty-three (58.8%) women had markers of HGV infection, including 7/15 (46.6%) with no history of parenteral exposure to blood. Sixteen (48%) had HGV RNA in serum by a polymerase chain reaction assay, and 17 (52%) had antibody to E2 viral protein. No woman was positive for both markers. Of 20 infants born to the 16 mothers with HGV viremia, 9 (45%, 95% CI 34-56%) acquired the infection. No infected child seroconverted to HGV during the first year of life. At the latest visit (mean: 37.1 mo, range: 9-89 mo) 7 children were still seronegative HGV RNA carriers, 1 was both RNA- and antibody-negative, while 1 RNA-negative child had developed the E2 antibody. Of the 20 HGV-exposed infants, 2 contracted HCV and 1 HIV-1 (all 3 with HGV coinfection). No abnormalities in clinical findings and ALT levels were observed throughout the follow-up period in the six children with HGV infection alone. Our findings show that HGV infection is widespread among HIV-1- and HCV-infected women. Maternal-infant transmission of HGV is common and occurs independently from that of HIV-1 and HCV in women with triple infection. Most perinatally HGV-infected children develop persistent infection with no clinical or biological signs of liver damage, at least in the first years of life.     

Hepatitis C prevalence in children with perinatal human immunodeficiency virus infection enrolled in a long-term follow-up protocol

OBJECTIVE: To evaluate the prevalence of hepatitis C virus (HCV) infection in children with perinatal human immunodeficiency virus (HIV) infection. DESIGN: Cross-sectional substudy. SETTING: Multicenter study from 41 sites in the United States. PATIENTS: Children with perinatal HIV infection were randomly selected from a large, long-term, follow-up protocol. MAIN OUTCOME MEASURE: Hepatitis C infection was defined as having positive test results on both HCV antibody and HCV RNA assays. RESULTS: Five hundred thirty children enrolled in the substudy; definitive HCV test results were available for 525 children. Eighty-three percent were of a minority race or ethnicity.They were equally distributed by sex, had a median age of 10.7 years, and were relatively healthy, with 75% having CD4+ lymphocyte counts greater than 500 cells/mm3. Eight of 525 children (1.5%; 95% confidence interval [CI], 0.7%-3.0%) infected with HIV were coinfected with HCV. In contrast, the rate of HCV infection in a serosurvey of more than 2700 children aged 6 to 11 years from the National Health and Nutrition Examination Survey was 0.2% (95% CI, 0.04%-0.6%). In our study, there were no differences between children coinfected with HIV and HCV and those without HCV infection in terms of demographic characteristics, CD4+ or CD8+ T-lymphocyte counts, HIV 1 RNA levels, preterm or mode of delivery, or liver disease; however, the number of children coinfected with HIV and HCV was small. CONCLUSION: While HCV prevalence infection rates are low in children with perinatal HIV infection, they are 8 to 10 times higher than reported in HCV serosurveys of children in the United States.     

The prevalence of GB virus C/hepatitis G virus RNA among healthy and HCV-infected Catalan children

GB virus C (GBV-C) is a blood-borne flavivirus. The prevalence of GBV-C viremia among healthy adults is 0.5% to 4% and, to date, no disease has been definitely associated with GBV-C infection. We conducted a cross-sectional study to evaluate GBV-C viremia prevalence in a group of 327 healthy children with normal alanine amino transferase (ALT) levels (Group A) and elevated ALT levels (Group B) of unknown origin, and among 38 pediatric patients with mother-to-child-transmitted hepatitis C virus (HCV) infection (Group C). No statistically significant differences were observed between prevalences in Groups A and B (2.2% vs 6.7%, p = 0.06). None of the children in Groups A or B who tested positive for GBV-C RNA showed any clinical symptoms. The prevalence of GBV-C viremia in Group A was lower than for patients in Group C (2.2% vs 13.2%, p = 0.007); no differences were observed in HCV infection characteristics between those patients who were co-infected with GBV-C and those who were not. In conclusion, while GBV-C viremia is more frequent among HCV-infected pediatric patients, it is neither associated with liver disease nor has any influence on HCV-related chronic hepatitis.     

