- Email: [email protected]
Metabolic Disorders across Hepatocellular Carcinoma in Italy
POSTER PRESENTATIONS CI, 1.1–8.3; p = 0.037), and the >40 kPa group had a HR of 4.8 (95% CI, 1.7–13.4; p = 0.003). Differences between the 20–25 kPa group and 25–30 kPa group were not significant.
Conclusions: This multicentre retrospective observational study shows an association between LSM at the upper extreme and HCC risk. LSM by FibroScan™ allows simple, non-invasive stratification of HCC risk in cirrhotic patients. Physicians may find this beneficial as a dynamic approach to monitor HCC risk. THU-076 HEPATOCELLULAR CARCINOMA RESPONSE TO LOCAL REGIONAL THERAPY; CORRELATIONS BETWEEN PRE-LIVER TRANSPLANTS IMAGING AND EXPLANT PATHOLOGY M. Alghanem1, K. Qumosani1, P. Marotta1, D. Driman2, B. Aljudaibi1, N. Kakani3. 1Hepatology; 2Pathology; 3Radiology, University of Western Ontario, London, Canada E-mail: [email protected] Background and Aims: HCC therapy includes Local regional Therapy (LRT) such as Radiofrequency Ablation (RFA) and Trans-Arterial Chemoembolization (TACE). Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were developed to assess the response to treatment in patients with HCC, based on measurements of viable tumor using dynamic imaging (CT/MRI). Aim: To compare the estimate of viable HCC after LRT by CT imaging and before liver transplant, to the histopathological assessment of viable HCC in the hepatic explant. Methods: We prospectively evaluated fourty one patients with HCC who undwerent both LRT and liver transplantation at london health science center. Using mRECIST criteria, the response to LRT was assessed by two blinded radiologists and the percentage of necrosis was reported separately for the reference CT(rCT) completed done after the last LRT and prior to liver transplantation. The results from the radiologists were compared to the findings of an expert pathologist reporting on viable tumour present and tumour necrosis in the hepatic explants. Both parties were blinded so prevent bias in the results. Results: A total of forty one transplant recipients fulfilled the inclusion criteria for the study. At time of listing 100% were within total volume criteria, 86% within UCSF, and 68% within Milan. The average time frame from the last reference CT scan to liver transplant was 57.7 days; the average time from last LRT to reference CT was 72.5 days. Thirty four recipients (83%) had accurate assessment for necrosis (mRECIST) within 20% comparing rCT to explant (i.e. concordant). ninteen (46%) of the 41 predicted 100% concordance.
Only 7/41 (17%) had a poor concordance (>50%) between histology and reference CT images. positive correlation was detected with the correlation coefficient is calculated as 0.5723. Our study demonstarted CT-pathologic correlation in predicting number and size of tumors with Correlation coefficient 0.64 and 0.31,respectively. However, there was poor correlation in predicting total volume with correlation coefficient is calculated as 0.014. Conclusions: Dynamic CT is an accurate tool to evaluate the tumour response prior to liver transplantation and the likelihood of underestimating the tumour burden is low. With expert radiologists and pathologists, the correlation is acceptable and supports the ongoing use of frequent dynamic imaging to evaluate responses to LRT and determining transplant eligibility. THU-077 PROGNOSTIC VALIDATION OF PROPOSED BCLC-B SUBSTAGING SYSTEM IN HEPATOCELLULAR CARCINOMA PATIENTS TREATED BY TRANSARTERIAL CHEMOEMBOLIZATION M. Biolato1, G. Gallusi2, M. Iavarone3, G. Cabibbo4, S. Racco1, A.D. Santis2, C. Della Corte3, M. Maida4, A.F. Attili2, A. Sangiovanni3, C. Cammà4, G. La Torre5, A. Gasbarrini1, A. Grieco1. 