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Sa1018 Serum Cytokine Profiles in Patients With Hepatitis B Virus (HBV) Infection and Associated Hepatocellular Carcinoma (HCC)
Sa1017 Enhanced HMGB1 Expression Can Promote TH17 Cells Differentiation via TLR4/NF-KB Signaling in HBV-Infected Chronic Liver Diseases Wei Jiang, Fuping Wang, Jing Li T helper 17 (Th17) cells, have been shown to inhibit HBV replication and cause immunemediated liver injury in chronic HBV infection. Recently, High-mobility group box 1 (HMGB1) protein has been implicated as a potent proinflammatory cytokine. In order to further elucidate the mechanism of inflammation with liver fibrosis, we designed this study to evaluate whether HMGB1 can promote Th17 cell differentiation in HBV-infected chronic diseases and to explore the possible mechanism. Thirty HBV-inactive carriers, fifty CHB patients and eighty HBV-infected liver cirrhosis patients were enrolled in this study. Peripheral HMGB1 level was up-regulated during the process of chronic liver injury and correlated with the increased Th17 cells-related transcription factors (RORct) expression and Th17associated cytokines secretion. In addition, HMGB1 stimulation induced the elevated expressions of TLR2 and TLR4, especially TLR4, on CD4+T cells from the patients of CHB and HBV-infected liver cirrhosis. Enhanced HMGB1 stimulation can induce Th17 cell differentiation and Th17 -associated cytokines secretion in CHB patients with dose- and time- dependent manner, but the pretreatment of increased TLR4 neutralization antibody inhibited the above stimulatory effects of HMGB1. Furthermore, HMGB1 can induce increased NF-KB/p65 expression, IKB phosphorylation, nuclear translocation of NF-KB/p65 and NF-KB activity in CD4+T cells from CHB patients with the prolonged times, and blockage of TLR4 markedly inhibited HMGB1-stimulated functional change of NF-KB. In conclusion, these results indicated HMGB1 can induce Th17 differentiation in HBV-infected chronic liver injury and TLR4/ NF-KB signaling may be involved in the molecule mechanism pathway of HMGB1 stimulation on CD4+T cells. Long Duration of Effect From RNAI Therapeutic to Treat Chronic Hepatitis B Virus Infection Correlates With Persistence of the Phosphorylated Guide Strand Christine I. Wooddell, Vladimir Trubetskoy, Collin Hagen, Anthony Perillo-Nicholas, Jacob B. Griffin, Holly Hamilton, Qili Chu, Alan McLachlan, David Rozema, David Lewis
Sa1018 Serum Cytokine Profiles in Patients With Hepatitis B Virus (HBV) Infection and Associated Hepatocellular Carcinoma (HCC) Philip Vutien, Ellen Chang, David O. Nelson, Linyi Gao, Yael Rosenberg-Hasson, Mindie H. Nguyen
Chronic hepatitis B virus (HBV) infection is a major disease for which there remains an unmet medical need. Current therapies for chronic hepatitis B include reverse transcriptase inhibitors and interferon. These therapies either require life-long administration or have significant side effects and limited efficacy. We have taken a novel approach toward the treatment of chronic hepatitis B by developing an siRNA-based therapeutic. In contrast to current therapies, our approach has the promise of significantly decreasing viral protein load which is primarily responsible for disease progression. In our formulation, liver-tropic cholesterol-conjugated siRNAs against HBV (chol-siHBVs) are co-injected intravenously with a reversibly masked, hepatocyte-targeted melittin-like peptide (NAG-MLP). Co-injection of chol-siHBVs and NAG-MLP results in multi-log repression of viral RNA, proteins and viral DNA with long duration of effect in transient and transgenic mouse models of chronic HBV infection, without toxicity. Using a hybridization/HPLC-based method of detection, we are able to correlate the degree of repression of the virus with the amount of the active form of the siRNA guide strand in the liver. In addition, this form of the guide strand can be detected up to one month after a single administration, correlating with the duration of effect. High efficacy, a long duration of effect and establishment of a robust pharmacokinetic/ pharmacodynamic relationship in the liver suggest co-injection of NAG-MLP and cholsiHBVs holds great promise as a novel therapeutic for chronically HBV infected patients.
