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486 Hepatitis B Immunity and Response to Booster Immunization in Children With Inflammatory Bowel Disease Treated With Infliximab Jonathan Moses, Naim Alkhouri, Angela Shannon, Kathy Raig, Rocio Lopez, Lara Danziger-Isakov, Ariel E. Feldstein, Nizar N. Zein, Robert Wyllie, Christine A. Carter-Kent Introduction: Hepatitis B virus (HBV) reactivation has been described in patients treated with infliximab (IFX) for inflammatory bowel disease (IBD). This has resulted in a “black box” warning. Although universal vaccination against HBV was implemented in the US in 1991, up to 10% of vaccine recipients fail to respond with adequate anti-hepatitis B surface antibodies (anti-HBs) titers after vaccinations. In addition, anti-HBs titers are expected to decline with time. The aims of this study were to determine HBV immunity in children with IBD on IFX therapy and to determine response to a booster dose of the HBV vaccine in patients who were found to be non-immune. Methods: This was a prospective cross- sectional, single-center study that included 100 pediatric IBD patients on infliximab. Serologic specimens were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and anti-HBs. Patients with an anti-HBs level ≥10 mIU/mL were considered to be immune. One booster dose was given to non-immune patients and a serum sample was collected after 4 weeks to assess the presence of anamnestic response (anti-HBs level ≥10 mIU/mL after booster). Results: The mean age of patients was 17.9 (± 4.0) years. None of the patients were positive for HBsAg or anti-HBc. 87 patients were vaccinated against HBV and 49/87 (56%) had immunity to HBV as defined by anti-HBs level ≥10 mIU/mL. The mean concentration of anti-HBs levels in immune patients was 295.6 (± 350.6) mIU/mL. Older age, lower albumin levels and presence of pancolitis were associated with loss of protective antibodies; however, infliximab dose, frequency, duration and the concurrent use of immunomodulators were not significantly different between immune and non-immune patients. The remaining 38 patients received booster immunization and 26/38 (68%) had an anamnestic response. Interestingly, non-responders were given infliximab with higher frequency (every 5.9 ± 1.2 weeks vs every 7.1 ± 1.8 weeks, P = 0.01). Overall 75/87 (86%) of previously immunized patients were considered immune against hepatitis B infection. Conclusion: In pediatric IBD patients seen at a large, urban tertiary care facility in the US, a significant minority (13%) have not been vaccinated against hepatitis B. Nearly one half of all patients (and 44% of previously vaccinated patients) did not have protective anti-HBs levels. Moreover, of those previously vaccinated, a significant minority (14%) appear at risk for HBV because protective anti-HBs levels were absent and could not be elicited through booster immunization. Given the high risk for severe HBV infection in this group, efforts should be made to screen for HBV immunity at the time of diagnosis of IBD. Booster immunization should be considered in patients without protective antibodies. 487 Positive HBV Screening in Children With Oncologic or Hematologic Conditions: Taking the Next Step David Ahamba, Mahjabeen Khan, Lekshmi Pillai, Stephanie Howe, Daniel H. Leung Background: Hepatitis B virus (HBV) reactivation is a well-described complication in cancer patients who receive cytotoxic chemotherapy. During active surveillance of hepatitis B through serologic testing over a 10 year period at a major children's hospital, a significant number of children with oncologic or hematologic conditions were found to be Hep B core Ab. There is also risk in children with hematologic diseases (e.g aplastic anemia or ITP) requiring steroid or immunosuppressive therapy, underscoring the importance of knowing HBV status. Aims: 1) To characterize the oncologic and hematologic conditions in children who tested positive for HBV by serology 2)To investigate current practices among oncologists given positive HBV screening among children (ages 0-17) at a quaternary children's hospital. Methods: A retrospective analysis of hospital-affiliated patients (0-17 yrs) who tested positive on HBV screening by core Ab or surface Ag or from 1999-2009 was performed. Results: 127 of 497 children (26%) who screened positive for HBV carried an oncologic or hematologic diagnosis. Leukemias, anemia (aplastic, autoimmune, hemolytic), and thrombocytopenia comprised 32%, 27% and 25% of these cases respectively. Neutropenia, pancytopenia, lymphoma, and neuroblastoma comprised the remainder. 