- Email: [email protected]
[268] RESECTION VS RADIOFREQUENCY ABLATION FOR HCC FROM 3 TO 5cm: A SINGLE CENTRE EXPERIENCE ON 101 CHILD-PUGH CLASS A-B NAIVE PATIENTS
03. LIVER TUMORS (EPIDEMIOLOGE DIAGNOSIS, MANAGEMENT) in high risk patients including those with chronic viral hepatitis, it is still debated whether such surveillance may increase the patient survival. The purpose of this study was to compare the clinical outcomes of patients diagnosed with HCC during different periods of surveillance. Methods: Between May 1990 and December 2004, a total 10,307 high risk patients (32-87 years of age) were followed-up with at least two times of regular ultrasound examination and serum alpha-fetoprotein measurements for at least one year in OUT institution. Among those, 400 patients diagnosed with HCC were divided into three groups according to surveillance period; Group l(1990-1994, n = 123), Group 11 (1995-1999, n = 157), and Group I11 (2000-2004, n = 120). The clinical outcomes including survival were compared among these groups. Results: The mean follow-up duration was 30+24 months (range; 1141). The mean age of all patients was 57 years (range; 33-85) and there was a male predominance (72%). The etiology of HCC was hepatitis B virus in 289 (72.3%) patients, hepatitis C virus in 76 (19.0%), and non B-non C in 32 (8.0%). The patients in Group I11 were diagnosed with HCC at an earlier stage compared to Group 1 or 11; the frequency of patients in TNM stage 1/11 was 65.1%, 67.6%, and 85.8%, respectively (P i 0.05). Furthermore, the frequency of single nodular HCC was 82.1%, 73.2%, and 95.0%, respectively (P i 0.05). The mean tumor size was also significantly lower in Group I11 compared to Group I or I1 (4.2cm vs. 3.2cm 0.005). Interestingly, the proportion of patients in whom vs. 2.9cm, P i surveillance interval was <6 months was significantly higher in Group 111 compared with Group I or I1 (46.3% vs. 39.5% vs. 80.8%, P 0.001). The comparison of 5-year survival among three groups showed a significant difference between Group I (or TI) and Group I11 ( I 7%, I9%, and 65%, P < 0.0001). Conclusion: Our data suggest that patients developing a HCC during the last 5 years survived longer than previously, probably as a consequence of more intensive surveillance program in this period.
12661 HDACIO PROMOTER POLYMORPHISM ASSOCIATED WITH THE HEPATOCELLULAR CARCINOMA OCCURRENCE AMONG CHRONIC HEPATITIS B PATIENTS
Y.J. Kim’, B.L. Park’, H.S. Cheong’, S.O. Lee2, C.S. Han2, H.D. Shin’, W. Kim’, J.H. Yoon’, H.S. Lee’. ‘Department gf’lnternal Medicine and
Lioer Research Institute, Seoul National Uniuersity College of Medicine, Seoul; 2Department of Genetic Epideniiology, SNP Genetics, Inc., Seoul, South Koreu E-mail: [email protected] Background and Aims: Chronic infection with hepatitis B virus (HBV) plays a major role in the development of hepatocellular carcinoma (HCC). Histone deacetylases (HDACs) are key enzymes responsible for the removal of acetyl groups from acetylated histone and non-histone proteins, and play important roles in various biological processes including transcription regulation and DNA repair. In this study, we investigated the genetic polymorphisms in HDAClO to evaluate the gene as a potential candidate for a host genetic study of HCC in chronic HBV infected patients. Methods: By direct DNA sequencing in 24 individuals, we identified 22 sequence variants within exons and flanking regions including a 1.5kb promoter region of HDACIO; five common polymorphic sites were selected for genotyping in larger-scale subjects. A total of 1,095 Korean subjects were prospectively enrolled in this caseecontrol study. Results: Statistical analysis revealed that one promoter polymorphism, HDAC 10-589C > T, showed significant association with HCC occurrence among chronic HBV patients (OR=2.39, Pcor. = 0.04). In addition, SUTviva1 analysis also showed that progression to HCC was accelerated among chronic HBV patients who were carrying the HDAC 10-589T allele (RH = I .97, Pcor. = 0.002). Conclusions: HDACl0 promoter polymorphism might be a valuable genetic factor for HCC progression, and HDACl0 variantihaplotype in-
S107
formation identified in this study might provide valuable information for strategies to control HCC occurrence.