Purpose: Infection with HBV is a global health concern that has been estimated to be responsible for over half of the HCC cases worldwide. One major driving force in this carcinogenesis is the prolonged immune and inflammatory response HBV infection causes. Several studies have examined various cytokines and their role in HBV-associated HCC but these studies have focused predominately on a single or a group of few cytokines. There is a paucity of data characterizing the immune profiles consisting of several cytokines in HBVassociated HCC. Methods: Serum specimens and clinical data were collected from 237 patients who were seen at a U.S. university liver clinic. Serum levels of 51 cytokines were measured with the Luminex 200 system. These serum cytokine levels were normalized and differences in medians between select cohorts were analyzed and graphed on half-normal plots. Results: Of the 237 patients in our study, 154 (65%) had HBV infection and 47 (20%) had HCC. Compared to HBV- patients, HBV+ patients were younger (50 vs. 61, p ,0.001), were more likely to be male (68% vs. 51%, p = 0.01), were more likely to be Asian (95% vs. 16%, p,0.001), and were less likely to have cirrhosis (29% vs. 87%, p ,0.001). Analysis of differences in cytokine levels between HBV+ versus HBV- patients in a cohort without HCC (text only) showed overall decreased cytokine levels in HBV+ patients (p ,0.001). Figure 1 shows that within the HBV+ cohort, patients with HCC had significantly higher cytokine levels than non-HCC patients (p = 0.049. Figure 2 shows that in the HBV- cohort, cytokine levels were also elevated in HCC cases compared to controls (p = 0.024). However, when comparing the individual cytokines that were significantly different in HCC cases vs. controls in the separate analyses (Figures 1 and 2), VCAM-1, TGF- α, MIP-1β, GRO-α, MIG, TNF-β, and resistin levels were elevated in the HBV+ population but not the HBV- one. In contrast, IL-15 levels were higher and leptin levels were lower in the HCC cases of the HBV- cohort but not the HBV+ one. Conclusions: HBV infection without HCC is associated with overall decreased cytokine levels when compared to other liver diseases and the development of HCC is associated with elevated cytokine levels irrespective of HBV status. However, despite the shared overall increase of cytokine levels in HCC cases, the development of HCC in HBV+ patients was associated with elevations of a different set of cytokines compared to non-viral HCC patients. This difference in cytokine profiles may suggest that different inflammatory environments underlie the development of HCC in HBV+ compared to other etiologies.
Sa1016 Pyrosequencing Analysis of Synonymous Codon Usage Pattern of Rtm204i/V Mutation in Lamivudine-Resistant Chronic Hepatitis B Patients Wei Hou, Wukui Cao, Yuqiang Mi, Jiming Yang, Wei Lu BACKGROUND/AIM: The rtM204I/V mutation of the tyrosine-methionine-aspartate-aspartate (YMDD) motif in the C domain of the HBV DNA polymerase gene is associated with lamivudine (LAM) treatment. The synonymous codon usage pattern of isoleucine (I) or valine (V) substitutions instead of methionine (M) in the YMDD motif is still unknown. The aim of this study was to analyze the codon usage pattern of YMDD motif in patients with LAM-resistant chronic hepatitis B (CHB). METHODS: 514 CHB inpatients and outpatients from Tianjin Second People's Hospital with confirmed genotypic resistance to LAM were enrolled in this study between Jan 2008 and Oct 2012. The YMDD motif of these HBV isolates were analyzed using a pyrosequencing method. RESULTS: The baseline YMDD mutation patterns were as follows: rtM204I (298, 57.98%), rtM204V (168, 32.68%), and rtM204I+ rtM204V(48, 9.34%). For rtM204I mutation (I=AAT, ATC or ATA), I/ ATT(84.78%). I/ATC(8.97%).I/ATA(6.25%). Most of the I/ATC(90.91%), I/ATT(70.34%) and I/ATA(65.21%) variants were completely mutated. For rtM204V mutation (V=GTG, GTT, GTA or GTC), V/GTG(80.54%) .V/GTT(16.79%).V/GTA(1.53%).V/GTC(1.14%). More than half of V/GTG(53.55%) variants were completely mutated. However, V/ GTA(100%), V/GTT(90.91%) and V/GTC(66.67%) variants were always mixed with M/ATG wide-type isolates. CONCLUSION: We firstly report the synonymous codon usage pattern of YMDD variants in HBV isolates. The synonymous codons of YMDD variants are not chosen equally and randomly. I/ATT and V/GTG are predominant for rtM204I and rtM204V mutation, respectively. A further investigation of the mutation pressure with translation selection on codon usage might shed a new light on understanding the evolutionary trends of HBV and host adaptive response, which might assist control this disease.Supported in part by the National Natural Science Foundation of China (Nos. 30800974, 81271845) and Tianjin Municipal Health Bureau of science and Technology Fund (2012KR02).
