Importance of recall and follow-up screening for chronic hepatitis C in children receiving blood products prior to 1990 in Japan

The objective was to detect chronic hepatitis C virus infection in recipients of blood products using retrospective analysis by recall and enrollment of recipients. 226 patients who received blood products for open heart surgery from January 1983 to June 1992 were examined for HCV antibody by using a second generation assay and liver function test. 22 (14%) of the 161 patients who received blood products before November 1989 had detectable HCV antibody, but none of the 65 recipients receiving blood products after 1990, the year the Japanese blood bank began to screen for HCV-antibody. Abnormal alanine aminotransferase (ALT) levels, more than 25 iu/L, during the chronic phase of HCV infection was recognized in nine of 22 (41%) seropositive patients. The liver function test and second generation HCV antibody in the serum are effective markers to screen for chronic hepatitis C in blood product recipients transfused before 1990.     

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.     

Look-back study of Hepatitis C in teenagers after blood transfusions as neonates

AIM: To conduct a single-centre "look-back" study of the prevalence of hepatitis C in teenagers who had received blood products as newborns, prior to hepatitis C virus (HCV) blood donor screening. METHODS: Using blood bank records, we identified 732 surviving teenagers aged 14-18 years who had received blood products as neonates during 1986-1990. Letters recommending HCV antibody testing were sent to 732 surviving teenagers; 581 recipients were contacted and invited to undergo testing, and, of these, 429 consented (59% of the survivors). HCV antibody testing was performed on all and HCV-RNA was tested on those who were antibody positive. RESULTS: Three teenagers (0.7%, 95% CI 0.54-0.86) tested positive for HCV antibodies and all three were HCV-RNA positive. There were no cases in which antibodies were detected and polymerase chain reaction (PCR) was negative. Two of the three had mildly elevated liver enzymes and all three had mild inflammatory activity and low fibrosis scores on liver biopsy. CONCLUSIONS: The look-back process, even in a single centre with a stable urban population, is relatively inefficient in screening at-risk populations. Although the prevalence of hepatitis C in this sample was relatively low, paediatricians should offer screening to teenagers and young adults who received blood products in the neonatal period.     

Risk of hepatitis C virus infection in multiply transfused premature neonates

BACKGROUND: Reports from around the world indicate that multiply transfused patients are at increased risk of hepatitis C virus (HCV) infection, with reported rates of between 4% and 44%. Such reports are mostly of haematological and renal patients. As recipients of blood products in the newborn period, premature infants share this risk, but there is little information regarding their risk. AIM: To assess the risk of HCV infection in children who, as premature neonates, received multiple blood products prior to the introduction of screening of donated blood for HCV. METHODS: Premature infants born between January 1985 and January 1990 who had attended our high-risk follow-up clinic were selected on the basis of the number of transfusions of blood, platelets or fresh frozen plasma they received in the newborn period. Ethical approval to offer HCV testing to parents was obtained from the Central Sydney Area Health Service Ethics Review Committee. Parents of infants who received three or more transfusions were then contacted by mail with the approved letter explaining the study, and offered HCV testing. Detection of anti-HCV antibodies was undertaken using second, and later third generation enzyme immunoassay kits. Samples which were found to be 'indeterminate' were tested using a Wellcozyme HCV western blot assay (Murex Diagnostics Ltd, Datford, UK). Hepatitis C virus-ribonucleic acid (RNA) was detected using an 'in-house' polymerase chain reaction (PCR) assay. Alanine transaminase (ALT) was also measured, with values above 55 U/L considered abnormal. RESULTS: Consent was obtained for 45 children (25 males, 20 females). The mean (+/- SEM) gestational age and weight of the children at birth was 26.7 +/- 0.2 weeks and 938 +/- 27 g, respectively. The children received 198 transfusions of blood products, an average of 4.4 U per child. All of the infants except for one were negative for anti-HCV antibodies. One infant was 'indeterminate' (low positive on third generation test but negative on second generation test), but proved negative subsequently on both western blot and PCR testing. HCV-RNA was not detected in any of the infants on PCR testing. All of the samples had normal ALT values, the mean being 16 U/L (range 8-52). CONCLUSION: None of the children consenting to this study had evidence of current HCV infection. Because of the sample size, we were not able to estimate the true risk of infection from this study, except that the upper limit for the risk is about 1/200 per transfused blood sample.     

