Epidemiology, Transmission, and Prevention Issues


1107. A Novel Method for Reaching At Risk Populations in Community Outreach Hepatitis Screening Programs

H. J. Guerrero; W. Gosbee; C. Fullmer



Seventy percent of all Hepatitis C Virus (HCV) positive individuals are unaware that they are infected. The Hepatitis C Virus (HCV) is four times more prevalent than HIV. It is estimated that 4-5 million people are living with HCV in the United States (compared to 1 million with HIV). PCP’s do not regularly ask about hepatitis C risk factors and screening tests are not done. Health fairs may seem like the best way to reach the most people for HCV screening but our research has shown that this is not the case. Community outreach and screening efforts play a key role in identifying and treating infected individuals and it is important for organizations that are doing the screening to do so in the most effective and cost-saving way.


In 2007, the St. Luke’s Texas Liver Coalition performed 1,500 screenings at a total of 18 health fairs and Town Hall-style community lectures. The return results were a 2.7% positive rate.


New Approach:

In response we decided we needed to approach screening in a more effective way. Through extensive research, The Texas Liver Coalition piloted a way to increase the percent positive rate through partnerships in the HIV and recovery communities as well as community-based clinics. We began by inviting community based organizations and clinics to a dinner and talk on hepatitis C to educate them and let them know about our services (Liver Line, free screening and PCR tests, support groups). Through this program we established our first partnership with a local community based organization working in the HIV community. Using the TLC screening consent forms and requisitions, the community advocates in the field simply added HCV antibody test to the panel of tests they offered their clients. They merely draw an extra tube of blood, attach our requisition to the tube and the bill is directed to the Texas Liver Coalition account. Through these partnerships, our percent positive rate has increased to 37%.



Through partnerships with community-based organizations we were able to increase our screening percent positive rate from 2.7% to 37%. We have identified a methodology that leverages the best practices forged through the HIV community.



Utilizing this method of partnership with community based organizations the liver disease community can now offer free screenings in clinics, recovery centers, HIV community organizations or even PCP offices. This method allows the hepatology community to piggy back on work done over the past 20 years in HIV and provide targeted screening to those at risk individuals.


941. Perception of Chronic Hepatitis B in Asian Communities of the United States

D. Salinas-Garcia; M. C. Conti; H. Tang



Chronic hepatitis B (CHB) affects about 350 million people in the world. In the United States (US) there are about 1.25 million chronically infected patients with a high prevalence in the Asian population. The perception of CHB in this population and their knowledge about the disease has not been fully explored. The main objective of the research is to assess the level of CHB awareness among US Asians including awareness of the disease prevalence, screening test, and knowledge about the disease and available therapies.



Computer aided in-language telephone interviews were conducted using a structured questionnaire. A total of 600 surveys were conducted. Key participation criteria include: self-identified as Chinese, Korean or Vietnamese; age between18-65; first generation immigrants or, if born in US, able to read or write native language “natively” or “very well”.



Overall Hepatitis B (HBV) awareness is high but not a top of mind disease: HBV specific unaided mention is below 20% and it ranks under diabetes (43%), hypertension (40%) and cancer (21%). The great majority agrees that hepatitis B has serious consequences and requires attention (80% agree that CHB causes liver damage, 78% agree that it could slowly progress to liver cancer if untreated). However, there is less certainty about its transmittability and the availability of effective treatment (49% agrees that it is easily transmittable, 50% agrees that there are effective prescription drugs to treat CHB, less than a third are aware of antivirals as treatment options). A majority of those who have tested negative have been vaccinated (61% of those who tested negative claim to have been vaccinated). Nevertheless, lack of information is one of the main reasons claimed by those who have not received the vaccine (55% of all those failing to get vaccinated after a negative test attribute this to “don’t believe I need it / didn’t know about it / never heard about it / not offered to me”).



The overall awareness of the disease is relatively high among Asians living in the US. Awareness of hepatitis is higher in CHB prevalent states than non-prevalent states. The level of knowledge of disease symptoms, treatment options and vaccination is limited and varies across groups. More education about the disease and its transmittability and availability of vaccination and treatment is needed.


