Rou Li

Age at Time of Hepatitis Be Antibody Seroconversion in Childhood Chronic Hepatitis B Infection and Mutant Viral Strain Detection Rates

BACKGROUND Investigations of adult patients have demonstrated that with seroconversion, changes occur from wild-type strains of the infecting virus to mutant strains. However, to date, there have been few reports and insufficient investigation of this issue in children. METHODS The presence or absence of nucleotide base and amino acid sequence mutations in a portion of the X region containing the core promoter region, the pre-C region, and the C region of HBV genomic DNA were investigated using a polymerase chain reaction-direct sequencing method on serum samples collected from 14 children who were hepatitis Be antibody (HBeAb)-positive carriers. Samples from three children who were HBe antigen (HBeAg)-positive carriers served as the control subjects. RESULTS When patients were grouped based on whether they had had documented seroconversion before age 6 or at age 6 or older, differences in mutant viral detection rates involving the core promoter region and the pre-C region were apparent. Specifically, a mutant strain showing a G-to-A substitution at nucleotide 83 in the pre-C region, or a mutant strain showing an A-to-T substitution at nucleotide 1762 and a G-to-A substitution at nucleotide 1764, was detected in only two of eight cases (25%) from the HBeAb-positive carriers with documented seroconversion before age 6. In contrast, these findings were present in six of six patients (100%) with documented seroconversion at age 6 or older. CONCLUSIONS The results of the present study suggest that the mechanism of onset of HBeAb seroconversion differs between children aged less than 6 years and those who are aged 6 or more.

Prevalence of GB Virus C/Hepatitis G Virus Ribonucleic Acid and Anti-Hepatitis G Virus-E2 Antibodies among Japanese Children with Histories of Transfusions or with Liver Diseases

To clarify the prevalence of Japanese children thought to be at a risk for infection with GB virus-C (GBV-C)/hepatitis G virus (HGV), we investigated the detection rates of serum GBV-C/HGV ribonucleic acid (RNA) by reverse transcription-seminested PCR and serum anti-HGV-E2 antibody by ELISA in 162 children with histories of blood or plasma product transfusions or with liver diseases and performed phylogenetic analysis of the 5′ noncoding region sequences of GBV-C/HGV genomes. Children with histories of transfusions were divided into those who had been treated with antineoplastic agents for malignant diseases (malignant group) and those who had received transfusions for nonmalignant diseases (nonmalignant group). Children with liver diseases were divided into hepatitis B (HBV), hepatitis C (HCV), and non-A-C hepatitis groups. We detected GBV-C/HGV RNA in 11 of 33 (33.3%) and anti-HGV-E2 in 1 of 27 (3.7%) children in the malignant group and in 3 of 56 (5.4%) and 1 of 53 (1.9%) children, respectively, in the nonmalignant group. Neither GBV-C/HGV RNA nor anti-HGV-E2 was detected in the HBV and non-A-C hepatitis groups. GBV-C/HGV RNA and anti-HGV-E2 were detected in 7 of 23 (30.4%) and in 1 of 18 (5.6%) children, respectively, in the HCV group. All children positive for either GBV-C/HGV RNA or anti-HGV-E2, except one whose route of GBV-C/HGV infection suggested mother-to-infant transmission, had histories of transfusions. The phylogenetic analysis showed that all isolates in this study were divisible into three groups and that most of them were clustered into group 3 (Asian group).

SECOND GENERATION HEPATITIS C VIRUS ANTIBODY-POSITIVE RATE IN CHILDREN : INVESTIGATION OF THE ROUTE OF HEPATITIS C VIRUS INFECTION IN CHILDREN WITH NO HISTORY OF TRANSFUSION

Hepatitis C virus (HCV) antibody and HCV‐RNA screening was undertaken in 1864 children, aged from 0 to 15 years who did not have a history of transfusion. Anti‐HCV was tested by the second generation enzyme‐linked immunosorbent assay (ELISA). HCV RNA was examined by reverse transcriptase‐nested polymerase chain reaction (PCR). Two of the 1864 children were positive for serum HCV RNA. They had no history of transfusion, no episodes of horizontal transmission, but the mother in each case was positive for serum HCV RNA, implying mother‐to‐infant infection. Eleven children who were positive for HCV antibody with low values and negative for serum HCV RNA were classified as belonging to the high bovine milk (composed primarily of casein)‐specific IgG4 value group. This suggested that many of the children who were falsely positive for HCV antibody using ELISA had antibodies to casein.