96% tested core Ab positive, 4% tested surface Ag positive, and only 2% tested positive for both. Up to 60% of children with leukemia, lymphoma, thrombocytopenia, and anemia who tested positive on HBV screen demonstrated aminotransferase elevation (>45 U/L). Only 22 of 127 (17%) positively screened children with oncologic or hematologic diagnoses received confirmatory testing via HBV DNA while the remaining 83% did not. 25% of children with leukemia, 12.5% of children with anemia, and no children with thrombocytopenia, who had a positive HBV screen were confirmed to have HBV. The one child with lymphoma who tested positive on screen was confirmed to have HBV. Conclusions: Children with oncologic or hematologic conditions may have a higher risk of testing positive for Hep B core Ab. Whether these represent false positives secondary to multiple transfusions or a true diagnosis of HBV needs to be confirmed. However, less than 20% of positively screened children with oncologic or hematologic disorders received confirmatory or HBV DNA testing despite elevation of aminotransferases. Given our findings of a high HBV confirmation rate of 12.5-25% in the leukemia and anemia groups, it is likely that the number of true HBV cases is underreported. Children with malignancy or leukemia requiring chemotherapy or immunosuppression are at high risk of HBV reactivation. Greater education regarding risk of HBV reactivation is needed for clinicians treating patients with immunosuppressive therapies. S-893 AASLD Abstracts 488 Quality of Life in Young Adult Survivors of Biliary Atresia: Results From a National Cohort Willemien de Vries, Yuk-Kueng Sze, Egbert Sieders, Henkjan J. Verkade, Josette Hoekstra- Weebers, Jan B. Hulscher Introduction: Biliary atresia (BA) is a cholestatic disease of infancy characterized by oblitera- tion of the extrahepatic bile ducts. The disease is primarily treated by Kasai portoenterostomy, after which long-term (20 years) re-establishment of bile flow is currently achieved in ~25% of the patients. The second treatment option is liver transplantation (OLT). With the advent of these treatment options, an increasing number of patients survive into adulthood. Little is known about the long-term quality of life (QOL) of survivors of BA. We aimed to determine the QOL in a cohort of young adult survivors of BA. Methods: The RAND-36 health status questionnaire and Liver Disease Symptom Index score 2.0 (LDSI) questionnaire were sent to all eligible 55 surviving adult BA patients, who were born between 1977 and 1991. The RAND-36 encompasses eight quality of life domains from which a physical and mental summary score can be computed. The LDSI questionnaire consists of 24 items which scores symptoms on a 1-5 scale. Clinical patient characteristics were obtained from the NeSBAR (Netherlands Study group on Biliary Atresia Registry) database and the local OLT database. Results of the RAND-36 scores were compared to those of an age-matched Dutch reference group (ANOVA), and relationships between the RAND-36 scores and liver biochemistry parameters and LDSI scores were studied (Pearson's correlational analysis). Results: Eighty- one percent (25/31) of the non-transplanted and 63% (15/24) of the transplanted patients responded. The mean RAND-36 domain and summary scores of either transplanted or transplant-free BA patients did not significantly differ from the reference group's scores (see Table 1). The single exception was general health perception, which was decreased in transplant-free females (63±21) compared to the reference group (75±17; p=0.004). The mean LDSI score was similar in the studied groups, 1.4±0.4 (range found 1.0-2.5) in transplant-free patients, and 1.4±0.3 (range found 1.0-2.3) in transplanted patients. Trans- plant-free patients scored highest on the ‘sleepiness during day’ item (2.4±1.2) and trans- planted patients on the 'hindrance in financial affairs' item (2.3±1.7). RAND-36 summary scores were not correlated to serum bilirubin, ASAT or albumin levels, but significant relationships were found with LDSI total scores (see Table 1). Conclusions: Overall, young adult BA patients have a QOL similar to an age-matched reference group. However, perception of general health in transplant-free females was lowered. QOL is correlated to liver disease symptoms and not to serum liver biochemistry parameters. In order to improve the QOL of the individual BA patient, focus on the improvement of the various liver disease-associated symptoms might be important. Table 1: RAND-36 summary scores and correlation with LDSI scores AASLD Abstracts