936. Hepatitis B Seroprevalence and Disease Characteristics in Asian Immigrants

M. K. Dhamija; S. S. Wong; A. Bartram; F. Siqueira; T. J. Layden; S. Cotler


Chronic hepatitis B virus (HBV) infection is prevalent in Asian immigrants, affecting 9%-15% who were self-selected for screening (Hepatology 2007;46:1034-40; MMWR 2006;55:505-9). The aim of this study was to evaluate the seroprevalence and to characterize HBV in patients who presented to a large Chinatown medical practice in Chicago, IL.



Records were reviewed from 4,671 adult patients who had at least one office visit from 1/06-12/07. Data collection consisted of demographic information and laboratories including HBsAg, HBeAg, ALT level, and HBV DNA level. Elevated ALT level was defined as >19 IU/ml for women and >30 IU/ml for men. The practice policy was to aim to screen patients for HBV during the course of their care. Results: >99% of patients were ethnically Chinese and 97% were born in Asia. HBsAg status was available in 64% (3012/4671) of cases. HBsAg testing was more common in patients with insurance (p<0.001) and in women than in men (p<0.001). The HBsAg seroprevalence rate was 11% (335/3012). The mean age of the HBsAg+ patients was 51 ± 16 years and 59% were female. HBsAg seroprevalence was higher in patients aged 18-49 (177/1365, 13%) compared to those >50 years old (158/1645, 9.6%) [p=0.004]. HBeAg status was available for 57% (191/335) of HBsAg+ cases. 27% (51/191) were HBeAg+ and 73% were HBeAg-. The HBeAg+ patients were younger (p=0.001), had higher HBV DNA levels (p=0.001), and more frequently had elevated ALT levels (p=0.002) than the HBeAg- cases. 84% (31/37) of the HBeAg+ patients with virologic data had HBV DNA levels >105 copies/ml and ALT levels were elevated in 71% (22/31) of these cases. 59% (22/37) of HBeAg+ patients had HBV DNA >105 copies/ml and an elevated ALT level on one measurement.


With regard to HBeAg- patients, 23% (19/84) with virologic data had HBV DNA levels >104 copies/ml and ALT levels were elevated in 74% (14/19) of these cases. That is, 17% (14/84) of HBeAg- patients had HBV DNA >104 copies/ml and an elevated ALT level on one measurement.



The HBsAg seroprevalence of Asian immigrants presenting for general medical care was quite high (11%) and was greater in patients under age 50. A majority (73%) of HBsAg+ patients were HBeAg-. Although only one measurement was available, 59% of HBeAg+ cases and 17% of HBeAg- cases had both HBV DNA and ALT levels that reach the threshold for consideration of further evaluation and treatment. These data confirm the importance that all Chinese immigrants be tested for hepatitis B.

853. Estimated Prevalence of Chronic Hepatitis B (CHB) in Foreign-Born (FB) Persons Living in the United States (US) by Country/Region of Origin

S. Welch; B. Chiang; P. Shadday; C. L. Brosgart



Centers for Disease Control (CDC) report that <0.5% of the US population (800,000-1.4 million) are living with CHB. CDC estimates are based on NHANES III, a US national health survey conducted 1988-94. Blacks and Mexican-Americans are well represented in NHANES, but groups at higher risk for CHB (e.g., institutionalized persons, Asians, Native Americans) are excluded or under-represented. Published CHB estimates in foreign-born (FB) populations vary and are limited to Asians. The FB population in the US increased from 20 million in 1990 to 41 million in 2008.



US Census data were used to estimate the number of FB persons from 93 countries/regions living in the US in 2008. Published CHB prevalence rates by country/region were chosen to model low, mid, and high rates for each. Over 900 studies were reviewed; preference was given to large, peer-reviewed studies of relevant cohorts. The number of FB persons with CHB was estimated by multiplying each FB population by its prevalence rate.