12671 FUNCTIONAL ANALYSIS OF TELOMERE DYSFUNCTION AND DNA DAMAGE CHECKPOINT ABROGATION DURING HEPATOCARCINOGENESIS A. Lechel’, Y. Begus’, R.R. Plentz’ , Y.N. Park’, M. Roncalli3, M.P. Manns’, S. Kubicka’, K.L. Rudolph’. ’Departnient of’
Gastroenterology, Hepatology and Endocrinology, Medical School Hannouer; Hunnouer; Germany; ’Department of Puthology, Yonsei Uniuer~xit?,College of Medicine, Seoul, South Korea; ’Department of Puthology, Uniuersity of Milan und Humunitus Clinicul Institute of Rozzano, Milan, Italy E-mail: [email protected] Background and Aims: Telomere shortening and the inactivation of cell cycle checkpoints characterizes carcinogenesis in humans. The evolution of such alterations in human hepatocarcinogenesis and their functional relevance needs to be analysed. Methods: We analyzed telomere shortening and inactivation of cell cycle checkpoints in biopsies of patients with chronic liver disease, HCC and its precursor lesions (large cell changes = LCC, small cell changes = SCC). Additional we generated a mouse model in which hepatocellular carcinoma was induced by only p53 deletion. Results: The analysis of human samples revealed a decrease in telomere length in non dysplastic cirrhotic liver compared to normal liver and a further significant shortening of telomeres in LCC, SCC, and HCC. HCC had the shortest telomeres followed by SCC and LCC. In line with the telomere hypothesis of cirrhosis development, hepatocytes showed an increased p21-labeling index (p21-L1) at the cirrhosis stage, which remained elevated in the vast majority of LCC. In comparison, most SCC and HCC showed a strongly reduced p21-LI. In the mouse model, homozygous deletion ofp53 was sufficient to induce hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) at an age of 13-15 month. In a combined model of chronic liver damage (HBs-trangene expression) plus p53 deletion, massive telomere dysfunction and DNA damage evolved in telomerase deficient mice (mTERC-’-) and led to p53-independent tumor suppression. Conclusions: Our data indicate that LCC and SCC represent clonal expansion of hepatocytes with shortened telomeres in human liver cirrhosis. The inactivation of cell cycle checkpoints in SCC coincides with further telomere shortening and an accumulation of DNA damage suggesting that SCC represent more advanced precursor lesions compared to LCC. Our studies in mice indicate that loss of p53 is sufficient to induce hepatocarcinogenesis, but p53-independent tumor suppression occurs in the absence of telomerase by induction of massive telomere dysfunction and DNA damage in response to chronic organ damage.
12681 RESECTION VS RADIOFREQUENCY ABLATION FOR HCC FROM 3 TO 5cm: A SINGLE CENTRE EXPERIENCE ON 101 CHILD-PUGH CLASS A-B NAIVE PATIENTS L. Lupo’, P. Panzera’, G. Carbotta’ , A. Gentile2, A. Galleranil, M. Stefano’ , V Memeo’ . ‘Dipartiniento Emergenze e Tral,ianto di Organi, lstituto di Chirurgia Generake e Tral,ianto di Fegato, Unioersitu
di Bari, Buri; ’lstituto di Anutomiu Puttologicu, Uniuer~xitddi Bari, Buri, ltuly E-mail: [email protected] Background: The optimal therapy for HCC seems to be transplantation. For all those patients not eligible for transplantation (or waiting for it) the treatment of choice has been restricted in the last years to resection (RES) or radiofrequency ablation (RFA). RFA is supposed to lose part of its efficacy for HCC ranging over 3 cm.
