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Variants Associated with Vitamin D Metabolism and Progression to Hepatocellular Carcinoma in Chronic Hepatitis C: DBGAP Data from Halt-C Trial
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.
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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
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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