S-973
AASLD Abstracts
AASLD Abstracts
Sa1015
patients prior to treatment leads to appropriate prophylaxis against HBV reactivation. Prospective studies are needed to identify the optimal timing, duration and type of such prophylaxis with a goal of zero percent reactivation.
Sa1020 Hepatitis B Virus Infection and Risk of Non-Hodgkin Lymphoma: A MetaAnalysis of Case-Control Studies Rajan Kanth, Anupama Inaganti, Naga Swetha Samji, Sarah D. Komanapalli, Brian B. Borg, Praveen K. Roy
AASLD Abstracts
Purpose: Several studies have suggested association between hepatitis C virus (HCV) and non-hodgkin lymphoma (NHL). But the role of hepatitis B virus (HBV) in the pathogenesis of lymphoproliferative malignancy is not clear. We performed a meta-analysis of case-control studies to evaluate the role of HBV infection in NHL. Method: Pubmed, Embase, Web of knowledge, reference lists of retrieved articles and conference abstracts were searched for relevant studies (Search date Oct-2012). Case control studies were included. Studies related to HBV reactivation after chemotherapy and cohort studies were excluded. Standardized forms were used to extract data. Data was extracted by two reviewers independently. Odds ratio was calculated using comprehensive Meta-analysis software. Heterogeneity and publication bias were also assessed. Random effects model was used for pooling the data. Result: Nineteen studies were included (cases 13947/controls 1559448). Studies were reported from Europe (8), South Korea (4), Japan (1), Taiwan (1), Singapore (1), China (1), Pakistan (1), Egypt (1) and Saudi-Arabia (1). Hepatitis B was diagnosed by detection of HBsAg (17 studies) and by self-report history (2 studies). NHL was diagnosed by histopathology. Controls were non-lymphoma cancer/hospital patients (9 studies), healthy population (8 studies) and both (2 studies). 1205 cases of HBV infection were found in the NHL cases group and 40592 HBV infection were present in the control group. HBV infection was higher in patients with NHL compared to the controls (OR 2.53; 95% CI, 2.10-3.03, p ,0.001). Subgroup analysis showed higher risk of HBV infection in NHL in both developing countries (Asia) and developed countries (Europe). No difference was noted between hospitals based controls and population based controls. Significant heterogeneity was not present among the studies. Conclusion: The present meta-analysis based on 19 studies suggests hepatitis B virus infection as a risk factor for NHL. Further cohort studies are needed to prove this association. Sa1021 Real-Time Tissue Elastography for the Assessment of Liver Fibrosis in Patients With Chronic Hepatitis C and Correlation With Response to PegylatedInterferon-Alpha 2B and Ribavirin Combination Therapy Kazuhiko Hayashi, Yoshiaki Katano, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Masatoshi Ishigami, Hidemi Goto OBJECTIVES: Percutaneous liver biopsy is considered the gold standard for evaluating the stage of liver fibrosis, but has been pointed out the limitations. Therefore, many non-invasive methods for the assessment of liver fibrosis have been developed to replace liver biopsy. Liver stiffness measured by transient elastography has been reported the utility for assessment of liver fibrosis. Real-time tissue elastography (RTE) is a kind of transient elastography which could measure liver stiffness. However, the assessments of liver fibrosis by RTE are not well known. The primary aim of the present study was to determine whether RTE is useful in diagnosing liver fibrosis in patients with chronic hepatitis C. Several studies suggested that liver fibrosis might have impact on the response to interferon therapy. A secondary aim was to investigate the association between liver stiffness by RTE and response to pegylatedinterferon-alpha 2b and ribavirin combination therapy. (Methods) One hundred eleven patients with chronic hepatitis C were enrolled for this study. The patients consisted of 51 men and 60 women with a mean age of 54.2 (range, 19 to 78) years. Liver biopsy was performed and fibrosis stage was diagnosed according to the METAVIR criteria. Fifty patients received pegylated-IFN-alpha 2b once each week plus oral ribavirin daily for 48 or 72 weeks. Detection of the SNP of IL28B (rs8099917) was done by a real-time PCR system with specific probes. RESULTS: The fibrosis stage was diagnosed as F0 (n = 30), F1 (n = 40), F2 (n = 21), F3 (n = 13), and F4 (n = 17) by liver biopsy. Receiver Operatorating Characteristic (ROC) curve analysis was performed for fibrosis stage by RTE. Area Under the Curve (AUC) for F1,, F2,, F3,, and F4, were 0.761, 0.791, 0.819, and 0.7917 respectively (p ,0.05). The cut-off value of F3, was defined by ROC curve and divided into 2 groups (mild fibrosis and severe fibrosis). Of the 50 patients, 16 achieved sustained virologic response (SVR). SVR was achieved in 9% of patients with severe fibrosis by RTE and 38.5% of patients with mild fibrosis. Achievement of SVR occurred more frequently in patients with TT allele (37.5%) than in those with TG and GG alleles (22.2%). The best SVR rate was achieved in patients with mild fibrosis by RTE and T allele, and the worst response was achieved in patients with severe fibrosis by RTE and G allele. CONCLUSIONS: RTE could evaluate the degree of liver fibrosis. Combining RTE and IL28B could improve the predictive value of SVR in patients with chronic hepatitis C.
