Hong-Yuan Hsu
National Taiwan University
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Annals of Internal Medicine | 2001
Yen-Hsuan Ni; Mei-Hwei Chang; Li-Min Huang; Huey-Ling Chen; Hong-Yuan Hsu; Tai-Yuan Chiu; Keh-Sung Tsai; Ding-Shinn Chen
Hepatitis B virus (HBV) infection is an important cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in many parts of the world, including Taiwan (1, 2). Up to 15% to 20% of the general population in Taiwan are chronic carriers of hepatitis B surface antigen (HBsAg) (3, 4). Most chronic carriage of HBV results from infection in early childhood, especially before 2 years of age (57). Taiwan launched the worlds first nationwide universal vaccination program in 1984 to prevent infection in the early years of life (8). In addition to decreasing the proportion of carriers and the prevalence of HBV infection in the current young generation (9), the universal vaccination program has also resulted in a decreased incidence of childhood hepatocellular carcinoma (10). To study the effect of this universal vaccination program, we conducted a series of prospective seroepidemiologic surveys in Chung-Cheng District, Taipei City, Taiwan. The first survey was conducted shortly before the mass vaccination program began in 1984 (6), followed by similar surveys in 1989 (11) and 1994 (12). We report findings that extend our follow-up observations to 199915 years after the start of the program. Methods National Vaccination Program The national program of universal HBV vaccination in Taiwan began on 1 July 1984 (8). At that time, only the newborn infants of mothers who were HBsAg carriers were vaccinated. The vaccination program was extended in June 1987 to include all newborn infants and in July 1987 to cover all children of preschool age. The program was further extended to school children, teenagers, and then adults from 1988 to 1990. Since 1991, the vaccination records of first-grade children have been checked, and children without a complete set of previous vaccinations have been given catch-up HBV vaccinations. Before July 1992, four doses of plasma-derived vaccine were administered in children before 1 week of age and again at 1, 2, and 12 months of age; after July 1992, three doses of recombinant (yeast-derived) vaccine were administered before 1 week and at 1 month and 6 months of age. Since 1984, newborns whose mothers test positive for hepatitis B e antigen (HBeAg) have also received hepatitis B immunoglobulin, 0.5 mL (100 IU), within 24 hours after birth. The vaccination program has been described in greater detail elsewhere (8, 12). We defined the vaccination coverage rate as the percentage of children receiving at least three doses of HBV vaccine. We assessed the vaccination histories of the studied population by examining their vaccination cards and by taking a history from their parents. We classified the vaccination status as unknown for persons with a missing vaccination card or a vague vaccination history. Participants From March 1999 to October 1999, serum samples were collected from 1916 children and adolescents from two groups: 1) 1357 apparently healthy persons younger than 15 years of age [721 male participants and 636 female participants], who were born after the launch of the universal vaccination program, and 2) 559 persons (297 male participants and 262 female participants) 15 to 20 years of age, who were born before universal vaccination. We recruited participants for the baseline and follow-up seroepidemiologic studies in Chung-Cheng District, Taipei City. In 1999, Chung-Cheng had a population of 165 388 citizens; 35 005 of the citizens were younger than 15 years of age, and 47 565 were younger than 20 years of age. From 1994 to 1999, the population was stable, with an average annual migration rate of less than 4.8%. The annual family income,
The Journal of Pediatrics | 1995
Ho-Hsiung Lin; Jia-Horng Kao; Hong-Yuan Hsu; Yen-Hsuan Ni; Mei-Hwei Chang; Su-Cheng Huang; Lih-Hwa Hwang; Pei-Jer Chen; Ding-Shinn Chen
39 963 (in U.S. dollars), was the third highest among the 12 districts in Taipei (13). From 1985 through 1990, the HBsAg carrier rate among pregnant women14% (14)was similar to the national average (3, 4). The 1916 participants in our 1999 study consisted of 1) 157 children younger than 3 years of age enrolled from the Well-Baby Clinic of the National Taiwan University Hospital Department of Pediatrics and from two day care centers; 2) 232 children 3 to 6 years of age recruited from two kindergarten classes; 3) 763 children 7 to 12 years of age enrolled from one public elementary school; 4) 205 children and adolescents 12 to 15 years of age enrolled from one public junior high school; 5) 219 adolescents 15 to 18 years of age enrolled from one high school; and 6) 340 first-year undergraduate students at the National Taiwan University, 19 to 20 years of age. We recruited the child and adolescent participants through poster advertisements and by invitation from the health staff of the Department of Pediatrics, National Taiwan University Hospital. The university student participants and the parents of enrolled children gave written, informed consent and provided the vaccination history of the participant, according to his or her personal health booklet. (The booklet, which is used to record a persons vaccination history, is provided to the parents of all newborns by the Health Bureau of City Hall.) Serologic and Statistical Analyses We analyzed serum