Chih-Feng Lu

Transmission of hepatitis C virus in Taiwan: Prevalence and risk factors based on a nationwide survey

A nationwide community‐based survey on hepatitis C virus (HCV) was carried out in seven townships in Taiwan. A total of 11,904 men aged 30–64 years were recruited for testing for antibodies against HCV (anti‐HCV) by second‐generation enzyme immunoassay. A total of 272 seropositive cases and 282 seronegative controls were interviewed to explore risk factors for HCV infection in the study areas. Spouses of 214 seropositive cases were identified to assess the concordance of seropositivity of anti‐HCV between spouses; genotypes of HCV were also tested in 26 couples who were both seropositive. A significant geographic variation in seroprevalence of anti‐HCV was observed in the study townships (1.6–19.6%). Blood transfusions, medical injections, acupuncture and tattooing were related to an increased anti‐HCV seroprevalence showing multivariate‐adjusted odds ratios of 8.6, 2.5, 3.1, and 2.2, respectively, with corresponding population attributable risk percentages of 25%, 57%, 16%, and 3%, respectively. The anti‐HCV prevalence in spouses of index cases (24%) was significantly higher than that observed in the general population of the study areas (4%). However, a striking interspousal discrepancy in HCV genotypes (20/26 = 77%) was observed among both seropositive couples. Common exposures to medical injections and acupuncture were reported by 15 (58%) of these couples. This study identified some endemic areas of HCV infection in Taiwan. Iatrogenic factors were common vehicles for HCV infection, and a concordance of anti‐HCV seropositivity between spouses may primarily be due to extrafamilial iatrogenic infectious sources in study areas. J. Med. Virol. 59:290–296, 1999.

Seroepidemiologic Survey for Hepatitis B Virus Infection in Taiwan: The Effect of Hepatitis B Mass Immunization

A hepatitis B mass immunization program was launched in Taiwan in July 1984, beginning with newborns of hepatitis B carrier mothers for the first 2 years of the program, which was then extended to all newborns. Seroepidemiology was studied in 3 cohorts at age 6 years. Each cohort consisted of 1500 children proportionally and randomly sampled from those entering elementary school in 1989, 1991, and 1993, representing those born 1 year before the program began and years 1 and 3 of the program, respectively. By RIA, the hepatitis B surface antigen positivity rates in the groups were 10.5%, 6.3%, and 1.7%, respectively; hepatitis B surface antibody positivity rates were 36.9%, 62.0%, 65.4%; and hepatitis B infection rates were 25.0%, 15.9%, 4.3%. Thus, universal immunization was more effective in reducing hepatitis B carriage than selective immunization of newborns of carrier mothers only. The program has proved effective in controlling chronic hepatitis B infection in Taiwan.

Different viral aetiology of hepatocellular carcinoma between two hepatitis B and C endemic townships in Taiwan

In Taiwan, we found two hepatitis B virus (HBV)‐ and hepatitis C virus (HCV)‐endemic townships, Paisha and Tzukuan, with an anti‐HCV prevalence of 19 and 37% in men, and 26 and 38% in women, respectively. The hepatitis B surface antigen (HBsAg)‐positive rates were 25 and 18%, for men and women in Paisha, and 25 and 22% in Tzukuan, respectively. According to the national death certification database (1982 to 1991), the annual age‐adjusted mortality rates per 100 000 population for liver cancer among men and women were 83.0 and 13.8, respectively, in Paisha, and 55.9 and 17.0 in Tzukuan compared with 30.9 and 9.1 in Taiwan as a whole. The male‐to‐female ratios were 6.0 in Paisha and 3.3 in Tzukuan. Aetiology of 11 cases of hepatocellular carcinoma (HCC) from Paisha and 14 cases from Tzukuan were analysed. All HCC cases from Paisha were HBsAg positive, while 13/14 HCC cases from Tzukuan were anti‐HCV positive. The endemic duration of HCV in Tzukuan seemed long enough to induce HCC, but the HCV appeared to be a newly introduced infection in Paisha.

Prevalence and manifestations of hepatitis C seropositivity in children in an endemic area.

BACKGROUNDnAccording to our previous studies, Paisha Township in Penghu Islets is an endemic area for hepatitis B virus and hepatitis C virus (HCV) infection and for hepatocellular carcinoma. We conducted this study to understand the prevalence of anti-HCV seropositivity among children in this area and to observe clinical manifestations of anti-HCV-positive children.nnnMETHODSnIn March, 1994, 1164 (93.6%) of 1243 students from all 6 kindergartens, 9 primary schools and 3 middle schools in Paisha Township participated in the screening for anti-HCV by enzyme immunoassay with second generation commercial kits (Abbott EIA 2.0). Anti-HCV tests were duplicated for the positive sera in 2 laboratories. All anti-HCV-positive children were followed annually for 2 years.nnnRESULTSnThe prevalences of children from kindergartens (ages 3 to 6 years), primary schools (ages 7 to 12 years) and middle schools (ages 13 to 15 years) were 0% (0 of 229), 0.8% (5 of 617) and 1.9% (6 of 318), respectively. Initially the optic density (OD) values of anti-HCV were > 2.0 in 4 cases (36%), between 1.0 and 2.0 in 2 cases, and < 1.0 in the other 5 cases. None had sonographic parenchymal changes in the liver. In the 2-year follow-up of the anti-HCV-positive subjects, type 2a HCV-RNA persisted in 3 of 4 children with an OD of anti-HCV more than 2.0; 2 of them had 2 elevations of alanine transaminase values. Four of 7 children with an OD of 2.0 or less had a decrease in OD values in the follow-up examinations, and 2 of them became anti-HCV-negative.nnnCONCLUSIONnOnly 36% (4 of 11) of anti-HCV-positive children had an OD of > 2.0. Subjects with sequentially low OD might recover from chronic HCV infection without detectable HCV RNA and with normal alanine aminotransferase values.