1Department of Internal Medicine, Fondazione Policlinico Gemelli and Catholic University of the Sacred Heart; 2Division of Gastroenterology, Department of Clinical Medicine, La Sapienza University, Rome; 3UO Gastroenterologia ed Epatologia, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan; 4Section of Gastroenterology, DIBIMIS, University of Palermo, Palermo; 5Department of Public Health and Infectious Diseases, La Sapienza University, Rome, Italy E-mail: [email protected] Background and Aims: A subclassification system for intermediate hepatocellular carcinoma (HCC) was proposed to optimize treatment allocation. The aim of this study is to validate prognostic capacity of sub-staging proposal. Methods: Patients with intermediate HCC treated with TACE in four Italian tertiary centres were retrospectively reviewed. Predictors of survival were identified using the Cox proportional regression model. Results: 289 Barcelona Clinic Liver Cancer (BCLC) B patients were included. Median age was 68 years, 78% were male, 54% were HCVpositive, 72% had a Child A status, 61% patients were beyond Up-to-7 criterion. Median overall survival (OS) of the whole cohort was 23 months (C.I. 95% 20.2–25.8). Child A status (H.R. 1.35, C.I. 95% 1.02– 1.78) and tumor burden beyond Up-to-7 criterion (H.R. 1.39, C.I. 95% 1.07–1.80) were independent prognostic factors for overall survival on multivariate analysis. Median survival was 33.0 months for B1 stage (n = 81), 20.8 months for B2 stage (n = 106), 16.1 months for B3 stage (n = 24), 22.2 months for B4 stage (n = 42) and 15.0 months for Quasi-C stage (n = 36). Regarding discriminatory ability of sub-staging proposal, log rank test showed significant survival difference for B1 vs B4 ( p = 0.003) and B1 vs Quasi-C ( p = 0.039) and a trend for B1 vs B2 ( p = 0.05) and B1 vs B3 ( p = 0.05). Conclusions: Substage B1 correctly identified intermediate HCC patients who have the best prognosis and are the best candidates for TACE. Further studies are needed to demonstrate the real prognostic gradient and the benefit of different therapeutic allocation by TACE for patients in other intermediate HCC sub-stages. THU-078 METABOLIC DISORDERS ACROSS HEPATOCELLULAR CARCINOMA IN ITALY F. Morisco1, M. Guarino1, R. Valvano2, N. Caporaso1, F. Farinati3, E.G. Giannini4, F. Ciccarese5, F. Piscaglia6, G.L. Rapaccini7, M. Di Marco8, E. Caturelli9, M. Zoli6, F. Borzio10, R. Sacco11, C. Cammà12, M. Felder13, A. Gasbarrini7, G.S. Barone14, F.G. Foschi15, G. Missale16, A. Masotto17, R. Virdone18, F. Trevisani19 and for the Italian Liver Cancer (ITA.LI.CA) group. 1Dipartimento di Medicina Clinica e Chirugia, Università di Napoli “Federico II”, Napoli; 2Divisione di
Journal of Hepatology 2016 vol. 64 | S213–S424
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POSTER PRESENTATIONS Gastroenterologia, Ospedale Casa Sollievo Sofferenza, IRCCS, San Giovanni Rotondo; 3Università di Padova, Padova; 4Università di Genova, Genova; 5Policlinico San Marco, Zingonia; 6Università di Bologna, Bologna; 7Università Cattolica di Roma, Roma; 8Azienda Ospedaliera Bolognini, Seriate; 9Ospedale Belcolle, Viterbo; 10Ospedale Fatebenefratelli, Milano; 11Azienda Ospedaliero-Universitaria Pisana, Pisa; 12Università di Palermo, Palermo; 13Ospedale Regionale di Bolzano, BolzanoOspedale Regionale di Bolzano, Bolzano; 14Università Politecnica delle Marche, Ancona; 15Ospedale per gli Infermi di Faenza, Faenza; 16 Azienda Ospedaliero-Universitaria di Parma, Parma; 17Ospedale Sacro Cuore Don Calabria, Negrar; 18Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo; 19Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy E-mail: [email protected] Background and Aims: Metabolic disorders, such as obesity and diabetes, are well known risk factors for hepatocellular carcinoma (HCC). Conversely, the impact of metabolic disorders on natural history of HCC patients, independently from the etiology of liver disease, is not well established. This study aimed at evaluating the relationship among metabolic disorders, clinical presentation, tumor staging and survival of patients with HCC. Methods: We retrospectively analyzed the Italian Liver Cancer (ITA.LI.CA) database regarding 839 patients with HCC and with metabolic data at cancer diagnosis prospectively collected from 2009 to 2014.The following metabolic risk factors (RFs) were analyzed: BMI ≥ 25, diabetes, arterial hypertension, hypercholesterolemia and hypertriglyceridemia. According to these features, patients were divided into 3 groups: 0–1 metabolic RFs, 2 metabolic RFs, 3–5 metabolic RFs. Results: As compared with