samples for HBsAg, HBsAg antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) by using enzyme immunoassay (Abbott Laboratories, North Chicago, Illinois). We examined between-group differences in frequency by using the chi-square test with Yates correction or the Fisher exact test, where appropriate. A P value less than 0.05 was considered significant. Data analyses were performed by using GraphPad Prism, version 3.00 (GraphPad Software, Inc., San Diego, California). Role of the Funding Source The funding source had no role in the collection, analysis, and interpretation of the data or in the decision to submit the paper for publication. Results In 1999, the vaccination coverage rate was greater than 90% among children younger than 8 years of age and 80% to 86% among children 8 to 15 years of age (Table). These figures might be underestimates because some of the participants, particularly in the older age group, had missing vaccination cards; in other cases (for 23 of the 541 children younger than 8 years of age and 63 of the 766 participants 8 to 15 years of age), the parents could not recall the vaccination history. Infants had a lower coverage rate than other age groups because some of them had not yet finished their vaccination schedule (Appendix Table). Table. Seroprevalence of Hepatitis B Surface Antigen and Its Antibody in Chung-Cheng District, Taipei City, Taiwan, in 1984, 1989, 1994, and 1999 The prevalence of HBsAg in children younger than 15 years of age, 0.7% (9 of 1357), was considerably lower than the rate of 7% (39 of 559) observed in participants older than 15 years of age, who were born before the universal vaccination program (P < 0.001). Of the 9 children who were born after the vaccination program was instituted and tested positive for HBsAg, only 1 had not received the scheduled vaccinations, and the mother of this child was also HBsAg positive. According to their vaccination cards, the 8 other participants had received at least three doses of the HBV vaccine, and the first dose had been given within 1 week of birth. Seven of these 8 participants had mothers who were HBsAg carriers, and the remaining participant was living with two grandparents who were HBsAg positive. All 9 participants tested positive for anti-HBc. Eight of these 9 HBsAg carriers had received the plasma-derived vaccine, and 1 had received the yeast-derived recombinant vaccine; however, type of vaccine did not affect the rate of HBsAg seropositivity (8 of 968 persons who received the plasma-derived vaccine were carriers vs. 1 of 389 who received the yeast-derived vaccine; P > 0.2, Fisher exact test). The overall prevalence of anti-HBs in persons younger than 15 years of age in 1999 was 75.8%. We observed the highest prevalence of anti-HBs in children younger than 5 years of age (Table). The longitudinal perspective of HBsAg carriers in cohorts 0 to 1 years of age is shown in the Figure. Figure. Longitudinal perspective of the proportion of hepatitis B surface antigen carriers among the cohorts of 0 to 1 year of age in 1984 (circles) and 1989 (squares) in Chung-Cheng District, Taipei City, Taiwan. Children in the 1984 0- to 1-year age cohort, who were born before universal vaccination in Taiwan, had a carrier rate of 5.1% in 1984, 3.9% in 1989 (at age 5 to 6 years), 4.7% in 1994 (at age 10 to 11 years), and 7.5% in 1999 (at age 15 to 16 years). These proportions are significantly higher than those observed over time in the 1989 0- to 1-year age cohort, who were born since the national vaccination program started, at the corresponding age points (from the survey years 1989, 1994, and 1999, respectively). The rate of anti-HBc seropositivity was 2.9% in persons younger than 15 years of age but was 20.6% in persons 15 years of age or older (P < 0.001). In contrast, the rate of anti-HBc seropositivity among children younger than 15 years of age was 26.2% in 1984 (6), 14.5% in 1989 (11), and 4.0% in 1994 (12). Discussion The prevalence of HBsAg among children younger than 15 years of age decreased from 9.8% to 0.7% in the 15 years since implementation of the universal vaccination program. A high coverage rate for HBV vaccination is crucial for decreasing the prevalence of HBV infection. We observed a vaccination rate of at least 80% among children younger than 15 years of age and as high as 97% among children 4 years of age or younger. A nationwide series of seroepidemiologic studies of three cohorts of children 6 years of age in 1989, 1991, and 1993 reported that the vaccination rates for HBV ( 3 doses of vaccine) were 27.8%, 60.7%, and 88.7%, respectively (9). The age of these three cohorts in 1999 correspond to the age groups of 15 to 18 years, 13 to 14 years, and 11 to 12 years in our study. The data from these three national cohort studies confirm that the vaccination rate in our sample is similar to the vac
Gut | 2004
Hong-Yuan Hsu; Mei-Hwei Chang; Yen-Hsuan Ni; Hui-Ju Chen
The role of breast-feeding in perinatal transmission of hepatitis C virus (HCV) was explored in 15 HCV-infected mothers and their infants. The 15 carrier mothers had anti-HCV titers ranging from 1:80 to 1:40,000 and also had HCV-ribonucleic acid with concentrations ranging from 10(4) to 2.5 x 10(8) copies/ml. Both anti-HCV antibody and HCV-ribonucleic acid were present in colostral samples in much lower levels, but none of the 11 breast-fed infants had evidence of HCV infection for up to 1 year of age. Thus breast-feeding seems safe for these infants.
