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Mo1517 Differential Cytokine Profiles in Patients With Hepatocellular Carcinoma Related to Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Infection
AASLD Abstracts
were Caucasian, and 73 (58.9%) were male. 21 (16.9%) had cirrhosis, 25 (20.2%) had chronic hepatitis C (HCV), and 8 (6.5%) had chronic hepatitis B (HBV). A majority of patients, 108 (87.1%), were Child-Pugh class A and the mean calculated MELD score at surgery was 9±3. Mean total tumor volume was 487.4 ± 963.5 cm3. Overall 1, 3, and 5 year survival post resection was 76.1%, 53.1%, and 34.9%, respectively. On univariate analysis, cirrhosis (p=.041), chronic HCV (p=.005), AFP1 >100 ng/ml (p=.024), AFP2 >100 ng/ml (p=.012), peak AFP >100 ng/ml (p<.001), peak AFP to TTV ratio >20 (p=.004), poor tumor differentiation (p=.029) and lymphovascular space invasion (LVSI) (p<.001) were predictive of disease recurrence. On multivariate analysis, peak pre-operative AFP >100 ng/ ml (p<.001, HR=3.035, 95% CI [1.700-5.418]) and LVSI (p=.007, HR=2.431, 95% CI [1.280-4.615]) were found to affect HCC recurrence-free survival (Figure 1). Peak AFP to TTV ratio > 20 was predictive of HCC recurrence (p=.004) on univariate analysis (Figure 2), however lost significance on Cox regression analysis (p=.914, HR=1.047, 95% CI [.451 - 2.432]). Conclusions: A variety of prognostic values predict the recurrence of HCC postresection. Peak pre-operative AFP > 100 ng/ml has been shown to predict HCC recurrencefree survival post-resection. Peak AFP to TTV ratio > 20 did not affect HCC recurrence. Our study does not confirm findings from East Asian studies. Thus, larger studies are needed.
pathogenesis and/or disease characteristics. Further studies are needed to characterize specific biomarkers associated with HCC among diverse underlying liver diseases.
Figure 1: Comparison of cytokine and other biomarker profiles between patients with HBV-related HCC and HCV-related HCC Figure 1 Mo1518 HCC Surveillance Is Associated With Early Tumor Detection and Improved Survival: A Multi-Center United States Study Olutola A. Yerokun, Neehar D. Parikh, Steven J. Scaglione, Sahil Mittal, Rebecca J. Tsang, Paulina Devlin, Randy Chung, Adam Yopp, Amit G. Singal Background: Hepatocellular carcinoma (HCC) surveillance is recommended in patients with cirrhosis but few studies have evaluated HCC surveillance effectiveness in clinical practice. Our study's aim was to characterize HCC surveillance utilization and its association with early tumor detection, curative treatment and survival in a multi-center cohort. Methods: We identified patients newly diagnosed with HCC between June 1, 2012 and May 31, 2013 at four health systems in the United States. Demographic, laboratory, and clinical data were abstracted at each site using standardized forms. Patients were considered as detected by surveillance if HCC diagnosis was prompted by surveillance ultrasound and/or alpha fetoprotein (AFP). Chi-square analysis was used to compare categorical variables, e.g. tumor stage and treatments, between surveillance and non-surveillance patients. HCC staging was determined by the Barcelona Clinic Liver Cancer (BCLC) system, with early stage defined as BCLC stage A. Curative treatments included liver transplant, resection, or local ablation. Survival was determined by Kaplan-Meier analysis and Cox regression was performed to identify associated factors. Statistical significance was defined as p<0.05. Results:We identified 380 (range 68-149 per site) patients with HCC. The median age of our cohort was 59.8 years, and 75% were male. Our cohort was racially diverse with 53% Caucasians, 20% Blacks, and 20% Hispanics. The most common liver disease etiologies were 57% hepatitis C, 15% alcohol-related, and 15% NASH/cryptogenic. 