The number of FB with CHB in the US ranges from 850,000 to 2,240,000 persons. Over half are from Asia and 13-15% from Africa, where CHB is hyperendemic (>8% of the population); 9-18% are from Central America, which has lower CHB rates (0.4-2.5%) but more immigrants in the US. Average CHB prevalence rate among the FB is 2.0-5.4%.



The number of FB living with CHB in the US may be higher than previously thought. Assuming 400,000 to 800,000 US-born with CHB, total CHB disease burden could be as high as 3 million. The large CHB prevalence and high morbidity (end-stage liver disease and liver cancer) and related mortality argue for building surveillance systems. Knowledge of key FB CHB populations will help develop programs for prevention, earlier diagnosis and linkage to care. Published CHB prevalence rates vary widely and further analysis of temporal patterns of infection and emigration are planned.


Prevalence of foreign-born CHB in the U.S.


827. Perinatal Transmission of Hepatitis B Virus: Viral load and HBeAg status are significant risk factors

E. Wiseman; M. A. Fraser; S. Holden; A. L. Glass; B. Kidson; L. G. Heron; M. Maley; A. Ayres; S. Locarnini; M. Levy



Infants born to women who have replicating hepatitis B virus (HBV) infection have up to a 90% risk of perinatal transmission if left untreated. Passive-active immunoprophylaxis, with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccination, reduces the risk but does not remove it. Data from overseas cohorts report transmission rates varying from 2-27% despite passive-active immune prophylaxis.



To determine the rate of HBV perinatal transmission in an Australian setting and to identify maternal virological factors that are associated with greatest risk of transmission.


Patients and Methods:

HBsAg positive pregnant women were identified during antenatal screening. Eighty-seven of 298 (29.2%) HBsAg positive women were HBeAg positive and 202 (67.8%) HBV DNA positive. The HBV DNA level in the mothers allowed stratification into < 5 log10 copies/mL in 110 (54.5%), 5-8 log10 copies/mL in 27 (13.4%) and > 8 log10 copies/mL in 65 (32.2%). All babies are routinely offered HBIG and HBV vaccination. Babies born to HBV DNA positive mothers were tested at 9 months of age. In cases of perinatal transmission (HBsAg positive), further virological testing including HBV DNA sequencing was performed in order to identify possible risk factors for transmission. One hundred and twenty four infants had reached 9 months of age and were evaluated.



Three cases of transmission were identified. All 3 mothers had very high HBV DNA (> 8 log10 copies/mL) and were HBeAg positive. Two of the three infants were infected with wild-type HBV and the HBsAg sequence was identical to the maternal isolates. The third mother-baby pair had an S gene variant (sD144E) in both mother and infant (D144E previously reported in association with vaccine/HBIG breakthrough). In this case though, HBIG was inadvertently omitted from the immunisation schedule. The remaining 121 infants tested were anti-HBs positive and HBsAg negative. Overall transmission rate was 2.4% (3/124) from HBV DNA positive women, 5.5% (3/55) from HBeAg positive women and 7.2% (3/42) from women with very high HBV DNA (> 8 log10 copies/mL). No transmission was seen in 82 babies of mothers with HBV DNA < 8 log10 copies/mL.



In this cohort, HBV perinatal transmission was restricted to HBeAg positive mothers with very high HBV DNA. Further analysis to identify maternal and infant predictors of vaccine failure is ongoing.


839. Identifying Transmission Pairs in Hepatitis B Source and Contact Tracing: Agreement of epidemiological and phylogenetic analysis in the multi-ethnic community of Rotterdam (2002-2005)

I. K. Veldhuijzen; T. H. Mes; M. C. Mostert; H. G. Niesters; S. D. Pas; J. J. Voermans; R. A. De Man; H. M. Götz; G. J. van Doornum; J. Richardus


Molecular and epidemiological data typically give different types of information on the transmission of hepatitis B virus (HBV). Because both types of information are important for public health, the congruence of HBV sequence and epidemiological data from acutely and chronically infected patients seen at the Municipal Public Health Service in Rotterdam was assessed. Molecular clusters consisted of patients with identical sequences. Information from source and contact tracing was used to define epidemiological transmission pairs. We assessed the level of molecular support for epidemiologically defined transmission pairs using parsimony, by placing topological constraints during phylogenetic analyses in agreement with epidemiological information, and by taking the presence of polymorphic sites within patients into account.



