1294. Racial/Ethnic Differences in Barriers to Vaccination Against Hepatitis B Among Patients with Chronic Liver Disease Due to Hepatitis C Virus Infection. 

S. Dhalla; C. T. Tenner; N. B. Shukla; A. Aytaman; G. A. Villanueva; G. Punla; C. Patterson; J. Comas; E. J. Bini.



Despite widespread recommendations to vaccinate all patients with hepatitis C virus (HCV) infection against hepatitis B virus (HBV), only 25% of susceptible patients have been vaccinated in clinical practice, and rates are even lower among racial/ethnic minorities. The aim of this study was to evaluate racial/ethnic differences in barriers to HBV vaccination among patients with chronic HCV infection.



Patients with chronic HCV infection completed a detailed questionnaire at the time of their scheduled visit to the outpatient primary care or GI clinic at 3 study sites. Data collected included patient demographics, personal vaccination history, and barriers to vaccination.



Among the 1,930 patients with chronic HCV infection enrolled, 415 were white, 792 were black, 382 were Hispanic, and 341 self-reported their race/ethnicity as other. Overall, 332 of the 1,930 patients (17.2%) were told by their doctor that they had been exposed to HBV, including 14.7% of whites, 20.1% of blacks, 23.8% of Hispanics, and 6.2% of other races (P <0.001).


Among the 1,581 patients who were not previously exposed to HBV, only 475 (30.0%) reported that they received the vaccine, 857 (54.2%) were not vaccinated, and 249 (15.7%) did not know if they were vaccinated. However, 84.4% reported that they received the influenza vaccine. The proportion of the 1,581 unexposed patients who were vaccinated against HBV differed significantly according to race/ethnicity (43.1% whites vs 24.9% blacks vs 38.9% Hispanics vs 17.8% others; P <0.001). In the 857 unvaccinated subjects, the median number of barriers to HBV vaccination was 1 in whites, 2 in blacks, 2 in Hispanics, and 3 in other racial/ethnic groups (P < 0.001). In addition, there were significant racial/ethnic differences in the types of barriers (see table).



·        Racial/ethnic minorities with chronic HCV infection:

o       Are significantly less likely to be vaccinated against HBV

o       Have more barriers to vaccination than whites.

·        Public health programs to increase awareness of HBV vaccination and to overcome barriers to immunization are needed, especially among minority populations.








My doctor did not offer the vaccine to me






I am afraid of the vaccine






I am afraid of needles






I don’t like visiting the doctor






I don’t understand why I need the vaccine






I was feeling too sick






It takes me too long to get to my doctor






I did not know about a vaccine against HBV






I could not afford to pay for the vaccine







1296. Quality of care in Chronic Hepatitis C Virus (HCV) Infection. 

F. Kanwal; T. Hoang; B. M. Spiegel; M. Goetz; I. M. Gralnek; J. A. Dominitz; A. Di Bisceglie; S. Asch.



Chronic HCV is a prevalent and expensive condition with a large burden of illness. The AGA Task Force on Quality Measurement has identified HCV as a major priority area for quality measurement. We therefore sought to measure quality of care in HCV by measuring adherence to an explicit set of quality indicators (QI) in the VA Healthcare System-a large healthcare system with significant HCV burden of illness.



Using the current HCV guidelines from AASLD and the VA, we created a set of 7 QIs grouped into 3 domains—diagnosis, prevention, and treatment-related care. These QIs were developed using published quality measurement criteria and assessment from a group of 3 experienced hepatologists (Table 1). We set eligibility timeframes and characterized contraindications for each QI. We then measured adherence with the QIs in a demographically diverse group of patients from 5 VA Medical centers. We defined an HCV patient as a subject with >1 HCV-related ICD-9 code and/or a positive HCV test. To account for continuity of care, we included HCV patients if they had ≥2 visits/year to the treating facility from 1/1/2000 to 12/30/2005. We defined active viremia as ≥1 documented positive HCV PCR or genotype test. We calculated QI scores as the number of patients receiving the indicated process divided by the number of patients eligible for QIx100.