S108
POSTERS
Aim of this study is to compare RFA to RES in a restricted cohort of patients with a first diagnosis of single HCC ranging from 3 to 5 cm and with not end stage liver disease. Patients and Methods: 10 I patients never treated before were enrolled. Those patients whose HCC position required too parenchimal lost at RES (central or close to main vascular structures) were treated with RFA (60), others underwent RES (41). The two groups were similar for HCC size (mean RES:RFA = 40:36 mm) and liver disease status. The outcome was considered in terms of overall survival (O.S.) and disease free survival (DFS) calculated with Kaplan-Meier method. Differences among groups were validated by Log-rank test. Results: O.S.% in RESIRFA at I , 2, 3, 4, 5 years: 91/96, 72177, 55153, 45135,42130. DFS% in RESIRFA at I , 2, 3, 4, 5 years: 76167,44142, 3511 8, 18113, 1510. Even if RES group seems to present a better long term O.S. and DFS this difference does not reach a statistical significance. Patients with worse Child-Pugh score (B vs A) and patients that have a recurrence within the first 12 month after treatment show a worse long term survival. Conclusion: It seems that Resection and RFA have the same efficacy in treating HCC ranging from 3 to 5 cm. Survival may be mostly related to nature of HCC itself and to liver disease on the background. A larger sample size is required to confirm this observation.
12691 THE SIZE OF LARGEST NODULE - NOT THE NUMBER OF
NODULES - IS THE BEST PREDICTOR OF RECURRENCE OF HEPATOCELLULAR CARCINOMA AFTER LIVER TRANSPLANTATION
L. Marelli’, A. Grasso2, R. Stigliano’, F. Morisco’, H. Martines2, A.P. Dhillon3, D. Patch’, B.R. Davidson’, K. Rolles’, A.K. Burroughs’. ‘Liurr Trunspluntution und Hrputohiliury Medicine Unit, Royul Free Hospitul, London, UK; Li.0. Mrdicinu Internu 2, OsIirdulr S. Puolo, Suuonu, Ituly; ’Drpurtmrnt of Histoputhology, Royul Frrr Hospitul, London, UK E-mail: marelliIaura~tiscali.it Background: In patients with cirrhosis and hepatocellular carcinoma (HCC) recurrence is the main cause of death after liver transplantation (LT). Aim: To evaluate predictive factors for HCC recurrence after LT and to assess their impact on survival. Methods: 119 consecutive patients with cirrhosis and HCC (95 known HCC and 24 incidental HCC) undergoing LT. 21 variables evaluating patient and tumour characteristics, separately assessed before LT and at explant, were assessed by univariate and multivariate analysis. Survival differences were analysed by log rank test. Results: Median waiting list time was 38 days (range: 1-370). Size of largest nodule at radiology (n=95) and size of largest nodule at explant ( n = 119) were the sole variables independently associated with recurrence (OR 1.07; 95%CI 1.01-1.12; p=0.012 and OR 1.05; 95%CI 1.01-1.10; p=0.016). The number of nodules at imaging or explant did not influence recurrence. The ROC curve for size showed that the best performance in predicting recurrence was a cut off value for histology of 35 mm diameter (sensitivity 77%; specificity 7 I %) and for radiology of 30 mm diameter (sensitivity 82%; specificity 48%). For radiological size of 35 mm sensitivity dropped to 44%, specificity was 82%. Pre-LT imaging subestimated 30% of patients with nodules >35 mm at explant and overestimated only 9% with nodules 35 mm at explant. The cumulative probability for recurrence for nodules larger than 30 mm at radiology was only marginally significant (p = 0.052); whereas it was strongly significant for nodule larger than 35 mm at explant (p = 0.001). I , 3, 5, 7 and 10 years 35mm cumulative survival of patients with size of nodule at explant were 82, 73, 64, 53 and 44% compared to 79, 59, 41, 28 and 28% when size was &35 mm (p = 0.045). Conclusion: A diameter of largest nodule of more than 30 mm at imaging, due to the understaging at radiology, has a significant risk of recurrence.