Hepatic dysfunction in children with acute lymphoblastic leukemia in remission: relation to hepatitis infection

BACKGROUND: Viral hepatitis is a cause of hepatic dysfunction in children with ALL in remission during maintenance therapy is debated. The aims of the current study were (1) to explore the incidence of hepatic dysfunction in a group of children (Egyptian and Saudi) with ALL under maintenance therapy, (2) to study the prevalence of hepatitis B (HBV) and/or C (HCV) infection and their contributions to chronic liver disease that might be induced by maintenance therapy. PROCEDURE: The current study included 105 children with ALL (54 Egyptian and 51 Saudi). All eligible patients had been on maintenance therapy for at least 12 months and all had serial assessments of liver function. These included determination of total bilirubin, AST, ALT, and alkaline phosphatase. Markers for HBV and HCV including HBsAg, anti-HBC, and anti-HCV and for some patients HCV RNA by PCR were studied. Percutaneous liver biopsy was performed for a group of children. RESULTS: The prevalence of hepatitis infection (HBV and/or HCV) among Egyptian children was found to be high (43/54-80%). Only five Saudi children had evidence of exposure to HBV (5/51-9.8%), P<0.0001. During the period of study, 22 Egyptian patients vs. four Saudi patients (41 vs. 7.8%, P<0.0001) experienced at least one episode of elevation of liver enzymes, three times the upper limit of normal or more. Twenty-six of the 48 patients (54%) with HBV and/or HCV infection had episodes of elevated liver enzymes, while there was no occurrence among the patients negative for HBV and HCV. In patients with HBV infection, the presence of HBsAg was strongly associated (100%) with elevated liver enzymes. Histopathologic examination of liver biopsies obtained from 35 patients revealed that all five patients negative for HBV and HCV had normal liver biopsies in spite of being under maintenance therapy. CONCLUSION: In children undergoing treatment for ALL, elevations in liver enzymes may be primarily due to hepatitis viruses. However, maintenance therapy using known hepatotoxic drugs, may have additive deleterious effects. Liver enzymes are normalized in affected patients when maintenance therapy is temporarily suspended.     

Hepatitis C virus infection and interferon therapy in patients with Down syndrome.

BACKGROUND: The clinical features of hepatitis C virus (HCV)-associated liver diseases, or the efficacy of interferon (IFN) therapy in children with Down syndrome (DS) remain to be elucidated. The purpose of the present paper was to survey the features of liver diseases in this subset of children and evaluate the efficacy of IFN treatment in those patients. METHODS: A questionnaire was sent to 41 members of the Japan Society of Pediatric Hepatology. Ten of them reported on 11 patients with DS who had concomitant chronic HCV infection, providing information on liver disease and the response to IFN treatment. RESULTS: Interferon therapy of 24 weeks duration using natural IFN-alpha was instituted in six of the 11 patients with DS, but none of the six patients cleared HCV-RNA from their serum. Among 12 age- and sex-matched control children who were treated with IFN using the same regimen against chronic HCV infection, half of them had a favorable response to IFN therapy with a sustained clearance of HCV-RNA from their serum. The major baseline features including alanine aminotransferase levels, HCV genotype and viral load were not apparently different between the six patients with DS and the 12 controls. CONCLUSIONS: IFN therapy for HCV infection in patients with DS may be unfavorable as compared with non-DS children.     

TT virus infection in healthy children and in children with chronic hepatitis B or C

BACKGROUND: The existence of a novel human virus, designated TT virus (TTV), has been reported in association with acute and chronic liver disease of unknown cause. OBJECTIVES: To evaluate the prevalence and clinical significance of TTV infection in childhood. STUDY DESIGN: Sera from 104 healthy children, 85 patients with chronic hepatitis B (HBV) and 29 with chronic hepatitis C (HCV), were tested by polymerase chain reaction with primers corresponding to conserved regions within a part of ORF 2. To characterize polymerase chain reaction products, TTV isolates from 15 subjects were directly sequenced. RESULTS: TTV DNA was detected in 22 (21%) of 104 healthy children and in 55 (65%) of 85 and 20 (69%) of 29 HBV- and HCV-infected individuals, respectively. No significant difference was observed in aminotransferase levels of HBV- or HCV-infected patients with or without TTV coinfection. Sequence analysis showed a high degree of genetic heterogeneity between TTV isolates. CONCLUSIONS: A striking difference was found in the prevalence of TTV between healthy children and patients with chronic HBV or HCV infection (P <.0005). However, based on these results, TTV alone or as coinfection does not seem to cause or exacerbate liver damage in childhood.     