patients with 0-1 metabolic RFs, patients with 3 or more RFs showed lower percentage of diagnosis on surveillance programs ( p 0.021), larger main HCC nodule (p 0.038), better liver function ( percentage of patients with Child-Pugh A and MELD <10, p 0.007 and p 0.003, respectively), higher percentage of metastases ( p 0.024), and lower percentage of portal vein thrombosis ( p 0.010). The BCLC stage and treatment options were equally distributed among the 3 groups. The only significant difference was the less frequent access to locoregional therapy and/or TACE of BCLC stage B patients with 3 or more RFs as compared with the counterpart with 0–1 metabolic RFs ( p 0.012). The survival analysis did not show statistically significant difference among the 3 groups, both for the overall survival and for the survival according to BCLC stage and/or treatment option. Conclusions: Our study, conducted on a large series of patients with HCC managed in the “real world” of clinical practice, suggests that the presence of metabolic disorders shapes the clinical presentation of HCC but do not seem to play a major role in setting the patient survival. THU-079 VARIANTS ASSOCIATED WITH VITAMIN D METABOLISM AND PROGRESSION TO HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS C: DBGAP DATA FROM HALT-C TRIAL L.A. De Azevedo1, U.D.S. Matte1, T.R. Silveira1, M.R. Alvares-da-Silva2. 1 Universidade Federal do Rio Grande do Sul (UFRGS)/ Hospital de Clinicas de Porto Alegre, Porto Alegre; 2GI-Hepatology Division, Universidade Federal do Rio Grande do Sul (UFRGS)/ Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil E-mail: [email protected] Background and Aims: Vitamin D status has been associated to progression of chronic liver disease, but data are somehow controversial. In this study, we evaluated 24 polymorphisms related to vitamin D metabolism pathway and their relationship with hepatocellular carcinoma (HCC) in chronically hepatitis C virus (HCV) infected patients.
S334
Methods: Data are from the 4-year follow-up of Hepatitis C Antiviral Long-term Treatment Against Cirrhosis cohort and access to datasets were obtained from dbGaP ( phs000430.v1.p1). Patients were originally genotyped for 601,273 polymorphisms in Illumina Human610_Quadv1_B platform. Twenty four SNPs from candidate genes related to vitamin D metabolism were selected and entered the analysis (DHCR7, GC, CYP2R1, CYP27B1, CYP24A1, VDR, TGF, and SMAD3). The SNPs not genotyped in the platform were imputed with Mach-Admix package using 1000 Genomes Phase 3 v.5 as reference panel. Outcome of interest was development of HCC during the 4-year follow-up. Logistic regression was employed in the association analysis. Age, sex, and race were used as covariates. Quality control and statistical analysis were computed in Plink software, v. 1.07. Results: Of the 24 studied polymorphisms, only CYP2R1 rs1562902 T/C significantly affected development of HCC. Homozygosity for allele C was present in 31% of HCC cases and in 19.5% of non-HCC (OR = 1.912, P = 0.03838). Conclusions: The only genotype related to HCC in this cohort (CYP2R1) is responsible for higher levels of vitamin D, according to the literature. Thus, this may suggest vitamin D levels would not have an impact in progression to HCC in HCV infected patients. THU-080 SURVIVAL IN PATIENTS WITH HEPATCELLULAR CARCINOMA AFTER TRANSARTERIAL CHEMOEMBOLISATION IS DETERMINED BY TUMOR BIOLOGY AND HEPATIC FUNCTION M.M. Kirstein1, N. Schweitzer1, N. Ay1, C. Boeck1, J. Hinrichs2, T. Voigtländer1, M. Manns1, T. Rodt2, A. Vogel1. 1Gastroenterology, Hepatology and Endocrinology; 2Institute for Radiology, Hannover Medical School, Hannover, Germany E-mail: [email protected] Background and Aims: Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers worldwide. Early randomized trials and more recent reviews and meta-analyses reported improved survival rates of patients with unresectable lesions managed with TACE so that TACE has been accepted as the standard treatment for intermediate stage disease. Several prognostic scores have been proposed for patients treated with TACE. Deterministic factors for survival post-TACE have not been sufficiently investigated. Methods: In this study, we characterized 606 HCC patients from Hannover Medical School treated with TACE and evaluated the outcome during and beyond TACE. Results: 606 HCC patients treated with TACE were identified between 2000 and 2015. Most patients (59.8%) were at intermediate stage disease prior first TACE (Barcelona Clinic Liver Classification B). 