HBV genotypes of 62 acute and 347 chronic HBV patients indicated that the acute infections were predominantly with an endemic genotype (A2; 52%) and a non-endemic genotype (D; 32%). Chronic HBV infections largely involved non-endemic genotypes (A1, B, C, D and E). Interestingly, while genotype A2 was least variable, which is consistent with a frequent exchange of HBV in the homosexual community, genotype D comprised multiple divergent groups of closely related sequences. Forty (65%) of the 62 acute patients were included in clusters with identical sequences, of which more than half (22) in a large cluster of genotype A2. In total 15 clusters including 93 patients (range 2-39 patients per cluster) with identical sequences were identified. Six of these clusters included epidemiological transmission pairs. Epidemiological transmission pairs differed greatly in the level of molecular support. Of 22 epidemiological clusters, six could be refuted (three harbored multiple genotypes, three conflicted with the epidemiological data in constrained analyses), four clusters received support from the molecular analysis and the support for the remaining 12 was ambiguous. Two of the four epidemiological pairs that also received molecular support had diverged considerably (3 and 15 mutations respectively). This shows that levels of divergence cannot be simply used as an indicator of the likelihood that groups of sequences constitute transmission pairs. Instead, it is necessary to assess the likelihood of a common origin of individuals in supposed transmission groups given the variation in the local community.



The combined approach of source and contact tracing and molecular epidemiology provides insight in the HBV transmission routes in a multi-ethnic community and allows a refinement of the identification of transmission pairs.


865. Preference and Non-preference Based Measures of Quality of Life in Patients with Chronic Hepatitis B

G. Woo; M. Sherman; E. Heathcote; M. Krahn



Over 400,000 individuals worldwide are infected with the hepatitis B virus. Chronic hepatitis B (CHB) accounts for up to 50% of the cases of cirrhosis, end-stage liver disease and hepatocellular carcinoma. The effects of HBV on liver-related mortality have been described; effects of HBV on HRQOL are less well understood.



To assess the health utility values and HRQOL of patients infected with hepatitis B attending tertiary care centers in downtown Toronto.
Methods: A convenience sample of individuals was approached during follow-up visits in two downtown
Toronto liver clinics. HRQOL and patient preference scores were elicited using the Visual Analogue Scale, Health Utility Index3, Short Form36v2 and EQ5D. Chart reviews were performed to collect relevant clinical data and patient demographics. Patients were stratified by presence or absence of liver cirrhosis.



Two hundred and sixty-eight patients, 195 patients with CHB, and 73 with compensated cirrhosis (CC) were recruited. The mean age was 48 years, 70% were male, 25% HBeAg-positive, 62% of Chinese descent, 68% married, 61% worked full-time and 66% responded in English.This interim-analysis shows that although there is no significant difference between patients with CHB and those with CC; a pattern suggests that there is a decline in HRQOL as patients progress from CHB to CC. In comparison to population norms, both groups are found to have statistically significantly lower scores when measured with the HUI3. There is no significant difference in SF36v2 Physical Component Summary and Mental Component Summary scores or EQ5D scores in comparison to population norms.



The data suggests that there is no significant difference in the HRQOL between individuals infected with the hepatitis B virus in comparison to population norms. The analysis suggests that there is a decline in HRQOL when comparing CHB to CC patients. Continuing patient recruitment of individuals with decompensated cirrhosis, hepatocelluar carcinoma and post liver transplant due to infection with the hepatitis B virus will provide further insight into the HRQOL of these patient populations.