40% of patients were receiving Hepatology subspecialty care. HCC was diagnosed via surveillance in 42% of cases, ranging from 35% to 49% between study sites. Receipt of HCC surveillance was significantly associated with Hepatology care (OR 24.7, 95%CI 13.4-45.6), female gender (OR 3.2, 95%CI 1.68-6.25), performance status £1 (OR 3.56, 95%CI 1.55-8.18), and viral etiology (OR 3.25, 95%CI 1.75-6.06). Patients detected by surveillance were more likely to be diagnosed at an early stage (BCLC stage A 63% vs. 36%, p<0.001) and undergo curative treatment (31% vs. 13%, p<0.001). HCC surveillance was significantly associated with improved survival on multivariate Cox regression (HR 0.48, 95%CI 0.34-0.70) after adjusting for patient demographics, degree of liver dysfunction, and ECOG performance status. The median survival of surveillance patients was 14.6 months, compared to only 6.0 months for non-surveillance patients, with the difference remaining significant after adjusting for lead-time bias. Conclusion: HCC surveillance is significantly associated with early tumor detection, receipt of curative treatment, and improved survival in clinical practice. However, less than 50% of HCC at each site were detected by surveillance, highlighting the urgent need for interventions to increase HCC surveillance utilization.
Figure 2
Mo1517 Differential Cytokine Profiles in Patients With Hepatocellular Carcinoma Related to Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Infection Jacqueline Estevez, Vincent L. Chen, Ondrej Podhala, Biao Li, An K. Le, Philip Vutien, Ellen Chang, Zhaoshi Jiang, Stefan Pflanz, Dongliang Ge, Anuj Gaggar, Mindie H. Nguyen Background and Aims: Cytokines play an important role in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC). Several studies have examined differences in individual cytokines in patients with chronic liver disease, but data on comprehensive cytokine profiling across different clinical characteristics are lacking. Previously, we found significant differences in serum cytokine profiles among non-HCC patients with HBV vs. HCV with an area under the curve (AUC) of 0.91. The five cytokines with highest predictive power were M-CSF, sFas-ligand, TNF-b, IP-10, and IL-8. Our goal was to examine and compare cytokine profiles of HCC patients with different underlying liver disease etiologies. Methods: We enrolled a total of 88 patients with HCC at a US medical center from 2000 to 2007. Microplex analysis (Luminex 200 IS) was used to measure serum levels of 51 common cytokines and other biomarkers. Random forest machine learning was used to obtain receiver operator characteristic (ROC) curves and determine individual cytokine importance, using Z scores of mean fluorescence intensity for individual cytokines. Results: Patient mean age at the time of serum collection was 62±10 years, and the majority were male (83%). Out of the 88 HCC patients, 33 had HBV-related HCC (38%) and 55 patients had HCV-related HCC (63%). Most patients were cirrhotic (91%); and of these patients, 89% had hepatic decompensation. Cytokine profiles distinguish HCC patients with HBV and HCV infection with an area under the curve of 0.819 (Figure 1). The top five cytokines with highest predictive power were IP-10, IL-12, p40, VCAM1, and IL-1a. Conclusions: Patients with HBV or HCV-related HCC have distinctively different cytokine profiles, suggesting potential differences in disease
AASLD Abstracts
X : 10052$CH02 03-28-16 22:36:37 PDFd : 10052B : e
Mo1537 Decompensated Cirrhosis Is Not Associated With Increased Circulating Extracellular Vesicles William C. Palmer, Tushar Patel, Colleen S. Thomas, Nancy N. Diehl, Andrew Keaveny Purpose: Extracellular vesicles (EV) such as exosomes and microvesicles can be released during cell stress. Alterations in circulating EV have been associated with liver diseases. However, the relation of serum EV levels to clinical decompensation in patients with cirrhosis is unknown. We aimed to assess if clinical decompensation in patients with cirrhosis was associated with alterations in circulating EV counts. Methods: Demographic, serological,