57.4% of the patients were diagnosed with more than three nodules. The mean diameter of the largest lesion was 56 ± 36 mm (ranging 4–226). 26.2% of the patients presented with a lesion larger than 7 cm. Most patients (90.6%) were treated with conventional TACE using doxorubicin, ciplatin and/or mitomycin and lipiodol either alone or in combination with degradable starch microspheres. The mean/ median number of TACEs was 2.3 ± 1.95/2 (maximum 17). Hepatic function progressively deteriorated with TACE but did not jeopardize the survival benefit from TACE. Median overall survival (OS) was 19 months, whereas patients treated 35 times had the longest OS (30 months). Patients with subsequent therapies after TACE had a longer OS than patients with best supportive care (BSC, 27 versus 12 months, p < 0.001). Reflecting the prognostic significance of hepatic function and tumor biology, ascites, cholinesterase, c-reactive and alpha-feto protein and tumor size were identified as significant factors within the multivariate cox regression analysis for survival during TACE. These factors remained significantly prognostic also for post-TACEsurvival as single parameters and within the prognostic HAP and STATE score ( p < 0.05). Radiological or biochemical response to first TACE did not influence post-TACE survival. Conclusions: Patients with sequential therapies live significantly longer than patients with best supportive care post TACE. Hepatic
Journal of Hepatology 2016 vol. 64 | S213–S424
Conclusions: This multicentre retrospective observational study shows an association between LSM at the upper extreme and HCC risk. LSM by FibroScan™ allows simple, non-invasive stratification of HCC risk in cirrhotic patients. Physicians may find this beneficial as a dynamic approach to monitor HCC risk. THU-076 HEPATOCELLULAR CARCINOMA RESPONSE TO LOCAL REGIONAL THERAPY; CORRELATIONS BETWEEN PRE-LIVER TRANSPLANTS IMAGING AND EXPLANT PATHOLOGY M. Alghanem1, K. Qumosani1, P. Marotta1, D. Driman2, B. Aljudaibi1, N. Kakani3. 1Hepatology; 2Pathology; 3Radiology, University of Western Ontario, London, Canada E-mail: [email protected] Background and Aims: HCC therapy includes Local regional Therapy (LRT) such as Radiofrequency Ablation (RFA) and Trans-Arterial Chemoembolization (TACE). Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were developed to assess the response to treatment in patients with HCC, based on measurements of viable tumor using dynamic imaging (CT/MRI). Aim: To compare the estimate of viable HCC after LRT by CT imaging and before liver transplant, to the histopathological assessment of viable HCC in the hepatic explant. Methods: We prospectively evaluated fourty one patients with HCC who undwerent both LRT and liver transplantation at london health science center. Using mRECIST criteria, the response to LRT was assessed by two blinded radiologists and the percentage of necrosis was reported separately for the reference CT(rCT) completed done after the last LRT and prior to liver transplantation. The results from the radiologists were compared to the findings of an expert pathologist reporting on viable tumour present and tumour necrosis in the hepatic explants. Both parties were blinded so prevent bias in the results. Results: A total of forty one transplant recipients fulfilled the inclusion criteria for the study. At time of listing 100% were within total volume criteria, 86% within UCSF, and 68% within Milan. The average time frame from the last reference CT scan to liver transplant was 57.7 days; the average time from last LRT to reference CT was 72.5 days. Thirty four recipients (83%) had accurate assessment for necrosis (mRECIST) within 20% comparing rCT to explant (i.e. concordant). ninteen (46%) of the 41 predicted 100% concordance.
