- Email: [email protected]
S1901 Biomarkers for Hepatic Hemangiosarcoma
was 10.83 ± 4.92. Mean CA 19-9 level was 129.95 ± 490.72. Over the study period, 6 patients (5.94%) were diagnosed with CCA. Patients received a mean number of 1.65 MRIs, 0.93 ERCPs, 0.34 CT scans, and 0.69 ultrasounds as screening tests during the observation period. 4 patients were found to have CCA on MRI, while 2 were diagnosed by biliary aspirate or brushings. The group with CCA was slightly older (63.5 years vs 53.0 years, p= 0.025). There was no significant difference in creatinine levels (1.42 vs 0.87, p=0.46), bilirubin levels (5.34 vs 3.26, p=0.39) or INR (1.16 vs 1.13, p=0.75). Those with CCA had a slightly higher MELD score (14.26 vs 10.62), but the difference was not significant (p= 0.335). As expected, CA 19-9 levels appeared higher among the CCA group, but were not significantly different (148.5 vs 89.4, p=0.63). There were no independently predicted factors that were associated with the development of CCA. In Kaplan-Meier survival analysis, oneyear survival in patients with CCA was statistically different than those without CCA (94.5% vs 77%, log rank = 0.01). In a multivariate one-year survival model, none of the imaging modalities studied were independent predictors of the diagnosis of CCA. Patients without CCA underwent more MRI/MRCPs, C T scans, and total imaging tests. Conclusion: Using clinical characteristics to stratify patients with PSC at risk for CCA remains problematic, as no parameters were found to impact risk. Using imaging techniques to screen for CCA did not appear to improve survival. Mean numbers of imaging tests based on CCA status
who did not develop HH demonstrate the HA did not correlate with cumulative VC exposure. Conclusions: These results suggest that HA, IL-8, IL-6, and CK-18 M65 could be biomarkers for hepatic hemangiosarcoma in highly-exposed VC workers. Increased levels of IL-8 and IL-6 are characteristic of an inflammatory response to cell injury and are not specific for HH. The applicability of these findings to other etiologies of hemangiosarcoma such as prescription medications (observed in rodents) should be explored. S1902
Background/Aims: It is commonly believed that hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection occurs exclusively in patients with cirrhosis. In contrast, carcinogenesis in patients with hepatitis B virus (HBV) infection may be independent of fibrosis. However, published data are sparse to demonstrate this difference. The aim of this study is to compare the proportion of advanced fibrosis and cirrhosis in the background liver between HBV and HCV patients diagnosed with HCC. Methods: Based on a prospective database tracking all HCC cases, patients with HCC and HBV evaluated between 1994 and 2008 were identified. Age- and sex-matched HCC patients with HCV were selected out of the same database (in 1:2 ratio). All available pathology reports were obtained to document advanced fibrosis (Batts-Ludwig stage 3 or 4). If histologic assessment of fibrosis was not available, clinical indicators were utilized to define cirrhosis, including (1) ascites or varices, (2) platelets <150K or splenomegaly, and (3) cirrhotic configuration of the liver by crosssectional imaging. Results: A total of 182 patients were included in the analysis including 64 with HBV and 118 with HCV. By design, the two groups were identical in age (mean= 57 years) and sex (male=88%) distribution. Reliable histologic data to assess fibrosis were available in 31 patients (48%) with HBV and in 69 (58%) with HCV. Of those, stage 3-4 fibrosis was present in 87% (n=27) with HBV versus 93% (n=64) with HCV. The table shows the prevalence of advanced fibrosis by histology or clinical indicators. When the most stringent clinical criteria (3 out of 3) are used, 72% of HBV and 79% of HCV patients had advanced fibrosis. If the most inclusive criteria (any 1 of 3) are used, the prevalence of advanced fibrosis was 91% of HBV patients and 97% of HCV. Conclusion: Advanced fibrosis, as gauged by histology and/or clinical evidence of cirrhosis, was highly prevalent in patients with HCC. Although the proportion of advanced fibrosis was consistently higher in HCV patients than in HBV, the vast majority of HBV patients with HCC had evidence of advanced fibrosis or cirrhosis. These data highlight the importance of fibrosis assessment in identifying HBV and HCV patients at risk of HCC and thus candidates for surveillance.