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486
Hepatitis B Immunity and Response to Booster Immunization in ChildrenWith Inflammatory Bowel Disease Treated With InfliximabJonathan Moses, Naim Alkhouri, Angela Shannon, Kathy Raig, Rocio Lopez, LaraDanziger-Isakov, Ariel E. Feldstein, Nizar N. Zein, Robert Wyllie, Christine A. Carter-Kent
Introduction: Hepatitis B virus (HBV) reactivation has been described in patients treatedwith infliximab (IFX) for inflammatory bowel disease (IBD). This has resulted in a “blackbox” warning. Although universal vaccination against HBV was implemented in the US in1991, up to 10% of vaccine recipients fail to respond with adequate anti-hepatitis B surfaceantibodies (anti-HBs) titers after vaccinations. In addition, anti-HBs titers are expected todecline with time. The aims of this study were to determine HBV immunity in childrenwith IBD on IFX therapy and to determine response to a booster dose of the HBV vaccinein patients who were found to be non-immune. Methods: This was a prospective cross-sectional, single-center study that included 100 pediatric IBD patients on infliximab. Serologicspecimens were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody(anti-HBc), and anti-HBs. Patients with an anti-HBs level ≥10 mIU/mL were considered tobe immune. One booster dose was given to non-immune patients and a serum sample wascollected after 4 weeks to assess the presence of anamnestic response (anti-HBs level ≥10mIU/mL after booster). Results: The mean age of patients was 17.9 (± 4.0) years. None ofthe patients were positive for HBsAg or anti-HBc. 87 patients were vaccinated against HBVand 49/87 (56%) had immunity to HBV as defined by anti-HBs level ≥10 mIU/mL. Themean concentration of anti-HBs levels in immune patients was 295.6 (± 350.6) mIU/mL.Older age, lower albumin levels and presence of pancolitis were associated with loss ofprotective antibodies; however, infliximab dose, frequency, duration and the concurrent useof immunomodulators were not significantly different between immune and non-immunepatients. The remaining 38 patients received booster immunization and 26/38 (68%) hadan anamnestic response. Interestingly, non-responders were given infliximab with higherfrequency (every 5.9 ± 1.2 weeks vs every 7.1 ± 1.8 weeks, P = 0.01). Overall 75/87 (86%)of previously immunized patients were considered immune against hepatitis B infection.Conclusion: In pediatric IBD patients seen at a large, urban tertiary care facility in the US,a significant minority (13%) have not been vaccinated against hepatitis B. Nearly one halfof all patients (and 44% of previously vaccinated patients) did not have protective anti-HBslevels. Moreover, of those previously vaccinated, a significant minority (14%) appear at riskfor HBV because protective anti-HBs levels were absent and could not be elicited throughbooster immunization. Given the high risk for severe HBV infection in this group, effortsshould be made to screen for HBV immunity at the time of diagnosis of IBD. Boosterimmunization should be considered in patients without protective antibodies.
487
Positive HBV Screening in Children With Oncologic or HematologicConditions: Taking the Next StepDavid Ahamba, Mahjabeen Khan, Lekshmi Pillai, Stephanie Howe, Daniel H. Leung
Background: Hepatitis B virus (HBV) reactivation is a well-described complication in cancerpatients who receive cytotoxic chemotherapy. During active surveillance of hepatitis Bthrough serologic testing over a 10 year period at a major children's hospital, a significantnumber of children with oncologic or hematologic conditions were found to be Hep B coreAb. There is also risk in children with hematologic diseases (e.g aplastic anemia or ITP)requiring steroid or immunosuppressive therapy, underscoring the importance of knowingHBV status. Aims: 1) To characterize the oncologic and hematologic conditions in childrenwho tested positive for HBV by serology 2)To investigate current practices among oncologistsgiven positive HBV screening among children (ages 0-17) at a quaternary children's hospital.Methods: A retrospective analysis of hospital-affiliated patients (0-17 yrs) who tested positiveon HBV screening by core Ab or surface Ag or from 1999-2009 was performed. Results:127 of 497 children (26%)who screened positive for HBV carried an oncologic or hematologicdiagnosis. Leukemias, anemia (aplastic, autoimmune, hemolytic), and thrombocytopeniacomprised 32%, 27% and 25% of these cases respectively. Neutropenia, pancytopenia,lymphoma, and neuroblastoma comprised the remainder. 