We identified 25,715 HCV patients. Of these, 14,246 had active viremia. We have results from 4/7 QIs to date (Table 1). Quality scores in the diagnosis domain exceeded 70%. However, there were significant deficits in the prevention domain. For example, among patients with active viremia and no prior evidence of HIV, only 12% received HIV testing within the first year of HCV diagnosis. These QI scores were consistent both with our a-priori hypotheses and previous empirical work within the VA, lending support to the validity of the QIs.



We found low overall adherence to evidence-based QIs in a large secondary analysis of HCV care, and observed significant variation in overall care. Future research will: (1)determine adherence to treatment related care, and (2)identify sources of the observed variation in care processes. These data may ultimately assist researchers and policy-makers in focusing quality improvement efforts in HCV.


Table 1: Quality Indicators in Chronic Hepatitis C


Quality Indicators



Among patients with a (+) antibody test, % received an HCV RNA test within 1 yr of diagnosis (for confirmation of active viremia)


Among patients with (+) RNA test, % received ALT test within 1 yr of diagnosis



Among patients with (+) RNA and no prior evidence of HIV, % tested for HIV within 1 yr of diagnosis


Among patients with (+) RNA and no prior evidence of immunity against hepatitis A, % received hepatitis A vaccination



1298. Increased activity of regulatory T cells in recurrent hepatitis C after liver transplantation. 

A. Carpentier; F. Conti; P. Podevin; V. Pancre; O. Morales; C. Sandrine; C. Yvon; C. Ariault; N. Delhem.


Introduction :

Cirrhosis due to hepatitis C virus (HCV) is a common indication for liver transplantation. HCV infection of the graft is universal, and liver damage is accelerated, with cirrhosis occurring in 10-30% of patients within five years. Failure of immune response during HCV primo-infection in non transplanted patients is associated with increased regulatory T cells (CD4+CD25+) activity. The aim of this study was to evaluate the implication of regulatory T cells during HCV recurrence after liver transplantation.


Patients and Methods :

Different regulatory T cells sub-populations were evaluated using transcriptomic analysis of serum and liver samples from patients 5 years after transplantation. The analysis of 23 regulatory T cells associated genes was performed. Three groups of patients have been evaluated : stable liver recipients without HCV infection (n = 8), liver recipients with minimal hepatitis C recurrence (METAVIR ≤A1F2, n = 10) and patients with severe recurrence (METAVIR> A1F2, n = 10).


Results :

The expression of markers associated with T CD4+CD25+ sub-population, particularly CD4, CD25, OX40, GITR, and ICAM1 was significantly enhanced in liver recipients with hepatitis C recurrence (p<0.05 versus stable recipients). Markers co-expressed by T regulatory-1 cells (CD49b, CD18) were over-expressed in patients with severe hepatitis C recurrence when compared to minimal hepatitis C recurrence or stable recipients (p<0.05). Moreover, expression of immunosuppressive cytokines, IL-10 and TGF-b, was significantly increased during HCV recurrence. This latter result was confirmed in situ by immunohistochemistry and in serum by ELISA assays.


Conclusion :

Our results suggest, for the first time, that regulatory T cells could be implicated in hepatitis C recurrence following liver transplantation. Identification of regulatory T cells sub-populations able to modulate liver injury could give important insights in order to elaborate new therapeutic strategies.


1299. Self-Reporting of HCV Risk Factors and Primary Care Provider Behavior . 

M. Velez; S. B. Trooskin; S. K. Herrine; S. Rossi; D. J. Axelrod; R. Winn; S. McNeal; V. J. Navarro.



Hepatitis C virus (HCV) infection is the most common chronic bloodborne infection in the US with an estimated 3.9 million persons infected, yet HCV risk assessment and testing among primary care providers (PCPs) remain uncommon. For example, only between 10% and 16% of patients are tested based on physician identified risk factors (Shehab et al., 2003). In an effort to improve these practices, we explored the effect of a self-reported HCV risk factor history on PCPs’ HCV management practices.



Consecutive first-time patients, 18 or older, were prospectively enrolled at four primary care practices in Philadelphia. Upon enrollment, patients completed an HCV risk factor history and were instructed to give the completed form to their PCP. Patients with HCV risk factors were contacted by phone after their appointment to determine if their HCV risks had been discussed and if testing had been recommended.