Sa1019 Incidence of Hepatitis B Surface Antigen and Hepatitis B Core Antibody in a Screening Population Undergoing Chemotherapy Mary K. Sammons, Robin B. Mendelsohn, Kent Sepkowitz, Dhruv Patel, Eric J. Sherman, Andrew D. Zelenetz, Emmy Ludwig Background: Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication after immunosuppression from chemotherapeutic agents and can lead to significant morbidity and mortality. We previously reported 23 HBV reactivations in patients of diverse nationalities without association with a particular malignancy or medication. Our institution subsequently initiated a protocol in which all new patients receiving immunosuppressive therapy are screened for HBV and offered anti-viral prophylaxis. The aim of this study is to report the prevalence of HBV surface antigen (HBsAg) and HBV core antibody (HBcAb) positivity since the inception of this screening program. Methods: We conducted a prospective study of all patients at Memorial Sloan-Kettering Cancer Center who were started on immunosuppressive therapy and screened for HBV from May 2009 to November 1, 2012. Patients were screened using tests for HBsAg and HBcAb. If either of these were positive, PCR for HBV DNA was reflexively measured. Patient demographics --including type of malignancy-were recorded. Results: Between May 1 2009 and November 1 2012, 17183 patients met criteria for screening and 12,328 patients (median age 64 years [24-95], 54.4% male) were screened for HBV prior to initiation of immunosuppression (71.75% compliance). Testing revealed 78(0.6%) patients positive for both HbsAg and HbcAb (median age 58, 69.2% male).Of this group, 47/78 (60.26%) had detectable HBV DNA PCR (955766.7 mean, 521 median) .Primary diagnoses of these patients included lymphoma 6.4%, leukemia 2.6%, and myriad solid tumors 91.0%. In addition, 994 patients (8.1%) were negative for HBsAg and positive for HBcAb (median age 58, 53.2% male), Diagnoses among this group included 6.0% lymphoma, 2.0% leukemia and 92.0 % solid tumor. Of this group, 7 (0.7%) had detectable HBV DNA PCR ([41-1,740,000 IU/mL]). Conclusion: In our population screened for HBV prior to initiation of immunosuppression, we report a prevalence of 0.6% for HBsAg positive patients and 8.1% for HBsAg negative, HBcAb positive patients. Screening of these
AASLD Abstracts
S-974
Sa1018 Serum Cytokine Profiles in Patients With Hepatitis B Virus (HBV) Infection and Associated Hepatocellular Carcinoma (HCC) Philip Vutien, Ellen Chang, David O. Nelson, Linyi Gao, Yael Rosenberg-Hasson, Mindie H. Nguyen
Chronic hepatitis B virus (HBV) infection is a major disease for which there remains an unmet medical need. Current therapies for chronic hepatitis B include reverse transcriptase inhibitors and interferon. These therapies either require life-long administration or have significant side effects and limited efficacy. We have taken a novel approach toward the treatment of chronic hepatitis B by developing an siRNA-based therapeutic. In contrast to current therapies, our approach has the promise of significantly decreasing viral protein load which is primarily responsible for disease progression. In our formulation, liver-tropic cholesterol-conjugated siRNAs against HBV (chol-siHBVs) are co-injected intravenously with a reversibly masked, hepatocyte-targeted melittin-like peptide (NAG-MLP). Co-injection of chol-siHBVs and NAG-MLP results in multi-log repression of viral RNA, proteins and viral DNA with long duration of effect in transient and transgenic mouse models of chronic HBV infection, without toxicity. Using a hybridization/HPLC-based method of detection, we are able to correlate the degree of repression of the virus with the amount of the active form of the siRNA guide strand in the liver. In addition, this form of the guide strand can be detected up to one month after a single administration, correlating with the duration of effect. High efficacy, a long duration of effect and establishment of a robust pharmacokinetic/ pharmacodynamic relationship in the liver suggest co-injection of NAG-MLP and cholsiHBVs holds great promise as a novel therapeutic for chronically HBV infected patients.
