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Background Prolonged endurance exercise is known to cause elevation of cardiac troponin I (cTnI). Previous studies have reported the correlation of several factors with exercise-induced cTnI release. However, the investigation of the predictors for elevated cTnI and postrace kinetics of cTnI after ultramarathon running is lacking, especially in an Oriental population. Methods Twenty-six participants, including eight hepatitis B virus carrier (HBVc) runners, who finished a 100-km ultramarathon in Taiwan were enrolled. For each participant, blood samples were collected 1 week before the race, as well as immediately and 24 hours after the finish. Results The results showed that 19 runners (73.1%) had postrace elevated cTnI levels and eight (30.8%) had elevated cTnI values lasting more than 24 hours after the run. A multiple linear regression analysis demonstrated that the HBV status was a factor related to the high level of cTnI after 24 hours of running ( β = 0.03, p = 0.08). The recovery of plasma cTnI levels was delayed in ultramarathon runners with latent HBV infection. Among HBVc runners, multiple linear regression analyses showed age ( β = −0.01), previous running experience ( β = −0.06), training distance ( β = 0.37), and 4 hours of running distance ( β = −0.04) as significant predictors of higher postrace cTnI levels. Conclusion For most athletes, cTnI values significantly increased immediately following the race in the absence of adverse clinical sequelae, and HBVc runners had higher and prolonged cTnI levels. While several factors are identified for such HBV effects, the specific causes need further elucidation. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is endemic in Taiwan. After the implementation of universal hepatitis B vaccination, there was a significant reduction of hepatitis B surface antigen (HBsAg) seropositivity and HBV-related hepatocellular carcinoma (HCC) incidence in children, teenagers, and young adults. However, the incidence of HBV-related HCC in adults remains high. Through several community- and hospital-based cohort studies, the viral factors affecting the prognosis of HBV carriers have been illustrated. Serum HBV DNA level > 2000 IU/mL at study entry starts to increase the risks of cirrhosis and HCC in adult patients with chronic HBV infection. In addition, serum HBsAg level > 1000 IU/mL is associated with a higher risk of HCC in HBeAg-negative patients with low viral load. Virologically, HBV genotype C/D and core promote/pre-S mutations correlate with an increased HCC risk. Recently, a risk calculator has been developed to predict HCC in noncirrhotic patients with external validation. Therapeutically, hospital-based cohort and population-based nationwide studies indicated that interferon and nucleos(t)ide analogue treatments could reduce the incidence of HCC over time. Towards the ultimate goal of HBV eradication, several novel agents aiming at viral and host targets are under development. In addition, the immune therapy may play a key role in HBV cure in the foreseeable future. [ABSTRACT FROM AUTHOR]

Clustering of hepatitis B surface antigen (HBsAg) with both subtypes adr and adw in three families of patients with chronic liver diseases or hepatocellular carcinoma was demonstrated in Taiwan where adw is the main subtype. The subtype in the children was similar to that in their mothers, suggesting maternal transmission. In all the family units clustered with different subtypes, the same pattern occurred, invariably with fathers carrying HbsAg/adr and the children carrying HBsAg/adw. The subtype difference clearly rules out the transmission of hepatitis B virus (HBV) from father. Horizontal infection with the locally dominant adw-subtyped HBV in the children of fathers carrying HBsAg/adr explains the discrepancy of the subtypes in these families. Clustering of two HBsAg-positive brothers with hepatocellular carcinoma in one of the families was found. That both adr-subtyped and adw-subtyped HBV are capable of inducing chronic active hepatitis in another family suggests that host factors are probably more important in determining the clinical course of HBV infection. [ABSTRACT FROM AUTHOR]

The author reflects on a study related to the efficacy of Taiwan's national newborn vaccination program which aims to eradicate the hepatitis B virus (HBV) infections in newborns and infants. He argues that though the vaccine program has proved effective in preventing transmission of HBV from mothers to neonates, changes need to be made in Taiwan's national vaccine policy. He acknowledges the remarkable success achieved by the program in reducing the rates of chronic HBV in children.

Objective: To compare the cost-effectiveness of hepatitis B virus (HBV) control strategies combining universal vaccination with hepatitis B immunoglobulin (HBIG) treatment for neonates of carrier mothers., Methods: Drawing on Taiwan's experience, we developed a decision-analytic model to estimate the clinical and economic outcomes for 4 strategies: (1) strategy V-universal vaccination; (2) strategy S-V plus screening for hepatitis B surface antigen (HBsAg) and HBIG treatment for HBsAg-positive mothers' neonates; (3) strategy E-V plus screening for hepatitis B e-antigen (HBeAg), HBIG for HBeAg-positive mothers' neonates; (4) strategy S&E-V plus screening for HBsAg then HBeAg, HBIG for all HBeAg-positive, and some HBeAg-negative/HBsAg-positive mothers' neonates., Results: Strategy S averted the most infections, followed by S&E, E, and V. In most cases, the more effective strategies were also more costly. The willingness-to-pay (WTP) above which strategy S was cost-effective rose as carrier rate declined and was <$4000 per infection averted for carrier rates >5%. The WTP below which strategy V was optimal also increased as carrier rate declined, from $1400 at 30% carrier rate to $3100 at 5% carrier rate. Strategies involving E were optimal for an intermediate range of WTP that narrowed as carrier rate declined., Conclusions: HBIG treatment for neonates of HBsAg carrier mothers is likely to be a cost-effective addition to universal vaccination, particularly in settings with adequate health care infrastructure. Targeting HBIG to neonates of higher risk HBeAg-positive mothers may be preferred where WTP is moderate. However, in very resource-limited settings, universal vaccination alone is optimal.