Of 611 patients, 379 (62%) identified themselves as having a risk factor, however 83 (22%) were excluded from further analysis because the type of risk factor was not specified. Of the remaining 296 patients, 73 (25%) individuals reported at least one conventional HCV risk factor (IDU or needlestick, blood transfusion prior to 1992, organ transplant, kidney dialysis) and 257 (87%) reported at least one non-conventional HCV risk factor (HCV+ significant other, incarceration for over 24 hours, or tattoo/body piercing). Of those individuals with any risk factor (conventional or non-conventional), 50 (17%) reported being sent for an HCV test; there was no difference in the rates of patients who reported being tested for HCV, with regards to the type of risk factor. Of the 222 patients who reported that they were not tested, 200 (90%) verified that they had given the completed history form to his/her PCP as instructed; however, only 33 (16.5%) of the 200 reported that the PCP actually addressed their HCV risk factors. Among the 146 patients who stated that their PCP did not discuss HCV risks, 35 (24%) had a conventional risk factor for HCV acquisition. Finally, there were no differences among PCPs with regards to the rates for which HCV testing was recommended in the presence of a risk factor.



Self reporting of HCV risks did not improve upon the reported rate of risk factor-based testing by PCPs. Approaches are needed to facilitate a more open dialogue regarding HCV risks between PCPs and patients. Such approaches must involve education of PCPs with regards to the appropriate testing for HCV.


 1301. HEV genotype 3 reservoirs in the Netherlands . 

S. Rutjes; T. Schreuder; H. Reesink; P. L. Jansen; W. Lodder; F. Lodder-Verschoor; H. van den Berg; M. Bouwknegt; E. Duizer; A. de Roda Husman.



Hepatitis E virus (HEV) is a major cause of viral hepatitis in human in developing countries. HEV infections in the Netherlands were assumed to be related to travel to endemic countries, but evidence increases that locally acquired HEV infections do occur. We have reported the presence of HEV genotype 3 sequences in 22% of pig stables in 1998-1999. In addition, several sporadic human cases were reported in 2001. To be able to directly compare swine HEV sequences to human sequences we analyzed stool samples collected at pig farms in 2005. Moreover, the presence of HEV sequences in wild boar and deer were shown to be a potential health risk in Japan. In India surface waters were implicated in hepatitis E outbreaks. Therefore, not only pigs but also boar and water were studied in the Netherlands as possible sources of HEV.



Pooled stool specimens from swine (n = 97) were collected from pig farms and individual fecal samples from wild boar (n = 26). Porcine livers (n = 62) were obtained from local butcher shops. Large volume river water samples (n = 12) were collected monthly. All samples were collected throughout the Netherlands. Samples were processed for optimal RNA extraction and analyzed by RT-PCR for the presence of HEV RNA. Resulting products were sequenced and compared with human HEV sequences by phylogenetic analysis.



The percentage of pooled swine specimens in which HEV RNA was detected in 2005 was more than 50%. Furthermore, HEV RNA was detected in one of 26 wild boar fecal samples. Six percent of 62 analyzed commercial porcine livers were found to contain HEV RNA. The presence of HEV RNA in surface water was shown in 2 out of 12 samples, collected in September 2004 and March 2005. Sequence analysis of the RT-PCR products originating from different samples revealed that all sequences belonged to genotype 3.



We show for the first time in Europe the presence HEV sequences in surface water, commercially available pig livers and wild boar. The existence of several reservoirs for HEV genotype 3 may suggest that, besides travel to endemic countries, other transmission routes should be considered, such as contact with swine or recreational water or consumption of underprocessed pig liver.


1302. The Impact of Polymorphisms in Inflammation-Related Genes on the Severity of Liver Disease and Response to Therapy in Patients Co-infected with HIV and Hepatitis C. 

O. K. Fix; J. Andersen; M. J. Koziel; K. E. Sherman; R. T. Chung; L. Steiner; R. Apple; M. G. Peters.



Host factors may play a role in the severity of hepatitis C virus (HCV) infection. There is variability in response to treatment and severity of disease in patients that is not explained by human immunodeficiency virus (HIV) or HCV status. AIM: Assess the role of DNA polymorphisms in 35 inflammation-related genes (coding region and/or promoter) on the histologic severity of HCV and on the response to treatment in HIV-HCV subjects receiving interferon (IFN) or pegylated IFN (PEG-IFN) + ribavirin, in a randomized, multicenter trial in 81 co-infected subjects.