Mean Utilities and SF-36v2 Scores (95% CIs) of CHB and CC patients




Population Norms


0.81 (0.79-0.83)

0.81 (0.78-0.84)



0.87 (0.85-0.89)

0.81 (0.76-0.86)

0.90 (0.90-0.91)


0.92 (0.90-0.94)

0.90 (0.87-0.93)

0.88 (0.88-0.89)

SF36v2: PCS

53.2 (52.3-54.2)

50.5 (48.8-52.3)

51.3 (50.9-51.7)

SF36v2: MCS

49.8 (48.2-51.3)

50.1 (47.8-52.4)

51.4 (51.0-51.8)


1093. Are There Any Differences in Quality of Life Between Chronic Hepatitis B Patients with Cirrhosis and Those Without? A Cross-sectional Study

L. Wah-Yun; C. Ng; W. Li-Ping; M. Rosmawati



Hepatitis B affects the quality of life of patients. This paper compares the health-related quality of life (HRQOL) between chronic hepatitis B patients with and those without cirrhosis.



A cross-sectional study was utilized. 483 patients with chronic Hepatitis B who were followed-up at the hepatology clinic of a tertiary hospital in Kuala Lumpur, Malaysia. Apart from the socio-demographic data and other medical information collected, all patients also completed the Health-Related Quality of Life Questionnaire (SF-36V). The SF-36V contains 36 items assessing 8 domains of quality of life: physical functioning, social functioning, role physical, role emotional, mental health, vitality, bodily pain and general health, and two main summary score, the physical and mental health component score. Each domain is given a score ranging from 0 to 100, with higher scores indicative of better quality of life. The normative score is 50.



Of the 483 chronic hepatitis B patients, 74 (15%) of them were diagnosed with cirrhosis (with or without hepatocellular carcinoma). Cirrhosis is diagnosed either histologically, or clinically (US evidence of nodular or shrunken liver, or presence of portal hypertension). The remaining 409 (85%) of them did not have histological or clinical evidence of cirrhosis. Patients with cirrhosis were significantly older (mean 54 ± 12.87 years) than patients who are not cirrhotic (mean 44.86 ± 14.62 years). Mean duration from the time of diagnosis of hepatitis B was 12 years (sd 8.8 years).


Overall SF-36V scores (mean ± sd) were: physical functioning (90.31±17.42), role physical (87.83±19.89), bodily pain (83.27±20.00), general health (65.58±19.14), vitality (66.21±17.30), social functioning (88.89±17.36), role emotional (89.22±19.14), mental health (75.98±16.61), physical component score (52.77±6.51), and mental health component score (75.98±16.61).


Mean scores for the SF-36V domains between patients with cirrhosis vs. without were: physical functioning (87.49 vs. 90.82), role physical (85.81 vs. 88.20), bodily pain (84.99 vs. 82.97), general health (63.74 vs. 65.91), vitality (66.30 vs. 66.19), social functioning (88.68 vs. 88.94), role emotional (88.63 vs. 89.32), mental health (75.13 vs. 76.14), physical component score (52.16 vs. 52.88), mental health component score (50.67 vs. 50.73). No significantly differences were shown between patients with cirrhosis and those without in SF-36V domains, and the two main summary scores.



Patients with hepatitis B showed a good quality of life, but HRQOL between chronic Hepatitis B patients with and without cirrhosis were no different.


1098. Prevalence of HBsAg in Pregnant Women in Picardy, France in 2006.

E. Nguyen-Khac; D. Capron; S. Delmas-Lanta; H. Robillard; J. Merlin; G. Dubois; A. Braillon


Rationale and objectives:

In France, data on the prevalence of HBsAg during pregnancy are outdated (1). HBsAg screening during pregnancy (mandatory since 1992) has only been assessed from databases of the health insurance sytem. The province of Picardy (1,9 millions of inhabitants) belongs to Northeastern France which is characterized by the highest HBsAg seropositivity rates of the country (11.2 per 1000, Institut de veille sanitaire, 2004). Our objective was to study (i) the prevalence of HBsAg in pregnant women in Picardy and (ii) the traceability of the screening.



In 2006, 22,595 deliveries were registered in the 20 maternity clinics (public and private-sector). Three methods were used to investigate the prevalence of HBsAg: (i) from HBsAg screening results in a sample of 1,198 hospital case files, which were randomized and stratified on the number of births; (ii) from HBsAg assay reimbursements for all pregnancies recorded by the main regional health insurance system (URCAM); (iii) we also looked for mothers with viral liver diseases and for neonates with hepatitis B immune globulin and vaccine administration from the medico-administrative databases (PMSI which record diagnosis and medical acts is a national requirement) and from the registries of hospital pharmacies and obstetric theatres.