Background & Aims: Hepatitis B virus (HBV) infection was hyperendemic in Taiwan before the implementation of the universal infant hepatitis B immunization program, which was launched in 1984. Five previous seroepidemiologic surveys were conducted at 0, 5, 10, 15, and 20 years after the launch of the vaccination program., Methods: We enrolled 3332 subjects younger than 30 years of age, with approximately 100 of them in each age cohort. Subjects were recruited voluntarily from schools and other institutions in Taipei, as in previous surveys. HBV seromarkers included hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc). HBV DNA levels were measured in anti-HBc positive/HBsAg negative subjects (anti-HBc only)., Results: The HBsAg, anti-HBs, and anti-HBc seropositive rates were very different between subjects born after the program in 2009 and the baseline group in 1984 (0.9% vs. 10%, 55.9% vs. 24.5%, and 7.0% vs. 28%, respectively). In this 6th survey, we showed that HBsAg prevalence further decreased in the vaccinated cohorts. A positive maternal HBsAg status was found in 86% of vaccine failures. Serum HBV DNA was detected in 4.2% (6/142) of anti-HBc positive/HBsAg negative subjects, with a low level of HBV DNA. All of these six subjects' HBV were genotype C., Conclusions: The universal infant HBV immunization program in Taiwan has completed its 25-year follow-up and its efficacy in young adults is clear. The continued decrease in HBsAg prevalence suggests that the elimination of HBV infection is becoming a reality., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: As neonates born to mothers with positive hepatitis B e antigen may not be completely protected by hepatitis B vaccination, prophylactic lamivudine use in mothers with high viraemia has been proposed. However, the overall effectiveness and the balance between cost and benefit for such a prophylactic strategy have rarely been addressed., Objective: Using a review of recent literature, we aimed to assess the cost effectiveness, from the Taiwanese societal perspective, of administering prophylactic lamivudine to mothers to reduce vertical transmission of hepatitis B virus and its long-term sequelae in neonates., Methods: A meta-analysis of three randomized controlled trials was conducted to evaluate the efficacy of lamivudine versus placebo. A Markov decision model was constructed in which in both treatment arms infants received active and passive immunoprophylaxis. An economic evaluation was performed to calculate costs, acute infections averted, and QALYs gained. Probabilistic sensitivity analyses were conducted and a cost-effectiveness acceptability curve drawn. All these analyses were from the societal perspective. Costs ($US) were valued in year 2008 prices., Result: Supplemental lamivudine use gained an additional 0.0024 QALYs and averted 0.23 acute infections per birth compared with the routine active-passive immunization without lamivudine. The cost-effectiveness analysis suggested that the use of additional prophylactic lamivudine dominated the routine strategy. The acceptability curve suggested that the probability of being cost effective under the willingness-to-pay threshold of $US20,000 was 94%., Conclusion: This analysis suggests that supplemental use of lamivudine in mothers with high hepatitis B viraemia is effective in reducing vertical transmission and may be cost effective, from a Taiwanese societal perspective, compared with the routine active-passive immunization without lamivudine.

The world's first nationwide hepatitis B virus (HBV) universal vaccination program for infants was launched in Taiwan in July, 1984. All infants received three to four doses plasma or recombinant HBV vaccines. In addition, infants of HBeAg-positive mothers received 0.5ml of hepatitis B immunoglobulin within 24hours after birth. The vaccination coverage rate is as high as 97%. Seroprevalence of hepatitis B surface antigen (HBsAg) declined from 9.8% (prevaccination period) to 0.6% in children in Taipei City after 20years of mass vaccination. The seropositive rates for HBsAg, antibody to HBsAg, and antibody to hepatitis B core antigen were 1.2%, 50.5%, and 3.7%, respectively, in those born after the vaccination program (<20years old) in 2004. In line with the decrease of chronic HBV infection, the incidence of hepatocellular carcinoma (HCC) also decreased in children in Taiwan. From 1981 to 1994, the incidence of HCC in 6- to 9-year-olds declined from 0.52/100,000 for those born between 1974 and 1984 to 0.13 for those born between 1984 and 1986 (p<0.001). We extended the observation to 2000, the incidence of HCC per 100,000 children declined from 0.54 to 0.20. The prevalence of a determinant mutants (amino acids 121-149 of HBsAg) in Taiwanese carrier children was 7.8% (eight out of 103) in 1984, increased to 19.6% (10 out of 51) in 1989, peaked at 28.1% (nince out of 32) in 1994, and remained stationary at 23.1% (three out of 13) and about 25% in 1999 and 2004, respectively; it was higher in those fully vaccinated compared with those not vaccinated. The other group of subjects who are susceptible to vaccine failure is the immunocompromized hosts. We observed some de novo HBV infection in children after liver transplantation. Despite of the success of hepatitis B immunization, childhood chronic HBV infection and HCC were not eliminated by the universal vaccination program. Among those HBsAg carriers born after the vaccination program, 89% of their mothers were found to be positive for HBsAg, indicating the importance of maternal transmission. This was also true in the mothers of children with HCC, of them 96% were HBsAg positive. After two decades of universal infant HBV vaccination, we found this program provides long-term protection for up to more than 20years, and a universal booster is not required for the primary HBV vaccinees before adulthood. Mother-to-child transmission, although largely diminished, is still the main cause for immunoprophylaxis failure. The emergence of escape mutant did not impose increased risk of chronic infection at present. Nevertheless, development of new vaccines may overcome the vaccine failure., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Background & Aims: The risk and the predictors of liver disease progression in carriers of inactive hepatitis B virus (HBV) are unclear., Methods: Participants in the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) study who were seronegative for hepatitis B e antigen; had serum levels of HBV DNA <10,000 copies/mL; and did not have cirrhosis, hepatocellular carcinoma, or increased serum levels of alanine aminotransferase were classified as carriers of inactive HBV (n = 1932). Study participants who were seronegative for HB surface antigen and antibodies against hepatitis C virus, yet had similar clinical liver features, were the controls (n = 18,137). Liver-related death and new cases of hepatocellular carcinoma were ascertained through computerized data linkage with National Cancer Registry and Death Certification profiles. The disease progression rates were estimated. The multivariate-adjusted hazard ratios for risk predictors were derived from Cox regression models., Results: There were 20,069 participants, contributing a total of 262,122 person-years, with a mean follow-up of 13.1 years. Annual incidence rates of hepatocellular carcinoma and liver-related death were 0.06% and 0.04%, respectively, for inactive HBV carriers; rates were 0.02%, and 0.02% for controls, respectively. The multivariate-adjusted hazard ratios for carriers of inactive HBV, compared to controls, were 4.6 (95% confidence interval: 2.5-8.3) for hepatocellular carcinoma and 2.1 (95% confidence interval: 1.1-4.1) for liver-related death. Older age and alcohol drinking habits were independent predictors of risk for carriers of inactive HBV to develop hepatocellular carcinoma., Conclusions: Carriers of inactive HBV have a substantial risk of hepatocellular carcinoma and liver-related death compared with individuals not infected with HBV., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Financial constraints are the main concern in implementing nucleic acid testing (NAT) as routine blood screening in Taiwan. The PROCLEIX ULTRIO assay (Ultrio) on the TIGRIS System (Novartis Diagnostics) was evaluated for its operational performance both for individual-donation testing (IDT) and in minipools of 4 (MP4) to develop a feasible solution., Study Design and Methods: Analytical sensitivity was determined by testing WHO international standards. We tested 10,290 blood donors, 4210 in IDT and 6080 in MP4. Potential hepatitis B virus (HBV) yield donors (hepatitis B surface antigen [HBsAg] negative/NAT reactive) were evaluated for up to 9 months' follow-up. Discordant results between the Ultrio assay and the HBsAg tests were further analyzed by HBV antibody serology, alternative NATs, HBV DNA quantification, and sequencing., Results: The 95% limits of detection in IU/mL (95% confidence interval) were as follows: human immunodeficiency virus Type 1 (HIV-1), 18 (12-34); hepatitis C virus (HCV), 4.4 (2.8-8.9); and HBV, 6.3 (4.4-11). The retest rates were 0.55% for IDT and 0.33% for MP4. No HIV or HCV yield cases were found, while there were 12 potential HBV yield cases, nine from IDT and three from MP4 testing. Eleven of them were successfully genotyped as B2. Ten of them returned for follow-up and mostly were determined as occult HBV infection (OBI). The IDT yield rate of 9 in 4210 (0.21%) was fourfold greater than the MP4 yield rate of 3 in 6080 (0.05%; p < 0.05)., Conclusion: The higher yield rate for IDT versus MP4 demonstrates the benefit to implement a more sensitive NAT strategy in regions having significant OBI carriers such as Taiwan.