Only 7/41 (17%) had a poor concordance (>50%) between histology and reference CT images. positive correlation was detected with the correlation coefficient is calculated as 0.5723. Our study demonstarted CT-pathologic correlation in predicting number and size of tumors with Correlation coefficient 0.64 and 0.31,respectively. However, there was poor correlation in predicting total volume with correlation coefficient is calculated as 0.014. Conclusions: Dynamic CT is an accurate tool to evaluate the tumour response prior to liver transplantation and the likelihood of underestimating the tumour burden is low. With expert radiologists and pathologists, the correlation is acceptable and supports the ongoing use of frequent dynamic imaging to evaluate responses to LRT and determining transplant eligibility. THU-077 PROGNOSTIC VALIDATION OF PROPOSED BCLC-B SUBSTAGING SYSTEM IN HEPATOCELLULAR CARCINOMA PATIENTS TREATED BY TRANSARTERIAL CHEMOEMBOLIZATION M. Biolato1, G. Gallusi2, M. Iavarone3, G. Cabibbo4, S. Racco1, A.D. Santis2, C. Della Corte3, M. Maida4, A.F. Attili2, A. Sangiovanni3, C. Cammà4, G. La Torre5, A. Gasbarrini1, A. Grieco1. 1Department of Internal Medicine, Fondazione Policlinico Gemelli and Catholic University of the Sacred Heart; 2Division of Gastroenterology, Department of Clinical Medicine, La Sapienza University, Rome; 3UO Gastroenterologia ed Epatologia, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan; 4Section of Gastroenterology, DIBIMIS, University of Palermo, Palermo; 5Department of Public Health and Infectious Diseases, La Sapienza University, Rome, Italy E-mail: [email protected] Background and Aims: A subclassification system for intermediate hepatocellular carcinoma (HCC) was proposed to optimize treatment allocation. The aim of this study is to validate prognostic capacity of sub-staging proposal. Methods: Patients with intermediate HCC treated with TACE in four Italian tertiary centres were retrospectively reviewed. Predictors of survival were identified using the Cox proportional regression model. Results: 289 Barcelona Clinic Liver Cancer (BCLC) B patients were included. Median age was 68 years, 78% were male, 54% were HCVpositive, 72% had a Child A status, 61% patients were beyond Up-to-7 criterion. Median overall survival (OS) of the whole cohort was 23 months (C.I. 95% 20.2–25.8). Child A status (H.R. 1.35, C.I. 95% 1.02– 1.78) and tumor burden beyond Up-to-7 criterion (H.R. 1.39, C.I. 95% 1.07–1.80) were independent prognostic factors for overall survival on multivariate analysis. Median survival was 33.0 months for B1 stage (n = 81), 20.8 months for B2 stage (n = 106), 16.1 months for B3 stage (n = 24), 22.2 months for B4 stage (n = 42) and 15.0 months for Quasi-C stage (n = 36). Regarding discriminatory ability of sub-staging proposal, log rank test showed significant survival difference for B1 vs B4 ( p = 0.003) and B1 vs Quasi-C ( p = 0.039) and a trend for B1 vs B2 ( p = 0.05) and B1 vs B3 ( p = 0.05). Conclusions: Substage B1 correctly identified intermediate HCC patients who have the best prognosis and are the best candidates for TACE. Further studies are needed to demonstrate the real prognostic gradient and the benefit of different therapeutic allocation by TACE for patients in other intermediate HCC sub-stages. THU-078 METABOLIC DISORDERS ACROSS HEPATOCELLULAR CARCINOMA IN ITALY F. Morisco1, M. Guarino1, R. Valvano2, N. Caporaso1, F. Farinati3, E.G. Giannini4, F. Ciccarese5, F. Piscaglia6, G.L. Rapaccini7, M. Di Marco8, E. Caturelli9, M. Zoli6, F. Borzio10, R. Sacco11, C. Cammà12, M. Felder13, A. Gasbarrini7, G.S. Barone14, F.G. Foschi15, G. Missale16, A. Masotto17, R. Virdone18, F. Trevisani19 and for the Italian Liver Cancer (ITA.LI.CA) group. 1Dipartimento di Medicina Clinica e Chirugia, Università di Napoli “Federico II”, Napoli; 2Divisione di