Serum levels of hepatitis C virus RNA in infants and children with chronic hepatitis C.

BACKGROUND: The role of serum hepatitis C virus (HCV) load in infectivity, disease activity, and response to interferon treatment has been investigated in adults, and controversial results have been obtained. Little is known about HCV load in infants and children with HCV infection. PURPOSE: To investigate the relation between HCV load in serum and features of associated liver disease in infants and children with HCV infection. METHODS: Hepatitis C viral load was investigated in serial samples in 43 children with chronic HCV infection, including 32 patients aged 4 to 16 years infected by different routes and 11 vertically infected infants observed prospectively since birth. RESULTS: Overall viremia ranged between 2.7 and 6.9 log copies/ml (median, 5.56 log/ml) and fluctuated slightly during the follow-up. Median HCV RNA levels did not significantly differ among infants, children, and adolescents. Viral load was also independent of sex, route of infection, clinical manifestation, alanine aminotransferase levels, and liver histology. All 11 perinatally infected children became chronic HCV carriers, whatever their initial viral load; retrospective testing of sera taken in the first day of life in three infants showed high viremia levels. CONCLUSIONS: Viremia levels observed in children were similar to those reported in adults, were independent of age, biochemical activity of liver disease, and chronicity of infection. They were also relatively stable, suggesting that serial measurement of viral load is useless in untreated infants and children. The detection of viremia at birth in children in whom chronic hepatitis developed later suggests the possibility of in utero infection.     

Hepatitis C in children: a quaternary referral center perspective

INTRODUCTION: Chronic hepatitis C virus (HCV) infection affects 0.3% of children in the United States, and the general impression is that it has a benign course in childhood. We analyzed a pediatric population with chronic HCV in a quaternary referral center. MATERIAL AND METHODS: This is a retrospective clinical review comprising all patients with chronic HCV referred to the Pediatric Liver/Liver Transplant Program between January 1999 and December 2004. RESULTS: Ninety-one patients (52% female; mean age, 9 years) were assessed. Eight-three percent of the patients were genotype 1. Twenty-one patients received/are receiving interferon and ribavirin for chronic HCV (treatment indications--advanced disease, 9; clinical trial, 6; genotype 2, 2; social, 2; prerenal transplant, 1). Eight (53%) of 15 patients, who have completed therapy and follow-up, achieved sustained viral response. Seven of 91 patients had cirrhosis at presentation (mean age, 11.7 years). Four underwent liver transplantation, all experienced HCV recurrence, 2 died, 1 was retransplanted, and 1 has compensated cirrhosis. CONCLUSION: Although, in general, HCV in children has a slow progression, there are cases with an accelerated course and early development of cirrhosis requiring liver transplant. Hepatitis C virus recurs universally after transplant, and its prognosis is usually poor; therefore, the most promising long-term approach is to clear this infection before transplantation.     

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.     

Transfusion-transmitted virus prevalence in Turkish patients with thalassemia

In hematology patients on chronic transfusion regimes, liver diseases are frequent, and mostly related to the agents transmitted by blood products and concominant iron deposition in liver. Besides hepatitis B (HBV) and C (HCV) viruses, new viral agents like hepatitis G virus (HGV) and TorqueTeno virus (TTV) are identified in these patients, although their association with any pathology or disease is not yet proved. In the present work, the authors studied the clinical importance of TTV in Turkish multitransfused patients with thalassemia. Forty-six healthy and 57 thalassemic patients were enrolled in the study. TTV was detected in serum samples by 3'-UTR nested PCR. Transaminase and ferritin levels, hepatitis B and C virus markers and number of transfusions were interpreted for possible association with TTV infection. As a result, TTV was detected in 63% of the thalassemia and 54% of the control patients. Prevalence of TTV infection, clinical features, laboratory data, and annual transfusion numbers of TTV-positive and -negative patients were not observed to be statistically significant. In conclusion, in Turkish patients with thalassemia, TTV infection cannot be considered as a risk factor for liver disease.     