The universal HBV vaccination programme in Taiwan has effectively led to the reduction of acute and chronic hepatitis B, and of hepatocellular carcinoma among vaccinated children. Seropositivity rates for hepatitis B surface antigen (HBsAg) decreased from 10-17% in those born before the start of the vaccination programme to the current 0.5-1.7%. Nonetheless, breakthrough infection continues to be observed. The main causes include high maternal viral load, intrauterine infection, emergence of S gene mutants and immunosuppression. Among vaccinated individuals with breakthrough HBV infection, sG145R & sT126A/S mutations (which account for 48% of the mutants detected) have become prominent. However, owing to the marked reduction in the HBsAg carrier rate, the prevalence rate of S gene mutants in the total vaccinated population has not increased. With limited evidence of spread, S gene mutants do not need to be incorporated into the HBV vaccine. Further studies are required to design better strategies to prevent breakthrough HBV infection of both wild-type and S gene mutants.

Hepatitis B virus (HBV) is a public health problem worldwide, and apart from infecting humans, HBV has been found in nonhuman primates. This study investigated the prevalence and phylogenetic analysis of hepatitis B virus (HBV) and hepatitis D virus (HDV) among nonhuman primates in Taiwan, an area where human HBV remains endemic. Serum samples from 286 captive nonhuman primates (i.e., 32 great apes [Pan troglodytes and Pongo pygmaeus], 42 gibbons [Hylobates sp. and Nomascus sp.], and 212 Cercopithecidae monkeys) were collected and tested for the presence of HBV- and HDV-specific serologic markers. None of the Cercopithecidae monkeys were reactive against serologic markers of HBV. In contrast, 21.9% (7/32) of great apes and 40.5% (17/42) of gibbons tested positive for at least one serologic marker of HBV. Of these, five gibbons were chronic HBV carriers, characterized by presence of HBV DNA and hepatitis B surface antigen in the serum. HBV DNA was also detected in the saliva of three of the chronic carries. None of these HBV carrier gibbons exhibited symptoms or significant change in serum clinical chemistry related to HBV infection. Phylogenetic analysis of the complete HBV genome revealed that gibbon viruses clustered with other HBV isolates of great apes and gibbons from Southeast Asia and separately from human-specific HBV. None of the HBV-infected animals were reactive against HDV. These findings indicate that HBV found in these animals is indigenous to their respective hosts and might have been introduced into Taiwan via the direct import of infected animals from Southeast Asia. To reduce the horizontal and vertical transmission of HBV in captive animals, the HBV carriers should be kept apart from uninfected animals.

Several reports recently found that patients with B cell non-Hodgkin's lymphoma (NHL) had a higher carrier rate of hepatitis B surface antigen (HBsAg). The current study aimed to examine the hepatitis B virus (HBV) infection status of NHL patients in Taiwan, an HBV-endemic area. Serum HBV and serum hepatitis C virus were measured in 471 NHL patients and 1,013 non-lymphoma cancer patients enrolled between February 2000 and March 2007. Furthermore, nested polymerase chain reaction of HBV-DNA was used to examine the sera from selected patients in these two populations and healthy volunteers for the presence of occult HBV infection. The infection rates (as indicated by the rates of HBsAg and occult HBV) were compared between different groups. There was a higher incidence of HBV infection in B cell NHL patients (23.5%), especially patients with diffuse large B lymphoma, than solid tumor patients (15.6%, P = 0.001). Among HbsAg-negative patients, those with B cell NHL had a higher prevalence of occult HBV infection (6%) than those with non-lymphoma solid tumors and healthy volunteers, 0% and 0.9%, respectively (P = 0.005). B cell NHL patients, even HBsAg-negative B cell NHL patients, but not T cell NHL patients, have a higher incidence of HBV infection than patients with solid tumors. Our findings support the etiologic role of HBV infection in B cell NHL.

Background: Blood donors in Taiwan currently are screened for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection by immunoassay. The risk of enzyme immunoassay (EIA)-negative, nucleic acid amplification technology (NAT)-reactive donations is not well understood. This study aimed to screen for such donors in Taiwan by a multiplex test (cobas TaqScreen, Roche) on a commercially available NAT system (cobas s 201 system, Roche)., Study Design and Methods: NAT was performed on donors without prescreening in pools of six and NAT-reactive pools were then resolved to the single donation. Individual-donor NAT-reactive samples were discriminated by a commercially available polymerase chain reaction (PCR)-based diagnostic assay (COBAS AmpliScreen, Roche). Samples with EIA- and NAT-discordant results were investigated with supplemental serologic and confirmatory tests. Each sample taken from follow-up of HBV NAT yield cases was tested for HBV serologic profile, NAT, and viral load. The sensitivity and performance efficacy were also evaluated., Results: The 95 percent limit of detection (LOD) for HBV, HCV, and HIV were 5.09, 11.83, and 62.53 IU per mL, respectively. Among 10,727 seronegative donations, 12 HBV NAT yield cases (0.11%) and 1 HCV NAT yield case (0.01%) were detected. Follow-up results for 1 to 8 months showed that the HCV yield case was a window case and all HBV NAT yield cases were occult carriers., Conclusion: The use of NAT detected occult HBV and reduced HCV window period. The yield rate, especially occult HBV, was 10- to 100-fold higher than that in developed, HBV nonendemic countries. Therefore, NAT implementation for routine donor screening in a more cost-effective manner should contribute to safer blood transfusion in Taiwan.