Patterns of Circulating Hepatitis B Surface Antigen Variants among Vaccinated Children Born to Hepatitis B Surface Antigen Carrier and Non-Carrier Mothers

Hepatitis B virus (HBV) variants that possessed missense mutation within the neutralization epitope of the major S antigen as defined by amino acid residues (aa#) 124–147, termed the ‘a’ determinant variants, were identified through a population-based serosurvey of 2,305 children of the vaccinated birth cohorts born after 1986. Data on the 678 nucleotides encoding the S antigen of HBV were available for 75 HBV strains that were collected from 63 vaccinated children and 12 unvaccinated or incompletely vaccinated children, and 21 HBV strains from 25 unvaccinated adults. Among the diverse patterns of one to three amino acid substitutions within the ‘a’ determinant, 145-Arg occurred most frequently (5/14); other variants were: 126-Ala, 127-Thr, 126-Ser/131-Asn/133-Thr, 129-His, 129-Arg, 123-Asn/131-Ile, 133-Leu, 141-Glu, and 141-Arg/144-Ala. Only one of these variants occurred in the 16 hepatitis B surface antigen (HBsAg)-carrier children born to HBsAg-negative mothers, whereas 12 of these variants occurred in the 20 (50%) children born to HBsAg-positive mothers. In addition, early administration of HBV vaccine within the noenatal period increased the likelihood of the emergence of these variants to 64.7% (11/17). Five of the 21 (23.8%) unvaccinated HBsAg-carrier adults harbored the ‘a’ determinant variants possessing mutations within aa# 125–136, i.e. the putative first loop formed by the cysteine disulfide bonds. Vaccinated children were likely to harbor HBV variants possessing mutations involving altered charge of side chains and/or its hydrophobicity of amino acid residues within the putative second loop between aa#140 and 146. Our data suggest that emergence of these HBV S gene mutants in the phase of HBV vaccination program would be most common among populations in whom perinatal/vertical transmission of HBV is most common, i.e. southeast Asian and the Taiwanese.

Advances in Biomedical Research

The National Institute of Health (NItl)/US Food and Drug Administration (FDA) and Chinese American Association (CAA) and the Washington DC Chapter of Society of Chinese Bioscientists in America (SCBA) have succesfully sponsored five consecutive annual joint scientific symposia since 1994. Leading experts at the forefront of various biomedical fields have been invited to present their research findings. These joint symposia have sparkled spirited discussions and led to productive collaborations among Chinese bioscientists in the great Washington DC metropolitan area. The sixth symposium was held in the NIH Bethesda campus (Bldg. 10, Lippsett Amphitheater) on October 9, 1999. This years symposium highlighted recent advances in biomedical sciences, especially the HIV and tumor biology that has attracted attention from both the scientific community as well as the popular press. HIV infection has been a serious worldwide health concern. Prevention, intervention and treatment of this deadly diseae represent major challenges and opportunities to biomedical researchers. Three talks were devoted to this issue. The first two presentations by Drs. Sylvia Lee-Huang (NYU) and Hao Chia Chen (NIH) described the exciting discovery of new anti-HIV agents of promising clinical potentials. Several new anti-HIV agents including (1) MAP30 and GAP31 from medical plants and (2) AVL and AVR from urine of pregnant women and (3) RNase U and urinary lysozyme C from pregnant women were described. The third talk by Dr. Kuan-Teh Jeang (NIH) focused on the pivotal role of CXCR4 in the treatment of HIV infection. The EGF signaling pathway plays an important role in tumorigenesis and angiogenesis. A new regulatory protein CAIR-1 that can control the releasing PLC-g in response to growth tactor stimulation was presented by Dr. Howard Doong (NIH). Defects in the mismatch repair genes have been identified in various tumors. The human MYH, a homologue of Escherichia coli MutY, have been identified. Dr. A-lien Lu (University of Maryland) presented the linkage between inactivation of hMYH and tumor progression. Immunological regulation and response to diseases via an intricate network of pathways in the human body: three presentations addressed this topic; Dr. XiaoDong Li (Johns Hopkins University) presented the rapid identification of differentially expressed genes in human TH2 cells and their functional significance in allergic asthma. Dr. J. Qian (American Red Cross) focused on the prevention and treatment of heraophilic inhibitors by exploiting the CD40L/CD40 and B7/CD28 pathways to develop an anti-hemophilic inhibitor in the murine model. Dr. Tiang-Li Wang (Johns Hopkins University) described the use of nucleic acid vaccine to prevent human papiltomavirus-induced cervical cancer. Linkage E7 antigen with targeting signal of the MCH II pathway of LAMP-1 significantly enhances the potency of DNA vaccine. Dr. Yufan Shi, Dr. Andrew Chang, Dr. T.-C. Wu, and Dr. Yunbo Shi provided valuable advice in organizing this symposium. We would like to thank Dr. M.K. Jeang, Cardiovascular Center, University of Texas of Health Sciences Center at Houston, the Science Division of Taipei Economic and Cultural Representative Office in US, and generous support from a number of companies. We especially thank Dr. K.-T. Jeang, a former president ofNIH/FDA CAA, for his insights and enthusiastic and continuing support for this joint symposium.