DNA was obtained from 81 subjects consented for genetic analysis. Single nucleotide polymorphisms (SNPs) were tested and reported as homozygous for wild type (wt) or variant (v), or heterozygous for 35 genes. Allelic frequencies were compared: (1) between 81 co-infected subjects and 2000 normal controls; (2) with respect to entry liver histology (hepatic activity index and fibrosis); (3) and between HCV responders (viral response [VR] at 24 weeks [w] or sustained viral response [SVR] 6 months after therapy) and non-responders (NR). Multivariable models previously showed PEG-IFN, white race, Karnofsky score=100, and low fibrosis score to be jointly associated with 24w VR in the parent study. Multivariate analysis of SVR was confined to 43 PEG-IFN subjects because few IFN SVRs consented to testing.



Variant allelic frequencies were 16-fold higher for ICAM-1 in HIV/HCV subjects compared to controls and >2 fold higher for IgE Fc receptor, IL4-receptor and P selectin. NR was associated with v ICAM1 (p<0.01 for 24w and <0.03 for SVR), wt CCR5 promoter (p<0.09 for SVR) and wt CCR5 (p<0.02 at 24w and <0.001 for SVR). Total HAI score correlated with wt ICAM1 (p<0.08) and v CCR5 promoter (p<0.02). None of these SNPs were significant when corrected for multiple comparisons. Classification and regression trees were used to identify factors jointly predicting 24w VR, SVR, and fibrosis score and ranked in order of importance below.



In HIV-HCV co-infected individuals, host genetic factors appear important in development of fibrosis and in response to therapy. Allelic variations in proteins critical to the inflammatory response may alter the hepatic response to HCV as well as the severity of chronic disease.



PREDICTORS OF SVR (n=43 receiving PEG-IFN)


treatment with PEG-IFN

genotype non-1

wild-type IL-10

genotype non-1

variant CCR5 promoter

variant homozygous C5 (if homozygous for wild-type IL-10)

variant VCAM1


variant homozygous IL1-α (in presence of variant IL-10)

low HCV RNA at entry


protease inhibitor-based therapy


Abbreviations: VR, viral response; SVR, sustained viral response; PEG-IFN, pegylated interferon; HCV, hepatitis C virus


1307. Is Hepatitis A and B Screening and Vaccination in Chronic Hepatitis C Patients Effective?

H. S. Yee; S. L. Currie; M. K. Chapko; A. Monto.



Coinfection with hepatitis A virus (HAV) and/or hepatitis B virus (HBV) in patients with chronic hepatitis C virus (HCV) infection can increase morbidity and mortality. The NIH Consensus panel and the ACIP recommend vaccinating against HAV and HBV in chronic HCV-infected patients who lack immunity. However, limited data on provider practices with HAV and HBV screening exist. Furthermore, in those who are vaccinated, antibody response has been varied in patients with chronic HCV. The primary aim of this study was to determine the proportion of HCV-infected veterans tested for HAV and/or HBV immunity and appropriately referred for vaccination. A secondary aim was to determine the antibody response in those vaccinated.



Data were retrospectively collected in 2,317 patients at the Veterans Affairs Medical Center, San Francisco. Subjects were HCV positive and accessing outpatient services between 2002 and 2003. Data were reviewed between January 1, 1997 and December 31, 2003 for HAV and HBV antibody status, vaccination referrals, and vaccine response. Additional information collected included demographics, comorbid diseases and social habits.