In pregnant women and children, the hepatitis B virus can cause acute or chronic hepatitis or liver cirrhosis. Perinatally-acquired infection causes persistent infection in 90% of cases and can be avoided through administration of the hepatitis B vaccine and specific immunoglobulin in the first day of life. Prevention of mother-to-child transmission requires screening for hepatitis B surface antigen (HBsAg) in pregnant women to identify which newborns should be immunized. In some countries this strategy is substituted by universal vaccination of neonates. In infected children, inactivation of viral replication with conversion of HBeAG-positive to anti-HBe-positive status usually occurs. If this seroconversion does not take place and necroinflammatory activity persists in the liver, the use of antiviral agents such as interferon or nucleoside and nucleotide analogs is warranted.

We established a standardized surveillance system using the Chinese Exposure Prevention Information Network to estimate the frequency of percutaneous injuries (PCIs) in Taiwanese healthcare workers (HCWs). Fourteen hospitals employing 8,132 HCWs participated and a total of 583 PCIs were reported. The annual number was estimated to be 8,058 PCIs per hospital size, 8,100 per HCWs, and 8,286 per inpatient-day; indicating similar estimates using different denominators. The estimated annual frequency of pathogen-specific PCIs was 1,168 for hepatitis B, 1,263 for hepatitis C, and 59 for HIV. This study documents the annual incidence of PCI among HCWs showing important potential exposure to viral hepatitis and HIV in Taiwan.

Background: Infection with hepatitis B virus (HBV) in early life frequently results in persistent infection, and clustering of the chronic infection within a family is common. However, the relative contribution of perinatal mother-to-infant transmission or early horizontal transmission to the intrafamilial clustering of HBV infection remains unclear. Therefore, we used HBV genotyping and phylogenetic analysis to elucidate the modes of intrafamilial HBV transmission in Taiwan., Methods: HBV genotypes and serological markers were determined for 103 individuals from 20 families with evidence of clustering HBV infection., Results: Three patterns of intrafamilial clustering of HBV infection were identified. Among the 20 families, 8 included a hepatitis B surface antigen (HBsAg)-positive mother (pattern I), 7 included an HBsAg-positive father (pattern II), and in the remaining 5, both parents were positive for HBsAg (pattern III). The rates of HBsAg positivity for children of the 3 representative groups of families were 85.7%, 65.4%, and 87.5%, respectively (P = .16). The identical genotyping results between index parent and carrier children indicated that pattern I clustering was caused by maternal transmission, whereas pattern II clustering was caused by paternal transmission. In pattern III clustering, a concordant HBV genotype between carrier children and mother or father was found in 3 and 2 families, respectively. The modes of transmission were confirmed by phylogenetic analysis in 1 family of each pattern., Conclusions: In Taiwan, maternal and paternal transmissions are both important in the intrafamilial spread of HBV infection.

This study investigated and compared Taiwanese dental students' knowledge of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV infection, attitudes toward infected patients, and important factors associated with the willingness to treat infected patients. In 2001, a self-administered questionnaire survey was conducted on all 1930 dental students enrolled from seven dental schools in Taiwan, with a response rate of 54.4%. Multiple logistic regression analysis was applied to assess the relationship between multiple factors and willingness to treat. Multivariate analysis was used to compare knowledge levels and the willingness. Of the respondents, 80%, 75%, and 49% were willing to treat HBV-, HCV-, and HIV-infected patients, respectively, and differences among the percentages were statistically significant. Students were less knowledgeable about HCV infection compared to HBV and HIV infection. Factors significantly associated with willingness to treat HBV- or HCV-infected patients were: feeling morally responsible and being able to treat infected patients safely. Those feeling morally responsible (odds ratio [OR] = 33.0, 95% confidence interval [CI] = 15.2, 71.8) and those being able to treat infected patients safely (OR = 4.1, 95% CI = 1.7, 9.9) were more willing to treat HIV patients. Taiwanese dental students were more willing to treat HBV- and HCV-infected patients than to treat HIV-infected patients.

Background/aims: Familial clustering of hepatitis B virus (HBV) infection is related to perinatal transmission, and is the main cause of familial-type hepatocellular carcinoma (HCC). The route of HBV transmission differs between the children and siblings of patients with HCC. This study examined the differences in HBV carrier rates and HCC-related mortality between two generations in HCC families., Methods: From 1992 to 1997, relatives of individuals with HCC were screened prospectively with ultrasonography, alpha-fetoprotein, liver biochemistry tests and viral markers. Total HCC-related deaths during a 9-year period were compared between the generations of index patients and their children., Results: The study included a total of 13676 relatives in two generations. More HCC-related deaths occurred in the index patient generation than in the child generation. Furthermore, children of female index patients had higher rates of liver cancer related mortality than children of male index patients. The same was true when the analysis was limited to male HBV carriers. The prevalence of HBsAg in the offspring of HBsAg positive mothers was 66% in the child generation and 72% in the index patient generation. These high prevalences indicated high maternal HBV replication status., Conclusions: Perinatal transmission and maternal viral load are important risk factors in hepatocarcinogenesis.

Objectives: To estimate the number of health care workers (HCWs) in Taiwan at risk annually for contracting hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV after a needlestick and sharps injury (NSI) with a used hollow-bore needle., Methods: All patients hospitalized in 1 tertiary hospital between September 1997 and June 1998 had routine pathological work-ups. On the first day of the months of September 1997, December 1997, March 1998, and June 1998, 1805 samples of deidentified residual sera randomly sampled from 18,474 inpatients older than 6 years were serologically tested for antigens to HBV (HBsAg and HBeAg) and antibodies to HCV (anti-HCV) and HIV (anti-HIV) with enzyme-linked immunosorbent assay reagents. The frequency of NSIs with contaminated devices in HCWs from 16 public teaching hospitals between July 1996 and June 1997 and the serologic results were used to extrapolate the estimated annual rate of seroconversion in HCWs after an NSI., Results: Of the 1805 samples tested, 16.7% were seropositive for HBsAg (of which 1.7% were positive for HBeAg), 12.7% were positive for anti-HCV, and 0.8% were positive for anti-HIV. Of the 7550 NSIs reported by 8645 HCWs, 66.7% involved a contaminated hollow-bore needle. From these data, 308 to 924 HCWs were estimated to be at risk for contracting HBV; 334 to 836 were at risk for contracting HCV; and, at the most, 2 were at risk for contracting HIV. The estimated annual number of contaminated NSIs sustained by 4 categories of HCWs ranged from 0.3 to 0.7, resulting in 543 nurses, 113 technicians, 80 physicians, and 66 supporting staff to be at risk annually of acquiring HBV infection. The numbers of HCWs estimated to be at risk of acquiring HCV were 596 nurses, 90 physicians, 84 technicians, and 30 supporting staff. The risk of acquiring HIV was low, with 1 nurse and possibly 1 other staff potentially exposed annually., Conclusions: Our estimates of the risk for seroconversion after an NSI have demonstrated that an occult risk can be formulated into a quantifiable risk. The number of susceptible HCWs at risk for seroconversion is as many as 1762 annually. With the number of nurses employed and the frequency with which they use sharps and sustain an NSI, 64.7% of all possible seroconversions will be in the nursing staff. This is a salient reminder of the importance of the introduction of early training in safe-needle-handling techniques before nurses enter their internship in countries where safety equipment, safety instructions, and staff vaccination programs are absent.