96% tested core Ab positive, 4%tested surface Ag positive, and only 2% tested positive for both. Up to 60% of childrenwith leukemia, lymphoma, thrombocytopenia, and anemia who tested positive on HBVscreen demonstrated aminotransferase elevation (>45 U/L). Only 22 of 127 (17%) positivelyscreened children with oncologic or hematologic diagnoses received confirmatory testingvia HBV DNA while the remaining 83% did not. 25% of children with leukemia, 12.5% ofchildren with anemia, and no children with thrombocytopenia, who had a positive HBVscreen were confirmed to have HBV. The one child with lymphoma who tested positive onscreen was confirmed to have HBV. Conclusions: Children with oncologic or hematologicconditions may have a higher risk of testing positive for Hep B core Ab. Whether theserepresent false positives secondary to multiple transfusions or a true diagnosis of HBV needsto be confirmed. However, less than 20% of positively screened children with oncologicor hematologic disorders received confirmatory or HBV DNA testing despite elevation ofaminotransferases. Given our findings of a high HBV confirmation rate of 12.5-25% in theleukemia and anemia groups, it is likely that the number of true HBV cases is underreported.Children with malignancy or leukemia requiring chemotherapy or immunosuppression areat high risk of HBV reactivation. Greater education regarding risk of HBV reactivation isneeded for clinicians treating patients with immunosuppressive therapies.
S-893 AASLD Abstracts
488
Quality of Life in Young Adult Survivors of Biliary Atresia: Results From aNational CohortWillemien de Vries, Yuk-Kueng Sze, Egbert Sieders, Henkjan J. Verkade, Josette Hoekstra-Weebers, Jan B. Hulscher
Introduction: Biliary atresia (BA) is a cholestatic disease of infancy characterized by oblitera-tion of the extrahepatic bile ducts. The disease is primarily treated by Kasai portoenterostomy,after which long-term (20 years) re-establishment of bile flow is currently achieved in ~25%of the patients. The second treatment option is liver transplantation (OLT). With the adventof these treatment options, an increasing number of patients survive into adulthood. Littleis known about the long-term quality of life (QOL) of survivors of BA.We aimed to determinethe QOL in a cohort of young adult survivors of BA. Methods: The RAND-36 health statusquestionnaire and Liver Disease Symptom Index score 2.0 (LDSI) questionnaire were sentto all eligible 55 surviving adult BA patients, who were born between 1977 and 1991. TheRAND-36 encompasses eight quality of life domains from which a physical and mentalsummary score can be computed. The LDSI questionnaire consists of 24 items which scoressymptoms on a 1-5 scale. Clinical patient characteristics were obtained from the NeSBAR(Netherlands Study group on Biliary Atresia Registry) database and the local OLT database.Results of the RAND-36 scores were compared to those of an age-matched Dutch referencegroup (ANOVA), and relationships between the RAND-36 scores and liver biochemistryparameters and LDSI scores were studied (Pearson's correlational analysis). Results: Eighty-one percent (25/31) of the non-transplanted and 63% (15/24) of the transplanted patientsresponded. The mean RAND-36 domain and summary scores of either transplanted ortransplant-free BA patients did not significantly differ from the reference group's scores (seeTable 1). The single exception was general health perception, which was decreased intransplant-free females (63±21) compared to the reference group (75±17; p=0.004). Themean LDSI score was similar in the studied groups, 1.4±0.4 (range found 1.0-2.5) intransplant-free patients, and 1.4±0.3 (range found 1.0-2.3) in transplanted patients. Trans-plant-free patients scored highest on the ‘sleepiness during day’ item (2.4±1.2) and trans-planted patients on the 'hindrance in financial affairs' item (2.3±1.7). RAND-36 summaryscores were not correlated to serum bilirubin, ASAT or albumin levels, but significantrelationships were found with LDSI total scores (see Table 1). Conclusions: Overall, youngadult BA patients have aQOL similar to an age-matched reference group. However, perceptionof general health in transplant-free females was lowered. QOL is correlated to liver diseasesymptoms and not to serum liver biochemistry parameters. In order to improve the QOLof the individual BA patient, focus on the improvement of the various liver disease-associatedsymptoms might be important.Table 1: RAND-36 summary scores and correlation with LDSI scores
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