Purpose: Infection with HBV is a global health concern that has been estimated to be responsible for over half of the HCC cases worldwide. One major driving force in this carcinogenesis is the prolonged immune and inflammatory response HBV infection causes. Several studies have examined various cytokines and their role in HBV-associated HCC but these studies have focused predominately on a single or a group of few cytokines. There is a paucity of data characterizing the immune profiles consisting of several cytokines in HBVassociated HCC. Methods: Serum specimens and clinical data were collected from 237 patients who were seen at a U.S. university liver clinic. Serum levels of 51 cytokines were measured with the Luminex 200 system. These serum cytokine levels were normalized and differences in medians between select cohorts were analyzed and graphed on half-normal plots. Results: Of the 237 patients in our study, 154 (65%) had HBV infection and 47 (20%) had HCC. Compared to HBV- patients, HBV+ patients were younger (50 vs. 61, p ,0.001), were more likely to be male (68% vs. 51%, p = 0.01), were more likely to be Asian (95% vs. 16%, p,0.001), and were less likely to have cirrhosis (29% vs. 87%, p ,0.001). Analysis of differences in cytokine levels between HBV+ versus HBV- patients in a cohort without HCC (text only) showed overall decreased cytokine levels in HBV+ patients (p ,0.001). Figure 1 shows that within the HBV+ cohort, patients with HCC had significantly higher cytokine levels than non-HCC patients (p = 0.049. Figure 2 shows that in the HBV- cohort, cytokine levels were also elevated in HCC cases compared to controls (p = 0.024). However, when comparing the individual cytokines that were significantly different in HCC cases vs. controls in the separate analyses (Figures 1 and 2), VCAM-1, TGF- α, MIP-1β, GRO-α, MIG, TNF-β, and resistin levels were elevated in the HBV+ population but not the HBV- one. In contrast, IL-15 levels were higher and leptin levels were lower in the HCC cases of the HBV- cohort but not the HBV+ one. Conclusions: HBV infection without HCC is associated with overall decreased cytokine levels when compared to other liver diseases and the development of HCC is associated with elevated cytokine levels irrespective of HBV status. However, despite the shared overall increase of cytokine levels in HCC cases, the development of HCC in HBV+ patients was associated with elevations of a different set of cytokines compared to non-viral HCC patients. This difference in cytokine profiles may suggest that different inflammatory environments underlie the development of HCC in HBV+ compared to other etiologies.
Sa1016 Pyrosequencing Analysis of Synonymous Codon Usage Pattern of Rtm204i/V Mutation in Lamivudine-Resistant Chronic Hepatitis B Patients Wei Hou, Wukui Cao, Yuqiang Mi, Jiming Yang, Wei Lu BACKGROUND/AIM: The rtM204I/V mutation of the tyrosine-methionine-aspartate-aspartate (YMDD) motif in the C domain of the HBV DNA polymerase gene is associated with lamivudine (LAM) treatment. The synonymous codon usage pattern of isoleucine (I) or valine (V) substitutions instead of methionine (M) in the YMDD motif is still unknown. The aim of this study was to analyze the codon usage pattern of YMDD motif in patients with LAM-resistant chronic hepatitis B (CHB). METHODS: 514 CHB inpatients and outpatients from Tianjin Second People's Hospital with confirmed genotypic resistance to LAM were enrolled in this study between Jan 2008 and Oct 2012. The YMDD motif of these HBV isolates were analyzed using a pyrosequencing method. RESULTS: The baseline YMDD mutation patterns were as follows: rtM204I (298, 57.98%), rtM204V (168, 32.68%), and rtM204I+ rtM204V(48, 9.34%). For rtM204I mutation (I=AAT, ATC or ATA), I/ ATT(84.78%). I/ATC(8.97%).I/ATA(6.25%). Most of the I/ATC(90.91%), I/ATT(70.34%) and I/ATA(65.21%) variants were completely mutated. For rtM204V mutation (V=GTG, GTT, GTA or GTC), V/GTG(80.54%) .V/GTT(16.79%).V/GTA(1.53%).V/GTC(1.14%). More than half of V/GTG(53.55%) variants were completely mutated. However, V/ GTA(100%), V/GTT(90.91%) and V/GTC(66.67%) variants were always mixed with M/ATG wide-type isolates. CONCLUSION: We firstly report the synonymous codon usage pattern of YMDD variants in HBV isolates. The synonymous codons of YMDD variants are not chosen equally and randomly. I/ATT and V/GTG are predominant for rtM204I and rtM204V mutation, respectively. A further investigation of the mutation pressure with translation selection on codon usage might shed a new light on understanding the evolutionary trends of HBV and host adaptive response, which might assist control this disease.Supported in part by the National Natural Science Foundation of China (Nos. 30800974, 81271845) and Tianjin Municipal Health Bureau of science and Technology Fund (2012KR02).