Background: Hepatitis B virus (HBV) infection is hyperendemic in Taiwan. It is almost impossible for us to reject organ donors or recipients with positive serum hepatitis B surface antigen (HBsAg). We report our experience with HBV infection in heart transplant recipients with particular attention to outcome of recipients who were HBsAg+ or who had received donor hearts from HBsAg+ donors., Methods: We performed a retrospective review of medical records., Results: In the study, we included 101 heart recipients with post-transplant survival of more than 6 months. According to pre-transplant HBV serology markers, we divided patients into 4 groups. Group 1 (n = 8) had been HBsAg+ at the time of heart transplantation. Of these, 6 patients had HBV reactivation in the post-transplant follow-up and needed lamivudine treatment. Complete response was achieved in all 6 patients; however, HBV recurrence occurred in 1 patient after 8 months of lamivudine treatment. The recurrence remained under partial control. Group 2 (n = 16) was HBV naïve at the time of heart transplantation. Of these, 2 received HBsAg+ donor hearts under perioperative hepatitis B immunoglobulin prophylaxis. HBV infection was successfully prevented in 1 patient, but the other contracted HBV hepatitis, which was successfully treated with lamivudine. In Group 2, 10 patients received donor hearts from anti-HBs+ donors, and none contracted HBV hepatitis after transplantation. Group 3 (n = 55) had protective anti-HBs antibody at the time of heart transplantation either from previous HBV vaccination (n = 10) or from natural HGB infection (n = 45). HBsAg+ donor hearts were transplanted into 2 patients with anti-HBs from previous HBV vaccination, and into 8 patients with anti-HBs form natural HBV infection. However, none of these 10 patients who received HBsAg+ donor hearts had HBV hepatitis after transplantation. Group 4 (n = 22) was HBs-, anti-HBs-, and anti-HBc+ at the time of heart transplantation. Of these, 7 patients received HBsAg+ donor hearts. Six patients experienced no HBV hepatitis after heart transplantation, and serum HBV DNA by polymerase chain reaction (PCR) at the time of heart transplantation was negative in all 6 patients. One patient had HBV hepatitis after transplantation, and serum HBV DNA by PCR at the time of heart transplantation also was positive., Conclusion: HBV reactivation after the heart transplantation was common but usually well controlled with lamivudine treatment. Therefore, HBV carrier status should not contraindicate heart transplantation. HBsAg+ donor hearts were safely transplanted into anti-HBs+ recipients; therefore, HBsAg+ itself was not a contraindication to heart donation. Patients with HBsAg-, anti-HBs-, anti-HBc+, and negative HBV DNA in the serum by PCR could be protected from HBV infection from HBsAg+ donor hearts. However, patients with HBsAg-, anti-HBs-, anti-HBc+, and positive HBV DNA in the serum by PCR should be recognized as HBV carriers and closely followed for potential HBV flare-up after heart transplantation.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major agents responsible for hepatitis in Taiwan. The purpose of this study was to assess the serum alanine aminotransferase (ALT) activity in relation to HBV and HCV infection among drug abusers. This survey included 769 male drug abusers aged 14-59 years, from the Kaohsiung Narcotic Abstention Institute and Kaohsiung Prision. The prevalence of HBsAg seropositivity was 21.5%, and anti-HCV seropositivity was 27.2%, respectively. Drug abusers with HBsAg or anti-HCV had higher serum AST and ALT levels than those without HBsAg and anti-HCV. The prevalence of raised ALT and AST (> or =45 IU/liter) in the HCV-positive group was more significant than in the negative group, while that of the HBsAg-positive group did not reach statistical significance. Among the HCV-positive group, ALT levels are more closely associated with HCV infection than AST levels. Our results indicated that HCV infection plays an important role in the etiology of raised ALT activity among drug abusers, while HBV infection plays a minor role. ALT screening still remains a simple and valuable method in the early recognition of HCV infection.

In order to prevent liver cirrhosis and hepatocellular carcinoma in later life, it is essential to prevent HBV infection in infants. If the mother is chronically infected with HBV and is also positive for HBeAg, 80-90% of the newborns become chronically infected, whereas if the mother is positive for anti-HBe, only some newborns will develop acute hepatitis or fulminant hepatitis. It is necessary to screen pregnant women for HBsAg and prevent mother-to-infant infection of HBV, treating the infant with hepatitis B hyperimmune globulin at birth, followed by HBV vaccination. In highly endemic areas of HBV, universal HBV vaccination of all newborns is advisable.

A high prevalence of HBeAg among HBsAg-positive mothers at the time of delivery results in a high prevalence of hepatitis B vertical transmission. From 1990 to 1995, 896 pregnant HBsAg-positive women, including 411 (46 per cent) HBeAg-positive subjects, were enrolled in our study to analyse the secular change in HBeAg prevalence. Their mean age, number of pregnancies and parity were 29.5 +/- 4.1 years, 2.0 +/- 1.2, and 0.6 +/- 0.7, respectively. The prevalence rates of HBeAg were 48, 54, 49, 47, 40, and 40 per cent among the subjects enrolled in 1990, 1991, 1992, 1993, 1994, and 1995, respectively. In univariate analyses, prevalence of HBeAg decreased by the calendar year of pregnancy (p = 0.01), and also by age (p < 0.00001), number of pregnancies (p < 0.0001) and parity (p < 0.0002). After adjusting for age in multiple logistic regression, the calendar year of pregnancy was still the independent variable, while gravida and parity became insignificant. The odd ratios (95 per cent confidence interval) of HBeAg negative-seroconversion in the equations were 1.09 (1.00-1.19) per calendar year and 1.14 (1.10-1.18) per year of age. Our results have shown a secular decrease in HBeAg-prevalence among pregnant HBsAg-positive women in Taiwan.