In 2,317 veterans with chronic HCV, the mean age was 54.7 years, 97.5% were male, 65.7% were Caucasian, and 31.7% were African American. Each patient had 9.5 median outpatient clinic visits/year. Over 75% had been tested for HAV antibody (HAVAb) and/or hepatitis B surface antibody (HBsAb). However, referral for vaccination occurred in 53.6% of patients (435/812) who were susceptible to HAV and 47.8% of patients (369/772) who were susceptible to HBV. Post-vaccination antibody results were available in a subgroup of 119 patients who completed the HAV vaccine series and in another subgroup of 118 patients who completed the HBV vaccine series. HAVAb developed in 74.8% (p = 0.001) and HBsAb developed in 50.8% (p = 0.025) of patients, which is significantly lower than previously published studies. In multivariate logistic regression analysis, age >50, alcohol use, and advanced liver disease were not independent factors in vaccine response.



Screening and immunization of HCV-infected persons for HAV and/or HBV vaccinations are suboptimal. In addition, our data suggest that vaccine response appears reduced by 25 to 50% in these patients. Further studies are needed to determine whether vaccine screening and administration strategies should be targeted to those at highest risk.


1313. Exposure Pattern of Hepatitis E Virus in Greater Cincinnati

M. Atiq; M. T. Shata; G. W. Neff; N. J. Shire; S. D. Rouster; A. Barrett; M. Guan; K. E. Sherman.



Hepatitis E virus (HEV) is endemic in many parts of the world. The objectives of this study was to compare the seroprevalence of HEV antibody in patients with chronic hepatitis to that of healthy controls and determine the association with various demographic and clinical characteristics.


Materials and Methods:

This retrospective analysis was performed at the University of Cincinnati. Frozen serum samples for chronic hepatitis patients (n = 129) and healthy controls (n = 38) were tested for anti-HEV IgG antibody by enzyme-linked immunosorbent assay (ELISA). Demographic data, clinical/laboratory values, and risk factors for infection were collected from medical records. Student’s t-test, Fisher’s Exact test, and logistic regression were used as appropriate for comparisons between cases and controls. In all cases, a two-tailed alpha of 0.05 was considered statistically significant.



Mean age for cases was 41.88 ± 10.35 and for controls was 31.74 ± 8.52 (p < 0.01). There were 100 (59.9%) males and 67 (40.1%) females. Among patients with a history of hepatitis, the most common dignoses were HCV and HCV/HIV co-infection in 60 (46.5%) and 38 (29.5%) patients respectively. 49 out of a total 167 subjects (29.32%) were tested positive for anti-HEV IgG antibody. Patients with sero-positivity for HEV IgG were older than those without anti-HEV IgG antibody (43±10 years vs. 37±10 years; p-value <0.01), were more likely to be males (75.51% vs. 24.48%; p-value: 0.008). History of intravenous drug abuse, male homosexual behavior, use of nasal cocaine, diagnosis of hemophilia and history of blood transfusion before 1988 were not associated with HEV IgG seropositivity. Patients with chronic hepatitis were more likely to be HEV IgG positive as compared to controls (56.42% vs. 7.89%; p-value: 0.001). A logistic regression model identified age as a statistically significant factor in log-odds of HEV seropositivity regardless of a history of hepatitis (p < 0.001). A Mantel-Hanzel stratification by age revealed a direct association between age cohort and HEV seropositivity independent of the disease status. Among patients with hepatitis, HIV was not associated with HEV IgG seropositivity.



Although the prevalence of HEV IgG is higher in patients with chronic hepatitis as compared to controls, this appears to reflect a cohort effect independent of other risk factors. Male predominance in HEV +ve population has also been observed in previous studies. This might represent a variable immune or humoral response amongst females or a difference in exposure. HIV does not seem to be associated with HEV infection.


1314. Hepatitis B and C Screening Program Targeting Asian-Americans in New York. 

P. C. Benias; I. Zic; J. Park; S. Chan; D. Chu; J. Schappert; H. C. Bodenheimer; A. D. Min.


Recent studies show a 10-15% chronic hepatitis B (HBV) infection rate in the Asian-American population. However, the rate of chronic hepatitis C viral (HCV) infection or abnormal liver tests in the same community has not been reported. We examined the prevalence of HBV and HCV and the rate of abnormal liver tests in the Asian-American community in our area via a screening program.



Subjects were screened at 3 Chinese or Korean community centers in Manhattan in December 2005. A survey was used to gather demographic and historical information from each subject. Blood was drawn for HBsAg, anti-HBc, anti-HBs, and anti-HCV in addition to ALT and AST. Overall data and comparison of results between Chinese- and Korean-American subjects were analyzed.