S-973
AASLD Abstracts
AASLD Abstracts
Sa1015
patients prior to treatment leads to appropriate prophylaxis against HBV reactivation. Prospective studies are needed to identify the optimal timing, duration and type of such prophylaxis with a goal of zero percent reactivation.
Sa1020 Hepatitis B Virus Infection and Risk of Non-Hodgkin Lymphoma: A MetaAnalysis of Case-Control Studies Rajan Kanth, Anupama Inaganti, Naga Swetha Samji, Sarah D. Komanapalli, Brian B. Borg, Praveen K. Roy
AASLD Abstracts
Purpose: Several studies have suggested association between hepatitis C virus (HCV) and non-hodgkin lymphoma (NHL). But the role of hepatitis B virus (HBV) in the pathogenesis of lymphoproliferative malignancy is not clear. We performed a meta-analysis of case-control studies to evaluate the role of HBV infection in NHL. Method: Pubmed, Embase, Web of knowledge, reference lists of retrieved articles and conference abstracts were searched for relevant studies (Search date Oct-2012). Case control studies were included. Studies related to HBV reactivation after chemotherapy and cohort studies were excluded. Standardized forms were used to extract data. Data was extracted by two reviewers independently. Odds ratio was calculated using comprehensive Meta-analysis software. Heterogeneity and publication bias were also assessed. Random effects model was used for pooling the data. Result: Nineteen studies were included (cases 13947/controls 1559448). Studies were reported from Europe (8), South Korea (4), Japan (1), Taiwan (1), Singapore (1), China (1), Pakistan (1), Egypt (1) and Saudi-Arabia (1). Hepatitis B was diagnosed by detection of HBsAg (17 studies) and by self-report history (2 studies). NHL was diagnosed by histopathology. Controls were non-lymphoma cancer/hospital patients (9 studies), healthy population (8 studies) and both (2 studies). 1205 cases of HBV infection were found in the NHL cases group and 40592 HBV infection were present in the control group. HBV infection was higher in patients with NHL compared to the controls (OR 2.53; 95% CI, 2.10-3.03, p ,0.001). Subgroup analysis showed higher risk of HBV infection in NHL in both developing countries (Asia) and developed countries (Europe). No difference was noted between hospitals based controls and population based controls. Significant heterogeneity was not present among the studies. Conclusion: The present meta-analysis based on 19 studies suggests hepatitis B virus infection as a risk factor for NHL. Further cohort studies are needed to prove this association. Sa1021 Real-Time Tissue Elastography for the Assessment of Liver Fibrosis in Patients With Chronic Hepatitis C and Correlation With Response to PegylatedInterferon-Alpha 2B and Ribavirin Combination Therapy Kazuhiko Hayashi, Yoshiaki Katano, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Masatoshi Ishigami, Hidemi Goto OBJECTIVES: Percutaneous liver biopsy is considered the gold standard for evaluating the stage of liver fibrosis, but has been pointed out the limitations. Therefore, many non-invasive methods for the assessment of liver fibrosis have been developed to replace liver biopsy. Liver stiffness measured by transient elastography has been reported the utility for assessment of liver fibrosis. Real-time tissue elastography (RTE) is a kind of transient elastography which could measure liver stiffness. However, the assessments of liver fibrosis by RTE are not well known. The primary aim of the present study was to determine whether RTE is useful in diagnosing liver fibrosis in patients with chronic hepatitis C. Several studies suggested that liver fibrosis might have impact on the response to interferon therapy. A secondary aim was to investigate the association between liver stiffness by RTE and response to pegylatedinterferon-alpha 2b and ribavirin combination therapy. (Methods) One hundred eleven patients