GB virus C/hepatitis G virus infection in HIV infected patients with haemophilia despite treatment with virus inactivated clotting factor concentrates.

AIM: To determine the frequency of GB virus C (GBV-C)/hepatitis G virus (HGV) infection before and after switch to the use of virus inactivated concentrates in haemophiliac patients infected with human immunodeficiency virus (HIV). PATIENTS AND METHODS: Initial and follow up sera from 49 children with haemophilia were analysed for the presence of GBV-C/HGV RNA and antibodies to HGV (anti-HGV). All patients had been infected with HIV while receiving concentrates without virus inactivation before 1984 and were subsequently treated with virus inactivated concentrates. RESULTS: In the first available serum sample (1987 or later), two of 49 patients were GBV-C/HGV RNA positive and two further patients were anti-HGV positive. During follow up (mean, 6 years), 14 patients developed markers of GBV-C/HGV infection. Eleven of these had received no blood products except clotting factor concentrates that had been prepared with virus inactivation. CONCLUSIONS: Despite being treated with virus inactivated clotting factor concentrates, HIV positive patients with haemophilia are at an increased risk of manifesting GBV-C/HGV infection. We hypothesise that GBV-C/HGV is transmitted by these clotting factor concentrates. However, we cannot rule out the emergence of markers of GBV-C/HGV infection as a result of the progression of immune impairment in the course of HIV infection.     

HCV and HGV infection, iron overload and liver disease in multitransfused patients with thalassaemia and persistently normal or abnormal transaminase levels

Prevalence and influence on liver disease of HCV and HGV infections, and HCV genotypes were studied in 28 HCV-Ab positive multitransfused thalassaemia patients with persistently normal ALT levels (group A) matched by sex and age with 28 patients with increased ALT levels (group B). Laboratory and virologic tests (all patients), liver biopsy (28 patients) and LIC by SQUID (30 patients) were performed. In group A, HCV-RNA was positive in 39%, genotype 2a was detected in 91%. In Group B, HCV-RNA was positive in 89%, prevalence of genotype 1b and 2a was 52% and 48% respectively; compared with group A, they had significantly increased values of gammaGT, AF, BA, TP, IgG, IgA, LIC (group B: 2,142 -/+ 1,524 microg/g liver; group A: 1,084 -/+ 610 microg/g liver). Overall prevalence of HGV-RNA was low (12.5%) and not significantly different between groups. Liver biopsies revealed no cirrhosis and severe fibrosis was found in 3 HCV viremic patients in group B. In 14 viremic patients examined both for LIC and liver histology, mild fibrosis was observed in 71%, in which iron overload was below 5 times the normal value. In conclusion, in patients with normal ALT levels, active HCV infection must be excluded by evaluation of HCV-RNA. Liver biopsy is indicated in HCV viremic patients, independent of ALT levels; in non-viremic patients, increased ALT levels may be due to iron overload and LIC measurement is indicated. Our data emphasise the crucial role of chelation therapy to maintain low LIC levels in order to prevent progression of fibrosis to cirrhosis in patients with HCV chronic hepatitis.     

Chronic non-A, non-B hepatitis: role of hepatitis C virus.

Thirty three consecutive children with chronic non-A, non-B hepatitis (NANBH) were studied during a four year period to evaluate clinical and histological features and the role of hepatitis C virus (HCV). All patients were asymptomatic. Thirteen (39%) of them were anti-HCV positive. A history of parenteral exposure was significantly more frequent among anti-HCV positive (69%) than anti-HCV negative patients (15%). Aminotransferase serum values were not statistically different between anti-HCV positive and anti-HCV negative patients. Unlike adults, cirrhosis was never found in the children studied. Our results suggest that chronic NANBH is, during childhood, an asymptomatic disease and that the prevalence of HCV infection is lower than in adults. As the majority of the children with chronic NANBH showed no evidence of HCV infection, it seems unwarranted to identify NANBH with HCV infection in children. The lack of cirrhosis in paediatric patients is probably related to a shorter duration of liver disease.     