There were 230 subjects (136 M: 94 F) with a mean age of 51.9 years. All were born outside the U.S. (88 Chinese, 137 Korean, and 5 other). Overall, 45 of 230 (19.6 %) had (+) HBsAg, while 12 of 230 (5.2 %) had (+) anti-HCV. Of the Chinese and Korean subjects with no prior knowledge of HBV infection, 44.4% and 48.2% respectively had positive anti-HBc. There was a high prevalence of (+) HBsAg in both Chinese (28.4%) and Korean (14.6%) subjects (p < 0.0115). Among those without reported history of HBV, there was no difference in prevalence of (+) HBsAg between the two groups (7.9% Chinese and 7.4% Korean). About 25% of those with (+) HBsAg in all groups had abnormal aminotransferase values, in contrast to 50% in anti-HCV (+) subjects. In addition, only one-fifth of the population reported having HBV vaccination, and 40 (17.4%) patients qualified as potential recipients for HBV vaccine.



The overall rate of chronic HBV infection in our screened Asian-American population was higher than those found in recent studies. The rates of anti-HCV were also higher than expected. A quarter of our HBsAg(+) subjects had abnormal liver tests, suggesting a potential need for treatment. Recognizing the impact of immigration on the prevalence of viral hepatitis in the U.S., targeted screening in areas suspected of high prevalence may be effective in identifying clinically relevant HBV- and HCV-related disease.



 (n = 88)

 (n = 137)

 (n = 230)

Male (n, %)

55 (62.5%)

78 (56.9%)

136 (59.1%)

Mean age (years)




Anti-HBc +

63 (71.6%)

78 (56.9%)

144 (62.6%)

HBsAg +

25 (28.4%)

20 (14.6%)

45 (19.6%)

HBsAg (+) among no prior hx of HBV

5/63 (7.9%)

9/121 (7.4%)

14/189 (7.4%)

Anti-HCV +

4 (4.5%)

8 (5.8%)

12 (5.2%)


13 (14.8%)

19 (13.9%)

33 (14.3%)

AST or ALT > ULN among HBsAg +

6/25 (24%)

5/20 (25%)

11/45 (24.4%)

AST or ALT > ULN among anti-HCV +

1/4 (25%)

5/8 (62.5%)

6 (50%)


1317. Comparison of Outreach Methods to Increase Hepatitis A and B Vaccination Rates in Patients with Chronic Hepatitis C. 

L. M. Woolard; V. E. Smith; C. A. Jackson; A. K. Lamb; C. J. Bruno.



Hepatitis A (HAV) and hepatitis B (HBV) are vaccine preventable diseases and guidelines recommend vaccination of high-risk individuals. Patients with chronic liver disease, specifically hepatitis C (HCV), are part of this targeted population.



To increase vaccination rates for HAV and HBV in patients with chronic HCV in a managed care population.



A total of 163 patients in our Hepatitis C Clinic were identified through chart review as needing to initiate or complete the HAV/HBV vaccine series. All patients received an initial outreach letter indicating their need for vaccination. Those not responding were randomized (1:2) to receive an outreach telephone call or a second letter, respectively. The outreach period lasted 3.5 months.



After the initial outreach, 22 patients (13.5%) received vaccination. One patient declined vaccination. 140 patients were then randomized to the second outreach. With the second letter, 28 patients (30.4%) received vaccination. The telephone call resulted in the vaccination of 27 patients (61.4 %). Four patients stated previous completion of vaccine series. Overall, 48.4% (77/159) of patients needing vaccination started or completed the HAV/HBV series (Chart 1).



In our study, an outreach letter followed by a telephone call was more effective at increasing vaccination rates.  Overall 48% of patients needing vaccination started and completed the HAV/HBV series.


·        Duration – minimum of 6 months recommended to complete vaccination series for hepatitis A and B;  study period was 4 months

·        Cost—Analysis not completed to determine most cost effective method of outreach.

·        Randomization—Electronic randomization did not account for vaccine needed.


Regardless of contact method, focusing on vaccination for patients with chronic hepatitis C is essential in preventing further complications.

Chart 1