S1900 Both Hepatitis C and B Virus Were Major Underlying Etiologies for Hepatocellular Carcinoma (HCC) in Vietnamese Americans While the Vast Majority of HCC Cases in Chinese Americans Were Associated With Hepatitis B Virus Karan Verma, Long H. Nguyen, Aijaz Ahmed, Tami Daugherty, Gabriel Garcia, Emmet B. Keeffe, Mindie H. Nguyen BACKGROUND: Asian-Americans are known to have higher incidence of hepatocellular carcinoma (HCC) than other ethnic groups. However, even within the Asian population, there is significant heterogeneity in HCC incidences among the various subgroups with Vietnamese Americans having the highest rate that is almost twice as the rate in Chinese Americans, according to the California Cancer Registry. Since prevalence for infection with hepatitis C virus (HCV) is much higher in Vietnam (approximately 6% according to the WHO), our hypothesis is that HCC in the Vietnamese Americans are due not only to a high disease burden with hepatitis B virus (HBV) but also with HCV. Our goal was to examine etiologies of primary liver disease in a cohort of Asian patients who presented with HCC at a U.S. university liver center. METHODS: We performed a cross-sectional study of 237 consecutive HCC Asian patients identified via electronic query using ICD-9 codes and patient records. We excluded 5 patients with non-viral liver diseases. Etiologies of primary liver disease (HBV vs. HCV) associated with HCC were analyzed by Asian subgroups (Vietnamese, Chinese, and others). RESULTS: Among the 237 Asian HCC patients identified, 42% were Vietnamese, 36% were Chinese, 22% were other Asian ethnicities. Most patients were male (76%) with a median age of 60 (32-85). About half (52%) had unifocal HCC while 16% had more than 3 lesions. The average MELD and CPT scores were 10 (±5) and 6.1 (±1.5), respectively. Etiologies of primary liver disease in the study patients were HBV in 58% and HCV in 42%. Of those with HBV, 79% were Chinese and of those with HCV, 52% were Vietnamese. Compared with Chinese patients, Vietnamese patients were more likely to have HCV and less likely to have HBV: 52% vs. 21% and 48% vs. 79%, p<0.0001. Vietnamese patients also were significantly younger than Chinese patients with HCC with mean age of 57 (±12) vs. 61(±10), p=0.024. On multivariate analysis also inclusive of gender, significant independent predictors for HCV-associated HCC were Vietnamese ethnicity compared to Chinese (OR=3.7, p=0.006), age (OR=1.04, p=0.018), and presence of cirrhosis (OR=9.5, p=0.001). CONCLUSIONS: In this study of Asians with HCC, most patients were Vietnamese or Chinese American patients. The vast majority of HCC cases were associated with HBV in Chinese while only half were associated with HBV in Vietnamese with HCV associated with the remaining 50% of the cases. Vietnamese ethnicity is an independent predictor for HCV-associated HCC. Screening for HCV should be considered from patients coming from endemic area such as Vietnam.
*The proportion of stage 3/4 fibrosis among those with available histology was 87% for HBV and 93% for HCV. S1903 Dynamic Contrast Enhanced Ultrasound in Monitoring HCC Patients Treated With Sorafenib: Preliminary Results Maria Assunta Zocco, Andrea Lupascu, Laura Riccardi, Anna C. Piscaglia, Luisa Siciliani, Marialuisa Novi, Ernesto Cristiano Lauritano, Annalisa Tortora, Giovanni Gigante, Michele Cosimo Santoro, Emanuele Rinninella, Maria Elena Ainora, Francesca R. Ponziani, Maurizio Pompili, Gian Ludovico Rapaccini, Antonio Gasbarrini Background. Sorafenib is an oral multikinase inhibitor that recently received approval as a standard of care treatment for patients with advanced HCC. It acts by inducing alterations in tumor vascularity that can not be evaluated by traditional morphological criteria to assess tumor response. Contrast enhanced ultrasound (CE-US) is now recognized as a functional imaging technique able to evaluate tumor vascularization. In particular, recently developed quantitative approaches able to measure the amount and the time course of contrast uptake have shown great promise in revealing effective tumour response to antiangiogenic drugs before tumour changes occur. Aim. To evaluate the feasibility of dynamic CEUS (DCE-US) with perfusion software for the assessment of early vascular effect of Sorafenib in patients with advanced HCC. Patients and methods. Patients with advanced stage HCC treated with Sorafenib, 400 mg bid, were enrolled in this study. CEUS was performed at baseline and after 1, 2 and 3 months. Tumor vasculature was assessed in a specific harmonic mode associated with a perfusion and quantification software (Q-Lab, Philips) and two parameters extracted from the time-intensity curves of contrast uptake were evaluated: the peak intensity (PI) and the time to PI (TPI). For each kinetic parameter the impact of sorafenib treatment was analyzed based on the difference between the pre and post-treatment evaluation. CEUS results were also compared with tumor response evaluated according to RECIST at 3 months. Results. We report the preliminary results obtained in 5 patients treated with Sorafenib. A significant reduction in PI was observed in 4 out of 5 patients after 1 month of treatment, with a mean decrease of 38% of the initial value (range 20-58%). Similarly, the time required to reach the PI showed a significant increase from 11.2±0.8 seconds at baseline, to 15.4±1.6 seconds at 1 month. Changes in tumor vascularisation observed in these patients at 1 month were always consistent in the same patients at 2 and 3 months and were associated with a stable disease according to RECIST at 3 months. No significant modifications of both, PI and TPI, were observed in 1 patient at all the time points. This patient showed increase in tumor size (even if <20% of the initial diameter) and in number lesions at CT scan after