<
<
This correlates with the finding o f a maximal diameter of35 mm at explant being highly significant for recurrence. The number of nodules, providing they are less than 30mm diameter at imaging 35mm at explant does not influence HCC recurrence post-LT. -
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12701 PROSPECTIVE INFLUENCE OF HFE GENE MUTATIONS AND LIVER IRON OVERLOAD ON THE RISK OF HEPATOCELLULAR CARCINOMA OCCURRENCE IN PATIENTS WITH ALCOHOLIC OR HCV-RELATED CIRRHOSIS P. Nahon’, A. Sutton’, P. Rufat2, G. Thabut3, M. Ziol’, R. Fagard4, P.O. Schischmanofp, D. Vidaud’, N. Charnau’ , N. Ganne-Carrie’, J.C. Trinchet’ , L. Gattegno’, M. Beaugrand’. ’Hfipitul Jeun ErdieK Bondy; ’Groupe Hospitulier PitiC-Sulp6tviCve, Puris; .’H6pitul Bichut, Puris; 4Hfipitul Auicmne, Bohigny; ’Hfipitul Bruujon, Clichy, Fruncr E-mail: [email protected] Background and Aims: The possible influence of HFE gene mutations and liver iron overload on hepatocellular carcinoma (HCC) occurrence in patients with cirrhosis has been studied with controversial results. All were case-controls studies with small-sampled cohorts of patients with various causes of cirrhosis. The aim of this work was to assess this influence on a large cohort of prospectively followed-up cirrhotic patients classified according the aetiology of liver disease. Patients and Methods: 301 consecutive cirrhotic patients (162 alcoholics and 139 HCV-infected patients without alcohol consumption) were prospectively included at time of histological diagnosis of cirrhosis and prospectively followed-up. Liver iron overload was assessed on initial biopsy according to modified Deugnier’s score (ranging from 0 to 33) and C282YlH63D HFE gene mutations assessed on blood sample DNA. Results: In patients with alcoholic cirrhosis (mean age: 52.50+9.20 years, 1151162 males, mean iron score = 2.77+3.38, mean time of follow-up: 93.73&25.54 months), 40/162 (24.69%) developed HCC. 131162 (8.02%) were heterozygotes for C282Y HFE gene mutation with a non significant trend towards higher hepatic iron score in these patients (3.6f3.8 vs 1.9f2.8, p = 0. I ) . In univariate analysis, liver iron overload (HR: I .24 [1.14-1.351, Logranki0.001, with an optimal threshold value of iron score = 2.0) and C282Y mutation (HR:2.77 [1.21-6.321, Logrank= 0.01) were risk factors for HCC occurrence. In multivariate analysis including age and gender, liver iron overload remained an independant risk factor for HCC (HR: 1.17 [ 1.07-1.281, p i 0.001). In patients with HCV-related cirrhosis [mean age: 58.65+12.82 years, 661139 males, C282Y allele carriage = 17/139 (12.23%), mean iron score = l.Olfl.96, mean time of follow-up: 1 16.09+28.65 months, HCC=63/139 (45.32%)], C282Y mutation and liver iron overload were not associated with the risk of HCC occurrence. H63D mutation carriage was not a risk factor for liver iron overload or HCC occurrence in both cohorts. Conclusions: Conversely to patients with HCV-related cirrhosis, liver iron overload on initial biopsy and C282Y mutation carriage are associated with the risk of HCC ocurrence. Liver iron overload remains an independant predictive factor in multivariate analysis taking in account age and gender suggesting that iron depletion could be helpful in HCC prevention in patients with alcoholic cirrhosis and iron overload.
12711 AND CONTRIBUTION OF THE VASCULAR PROFILE ANALYSIS HISTOLOGICAL PATTERNS TO THE DIFFERENTIAL DIAGNOSIS OF HEPATIC NODULES C. Nascimento, A. Caroli-Bottino, J. Maia, V Panuain. Depurtmmt of Puthologj~,Frderul Uniuersity of Rio dr Junriro, Bruzil E-mail: [email protected] Background and Aims: Dysplastic hepatocellular nodules have received a variety of terminologies throughout the years. In 1994, a new system,
12661 HDACIO PROMOTER POLYMORPHISM ASSOCIATED WITH THE HEPATOCELLULAR CARCINOMA OCCURRENCE AMONG CHRONIC HEPATITIS B PATIENTS
Y.J. Kim’, B.L. Park’, H.S. Cheong’, S.O. Lee2, C.S. Han2, H.D. Shin’, W. Kim’, J.H. Yoon’, H.S. Lee’. ‘Department gf’lnternal Medicine and
Lioer Research Institute, Seoul National Uniuersity College of Medicine, Seoul; 2Department of Genetic Epideniiology, SNP Genetics, Inc., Seoul, South Koreu E-mail: [email protected] Background and Aims: Chronic infection with hepatitis B virus (HBV) plays a major role in the development of hepatocellular carcinoma (HCC). Histone deacetylases (HDACs) are key enzymes responsible for the removal of acetyl groups from acetylated histone and non-histone proteins, and play important roles in various biological processes including transcription regulation and DNA repair. In this study, we investigated the genetic polymorphisms in HDAClO to evaluate the gene as a potential candidate for a host genetic study of HCC in chronic HBV infected patients. Methods: By direct DNA sequencing in 24 individuals, we identified 22 sequence variants within exons and flanking regions including a 1.5kb promoter region of HDACIO; five common polymorphic sites were selected for genotyping in larger-scale subjects. A total of 1,095 Korean subjects were prospectively enrolled in this caseecontrol study. Results: Statistical analysis revealed that one promoter polymorphism, HDAC 10-589C > T, showed significant association with HCC occurrence among chronic HBV patients (OR=2.39, Pcor. = 0.04). In addition, SUTviva1 analysis also showed that progression to HCC was accelerated among chronic HBV patients who were carrying the HDAC 10-589T allele (RH = I .97, Pcor. = 0.002). Conclusions: HDACl0 promoter polymorphism might be a valuable genetic factor for HCC progression, and HDACl0 variantihaplotype in-
S107
formation identified in this study might provide valuable information for strategies to control HCC occurrence.