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were Caucasian, and 73 (58.9%) were male. 21 (16.9%) had cirrhosis, 25 (20.2%) had chronic hepatitis C (HCV), and 8 (6.5%) had chronic hepatitis B (HBV). A majority of patients, 108 (87.1%), were Child-Pugh class A and the mean calculated MELD score at surgery was 9±3. Mean total tumor volume was 487.4 ± 963.5 cm3. Overall 1, 3, and 5 year survival post resection was 76.1%, 53.1%, and 34.9%, respectively. On univariate analysis, cirrhosis (p=.041), chronic HCV (p=.005), AFP1 >100 ng/ml (p=.024), AFP2 >100 ng/ml (p=.012), peak AFP >100 ng/ml (p<.001), peak AFP to TTV ratio >20 (p=.004), poor tumor differentiation (p=.029) and lymphovascular space invasion (LVSI) (p<.001) were predictive of disease recurrence. On multivariate analysis, peak pre-operative AFP >100 ng/ ml (p<.001, HR=3.035, 95% CI [1.700-5.418]) and LVSI (p=.007, HR=2.431, 95% CI [1.280-4.615]) were found to affect HCC recurrence-free survival (Figure 1). Peak AFP to TTV ratio > 20 was predictive of HCC recurrence (p=.004) on univariate analysis (Figure 2), however lost significance on Cox regression analysis (p=.914, HR=1.047, 95% CI [.451 - 2.432]). Conclusions: A variety of prognostic values predict the recurrence of HCC postresection. Peak pre-operative AFP > 100 ng/ml has been shown to predict HCC recurrencefree survival post-resection. Peak AFP to TTV ratio > 20 did not affect HCC recurrence. Our study does not confirm findings from East Asian studies. Thus, larger studies are needed.
pathogenesis and/or disease characteristics. Further studies are needed to characterize specific biomarkers associated with HCC among diverse underlying liver diseases.
Figure 1: Comparison of cytokine and other biomarker profiles between patients with HBV-related HCC and HCV-related HCC Figure 1 Mo1518 HCC Surveillance Is Associated With Early Tumor Detection and Improved Survival: A Multi-Center United States Study Olutola A. Yerokun, Neehar D. Parikh, Steven J. Scaglione, Sahil Mittal, Rebecca J. Tsang, Paulina Devlin, Randy Chung, Adam Yopp, Amit G. Singal Background: Hepatocellular carcinoma (HCC) surveillance is recommended in patients with cirrhosis but few studies have evaluated HCC surveillance effectiveness in clinical practice. Our study's aim was to characterize HCC surveillance utilization and its association with early tumor detection, curative treatment and survival in a multi-center cohort. Methods: We identified patients newly diagnosed with HCC between June 1, 2012 and May 31, 2013 at four health systems in the United States. Demographic, laboratory, and clinical data were abstracted at each site using standardized forms. Patients were considered as detected by surveillance if HCC diagnosis was prompted by surveillance ultrasound and/or alpha fetoprotein (AFP). Chi-square analysis was used to compare categorical variables, e.g. tumor stage and treatments, between surveillance and non-surveillance patients. HCC staging was determined by the Barcelona Clinic Liver Cancer (BCLC) system, with early stage defined as BCLC stage A. Curative treatments included liver transplant, resection, or local ablation. Survival was determined by Kaplan-Meier analysis and Cox regression was performed to identify associated factors. Statistical significance was defined as p<0.05. Results:We identified 380 (range 68-149 per site) patients with HCC. The median age of our cohort was 59.8 years, and 75% were male. Our cohort was racially diverse with 53% Caucasians, 20% Blacks, and 20% Hispanics. The most common liver disease etiologies were 57% hepatitis C, 15% alcohol-related, and 15% NASH/cryptogenic. 