Based on the sample of hospital case files, the prevalence of HBsAg during pregnancy in Picardy was 1.8 per 1000 pregnant women. The traceability (presence of a written note or of the laboratory result) of the screening was 92.9% (extremes: 65-100). The regional health insurance system database covered 20,724 pregnancies and HBsAg assay reimbursement was noted in 47.9% of these cases. The results from medico-adminstrative databases and registries are under scrutiny (poor coherence between medico-adminstrative databases and registries), and prevalence of HBsAg largely varies from one maternity clinic to another, exceeding 11 per 1000 pregnant women in one).



The prevalence of HBsAg in pregnant women in Picardy is similar to the national average reported in 2004 (2.1 per 1,000 women). The traceability of HBsAg screening showed large variations from one maternity clinic to another. Health insurance system database does not allow for epidemiology or medical evaluation.


Denis et al. Bulletin Epidémiologique Hebdomadaire 2003; 33:157-9.

Funding: DHOS (FMESPP programme), Amiens University Hospital (DRRC programme), Sanofi-Pasteur-MSD, Roche, LFB-Biomédicaments.


1101. Prevention of HBV Infection by GPs Among Migrant People in France

J. Aubert; A. Di Pumpo; P. Santana; A. Gervais



In 2004, 22% of French citizens were vaccinated against hepatitis B virus (HBV), 7,3% had previously been protected by a contact with HBV, and 0,65% were carriers of HBV. Those rates are not known among migrant people, above all if they have no social security. It is not known whether those people follow accurate personal strategies of prevention


Aims and Method:

To assess the effectiveness of an internet-accessible expert system in helping the GP to determine the most accurate strategy of prevention, related to the serologic HBV profile of each patient, and to apply this strategy, among migrant people coming from Sub-Saharan Africa and Asia, attending their GP. The prevalence of each serologic profile was measured.



From 5.11 to 31.12.2007, 26 GPs included 373 migrant people. 11% are HBV carriers, 36% have been protected by a contact with HBV, 28% are vaccinated, and 25% have had no contact with virus nor vaccination. A full accurate preventive information strategy could be carried out with help of the expert system, respectively among 81% of HBV carriers, 100% of vaccinated people, 89% of people protected b HBV contact, and 84% of people who had no marker. A vaccination has been started among 79% of people who required it. For people whose only marker of HBV infection was anti HBc, 68% only of accurate preventive strategy was found, this lower result can be related to a lack of accuracy in international guidelines in this situation.



Prevalence of contact with HBV is much higher in migrant people coming from Sub-Saharan Africa and Asia, than in the average French population. An internet-accessible expert system is a useful tool for GPs in order to enhance strategies of prevention in HBV infection.


990. Epidemiology of Hepatitis B Virus (HBV) Infection in Luanda (Angola): Prevalence and Risk Factors

A. F. Constantino; H. M. Proenca; T. Rodrigues; L. Nicolau; M. C. de Moura



Data on epidemiology of HBV infection in sub-Saharan Africa are still insufficient, despite being one of the world regions with greater HBV prevalence. There is no information allowing us to know the actual estimate of this infection in Angola and the main risk factors to delineate appropriate public health strategies to prevent the transmission of HBV.



To assess the prevalence of HBV infection and risk factors in a primary health care setting in Luanda, capital city of Angola.



1,103 black individuals born and resident in Angola; with ages between 2 and 77 years (mean age 25, 9 years) were consecutively chosen in six randomly selected health centres in Luanda. Risk factors, serum markers of HBV and HDV infection, genotypes of HBV, serum levels of alanine aminotransferase (ALT) and alpha-fetoprotein (AFP) were also analyzed.