S1901 Biomarkers for Hepatic Hemangiosarcoma LaTasha Henry, Manny C. Zewdu, Keith C. Falkner, Craig J. McClain, Matthew C. Cave Purpose: Hepatic hemangiosarcoma (HH) is an extremely aggressive form of liver cancer which has historically been linked to high level occupational exposure to vinyl chloride (VC). This association was first recorded in 1974 in workers from a Louisville, KY plastics plant. To date, 26 VC workers have developed HH from this plant, and liver chemistries were surprisingly normal at diagnosis. Because of a long latency period, many workers are still at risk for developing this deadly tumor. Biomarkers are needed for the early detection of VC-related HH. Methods: Potential serologic biomarkers for HH were measured in samples from VC workers with HH in our specimen bank. Samples from healthy volunteers were used as controls. Hyaluronic acid (HA), cytokeratin-18 (CK-18), VEGF, IL-1β, IL-6, IL-8, IL-18, Leptin, TNF-α, MCP-1, PAI-1, TAS, and Adiponectin levels were measured. Results: Hyaluronic acid, IL-8, IL-6, and cytokeratin-18 M65 fragment levels were elevated at the time of diagnosis of HH compared to healthy controls. No significant differences were seen for the other potential biomarkers. Additional studies with other highly exposed VC workers
S-813
AASLD Abstracts
AASLD Abstracts
Liver Fibrosis in Patients With Hepatocellular Carcinoma: Comparison Between Hepatitis B and C Ju Dong Yang, Lewis R. Roberts, Hyung Joon Kim, Bohyun Kim, Joanne T. Benson, Rachel A. Pedersen, Teresa A. Mettler, Terry M. Therneau, Schuyler Sanderson, W. Ray Kim
who did not develop HH demonstrate the HA did not correlate with cumulative VC exposure. Conclusions: These results suggest that HA, IL-8, IL-6, and CK-18 M65 could be biomarkers for hepatic hemangiosarcoma in highly-exposed VC workers. Increased levels of IL-8 and IL-6 are characteristic of an inflammatory response to cell injury and are not specific for HH. The applicability of these findings to other etiologies of hemangiosarcoma such as prescription medications (observed in rodents) should be explored. S1902
Background/Aims: It is commonly believed that hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection occurs exclusively in patients with cirrhosis. In contrast, carcinogenesis in patients with hepatitis B virus (HBV) infection may be independent of fibrosis. However, published data are sparse to demonstrate this difference. The aim of this study is to compare the proportion of advanced fibrosis and cirrhosis in the background liver between HBV and HCV patients diagnosed with HCC. Methods: Based on a prospective database tracking all HCC cases, patients with HCC and HBV evaluated between 1994 and 2008 were identified. Age- and sex-matched HCC patients with HCV were selected out of the same database (in 1:2 ratio). All available pathology reports were obtained to document advanced fibrosis (Batts-Ludwig stage 3 or 4). If histologic assessment of fibrosis was not available, clinical indicators were utilized to define cirrhosis, including (1) ascites or varices, (2) platelets <150K or splenomegaly, and (3) cirrhotic configuration of the liver by crosssectional imaging. Results: A total of 182 patients were included in the analysis including 64 with HBV and 118 with HCV. By design, the two groups were identical in age (mean= 57 years) and sex (male=88%) distribution. Reliable histologic data to assess fibrosis were available in 31 patients (48%) with HBV and in 69 (58%) with HCV. Of those, stage 3-4 fibrosis was present in 87% (n=27) with HBV versus 93% (n=64) with HCV. The table shows the prevalence of advanced fibrosis by histology or clinical indicators. When the most stringent clinical criteria (3 out of 3) are used, 72% of HBV and 79% of HCV patients had advanced fibrosis. If the most inclusive criteria (any 1 of 3) are used, the prevalence of advanced fibrosis was 91% of HBV patients and 97% of HCV. Conclusion: Advanced fibrosis, as gauged by histology and/or clinical evidence of cirrhosis, was highly prevalent in patients with HCC. Although the proportion of advanced fibrosis was consistently higher in HCV patients than in HBV, the vast majority of HBV patients with HCC had evidence of advanced fibrosis or cirrhosis. These data highlight the importance of fibrosis assessment in identifying HBV and HCV patients at risk of HCC and thus candidates for surveillance.