Hepatitis C infection in children: a Melbourne perspective

OBJECTIVE: To examine the clinical spectrum of hepatitis C virus (HCV) infected children in our care by determining presentation, mode of acquisition, degree of co-infection, biochemical evidence of persisting hepatitis and treatment outcome. METHODOLOGY: A retrospective review of the medical records of all children attending the Royal Children's Hospital, Melbourne, between 1990 and 1998, who had antibodies to HCV infection detected. Detailed clinical information, investigations and the results of treatment were extracted from the clinical notes. RESULTS: A total of 94 children (age range 2 weeks to 19.7 years) were identified, of whom nine had passive transfer of maternal antibodies from HCV-positive mothers and were excluded from analysis. Sixty-seven children (79%) were infected by transfusion of blood or blood products. Perinatal transmission occurred in 11 children (13%), and six children (7%) had a history of i.v. drug abuse. The majority of children were asymptomatic at presentation. Of the 65 patients tested for HCV-ribonucleic acid, 43 (66%) were positive. Fifty-seven cases had serial alanine aminotransaminase (ALT) measurements over a mean of 28 months. Of these, 38 (67%) had an abnormal ALT. Ten cases (12%) were co-infected with hepatitis B virus, HIV or both. Of 12 patients treated with interferon, four responded with normalisation of ALT from 3 to 12 months post-commencement of therapy. CONCLUSIONS: Although HCV was largely an asymptomatic condition in our clinic population, more than half the patients had biochemical evidence of ongoing liver damage. Given the chronicity of this infection in the majority of patients and the long-term risks of cirrhosis and hepatocellular carcinoma, children with HCV infection represent a high-risk group worthy of regular follow up.     

Cost effectiveness analysis of different strategies of management of chronic hepatitis C infection in children

BACKGROUND: Chronic hepatitis C virus infection in the pediatric patients is commonly encountered by clinicians, and although interferon-based therapy has been shown to be reasonably effective in children no formal economic analysis of such treatment strategies is available. METHODS: With a Markov cycle tree simulation model, a cost effectiveness analysis was done to compare interferon-based treatment strategies for chronic HCV infection in children with a strategy of no treatment in a cohort of 10-year-old otherwise healthy children. Clinical probabilities used in the model was obtained from available literature, and cost estimates were obtained from two teaching hospitals. Cost per patient, quality-adjusted life years gained in each strategy and incremental cost-effective ratio were the primary outcome measures compared. RESULTS: In the baseline analysis the treatment strategies dominated the strategy of no treatment. A 12-month treatment strategy was better than the 6-month treatment strategy. Combination therapy for 6 months with interferon and ribavirin was at least equally if not more effective than 12-month monotherapy. All treatment strategies decreased the number of patients developing decompensated cirrhosis, hepatocellular carcinoma and also number of orthotopic liver transplants in the lifetime of the model cohort. CONCLUSIONS: Interferon-based treatment strategies were more effective in terms of quality-adjusted life years saved and at the same time cheaper when compared with the strategy of no treatment. Combination therapy may be more cost-effective than interferon monotherapy, and clinical trials of combination therapy in pediatric patients are needed.     

庚型肝炎病毒感染状况研究

为了解小儿庚型肝炎病毒（ＨＧＶ）感染状况，对５０６例各型病毒性肝炎患儿，采用以ＨＧＶ合成肽为抗原的酶联免疫吸附技术（ＥＬＩＳＡ）检测抗ＨＧＶ。结果表明，ＨＧＶ在小儿组感染率为４．０％。小儿组甲、乙、丙型肝炎中ＨＧＶ感染率分别为１．５％、５．４％和１．６％。其中乙型肝炎中感染率高于其他型（Ｐ＜０．０５）。抗ＨＧＶ在急性肝炎的检出率为１．５％，慢性肝炎中为４．８％。提示ＨＧＶ感染在小儿肝炎中占有一定比例，并有其特点，应重视儿童ＨＧＶ感染的研究