with chronic hepatitis C were enrolled for this study. The patients consisted of 51 men and 60 women with a mean age of 54.2 (range, 19 to 78) years. Liver biopsy was performed and fibrosis stage was diagnosed according to the METAVIR criteria. Fifty patients received pegylated-IFN-alpha 2b once each week plus oral ribavirin daily for 48 or 72 weeks. Detection of the SNP of IL28B (rs8099917) was done by a real-time PCR system with specific probes. RESULTS: The fibrosis stage was diagnosed as F0 (n = 30), F1 (n = 40), F2 (n = 21), F3 (n = 13), and F4 (n = 17) by liver biopsy. Receiver Operatorating Characteristic (ROC) curve analysis was performed for fibrosis stage by RTE. Area Under the Curve (AUC) for F1,, F2,, F3,, and F4, were 0.761, 0.791, 0.819, and 0.7917 respectively (p ,0.05). The cut-off value of F3, was defined by ROC curve and divided into 2 groups (mild fibrosis and severe fibrosis). Of the 50 patients, 16 achieved sustained virologic response (SVR). SVR was achieved in 9% of patients with severe fibrosis by RTE and 38.5% of patients with mild fibrosis. Achievement of SVR occurred more frequently in patients with TT allele (37.5%) than in those with TG and GG alleles (22.2%). The best SVR rate was achieved in patients with mild fibrosis by RTE and T allele, and the worst response was achieved in patients with severe fibrosis by RTE and G allele. CONCLUSIONS: RTE could evaluate the degree of liver fibrosis. Combining RTE and IL28B could improve the predictive value of SVR in patients with chronic hepatitis C.
Sa1019 Incidence of Hepatitis B Surface Antigen and Hepatitis B Core Antibody in a Screening Population Undergoing Chemotherapy Mary K. Sammons, Robin B. Mendelsohn, Kent Sepkowitz, Dhruv Patel, Eric J. Sherman, Andrew D. Zelenetz, Emmy Ludwig Background: Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication after immunosuppression from chemotherapeutic agents and can lead to significant morbidity and mortality. We previously reported 23 HBV reactivations in patients of diverse nationalities without association with a particular malignancy or medication. Our institution subsequently initiated a protocol in which all new patients receiving immunosuppressive therapy are screened for HBV and offered anti-viral prophylaxis. The aim of this study is to report the prevalence of HBV surface antigen (HBsAg) and HBV core antibody (HBcAb) positivity since the inception of this screening program. Methods: We conducted a prospective study of all patients at Memorial Sloan-Kettering Cancer Center who were started on immunosuppressive therapy and screened for HBV from May 2009 to November 1, 2012. Patients were screened using tests for HBsAg and HBcAb. If either of these were positive, PCR for HBV DNA was reflexively measured. Patient demographics --including type of malignancy-were recorded. Results: Between May 1 2009 and November 1 2012, 17183 patients met criteria for screening and 12,328 patients (median age 64 years [24-95], 54.4% male) were screened for HBV prior to initiation of immunosuppression (71.75% compliance). Testing revealed 78(0.6%) patients positive for both HbsAg and HbcAb (median age 58, 69.2% male).Of this group, 47/78 (60.26%) had detectable HBV DNA PCR (955766.7 mean, 521 median) .Primary diagnoses of these patients included lymphoma 6.4%, leukemia 2.6%, and myriad solid tumors 91.0%. In addition, 994 patients (8.1%) were negative for HBsAg and positive for HBcAb (median age 58, 53.2% male), Diagnoses among this group included 6.0% lymphoma, 2.0% leukemia and 92.0 % solid tumor. Of this group, 7 (0.7%) had detectable HBV DNA PCR ([41-1,740,000 IU/mL]). Conclusion: In our population screened for HBV prior to initiation of immunosuppression, we report a prevalence of 0.6% for HBsAg positive patients and 8.1% for HBsAg negative, HBcAb positive patients. Screening of these
AASLD Abstracts
S-974