S1900 Both Hepatitis C and B Virus Were Major Underlying Etiologies for Hepatocellular Carcinoma (HCC) in Vietnamese Americans While the Vast Majority of HCC Cases in Chinese Americans Were Associated With Hepatitis B Virus Karan Verma, Long H. Nguyen, Aijaz Ahmed, Tami Daugherty, Gabriel Garcia, Emmet B. Keeffe, Mindie H. Nguyen BACKGROUND: Asian-Americans are known to have higher incidence of hepatocellular carcinoma (HCC) than other ethnic groups. However, even within the Asian population, there is significant heterogeneity in HCC incidences among the various subgroups with Vietnamese Americans having the highest rate that is almost twice as the rate in Chinese Americans, according to the California Cancer Registry. Since prevalence for infection with hepatitis C virus (HCV) is much higher in Vietnam (approximately 6% according to the WHO), our hypothesis is that HCC in the Vietnamese Americans are due not only to a high disease burden with hepatitis B virus (HBV) but also with HCV. Our goal was to examine etiologies of primary liver disease in a cohort of Asian patients who presented with HCC at a U.S. university liver center. METHODS: We performed a cross-sectional study of 237 consecutive HCC Asian patients identified via electronic query using ICD-9 codes and patient records. We excluded 5 patients with non-viral liver diseases. Etiologies of primary liver disease (HBV vs. HCV) associated with HCC were analyzed by Asian subgroups (Vietnamese, Chinese, and others). RESULTS: Among the 237 Asian HCC patients identified, 42% were Vietnamese, 36% were Chinese, 22% were other Asian ethnicities. Most patients were male (76%) with a median age of 60 (32-85). About half (52%) had unifocal HCC while 16% had more than 3 lesions. The average MELD and CPT scores were 10 (±5) and 6.1 (±1.5), respectively. Etiologies of primary liver disease in the study patients were HBV in 58% and HCV in 42%. Of those with HBV, 79% were Chinese and of those with HCV, 52% were Vietnamese. Compared with Chinese patients, Vietnamese patients were more likely to have HCV and less likely to have HBV: 52% vs. 21% and 48% vs. 79%, p<0.0001. Vietnamese patients also were significantly younger than Chinese patients with HCC with mean age of 57 (±12) vs. 61(±10), p=0.024. On multivariate analysis also inclusive of gender, significant independent predictors for HCV-associated HCC were Vietnamese ethnicity compared to Chinese (OR=3.7, p=0.006), age (OR=1.04, p=0.018), and presence of cirrhosis (OR=9.5, p=0.001). CONCLUSIONS: In this study of Asians with HCC, most patients were Vietnamese or Chinese American patients. The vast majority of HCC cases were associated with HBV in Chinese while only half were associated with HBV in Vietnamese with HCV associated with the remaining 50% of the cases. Vietnamese ethnicity is an independent predictor for HCV-associated HCC. Screening for HCV should be considered from patients coming from endemic area such as Vietnam.