Gastroenterology | 2012
Huey–Ling Chen; Lung–Huang Lin; Fu–Chang Hu; Jian-Te Lee; Wen–Terng Lin; Yao–Jung Yang; Fu–Chen Huang; Wu Sf; Solomon Chih-Cheng Chen; Wan–Hsin Wen; Chia–Hsiang Chu; Yen-Hsuan Ni; Hong-Yuan Hsu; Pei–Lin Tsai; Cheng–Lun Chiang; Ming-Kwang Shyu; Ping-Ing Lee; Feng–Yee Chang; Mei-Hwei Chang
Background: It is not known whether hepatitis B virus (HBV) with mutations in the a determinant (amino acids (aa) 121–149) of the hepatitis B surface antigen (HBsAg) affect vaccination efficacy. Aim: To investigate the prevalence and clinical significance of these mutants in children, 15 years after universal vaccination in Taiwan. Methods: Nucleotide sequences encoding the a determinant region (aa 110–160) of HBsAg were analysed in all HBV-DNA positive sera from 1357 children and 219 adolescents serosurveyed in 1999. We then compared the prevalence and changes in the mutants in these children with our previous surveys in the same area conducted in 1984 (just before vaccination), 1989, and 1994. Results: The prevalence of a determinant mutants in HBV-DNA positive children was 7.8% (8/103) in 1984, which significantly increased to 19.6% (10/51) in 1989, peaked at 28.1% (9/32) in 1994, and remained at 23.1% ((3/13) (T131I, G145R, G145R)) in 1999; it was higher in those fully vaccinated compared with those not vaccinated (15/46 v 15/153; p<0.001). However, the number of mutant infected children in each survey was stable in the first 5–10 year period but decreased 10–15 years post vaccination. Increased amino acid variation in the a determinant region occurred in carrier children in the post vaccination survey. Mutated residues tended to occur more frequently in the region with greater local hydrophilicity (residues 140–149) in those vaccinated than in unvaccinated children with variant infection (12/15 v 6/15; p = 0.062). More HBsAg positive a determinant mutants emerged in children fully vaccinated with plasma derived vaccine than those given recombinant vaccine (10/2399 (0.46%) v 0/503; p = 0.122). Conclusion: We found that a determinant variants have an advantage in infecting immunised children but do not threaten current HBV vaccination strategies in Taiwan.