The prevalence of hepatitis C in survivors of paediatric malignancy

Objective: To assess the prevalence of hepatitis C in 200 patients with paediatric malignancies, surviving in remission more than 5 years from diagnosis, who had received blood product transfusions before 1990 when routine screening of blood products for hepatitis C began.
Method: The second and third generation Abbott Diagnostics ELISA was used to assess hepatitis C seropositivity. Seropositive patients and those with abnormal liver transaminases were assessed by hepatitis C virus RNA polymerase chain reaction (PCR).
Results: A low incidence (4%) of seropositivity for hepatitis C was found in survivors of paediatric malignancy who were transfused prior to routine screening of blood products in this cohort.
Conclusions: All patients identified have evidence of hepatitis and may be at high risk of developing cirrhosis.     

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 B and C virus infections in Turkish children with haemophilia

We examined 41 Turkish children with haemophilia for evidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections using the enzyme-linked immunosorbent assay (ELISA). Hepatitis B surface antigen was found to be positive in 11 patients (26. 8%) and HCV-specific antibody (anti-HCV) was detected in 10 (24. 4%) patients. There was a close relationship of the number of transfusions of blood plasma to the presence of HCV specific antibody, but not to the serum markers of HBV infection. In countries where HBV infection is commonly seen and problems in transfusion practice continue, as in Turkey, children with haemophilia are at greater risk for HBV and HCV infections.     

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.     

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.     

Hepatitis C virus infection and related liver disease in children of mothers with antibodies to the virus

Objective: To evaluate the clinical, biochemical, and virologic features associated with hepatitis C virus (HCV) infection acquired early in life from mothers with antibodies to HCV (anti-HCV).Study design: Multicenter prospective-retrospective study in Italian children.Patients: Two groups of children were investigated. Group 1 included 14 infants, born to mothers with anti-HCV but without human immunodeficiency virus infection, who became seropositive for HCV RNA during the first year of life and were thus considered infected. Group 2 included 16 children with chronic hepatitis C, aged 1 ½ to 14 years, whose mothers were the unique potential source of infection. Both groups were followed for 12 to 48 months.Methods: Alanine transaminase (ALT), anti-HCV, and HCV RNA were investigated by the polymerase chain reaction on entry to the study and during follow-up.Results: All children in group 1 had anti-HCV throughout follow-up, and all had ALT abnormalities, ranging from 1.5 to 10.5 times the normal value during the first 12 months. During further follow-up, 5 of 10 children had HCV RNA with abnormal ALT values, 3 had a return to normal of the ALT values but continued to have viremia, and 2 eventually had normal ALT values and clearance of HCV RNA. Of the 16 children in group 2, all were free of symptoms and 62% had only slight ALT elevations; 7 who underwent liver biopsy had histologic features of minimal or moderate hepatitis.Conclusions: HCV infection acquired early in life from mothers with anti-HCV is usually associated with biochemical features of liver damage during the first 12 months of life. Progression to chronicity seems to occur in the majority of cases, although HCV-associated liver disease is likely to be mild throughout infancy and childhood. (J Pediatr 1997;130:990-3)     

Chronic viral hepatitis

Among hepatitis A to E viruses, hepatitis B, C, and D viruses can cause chronic hepatitis, in both children and adults. Hepatitis B virus (HBV) infection is the most prevalent and important one. Perinatal transmission accounts for about 40–45% of chronic HBV infection in hyperendemic areas. Horizontal transmission through intramuscular injection using non-sterile needles and intrafamilial spread accounts for the other half of carriers. During the natural course of HBV infection, the host gradually clears HBV and hepatitis B e antigen (HBeAg), liver damage and elevation of aminotransferases occur during the process of HBV clearance. The most effective way to eliminate HBV infection is immunoprophylaxis starting since birth. It can prevent both HBV and hepatitis D virus (HDV) infections. Hepatitis C virus (HCV) infection in children occurs mainly in high risk children, such as those who received blood product or injection using non-sterile needles, or infants of HCV viremic mothers, etc. Screening of blood product reduced markedly the prevalence of post-transfusion HCV infection, but the prevention of sporadic cases requires HCV vaccination which is still under investigation.     