In the early 1980s, 15-20% of the population of Taiwan were estimated to be hepatitis B virus (HBV) carriers. A programme of mass vaccination against hepatitis B was therefore launched in 1984. In the first 2 years, newborns of all HBVsurface antigen (HBsAg)-positive mothers were vaccinated. Since 1986, all newborns, and then year by year pre-school children, primary school children, adolescents, young adults and others have also been vaccinated. Vaccination coverage is over 90% for newborns, with 79% of pregnant women screened for HBsAg. The proportion of babies born to highly infectious carrier mothers who also became carriers decreased from 86-96% to 12-14%; the decrease was from 10-12% to 3-4% for babies of less infectious mothers. Between 1989 and 1993, the prevalence of HBsAg in children aged 6 years also fell from 10.5 to 1.7%. The average annual incidence of hepatocellular carcinoma in children aged 6-14 years decreased significantly from 0.7 per 100,000 in 1981-1986 to 0.36 per 100,000 in 1990-1994 (P<0.01). Similarly, the annual incidence of hepatocellular carcinoma in children aged 6-9 years declined from 0.52 per 100,000 for those born in 1974-1984 to 0.13 per 100,000 for those born in 1986-1988 (P<0.001). The mass vaccination programme is highly effective in controlling chronic HBV infection and in preventing liver cancer in Taiwan. If a coverage rate of 90% of all newborns vaccinated against hepatitis B can be maintained, by the year 2010 the carrier rate in Taiwan is expected to decline to <0.1%.

Sharps injuries are a major cause of transmission of hepatitis B and C viruses and human immunodeficiency virus in health-care workers. To determine the yearly incidence and causes of sharps injuries in health-care workers in Taiwan, we conducted a questionnaire survey in a total of 8645 health care workers, including physicians, nurses, laboratory technicians, and cleaners, from teaching hospitals of various sizes. The reported incidence of needlestick and other sharps injuries was 1.30 and 1.21 per person in the past 12 months, respectively. Of most recent episodes of needlestick/sharps injury, 52.0% were caused by ordinary syringe needles, usually in the patient units. The most frequently reported circumstances of needlestick were recapping of needles, and those of sharps injuries were opening of ampoules/vials. Of needles which stuck the health-care workers, 54.8% had been used in patients, 8.2% of whom were known to have hepatitis B or C, syphilis, or human immunodeficiency virus infection. Sharps injuries in health-care workers in Taiwan occur more frequently than generally thought and risks of contracting blood-borne infectious diseases as a result are very high.

Objective: To elucidate possible routes and predictors of perinatal transmission of hepatitis B virus (HBV)., Method: This was a prospective follow-up study. One hundred and forty-seven out of 1762 pregnant women who were screened in the antenatal clinic of a university teaching hospital were HBsAg carriers. Enzyme immunoassay was used for determination of hepatitis B markers. Occurrence of HBsAg in newborns' gastric aspirates, newborns' and infants' blood, and maternal milk samples were determined. Their relationship with delivery routes and duration of the first stage of labor were analyzed by chi square test., Results: The presence of HBsAg in newborns' gastric aspirates was strongly associated with the acquisition of HBsAg by the babies. There was no correlation between the rate of infant antigenemia and the duration of the first stage of labor, nor did cesarean section decrease the rate of vertical transmission of HBV., Conclusions: This is the first report to provide direct evidence for the major role of the oral route in vertical transmission of HBV during delivery. In addition to maternal serum HBeAg, HBsAg status in newborn's gastric aspirates is another important determinant for vertical transmission of HBV.

We investigated underlying risks for hyperendemic hepatitis C virus (HCV) infection among the 1853 inhabitants of a mountainous village in Eastern Taiwan with high prevalence of HCV and hepatitis B virus (HBV). Among the 80 selected adults, we found that having resided away from the village before 1985 was protective against HCV infection, while residing in the village after 1985 posed little risk for HCV infection to children and young adults < 30 years of age. Among the 559 school children 7 through 14 years of age, anti-HCV prevalence was 1.9%, and the HBV carrier rate was 29%. Following up 270 children 1 year later, we found that new HCV infection occurred in 0.74% and new or repeated HBV infection occurred in 6.5% of the children, indicating distinct transmission patterns between HBV and HCV. Children of anti-HCV-positive mothers were either anti-HCV-negative or were infected by distinct genotypes of HCV from those infecting their mothers; most married couples in whom both were infected, were infected by HCV of discordant genotypes, indicating negligible importance of sexual or vertical HCV transmission. A case-control study comparing 13 anti-HCV-positive and 53 anti-HCV-negative children showed that having received parenteral medication in local clinics was a significant risk for HCV infection. Our data indicate that, unlike the case of HBV, HCV transmission by vertical or sexual route, or through casual contact are extremely inefficient, and our data further suggest that HCV hyperendemicity is unlikely to persist as a result of the more stringent practice of parenteral precautions in nearly all aspects of daily life.

Background: A nationwide hepatitis B vaccination program was implemented in Taiwan in July 1984. To assess the effect of the program on the development of hepatocellular carcinoma, we studied the incidence of this cancer in children in Taiwan from 1981 to 1994., Methods: We collected data on liver cancer in children from Taiwan's National Cancer Registry, which receives reports from each of the country's 142 hospitals with more than 50 beds. Data on childhood liver cancer were also obtained from Taiwan's 17 major medical centers. To prevent the inclusion of cases of hepatoblastoma, the primary analysis was confined to liver cancers in children six years of age or older. Data were also obtained on mortality from liver cancer among children., Results: The average annual incidence of hepatocellular carcinoma in children 6 to 14 years of age declined from 0.70 per 100,000 children between 1981 and 1986 to 0.57 between 1986 and 1990, and to 0.36 between 1990 and 1994 (P<0.01). The corresponding rates of mortality from hepatocellular carcinoma also decreased. The incidence of hepatocellular carcinoma in children 6 to 9 years of age declined from 0.52 for those born between 1974 and 1984 to 0.13 for those born between 1984 and 1986 (P<0.001)., Conclusions: Since the institution of Taiwan's program of universal hepatitis B vaccination, the incidence of hepatocellular carcinoma in children has declined.

Although most hepatitis B virus (HBV) related chronic liver diseases manifest themselves in adulthood, HBV infection usually begins in infancy or early childhood in hyperendemic areas. The following factors affect the natural course of HBV: 1) host factors: a) initial age of infection: the younger the patient at infection, the more chance the disease will run a chronic course. Immune tolerance to hepatitis B e antigen (HBeAg) and core antigen persists for a period of time in young children. b) the immune status of the host: the usage and tapering of immunosuppressants may induce a severe course with a fatal outcome; 2) maternal carrier status: children of HBeAg seropositive mothers are more immune tolerant to HBV, and thus have lower rates of HBeAg and hepatitis B surface antigen (HBsAg) seroconversion; and 3) viral factors: mutations of the HBV precore, core or core promoter genes are related to fulminant hepatitis B or severe chronic hepatitis B. However, this is a matter of contention. Since July 1984, a nationwide HBV vaccination program has been successfully conducted in Taiwan. In 1994, the HBsAg carrier rate in Taipei city was reduced to < 1% in children younger than 10 years of age. Continuous efforts in immunoprophylaxis will hopefully further reduce the incidence of hepatitis and hepatocellular carcinoma in the next generation.