Female gender was predominant, both in the global sample 856 (77.6%) and in the HBsAg positive population (65%). The most frequent risk factor was unprotected sex -98, 5%. Both ALT and AFP were normal in 98.3% and 87, 9% respectively. HBsAg was positive in 13%; HBeAg was positive in 20. %; 79.5% were HBeAg negative and anti- HBc positive; anti- HBs was positive (532 cases) 49 %, out of which 8, 4% were HBsAg positive. 17.4% individuals HBsAg positive (N = 143) were under 16 years old. HBsAg in pregnant women was positive in 14.5%; anti-HBs was more prevalent in non-pregnant women (54.2% vs. 46%) p < 0.03; ALT was similar in both groups (p= 0.29). HDV prevalence was 4.6%. Genotype “E” was predominant (95%). In the majority of cases where genotyping was attempted HBV DNA was undetectable, and these had normal ALT. AFP was abnormal in less than 5 % and there was no difference between HBsAg and HBsAg negative cases. Alcohol ingestion does not appear to be an enhancing risk factor for HBV infection.



HBsAg was positive in 13% of cases. Unprotected sex was the predominant risk factor. The high percentage of HBsAg in children suggests an early infection in life. The high proportion of AgHBe negative cases (79, 5 %) may indicate a change in the serologic profile of HBV infection in Africa. Predominance of anti-HBe positive cases with normal ALT and undetectable DNA-HBV suggests inactive HBsAg carriers and not immune tolerant cases. Our data emphasize the urgent need in Angola to implement a National Hepatitis B Vaccination programme.


992. Enhanced Humoral Responses to Hepatitis B Surface Antigen in Newborns Who Recognise the Hepatocyte Receptor Rather Than the Albumin Binding Site after Vaccination with the Third Generation “Sci-B-Vac”-Vaccine

U. B. Hellstrom; S. P. Sylvan; K. Madalinski


PreS-containing vaccines have been shown to induce rapid and enhanced anti-HBs responses when used in newborns, children and adults. However, the fine specificity of the preS1 and preS2 responses induced by third generation hepatitis B vaccines and its relation to the anti-HBs response has so far not been elucidated.


Using two site-specific peptide based ELISA we analysed, after a full vaccination schedule of the Sci-B-Vac vaccine in 28 newborns, the antibody reactivity towards aa 21-47 of the preS1 and aa 131-140 of the preS2.

Fourteen newborns, who exhibited antibody reactivity towards the preS2 peptide which mimics aa 131-140 of the preS2 protein, had an anti-HBs response after vaccination which was significantly lower (p<0.025) compared with those newborns (n=14) who lacked the preS2(131-140) reactivity.



The highest anti-HBs levels were found in a newborn who exhibited reactivity towards the aa 21-47 of the preS1 but lacked anti-preS2 (131-140) reactivity. Accessibility of preS1 antigens which mimics the hepatocyte receptor binding sites (21-47) to B- and T- cells is thus critical to elicit a strong anti-HBs response after vaccination with the Sci-B-Vac vaccine. The recognition of the so-called polymerized albumin receptor (131-140) of the preS2 on the other hand seemed to have suppressive effects on the anti-HBs response.



This study was partly financed by SciGen Ltd, Singapore.


878. Co-delivery of Hepatitis B Virus Surface Antigen and GM-CSF by Hydrogel Overcomes Non-responsiveness to Hepatitis B Vaccine Through Recruitment and Activation of Dendritic Cells