Prevalence of GBV‐C/HGV infection in pregnant Japanese women

Recently, a novel viral agent, hepatitis G virus, was identified by independent researchers from the serum of patients with liver disease, and termed GBV-C or HGV. At present, GBV-C and HGV are considered to be separate isolates of the same virus; however, the role of this virus in acute and chronic liver disease remains uncertain. Although vertical transmission is known to be one of the routes of transmission, the prevalence of GBV-C/HGV viremia in pregnant Japanese women is unknown. Thus, we determined this prevalence using the reverse transcription polymerase chain reaction (RT-PCR).

Analysis of the hypervariable region of hepatitis C virus E2/NS1 gene in an infant infected by blood transfusion

We investigated the sequential change in the hypervariable region 1 (HVR1) of hepatitis C virus (HCV) E2/NS1 gene in an infant. He was transfused with 160 mL of blood containing the HCV (0.7 Meq/mL) on the 6th d after birth and subsequently developed chronic viremia. At 16 mo, the HVR1 amino acid sequences of HCV observed in the infants sera were very similar to those from the donor (his maternal grandfather) on the day of transfusion. However, highly variable amino acid sequences of HVR1 were observed throughout infancy. These results demonstrate that an adaptive response of HCV to evade host immunity seems to occur, as in adult cases, even in early infancy when the ability to produce humoral immunoglobulin is thought to be low.

Clinical and serological courses of a newborn with post-transfusion hepatitis C

Summary. The clinical and serological course of a haemophilic baby who was transfused with 160 ml of blood containing the hepatitis C virus (HCV) (0.70 Meq. ml‐1) on the sixth post‐natal day is described. He is the infant of an HCV‐negative mother. One month after the transfusion, there was a marked increase in HCV RNA and a small amount of HCV antibody was detected. This case provides evidence that a newborn is capable of producing HCV antibodies.

Natural emergence of an anti-hepatitis B s escape mutant in a young female hepatitis B virus carrier.

determinant of the S region of the hepatitis B virus (HBV) genome abolish expression of determinant ‘a’ and the resultant anti-hepatitis B surface (anti-HBs) escape mutant HBV are able to survive in the presence of anti-HBs.1 Several types of anti-HBs escape mutant HBV have been reported.1–10 These mutations arise in children infected with HBV after they have received either immunoprophylaxis with hepatitis B (HB) immunoglobulin and HB vaccine1,2,4,6,8,10 or monoclonal antibodies to HBV after orthotopic liver transplantation.5 In addition, anti-HBs escape mutant HBV have also been found in chronic HBV carriers who are seropositive for anti-HBs due to host immune pressures.3,7,9 In the present report, we present a girl with chronic hepatitis B in whom an anti-HBs escape mutant HBV has emerged naturally.

Genetic analysis of hepatitis B virus isolated from an infant with acute self‐limited hepatitis

(HBeAg)-positive mother-to-infant transmission was started in 1986 and, consequently, the incidence of vertical transmission of hepatitis B virus (HBV) has substantially decreased.1,2 Nonetheless, a few infants of mothers positive for the hepatitis B e antibody (anti-HBe) have developed acute severe or fulminant hepatitis B.3 These infants did not receive any prophylactic treatment or received only a hepatitis B immunoglobulin (HBIG) injection at birth. Thus, in an effort to reduce the number of infants with acute severe or fulminant hepatitis, administration of HBIG shortly after birth, followed by active immunization with three doses of a hepatitis B vaccine was begun in 1995 as prophylactic treatment for newborns of HBeAg-negative carrier mothers. In the present case, although prophylaxis was performed under the new protocol described above, the infant’s serum level of hepatitis B surface antibodies (anti-HBs) acquired by immunoprophylaxis transiently became negative and she developed acute self-limited hepatitis at 10 months of age. In the present study, we analyze the genome of HBV isolated from the serum of this infant.