12671 FUNCTIONAL ANALYSIS OF TELOMERE DYSFUNCTION AND DNA DAMAGE CHECKPOINT ABROGATION DURING HEPATOCARCINOGENESIS A. Lechel’, Y. Begus’, R.R. Plentz’ , Y.N. Park’, M. Roncalli3, M.P. Manns’, S. Kubicka’, K.L. Rudolph’. ’Departnient of’
Gastroenterology, Hepatology and Endocrinology, Medical School Hannouer; Hunnouer; Germany; ’Department of Puthology, Yonsei Uniuer~xit?,College of Medicine, Seoul, South Korea; ’Department of Puthology, Uniuersity of Milan und Humunitus Clinicul Institute of Rozzano, Milan, Italy E-mail: [email protected] Background and Aims: Telomere shortening and the inactivation of cell cycle checkpoints characterizes carcinogenesis in humans. The evolution of such alterations in human hepatocarcinogenesis and their functional relevance needs to be analysed. Methods: We analyzed telomere shortening and inactivation of cell cycle checkpoints in biopsies of patients with chronic liver disease, HCC and its precursor lesions (large cell changes = LCC, small cell changes = SCC). Additional we generated a mouse model in which hepatocellular carcinoma was induced by only p53 deletion. Results: The analysis of human samples revealed a decrease in telomere length in non dysplastic cirrhotic liver compared to normal liver and a further significant shortening of telomeres in LCC, SCC, and HCC. HCC had the shortest telomeres followed by SCC and LCC. In line with the telomere hypothesis of cirrhosis development, hepatocytes showed an increased p21-labeling index (p21-L1) at the cirrhosis stage, which remained elevated in the vast majority of LCC. In comparison, most SCC and HCC showed a strongly reduced p21-LI. In the mouse model, homozygous deletion ofp53 was sufficient to induce hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) at an age of 13-15 month. In a combined model of chronic liver damage (HBs-trangene expression) plus p53 deletion, massive telomere dysfunction and DNA damage evolved in telomerase deficient mice (mTERC-’-) and led to p53-independent tumor suppression. Conclusions: Our data indicate that LCC and SCC represent clonal expansion of hepatocytes with shortened telomeres in human liver cirrhosis. The inactivation of cell cycle checkpoints in SCC coincides with further telomere shortening and an accumulation of DNA damage suggesting that SCC represent more advanced precursor lesions compared to LCC. Our studies in mice indicate that loss of p53 is sufficient to induce hepatocarcinogenesis, but p53-independent tumor suppression occurs in the absence of telomerase by induction of massive telomere dysfunction and DNA damage in response to chronic organ damage.
12681 RESECTION VS RADIOFREQUENCY ABLATION FOR HCC FROM 3 TO 5cm: A SINGLE CENTRE EXPERIENCE ON 101 CHILD-PUGH CLASS A-B NAIVE PATIENTS L. Lupo’, P. Panzera’, G. Carbotta’ , A. Gentile2, A. Galleranil, M. Stefano’ , V Memeo’ . ‘Dipartiniento Emergenze e Tral,ianto di Organi, lstituto di Chirurgia Generake e Tral,ianto di Fegato, Unioersitu
di Bari, Buri; ’lstituto di Anutomiu Puttologicu, Uniuer~xitddi Bari, Buri, ltuly E-mail: [email protected] Background: The optimal therapy for HCC seems to be transplantation. For all those patients not eligible for transplantation (or waiting for it) the treatment of choice has been restricted in the last years to resection (RES) or radiofrequency ablation (RFA). RFA is supposed to lose part of its efficacy for HCC ranging over 3 cm.