The Journal of Infectious Diseases | 2003
Yu-Cheng Lin; Mei-Hwei Chang; Yen-Hsuan Ni; Hong-Yuan Hsu; Ding-Shinn Chen
BACKGROUND & AIMS Mother-to-infant transmission is the major cause of hepatitis B virus (HBV) infection among immunized children. There has been much debate about screening pregnant women and administering hepatitis B immunoglobulin (HBIG) to newborns. We analyzed the rate of HBV infection among children born to hepatitis B surface antigen (HBsAg)-positive mothers and whether HBIG administration reduces transmission. METHODS We analyzed data from 2356 children born to HBsAg-positive mothers, identified through prenatal maternal screens. In addition to HBV vaccines, HBIG was given to all 583 children with hepatitis B e antigen (HBeAg)-positive mothers and to 723 of 1773 children with HBeAg-negative mothers. Serology tests for HBV were performed from 2007 to 2009, when children were 0.5-10 years old. RESULTS A significantly greater percentage of children with HBeAg-positive mothers tested positive for antibodies against the hepatitis B core protein (16.76%) and HBsAg (9.26%) than children with HBeAg-negative mothers (1.58% and 0.29%, respectively; P < .0001 and <.001). Among the HBV-infected children, the rate of chronicity also was higher among children with HBeAg-positive mothers than children with HBeAg-negative mothers (54% vs 17%; P = .002). Similar rates of antibodies against the hepatitis B core protein (0.99% and 1.88%; P = .19) and HBsAg (0.14% and 0.29%; P = .65) were noted in children born to HBeAg-negative mothers who were or were not given HBIG. Infantile fulminant hepatitis developed in 1 of 1050 children who did not receive HBIG (.095%). CONCLUSIONS Children born to HBeAg-positive mothers are at greatest risk for chronic HBV infection (9.26%), despite immunization. Administration of HBIG to infants born to HBeAg-negative mothers did not appear to reduce the rate of chronic HBV infection, but might prevent infantile fulminant hepatitis. Screening pregnant women for HBsAg and HBeAg might control mother-to-infant transmission of HBV.
Cancer | 1989
Mei-Hwei Chang; Ding-Shinn Chen; Hey-Chi Hsu; Hong-Yuan Hsu; Chin-Yun Lee
The long-term immunogenicity of universal hepatitis B virus (HBV) vaccine is seldom studied in large-scale prospective community-based populations, especially in adolescents. This study enrolled 1200 children aged 7 years with complete HBV immunization in infancy and determined HBV surface antigen (HBsAg), its antibody (anti-HBs), and HBV core antibody (anti-HBc) annually until the children were aged 14 years. Eleven children had new HBV infections with anti-HBc positivity as the only marker. None became positive for HBsAg or had detectable HBV DNA by polymerase chain reaction. The percentage of protective anti-HBs in 951 children without booster vaccination gradually decreased from 71.1% at age 7 years to 37.4% at age 12 years. Only 1 of the 200 children in the booster group and 2 of the 258 children in the nonbooster group developed new anti-HBc positivity. The results suggest that routine booster vaccination may not be required to provide protection against chronic HBV infection before age 15 years.
Journal of Hepatology | 2013
Wan-Hsin Wen; Mei-Hwei Chang; Lu-Lu Zhao; Yen-Hsuan Ni; Hong-Yuan Hsu; Jia-Feng Wu; Pei-Jer Chen; Ding-Shinn Chen; Huey-Ling Chen
Fifty‐one children, aged between 3 and 16 years, were diagnosed to have hepatocellular carcinoma (HCC) in the last 15 years. Serum hepatitis B surface antigen (HBsAg) was positive in all the latter 34 HCC children checked by radioimmunoassay, and was positive in five of the 17 earlier HCC children studied by double immunodiffusion method. Serum HBsAg was studied in 31 mothers of the latter 33 HCC children, including two pairs of affected siblings and was positive in 29 (94%). The positive rate was much higher than that (50%) of the mothers of control HBsAg carrier children (P < 0.001). The serum HBsAg positive rate was also higher in the siblings of HCC children than that of the control group. On the contrary, the serum HBsAg positive rate was not different between the fathers of HCC children and that of the control group. Our observation demonstrated that transmission of hepatitis B virus from the mothers during the perinatal period or early childhood is the most important mode of hepatitis B virus infection in HCC children in Taiwan.