Prevalence of hepatitis C virus (HCV) infection and its vertical transmission in Egyptian pregnant women and their newborns

We studied the prevalence of hepatitis C virus (HCV) antibody seropositivity using ELISA (Ortho Diagnostic system, 3rd generation test) polymerase chain reaction testing of HCV-RNA (PCR, Promega) and serum alanine transferase (ALT) level in 100 healthy, HIV-negative, pregnant women who delivered spontaneously at the Alexandria University Hospital, and their newborns. Some risk factors were studied using Fisher's exact test. Nineteen per cent of pregnant women were HCV seropositive and 14 of them (14/19) had circulating HCV-RNA, detected by PCR. Nine of the babies born to the 19 HCV seropositive females had circulating antibodies, whereas HCV-RNA was detected in five of them. This gives a vertical transmission risk of 5/14 (36 per cent) for mothers carrying the HCV-RNA and 5/19 (26 per cent) for those having circulating HCV antibodies. History of previous blood transfusion, elevated serum ALT level, and history of infection with schistosomiasis were significant risk factors for HCV infection in mothers. In addition to the previous factors, maternal history of jaundice, stillbirth and hepatomegaly were significant risk factors for neonatal infection. The occurrence of early jaundice and the presence of congenital anomalies in the newborns were non-significant risk factors. In conclusion, our data indicate a high prevalence of HCV seropositivity in Egyptian HIV-negative pregnant women with a significant high rate of vertical transmission of HCV.     

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     

Granulomatous hepatitis,perihepatic lymphadenopathies,and autoantibody positivity: an unusual association in a child with hepatitis C

A 10-year-old boy with hepatitis C had granulomatous hepatitis (GH) at initial liver biopsy. He also had enlarged perihepatic lymph nodes and smooth muscle antibody (SMA) positivity. GH is a rare finding in hepatitis C virus (HCV) infection. Our patient is special since GH secondary to HCV infection was associated with both autoantibodies and multiple intraabdominal lymphadenopathies. After interferon (IFN) and ribavirin therapy, HCV RNA became negative, along with the resolution of hepatic granulomas (HG), lymphadenopathies, and SMA positivity. Although early virologic response was not achieved under IFN treatment, the therapy period was extended, contrary to routine practice, and resulted in a delayed response. We conclude that the usage of IFN for longer periods in GH-associated HCV infection might be promising.     

Hepatitis A and B infections in transfusion-dependent thalassaemia from endemic areas

The aim of this study was to determine the prevalence of previous hepatitis A virus (HAV) and B virus (HBV) infection which is in 64 transfusion-dependent (TD) patients with thalassaemia including 26 patients who were transfused before blood donors were screened for HBV. Serial blood samples taken from these 64 patients and 10 non-TD beta-thalassaemia intermedia patients during a 3 year period, were tested for antibody to HAV (anti-HAV), hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to core antigen (anti-HBc) and when indicated, antibody to Delta virus (anti-Delta) and HBV DNA. Liver function tests were performed also. Similar tests were conducted on 50 donor blood units. None of the 64 TD patients had evidence of past HAV infection, but 50% of blood donors had evidence of past infection (P less than 0.001). Only 2 brothers and their mother were positive for HBsAg, and 38 patients (59.4%) had persisting HBV antibodies compared with 26% of blood donors (P less than 0.001). Our TD thalassaemic patients acquired passive immunity from donor plasma, which protected them against HAV and possibly modified the outcome of HBV infection.     

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.     

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.