*The proportion of stage 3/4 fibrosis among those with available histology was 87% for HBV and 93% for HCV. S1903 Dynamic Contrast Enhanced Ultrasound in Monitoring HCC Patients Treated With Sorafenib: Preliminary Results Maria Assunta Zocco, Andrea Lupascu, Laura Riccardi, Anna C. Piscaglia, Luisa Siciliani, Marialuisa Novi, Ernesto Cristiano Lauritano, Annalisa Tortora, Giovanni Gigante, Michele Cosimo Santoro, Emanuele Rinninella, Maria Elena Ainora, Francesca R. Ponziani, Maurizio Pompili, Gian Ludovico Rapaccini, Antonio Gasbarrini Background. Sorafenib is an oral multikinase inhibitor that recently received approval as a standard of care treatment for patients with advanced HCC. It acts by inducing alterations in tumor vascularity that can not be evaluated by traditional morphological criteria to assess tumor response. Contrast enhanced ultrasound (CE-US) is now recognized as a functional imaging technique able to evaluate tumor vascularization. In particular, recently developed quantitative approaches able to measure the amount and the time course of contrast uptake have shown great promise in revealing effective tumour response to antiangiogenic drugs before tumour changes occur. Aim. To evaluate the feasibility of dynamic CEUS (DCE-US) with perfusion software for the assessment of early vascular effect of Sorafenib in patients with advanced HCC. Patients and methods. Patients with advanced stage HCC treated with Sorafenib, 400 mg bid, were enrolled in this study. CEUS was performed at baseline and after 1, 2 and 3 months. Tumor vasculature was assessed in a specific harmonic mode associated with a perfusion and quantification software (Q-Lab, Philips) and two parameters extracted from the time-intensity curves of contrast uptake were evaluated: the peak intensity (PI) and the time to PI (TPI). For each kinetic parameter the impact of sorafenib treatment was analyzed based on the difference between the pre and post-treatment evaluation. CEUS results were also compared with tumor response evaluated according to RECIST at 3 months. Results. We report the preliminary results obtained in 5 patients treated with Sorafenib. A significant reduction in PI was observed in 4 out of 5 patients after 1 month of treatment, with a mean decrease of 38% of the initial value (range 20-58%). Similarly, the time required to reach the PI showed a significant increase from 11.2±0.8 seconds at baseline, to 15.4±1.6 seconds at 1 month. Changes in tumor vascularisation observed in these patients at 1 month were always consistent in the same patients at 2 and 3 months and were associated with a stable disease according to RECIST at 3 months. No significant modifications of both, PI and TPI, were observed in 1 patient at all the time points. This patient showed increase in tumor size (even if <20% of the initial diameter) and in number lesions at CT scan after
S1901 Biomarkers for Hepatic Hemangiosarcoma LaTasha Henry, Manny C. Zewdu, Keith C. Falkner, Craig J. McClain, Matthew C. Cave Purpose: Hepatic hemangiosarcoma (HH) is an extremely aggressive form of liver cancer which has historically been linked to high level occupational exposure to vinyl chloride (VC). This association was first recorded in 1974 in workers from a Louisville, KY plastics plant. To date, 26 VC workers have developed HH from this plant, and liver chemistries were surprisingly normal at diagnosis. Because of a long latency period, many workers are still at risk for developing this deadly tumor. Biomarkers are needed for the early detection of VC-related HH. Methods: Potential serologic biomarkers for HH were measured in samples from VC workers with HH in our specimen bank. Samples from healthy volunteers were used as controls. Hyaluronic acid (HA), cytokeratin-18 (CK-18), VEGF, IL-1β, IL-6, IL-8, IL-18, Leptin, TNF-α, MCP-1, PAI-1, TAS, and Adiponectin levels were measured. Results: Hyaluronic acid, IL-8, IL-6, and cytokeratin-18 M65 fragment levels were elevated at the time of diagnosis of HH compared to healthy controls. No significant differences were seen for the other potential biomarkers. Additional studies with other highly exposed VC workers
S-813
AASLD Abstracts
AASLD Abstracts
Liver Fibrosis in Patients With Hepatocellular Carcinoma: Comparison Between Hepatitis B and C Ju Dong Yang, Lewis R. Roberts, Hyung Joon Kim, Bohyun Kim, Joanne T. Benson, Rachel A. Pedersen, Teresa A. Mettler, Terry M. Therneau, Schuyler Sanderson, W. Ray Kim