To evaluate the role of maternal hepatitis B virus (HBV) DNA levels in perinatal infection, two nested case-control studies were done within a cohort of 773 hepatitis B surface antigen (HBsAg)-positive Taiwanese women and their infants. As serum HBV DNA levels increased from < 0.005 to > or = 1.4 ng/mL among the hepatitis B e antigen (HBeAg)-positive mothers, the odds ratio (OR) for having a persistently infected infant increased from 1.0 to 147.0 (P for trend < .001). Among HBeAg-negative mothers, the OR for having a persistently infected infant was 19.2 (95% confidence interval, 2.3-176.6) in mothers with high versus low levels of serum HBV DNA. A logistic regression analysis identified maternal HBV DNA to be a stronger independent predictor of persistent infection than HBeAg status. Thus, perinatal exposure to high levels of maternal HBV DNA is the most important determinant of infection outcome in the infant.

Sixty adult patients with acute viral hepatitis B (AVHB) and 93 controls were interviewed to assess potential risk factors of hepatitis B. Heterosexual contact was the only significant factor, and it was associated with 83% of cases. A history of having new sex partners or multiple sex partners within 6 months before the onset of AVHB or first sexual contact before 20 years of age were significantly associated with HBV infection (P < .005, respectively). There was a dose-response relationship between the number of sex partners and the risk of HBV infection. In multivariate analyses, a history of having new sex partners was the most important factor. Moreover, 18 of 24 sex partners of the patients were serum hepatitis B surface antigen- and HBV DNA-positive. Heterosexual contact is, therefore, the predominant route of HBV transmission among adults in Taiwan. Susceptible adults should receive vaccination.

During the last two decades an economic boom has occurred in Taiwan, a region where the prevalence of both hepatitis A and B virus infection was formerly very high. To examine the impact of socioeconomic developments on the secular trend and geographical variation in hepatitis A and B virus infection, 875 adolescents selected randomly from 20 junior high schools were studied. Serum samples collected from the subjects were tested for hepatitis A antibody (anti-HAV) and hepatitis B surface antigen (HBsAg) by enzyme immunoassay using commercial reagents. The anti-HAV prevalence increased from northern through central to southern Taiwan; the prevalence was highest in aboriginal townships and lowest in metropolitan precincts. This striking variation in anti-HAV prevalence in different geographical locations and at different urbanization levels remained significant in multiple logistic regression analysis. The HBsAg prevalence was significantly higher in aboriginal townships than in rural and urban townships and metropolitan precincts. In addition, HBsAg prevalence was related inversely to the number of physicians per 1,000 population. The prevalence of both anti-HAV and HBsAg declined significantly during the last decade in Taipei City and County. The decrease in anti-HAV prevalence may be due to improvements in environmental hygiene, water supply, and food sanitation, while the decline in the HBsAg carrier rate may result from the use of disposable needles and syringes as well as screening for HBsAg in blood banks.

The authors followed 147 children from 113 families who were susceptible to hepatitis B virus infection for a total of 275 person-years. Among these children, 19 became infected with the hepatitis B virus and thus became new subclinical cases. In this cohort study, parents played a minor role in hepatitis B virus horizontal transmission. On the other hand, the estimated incidence rate ratio of hepatitis B virus infection for siblings of a hepatitis B e antigen (HBeAg) carrier was 2.8 (95% confidence interval 1.1-7.4) when compared with those children without a HBeAg sibling carrier as analyzed by multiple logistic regression. The adjusted incidence rate ratio among siblings increased with increased number of HBeAg carriers. In addition, intramuscular injections played an important role in hepatitis B virus transmission in children. It was found that 61.8% (170/275 person-years) of the children had received intramuscular injections. Most of the injections were administered at private clinics over a 2-year period. Hepatitis B virus infection showed a correlation with injection (adjusted incidence rate ratio = 3.3, 95% confidence interval 1.1-9.5) and with frequency of injections. The authors concluded that HBeAg was a valuable marker for infectivity in hepatitis B virus horizontal transmission. Furthermore, the authors found that hepatitis B virus infection is independently transmitted from sibling to sibling, and by iatrogenic injections because improperly sterilized syringes were shared in areas where hepatitis B is prevalent and intramuscular injection is common.

From among 2,375 young men, examined by doctors, 111 tattooed subjects were found. Twenty one subjects reported engaging in promiscuous sexual behavior or being intravenous drug abusers, and so were excluded. The other 90 were evaluated. To make up the control group, 180 non-tattooed subjects from the remaining 2,264, who neither engaged in promiscuous sexual activity nor were intravenous drug abusers, were matched from household registry reports by age, sex, education, occupation, and geographic origin from Mainland China, where their parents were born. IgG antibody of hepatitis A (anti-HAV) and markers of hepatitis B were tested in serum with radioimmunoassay. In the prevalence rate of hepatitis A and carrier rate of HBsAg there were no differences between the tattooed and the non-tattooed groups. However, the prevalence odds ratio of hepatitis B virus (HBV) infection for the tattooed group was 8.1 (95% CI 1.9-34.8) as compared to the non-tattooed groups. Moreover, there was a trend correlation when the prevalence rates of hepatitis B were compared for the group with multiple sites of tattoos, for the group with one site of tattoos, and for the non-tattooed group (p = 0.002). These findings suggested an association between HBV infection and tattooing. Tattoo exposure, with improper or no sterilization of the needle, seems to appear to increase the risk of HBV infection in the already high risk endemic area in question.

A randomized double-blind, placebo-controlled efficacy trial of hepatitis B immune globulin (HBIG) for prevention of the mother-to-infant transmitted HBsAg carrier state was conducted in Taiwan where the carrier rate in the general population is 15 to 20%. HBIG was given immediately after birth to infants of e antigen positive HBsAg carrier mothers, and all infants were followed for at least 15 months. Among 61 placebo recipients, the carrier rate was 92%; compared with 26% among 57 infants who received 0.5 ml HBIG at birth, 3 months, and 6 months, and 54% among 67 infants who received a single 1.0 ml dose of HBIG at birth only. Efficacy was 71 and 42%, respectively, for the two treatment schedules. The most common response of HBIG-treated infants was passive-active immunization which was 27% in the single-dose group and 61% in the three-dose group. Some of the infants who became carriers were probably infected as HBIG protection waned, and we expect that higher efficacy can be achieved by hepatitis B vaccine in conjunction with HBIG.