Journal of Hepatology 2016 vol. 64 | S213–S424
S333
POSTER PRESENTATIONS Gastroenterologia, Ospedale Casa Sollievo Sofferenza, IRCCS, San Giovanni Rotondo; 3Università di Padova, Padova; 4Università di Genova, Genova; 5Policlinico San Marco, Zingonia; 6Università di Bologna, Bologna; 7Università Cattolica di Roma, Roma; 8Azienda Ospedaliera Bolognini, Seriate; 9Ospedale Belcolle, Viterbo; 10Ospedale Fatebenefratelli, Milano; 11Azienda Ospedaliero-Universitaria Pisana, Pisa; 12Università di Palermo, Palermo; 13Ospedale Regionale di Bolzano, BolzanoOspedale Regionale di Bolzano, Bolzano; 14Università Politecnica delle Marche, Ancona; 15Ospedale per gli Infermi di Faenza, Faenza; 16 Azienda Ospedaliero-Universitaria di Parma, Parma; 17Ospedale Sacro Cuore Don Calabria, Negrar; 18Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo; 19Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy E-mail: [email protected] Background and Aims: Metabolic disorders, such as obesity and diabetes, are well known risk factors for hepatocellular carcinoma (HCC). Conversely, the impact of metabolic disorders on natural history of HCC patients, independently from the etiology of liver disease, is not well established. This study aimed at evaluating the relationship among metabolic disorders, clinical presentation, tumor staging and survival of patients with HCC. Methods: We retrospectively analyzed the Italian Liver Cancer (ITA.LI.CA) database regarding 839 patients with HCC and with metabolic data at cancer diagnosis prospectively collected from 2009 to 2014.The following metabolic risk factors (RFs) were analyzed: BMI ≥ 25, diabetes, arterial hypertension, hypercholesterolemia and hypertriglyceridemia. According to these features, patients were divided into 3 groups: 0–1 metabolic RFs, 2 metabolic RFs, 3–5 metabolic RFs. Results: As compared with patients with 0-1 metabolic RFs, patients with 3 or more RFs showed lower percentage of diagnosis on surveillance programs ( p 0.021), larger main HCC nodule (p 0.038), better liver function ( percentage of patients with Child-Pugh A and MELD <10, p 0.007 and p 0.003, respectively), higher percentage of metastases ( p 0.024), and lower percentage of portal vein thrombosis ( p 0.010). The BCLC stage and treatment options were equally distributed among the 3 groups. The only significant difference was the less frequent access to locoregional therapy and/or TACE of BCLC stage B patients with 3 or more RFs as compared with the counterpart with 0–1 metabolic RFs ( p 0.012). The survival analysis did not show statistically significant difference among the 3 groups, both for the overall survival and for the survival according to BCLC stage and/or treatment option. Conclusions: Our study, conducted on a large series of patients with HCC managed in the “real world” of clinical practice, suggests that the presence of metabolic disorders shapes the clinical presentation of HCC but do not seem to play a major role in setting the patient survival. THU-079 VARIANTS ASSOCIATED WITH VITAMIN D METABOLISM AND PROGRESSION TO HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS C: DBGAP DATA FROM HALT-C TRIAL L.A. De Azevedo1, U.D.S. Matte1, T.R. Silveira1, M.R. Alvares-da-Silva2. 1 Universidade Federal do Rio Grande do Sul (UFRGS)/ Hospital de Clinicas de Porto Alegre, Porto Alegre; 2GI-Hepatology Division, Universidade Federal do Rio Grande do Sul (UFRGS)/ Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil E-mail: [email protected] Background and Aims: Vitamin D status has been associated to progression of chronic liver disease, but data are somehow controversial. In this study, we evaluated 24 polymorphisms related to vitamin D metabolism pathway and their relationship with hepatocellular carcinoma (HCC) in chronically hepatitis C virus (HCV) infected patients.