40% of patients were receiving Hepatology subspecialty care. HCC was diagnosed via surveillance in 42% of cases, ranging from 35% to 49% between study sites. Receipt of HCC surveillance was significantly associated with Hepatology care (OR 24.7, 95%CI 13.4-45.6), female gender (OR 3.2, 95%CI 1.68-6.25), performance status £1 (OR 3.56, 95%CI 1.55-8.18), and viral etiology (OR 3.25, 95%CI 1.75-6.06). Patients detected by surveillance were more likely to be diagnosed at an early stage (BCLC stage A 63% vs. 36%, p<0.001) and undergo curative treatment (31% vs. 13%, p<0.001). HCC surveillance was significantly associated with improved survival on multivariate Cox regression (HR 0.48, 95%CI 0.34-0.70) after adjusting for patient demographics, degree of liver dysfunction, and ECOG performance status. The median survival of surveillance patients was 14.6 months, compared to only 6.0 months for non-surveillance patients, with the difference remaining significant after adjusting for lead-time bias. Conclusion: HCC surveillance is significantly associated with early tumor detection, receipt of curative treatment, and improved survival in clinical practice. However, less than 50% of HCC at each site were detected by surveillance, highlighting the urgent need for interventions to increase HCC surveillance utilization.
Figure 2
Mo1517 Differential Cytokine Profiles in Patients With Hepatocellular Carcinoma Related to Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Infection Jacqueline Estevez, Vincent L. Chen, Ondrej Podhala, Biao Li, An K. Le, Philip Vutien, Ellen Chang, Zhaoshi Jiang, Stefan Pflanz, Dongliang Ge, Anuj Gaggar, Mindie H. Nguyen Background and Aims: Cytokines play an important role in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC). Several studies have examined differences in individual cytokines in patients with chronic liver disease, but data on comprehensive cytokine profiling across different clinical characteristics are lacking. Previously, we found significant differences in serum cytokine profiles among non-HCC patients with HBV vs. HCV with an area under the curve (AUC) of 0.91. The five cytokines with highest predictive power were M-CSF, sFas-ligand, TNF-b, IP-10, and IL-8. Our goal was to examine and compare cytokine profiles of HCC patients with different underlying liver disease etiologies. Methods: We enrolled a total of 88 patients with HCC at a US medical center from 2000 to 2007. Microplex analysis (Luminex 200 IS) was used to measure serum levels of 51 common cytokines and other biomarkers. Random forest machine learning was used to obtain receiver operator characteristic (ROC) curves and determine individual cytokine importance, using Z scores of mean fluorescence intensity for individual cytokines. Results: Patient mean age at the time of serum collection was 62±10 years, and the majority were male (83%). Out of the 88 HCC patients, 33 had HBV-related HCC (38%) and 55 patients had HCV-related HCC (63%). Most patients were cirrhotic (91%); and of these patients, 89% had hepatic decompensation. Cytokine profiles distinguish HCC patients with HBV and HCV infection with an area under the curve of 0.819 (Figure 1). The top five cytokines with highest predictive power were IP-10, IL-12, p40, VCAM1, and IL-1a. Conclusions: Patients with HBV or HCV-related HCC have distinctively different cytokine profiles, suggesting potential differences in disease
AASLD Abstracts
X : 10052$CH02 03-28-16 22:36:37 PDFd : 10052B : e
Mo1537 Decompensated Cirrhosis Is Not Associated With Increased Circulating Extracellular Vesicles William C. Palmer, Tushar Patel, Colleen S. Thomas, Nancy N. Diehl, Andrew Keaveny Purpose: Extracellular vesicles (EV) such as exosomes and microvesicles can be released during cell stress. Alterations in circulating EV have been associated with liver diseases. However, the relation of serum EV levels to clinical decompensation in patients with cirrhosis is unknown. We aimed to assess if clinical decompensation in patients with cirrhosis was associated with alterations in circulating EV counts. Methods: Demographic, serological,
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