S108
POSTERS
Aim of this study is to compare RFA to RES in a restricted cohort of patients with a first diagnosis of single HCC ranging from 3 to 5 cm and with not end stage liver disease. Patients and Methods: 10 I patients never treated before were enrolled. Those patients whose HCC position required too parenchimal lost at RES (central or close to main vascular structures) were treated with RFA (60), others underwent RES (41). The two groups were similar for HCC size (mean RES:RFA = 40:36 mm) and liver disease status. The outcome was considered in terms of overall survival (O.S.) and disease free survival (DFS) calculated with Kaplan-Meier method. Differences among groups were validated by Log-rank test. Results: O.S.% in RESIRFA at I , 2, 3, 4, 5 years: 91/96, 72177, 55153, 45135,42130. DFS% in RESIRFA at I , 2, 3, 4, 5 years: 76167,44142, 3511 8, 18113, 1510. Even if RES group seems to present a better long term O.S. and DFS this difference does not reach a statistical significance. Patients with worse Child-Pugh score (B vs A) and patients that have a recurrence within the first 12 month after treatment show a worse long term survival. Conclusion: It seems that Resection and RFA have the same efficacy in treating HCC ranging from 3 to 5 cm. Survival may be mostly related to nature of HCC itself and to liver disease on the background. A larger sample size is required to confirm this observation.
12691 THE SIZE OF LARGEST NODULE - NOT THE NUMBER OF
NODULES - IS THE BEST PREDICTOR OF RECURRENCE OF HEPATOCELLULAR CARCINOMA AFTER LIVER TRANSPLANTATION
L. Marelli’, A. Grasso2, R. Stigliano’, F. Morisco’, H. Martines2, A.P. Dhillon3, D. Patch’, B.R. Davidson’, K. Rolles’, A.K. Burroughs’. ‘Liurr Trunspluntution und Hrputohiliury Medicine Unit, Royul Free Hospitul, London, UK; Li.0. Mrdicinu Internu 2, OsIirdulr S. Puolo, Suuonu, Ituly; ’Drpurtmrnt of Histoputhology, Royul Frrr Hospitul, London, UK E-mail: marelliIaura~tiscali.it Background: In patients with cirrhosis and hepatocellular carcinoma (HCC) recurrence is the main cause of death after liver transplantation (LT). Aim: To evaluate predictive factors for HCC recurrence after LT and to assess their impact on survival. Methods: 119 consecutive patients with cirrhosis and HCC (95 known HCC and 24 incidental HCC) undergoing LT. 21 variables evaluating patient and tumour characteristics, separately assessed before LT and at explant, were assessed by univariate and multivariate analysis. Survival differences were analysed by log rank test. Results: Median waiting list time was 38 days (range: 1-370). Size of largest nodule at radiology (n=95) and size of largest nodule at explant ( n = 119) were the sole variables independently associated with recurrence (OR 1.07; 95%CI 1.01-1.12; p=0.012 and OR 1.05; 95%CI 1.01-1.10; p=0.016). The number of nodules at imaging or explant did not influence recurrence. The ROC curve for size showed that the best performance in predicting recurrence was a cut off value for histology of 35 mm diameter (sensitivity 77%; specificity 7 I %) and for radiology of 30 mm diameter (sensitivity 82%; specificity 48%). For radiological size of 35 mm sensitivity dropped to 44%, specificity was 82%. Pre-LT imaging subestimated 30% of patients with nodules >35 mm at explant and overestimated only 9% with nodules 35 mm at explant. The cumulative probability for recurrence for nodules larger than 30 mm at radiology was only marginally significant (p = 0.052); whereas it was strongly significant for nodule larger than 35 mm at explant (p = 0.001). I , 3, 5, 7 and 10 years 35mm cumulative survival of patients with size of nodule at explant were 82, 73, 64, 53 and 44% compared to 79, 59, 41, 28 and 28% when size was &35 mm (p = 0.045). Conclusion: A diameter of largest nodule of more than 30 mm at imaging, due to the understaging at radiology, has a significant risk of recurrence.