The relationship of e antigen (eAg) and its antibody (anti-e) to vertical transmission of hepatitis B surface antigen (HBsAg) from chronic asymptomatic HBsAg carrier women to their children was investigated in Taiwan. Sera from 20 of the 62 women studied were positive for eAg (32%); serum from only one woman was positive for anti-e (2%). A total of 85% of the babies born to eAg positive mothers became HBsAg carriers, while only 31% of the babies became carriers when the mother was eAg negative. Maternal e antigenemia correlated with a high HBsAg titer, and both parameters were equally good predictors of vertical transmission.

To determine the frequency of vertical transmission of hepatitis B antigen (HB5 Ag) from asymptomatic carrier mothers in Taiwan to their offspring, HB5 Ag was sought by radioimmunoassay and complement fixation. Of 158 babies born to carrier mothers, antigenemia developed in 63; 51 of these antigenemic babies had become antigen positive within the six months of life. Three inter-related factors were found to increase the risk that antigenemia would develop in the infant: a high maternal complement-fixation titer for HB5 Ag: presence of HB5 Ag in the baby's umbilical-cord blood: and antigenemia in siblings. In contrast to previous studies, these findings indicate that vertical transmission from carrier mothers frequently occurs, at least in Taiwan, and may partially explain Taiwan's high prevalence of HB5 Ag.

Hepatitis B antigen (HB Ag) was detected by complement fixation (CF) in serum samples of 7.5% of 1,106 pregnant Chinese women tested in Taipei, Taiwan. HG Ag persisted in all but one of 42 women followed for 1 to 18 months (average, nine months) after delivery, and 27 of the 43 infants (63%) born to those women became antigen-positive. Persistance of the antigen was more common than transient or intermittent antigenemia. Twelve had antigenemia when first tested, while 15 later developed antigenemia, usually during the first six months of life. Only one infant developed antibody to HG Ag (anti-HB Ag), and this occurred after transient antigenemia. The HB Ag was found in two of 32 (6%) fathers, and in 18 of 27 (67%) older siblings. The antigen was more common among siblings of antigen-positive than among those of antigen-negative infants. These findings demonstrate that in Taiwan, infants born to mothers who are asymptomatic carriers of HB Ag commonly become infected by heaptitis B (HB) virus. Exposure of infants near the time of birth may be important maintaining the high, chronic HB Ag carrier rate in Taiwan.

Three hundred thirty-seven community-based spouses were tested for the presence of hepatitis B virus (HBV) markers to assess the direction of HBV transmission between couples. The prevalence rate of HBV infection among husbands whose wives were hepatitis B surface antigen (HBsAg)-positive was higher compared with those whose wives were HBsAg-negative. Moreover, the frequency of HBV seropositivity among husbands was 100% if their wives carried HBeAg and showed a trend correlation (P = .009). The prevalence difference was 13.8%, and the 95% confidence interval (95% Cl) was 7.9-19.7% after adjusting for spouses' age. In contrast, HBV infection rate of wives did not show an association with the husbands' HBsAg or HBeAg carrier status. The prevalence difference was 7.1%, but 95% Cl was -2.5-16.8% after adjusting for spouses' age. Female to male transmission of HBV between spouses appears to be more efficient.

To study the usefulness of IgM hepatitis B core antibody (anti-HBc IgM) for detecting hepatitis B virus infections in infants of hepatitis B surface antigen (HBsAg) carrier mothers, serial serum samples from 86 infants of carrier mothers were tested for anti-HBc IgM with a highly specific enzyme immunoassay. Asymptomatic hepatitis B infection occurred frequently in infants under 12 mo of age. Anti-HBc IgM never became positive in 25 infants infected under 9 mo old. It was positive in only 1 of 6 infected at 9 mo and 4 of 13 infected at 12 mo of age. The IgM antibody lasted for less than 6 mo. Although the infection was delayed in 28 infants receiving hepatitis B immune globulin, the poor anti-HBc IgM response did not seem to be due to the immune prophylaxis. Our study clearly indicates the limitation of anti-HBc IgM for detecting acute hepatitis B infection in infants born to HBsAg carrier mothers.

A follow-up study of 147 babies born to mothers known to be carriers of hepatitis B surface antigen (HBsAg) revealed no evidence for a relationship between breast-feeding and the subsequent development of antigenaemia in the babies. All babies were tested at three or more months of age, and the mean age at last follow-up was eleven months with a mean of three serum specimens per baby (not counting cord-blood specimens). The frequency of acquisition of HBsAg and anti-HBs was almost identical among breast-fed and non breast-fed infants. The frequency of other variables known to influence the development of antigenaemia among infants of carrier mothers did not vary according to breast-feeding status: mother's HBsAg titre, HBsAg positivity rate in cord-blood specimens, and HBsAg prevalence among siblings. 32 breast-milk specimens from carrier mothers were all HBsAg negative.

A sensitive radioimmunoassay technique was used to detect hepatitis B e antigen (HBeAg). A strong correlation was found between HBeAg positivity of the serum of hepatitis B surface antigen (HBsAg) carrier women in Taiwan and the subsequent development of surface antigenemia in their babies. All babies who became chronic HBsAg carriers were born to HBeAg positive women, maternal HBeAg positivity being a better prior indication of chronic antigenemia developing in the baby than the HBsAg titer in the mother's serum.

To combat hepatitis B virus (HBV) infection in Taiwan, a mass immunoprophylaxis program was launched on July 1, 1984, aiming first at prevention of chronic HBV carriage from perinatal mother-to-infant infection. In the first 15-month period, 352,721 (78%) of 450,585 pregnant women were screened for hepatitis B surface antigen (HBsAg); HBsAg was present in 62,359 (18%), with 50% of them categorized as highly infectious. Infants born to HBsAg-positive women were given 5 micrograms of a plasma-derived hepatitis B vaccine at ages 1, 5, and 9 weeks, with a booster at age 12 months. Infants of highly infectious carrier mothers received an additional 0.5 mL of hepatitis B immune globulin within 24 hours after birth. The coverage rate of the hepatitis B immune globulin was 77% in 27,375 infants born to highly infectious mothers, and that of the first, second, third, and the fourth doses of vaccine was 88%, 86%, 84%, and 71%, respectively, in infants of 55,620 carrier mothers. The reported untoward reactions to immunization were negligible. We conclude that a mass hepatitis B vaccination program is feasible in hyperendemic areas such as Taiwan; this should be a significant step toward the effective control of HBV infection in these areas.