H. Chou; P. Wu; M. Tao


Nonresponsiveness to hepatitis B vaccine, composed mainly the major hepatitis B surface antigen (HBsAg), has been described in approximately 5-10% of healthy immunocompetent subjects. The underlying cellular and molecular events for the nonresponsiveness are not completely understood, but are likely associated with impaired T helper cell responses to HBsAg in subjects with particular HLA-DR alleles. In this study, we describe a novel formulation of HBsAg vaccine containing GM-CSF, one of the most potent cytokines that can mediate the maturation and function of dendritic cells, in a thermosensitive biodegradable copolymer (Hydrogel) system, acting as a sustained-release matrix for the loaded proteins. In responder inbreed or outbreed mouse strains, Hydrogel/HBsAg+GM-CSF vaccine elicited higher titers of anti-HBsAg antibody and strong T-cell proliferative responses than other vaccine preparations. Most importantly, a single injection of Hydrogel/HBsAg+GM-CSF vaccine was sufficient in the induction of significant anti-HBs antibody and T-cell immune responses in B10.M mice, a mouse strain with H-2 gene-linked HBsAg nonresponsive phenotypes. Repeated immunization with alum contained commercial HBsAg vaccine did not induce detectable anti-HBs antibody and T-cell immune responses in this nonresponding population. Local and sustained release of GM-CSF is required for its immunostimulatory function in nonresponder mice, because administration of Hydrogel/HBsAg and Hydrogel/GM-CSF in separate locations or a free mixture of HBsAg and GM-CSF failed to induce comparable humoral and cellular immune responses. Analysis of draining lymph nodes of Hydrogel/HBsAg+GM-CSF-treated mice revealed an elevated number of CD11c+ dendritic cells (DCs) with enhanced expression of costimulatory molecules, MHC II, CD40, CD80 and CD86.



These results suggest that the local adjuvant activity of GM-CSF creating a favorable microenvironment for antigen presentation by promoting DCs maturation and migration into the draining lymph nodes, leading to generation of T helper cells, which subsequently provide help for B cells to produce anti-HBs antibodies. Therefore this Hydrogel/HBsAg+GM-CSF vaccine provide an alternative vaccination strategy to human nonresponders to improve the seroconversion rate of hepatitis B vaccination. And this effective immunization approach may also be applicable to apply for design of vaccines for a variety of other diseases.


971. Evaluation and Management of Hepatitis B in Pregnancy: A Survey of AASLD Members

S. B. Salem; N. N. Shah; S. M. Cohen; J. Ahn



Data on the safety of oral antiviral therapy for hepatitis B (HBV) in pregnancy is limited. Treatment guidelines have not been definitive but have suggested individualization of treatment decisions. In the absence of data and clear guidelines, we sought to evaluate the practice patterns of AASLD members in managing these patients.



An 18-question survey was electronically sent to all AASLD members addressing diagnosis and management of HBV during pregnancy. Responses were gathered over a 4-week period.



226 (9.3% of those surveyed) AASLD members responded. 156 (69%) characterized their specialty as hepatology, 60 (26.5%) gastroenterology, and 10 (4.4%) other. 141 (62.4%) were academic-based and 85 (37.6%) were community-based physicians. The average years in practice was 13.3 (1-45). With regard to comfort level in managing these patients, 68 (30.1%) were “very comfortable”, 69 (30.5%) were “comfortable”, 52 (23%) were “somewhat comfortable”, and 37 (16.4%) were “not comfortable”.117 (51.8%) would initiate antiviral therapy in women newly diagnosed with HBV during pregnancy. Of those who would not initiate antiviral therapy during pregnancy, 64 (58.7%) cited an absence of guidelines, and 42 (38.5%) a lack of evidence to support efficacy or safety. For patients already on antivirals who become pregnant, 169 (74.8%) would continue antiviral therapy. With respect to breastfeeding, 130 (57.5%) would recommend breast feeding, 64 (28.3%) would not, and 32 (14.2%) were unsure. If antivirals were used, 69 (30.5%) would recommend breastfeeding, 100 (44.2%) would not, and 57 (25.2%) were unsure. Except for the timing of antiviral therapy initiation, there were no statistically significant differences between academic-based and community-based physicians and between hepatologists and gastroenterologists with regard to diagnostic modalities, choice of antiviral drugs, and treatment duration. Academic-based physicians were more likely to wait until after delivery to initiate antivirals as compared to community-based physicians. (p=0.01).



Based on this survey, it is clear that there is significant heterogeneity in evaluation and management of pregnant women with HBV. There were no differences in practice patterns and comfort levels between academic-based and community-based physicians with the exception of the timing of antiviral initiation. Additional research into the evaluation and management of pregnant women with HBV that would lead to evidence-based guidelines is needed.