<
<
This correlates with the finding o f a maximal diameter of35 mm at explant being highly significant for recurrence. The number of nodules, providing they are less than 30mm diameter at imaging 35mm at explant does not influence HCC recurrence post-LT. -
-
12701 PROSPECTIVE INFLUENCE OF HFE GENE MUTATIONS AND LIVER IRON OVERLOAD ON THE RISK OF HEPATOCELLULAR CARCINOMA OCCURRENCE IN PATIENTS WITH ALCOHOLIC OR HCV-RELATED CIRRHOSIS P. Nahon’, A. Sutton’, P. Rufat2, G. Thabut3, M. Ziol’, R. Fagard4, P.O. Schischmanofp, D. Vidaud’, N. Charnau’ , N. Ganne-Carrie’, J.C. Trinchet’ , L. Gattegno’, M. Beaugrand’. ’Hfipitul Jeun ErdieK Bondy; ’Groupe Hospitulier PitiC-Sulp6tviCve, Puris; .’H6pitul Bichut, Puris; 4Hfipitul Auicmne, Bohigny; ’Hfipitul Bruujon, Clichy, Fruncr E-mail: [email protected] Background and Aims: The possible influence of HFE gene mutations and liver iron overload on hepatocellular carcinoma (HCC) occurrence in patients with cirrhosis has been studied with controversial results. All were case-controls studies with small-sampled cohorts of patients with various causes of cirrhosis. The aim of this work was to assess this influence on a large cohort of prospectively followed-up cirrhotic patients classified according the aetiology of liver disease. Patients and Methods: 301 consecutive cirrhotic patients (162 alcoholics and 139 HCV-infected patients without alcohol consumption) were prospectively included at time of histological diagnosis of cirrhosis and prospectively followed-up. Liver iron overload was assessed on initial biopsy according to modified Deugnier’s score (ranging from 0 to 33) and C282YlH63D HFE gene mutations assessed on blood sample DNA. Results: In patients with alcoholic cirrhosis (mean age: 52.50+9.20 years, 1151162 males, mean iron score = 2.77+3.38, mean time of follow-up: 93.73&25.54 months), 40/162 (24.69%) developed HCC. 131162 (8.02%) were heterozygotes for C282Y HFE gene mutation with a non significant trend towards higher hepatic iron score in these patients (3.6f3.8 vs 1.9f2.8, p = 0. I ) . In univariate analysis, liver iron overload (HR: I .24 [1.14-1.351, Logranki0.001, with an optimal threshold value of iron score = 2.0) and C282Y mutation (HR:2.77 [1.21-6.321, Logrank= 0.01) were risk factors for HCC occurrence. In multivariate analysis including age and gender, liver iron overload remained an independant risk factor for HCC (HR: 1.17 [ 1.07-1.281, p i 0.001). In patients with HCV-related cirrhosis [mean age: 58.65+12.82 years, 661139 males, C282Y allele carriage = 17/139 (12.23%), mean iron score = l.Olfl.96, mean time of follow-up: 1 16.09+28.65 months, HCC=63/139 (45.32%)], C282Y mutation and liver iron overload were not associated with the risk of HCC occurrence. H63D mutation carriage was not a risk factor for liver iron overload or HCC occurrence in both cohorts. Conclusions: Conversely to patients with HCV-related cirrhosis, liver iron overload on initial biopsy and C282Y mutation carriage are associated with the risk of HCC ocurrence. Liver iron overload remains an independant predictive factor in multivariate analysis taking in account age and gender suggesting that iron depletion could be helpful in HCC prevention in patients with alcoholic cirrhosis and iron overload.
12711 AND CONTRIBUTION OF THE VASCULAR PROFILE ANALYSIS HISTOLOGICAL PATTERNS TO THE DIFFERENTIAL DIAGNOSIS OF HEPATIC NODULES C. Nascimento, A. Caroli-Bottino, J. Maia, V Panuain. Depurtmmt of Puthologj~,Frderul Uniuersity of Rio dr Junriro, Bruzil E-mail: [email protected] Background and Aims: Dysplastic hepatocellular nodules have received a variety of terminologies throughout the years. In 1994, a new system,