The Journal of Pediatrics | 1998
Jen-Ruey Tang; Hong-Yuan Hsu; Ho-Hsiung Lin; Yen-Hsuan Ni; Mei-Hwei Chang
BACKGROUND & AIMS Immunoprophylaxis reduces but does not completely eradicate hepatitis B virus (HBV) transmission. This prospective study aims at assessing the rate and risk factors of maternally transmitted HBV infection. METHODS We enrolled 303 mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg) under current immunization program. Maternal viral load was determined by a real-time PCR-based assay. The children were tested for HBsAg at 4-8 months and/or 1-3 years of age. Rates of HBV infection were estimated using a multivariate logistic regression model. RESULTS HBeAg-positive mothers (81/303, 26.7%) had higher viral loads than HBeAg-negative mothers (7.4 ± 1.9 vs. 2.7 ± 1.4 log10 copies/ml, p<0.0001). Ten children, born to HBeAg-positive mothers with high viral load (median, 8.4; range, 6.5-9.5 log₁₀ copies/ml), were chronically infected. After adjustment for maternal age, birth type, factors related to maternal-fetal hemorrhage, gestational age, infant gender, birth weight, timeliness of vaccination, and feeding practice, maternal viral load was significantly associated with risk of infection (adjusted odds ratio for each log₁₀ copy/ml increase, 3.49; 95% confidence interval (CI), 1.63-7.48; p=0.001). The predictive rates of infection at maternal viral load levels of 7, 8, and 9 log₁₀ copies/ml were 6.6% (95% CI, 0.5-12.6%; p=0.033), 14.6% (95% CI, 5.6-23.6%; p=0.001), and 27.7% (95% CI, 13.1-42.4%; p<0.001), respectively. CONCLUSIONS Additional strategies to further reduce transmission should be considered in mothers with a viral load above 7-8 log₁₀ copies/ml.
The Journal of Pediatrics | 1989
Mei-Hwei Chang; Juei-Low Sung; Chin-Yun Lee; Chien-Jen Chen; Juei-San Chen; Hong-Yuan Hsu; Ping-Ing Lee; Ding-Shinn Chen
OBJECTIVE To investigate the prevalence and outcome of hepatitis B surface antigenemia in newborns of hepatitis B e antigen (HBeAg)-positive hepatitis B surface antigen (HBsAg) carrier mothers under the current immunoprophylaxis program. STUDY DESIGN From 1984 to 1993, 665 high-risk newborns born to HBeAg-positive HBsAg carrier mothers were prospectively recruited. The newborns were tested for HBsAg soon after birth, before hepatitis B immune globulin administration. All newborns received hepatitis B immune globulin within 24 hours after birth plus subsequent hepatitis B vaccination. Those who were seropositive for HBsAg at birth were regularly followed up for their hepatitis B virus (HBV) markers, liver function profiles, and alpha-fetoprotein levels from 1984 to 1996. RESULTS Sixteen (2.4%) of the 665 subjects were found to be seropositive for HBsAg at birth, and all remained HBsAg-positive at 6 months of age. Twelve of the 16 received long-term follow-up care, and all were confirmed to have chronic HBV infection. Of the 12, 2 had HBeAg seroconversion, and 1 had alanine aminotransferase flares without HBeAg seroconversion. Delayed appearance of hepatitis B core antibody (anti-HBc) occurred in 2 without alanine aminotransferase elevation. CONCLUSIONS Current immunoprophylaxis strategy does not protect newborns with surface antigenemia, apparently acquired in utero, from becoming HBV carriers. Immunologic attempts to eliminate HBV may occur in carrier children infected in utero, despite their profound immune tolerance to HBV.
Journal of Pediatric Gastroenterology and Nutrition | 2006
Pei-Yin Hung; Chiu-Chiang Chen; Wei-Jao Chen; Hong-Shiee Lai; Wen-Ming Hsu; †Po-Hung Lee; Ming-Chih Ho; Tony Hsiu-Hsi Chen; Yen-Hsuan Ni; Huey-Ling Chen; Hong-Yuan Hsu; Mei-Hwei Chang
To understand the natural history of chronic hepatitis B virus infection in children, we studied factors affecting the clearance of hepatitis B e antigen (HBeAg). One hundred sixty-nine apparently healthy children whose sera were positive for HBeAg and hepatitis B surface antigen (HBsAg) and who were recruited by screening were followed prospectively to delineate the HBeAg clearance rate. Another 59 carrier children visiting the outpatient clinic because of symptoms or abnormal liver function were studied for comparison. The annual HBeAg clearance rate was low (less than 2%) during the first 3 years of life but increased with age. The HBeAg clearance rate in children older than 6 years of age was lower in those whose mothers had HBsAg positivity (14.3%) than in those whose mothers had no detectable HBsAg (35.3%). Children who were brought for medical care had higher HBeAg clearance rates (42.4%) than those who were recruited by screening (14.6%) because immune clearance of hepatitis B virus and hence HBeAg often led to hepatocellular damage manifested by abnormal liver function profiles or by symptoms that had caused the parents to seek medical care for their children. We conclude that age, source of subject recruitment, and maternal HBsAg status are important factors affecting HBeAg clearance rate in HBsAg carriers.