S334
Methods: Data are from the 4-year follow-up of Hepatitis C Antiviral Long-term Treatment Against Cirrhosis cohort and access to datasets were obtained from dbGaP ( phs000430.v1.p1). Patients were originally genotyped for 601,273 polymorphisms in Illumina Human610_Quadv1_B platform. Twenty four SNPs from candidate genes related to vitamin D metabolism were selected and entered the analysis (DHCR7, GC, CYP2R1, CYP27B1, CYP24A1, VDR, TGF, and SMAD3). The SNPs not genotyped in the platform were imputed with Mach-Admix package using 1000 Genomes Phase 3 v.5 as reference panel. Outcome of interest was development of HCC during the 4-year follow-up. Logistic regression was employed in the association analysis. Age, sex, and race were used as covariates. Quality control and statistical analysis were computed in Plink software, v. 1.07. Results: Of the 24 studied polymorphisms, only CYP2R1 rs1562902 T/C significantly affected development of HCC. Homozygosity for allele C was present in 31% of HCC cases and in 19.5% of non-HCC (OR = 1.912, P = 0.03838). Conclusions: The only genotype related to HCC in this cohort (CYP2R1) is responsible for higher levels of vitamin D, according to the literature. Thus, this may suggest vitamin D levels would not have an impact in progression to HCC in HCV infected patients. THU-080 SURVIVAL IN PATIENTS WITH HEPATCELLULAR CARCINOMA AFTER TRANSARTERIAL CHEMOEMBOLISATION IS DETERMINED BY TUMOR BIOLOGY AND HEPATIC FUNCTION M.M. Kirstein1, N. Schweitzer1, N. Ay1, C. Boeck1, J. Hinrichs2, T. Voigtländer1, M. Manns1, T. Rodt2, A. Vogel1. 1Gastroenterology, Hepatology and Endocrinology; 2Institute for Radiology, Hannover Medical School, Hannover, Germany E-mail: [email protected] Background and Aims: Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers worldwide. Early randomized trials and more recent reviews and meta-analyses reported improved survival rates of patients with unresectable lesions managed with TACE so that TACE has been accepted as the standard treatment for intermediate stage disease. Several prognostic scores have been proposed for patients treated with TACE. Deterministic factors for survival post-TACE have not been sufficiently investigated. Methods: In this study, we characterized 606 HCC patients from Hannover Medical School treated with TACE and evaluated the outcome during and beyond TACE. Results: 606 HCC patients treated with TACE were identified between 2000 and 2015. Most patients (59.8%) were at intermediate stage disease prior first TACE (Barcelona Clinic Liver Classification B). 57.4% of the patients were diagnosed with more than three nodules. The mean diameter of the largest lesion was 56 ± 36 mm (ranging 4–226). 26.2% of the patients presented with a lesion larger than 7 cm. Most patients (90.6%) were treated with conventional TACE using doxorubicin, ciplatin and/or mitomycin and lipiodol either alone or in combination with degradable starch microspheres. The mean/ median number of TACEs was 2.3 ± 1.95/2 (maximum 17). Hepatic function progressively deteriorated with TACE but did not jeopardize the survival benefit from TACE. Median overall survival (OS) was 19 months, whereas patients treated 35 times had the longest OS (30 months). Patients with subsequent therapies after TACE had a longer OS than patients with best supportive care (BSC, 27 versus 12 months, p < 0.001). Reflecting the prognostic significance of hepatic function and tumor biology, ascites, cholinesterase, c-reactive and alpha-feto protein and tumor size were identified as significant factors within the multivariate cox regression analysis for survival during TACE. These factors remained significantly prognostic also for post-TACEsurvival as single parameters and within the prognostic HAP and STATE score ( p < 0.05). Radiological or biochemical response to first TACE did not influence post-TACE survival. Conclusions: Patients with sequential therapies live significantly longer than patients with best supportive care post TACE. Hepatic
Journal of Hepatology 2016 vol. 64 | S213–S424