POSTERS
Background and Aims: Bile acids are known regulators of lipid, and glucose metabolism. The mammalian target of rapamycin (mTOR) has an important role in regulation lipid biosynthesis/metabolism. In our previous studies, that known ursodeoxycholic acid (UDCA) reduced lipid accumulation in obese mice. A comprehensive study addressing the role of UDCA in the coordinated regulation of mTORdependent manner of lipogenesis/gluconeogenesis homeostasis is lacking. Methods: Therefore, we used mouse models of non-alcoholic fatty liver disease (NAFLD) by ob/ob mice and alcoholic fatty liver disease (AFLD) by binging ethanol feed with UDCA two weeks per day. Liver tissue were analyzed for phosph-mTOR, SREBP1c, PEPCK, G6Pase and bile acid synthesis and transporters were assessed for CYP7A1 and BSEP by western blot, immunohistochemical and QRT-PCR. Results: NAFLD and AFLD represent high level ALT, bile acids, free fatty acid and triglycerol that have high phospo-mTOR, SREBP1c protein expression, and they were reduced after UDCA treatment. UDCA improved lipolysis (LPL, HSL) and b-oxdation (ACO) mRNA expression. Interestingly, protein expression of gluconeogenesis, PEPCK and G6Pase were increased in NAFLD mice, but they were decreased in AFLD. Nonetheless, PEPCK and G6Pase protein expression are significant improvement for UDCA treatment. Bile acids and CYP7A1 levels increase in our models, but only CYP7A1 protein expression was decreased after UDCA treatment. Therefore, UDCA is a strongly mediator to regulation lipogenesis/gluconeogenesis disorder in NAFLD and AFLD. Conclusions: The above results show that two models of fatty liver identify common and injury-specific roles for lipogenesis and gluconeogenesis, and functional relevance of bile acids in hepatocytic adaptive NAFLD and AFLD.
Median survival in those receiving Sorafenib was 21.0 months versus no Sorafenib 7.0 months (p = 0.003) (Figure 1). Survival advantage remained significant after adjusting for Child–Pugh score (HR 0.26, p = 0.02). Sorafenib duration was associated with a trend towards increased survival (p = 0.09, Cox regression analysis).
1.0
0.8
Cumulative survival
P429 URSODEOXYCHOLIC ACID VIA REGULATION OF BILE ACIDS AND MAMMALIAN TARGET OF RAPAMYCIN TO IMPROVE LIPID METABOLISM DISORDERS WITH NON-ALCOHOLIC AND ALCOHOL-INDUCED FATTY LIVER DISEASE H.M. Liu1 , T.Y. Lee2 , J.F. Liao1 , H.C. Lin3 . 1 Institute of Pharmacology, National Yang-Ming University, Taipei, 2 Graduate Institute of Traditional Chinese Medicine, Chang Gung Univervsity, Tao-Yuan, 3 Division of Gastroenterology, Department of Medicine, Taipei Veterans, Taipei, Taiwan E-mail:
[email protected]
SIRT / sorafenib
0.6
0.4
0.2
SIRT 0.0 0.0
10.0
20.0
30.0
40.0
Follow-up (months)
Figure 1.
Seven patients (18.9%) had adverse effects. 1 patient received SIRT/Sorafenib developed post-procedural ascites. 6 patients received SIRT only: 2 reported nausea, 3 developed ascites and 1 developed cardiac ischaemia intra-procedure. Conclusions: The combination of SIRT with Sorafenib significantly improves survival in patients with BCLC B/C HCC compared with SIRT alone. Both treatments were well tolerated by the majority of patients.
P430 SELECTIVE INTERNAL RADIATION THERAPY FOR HEPATOCELLULAR CARCINOMA: COMBINATION WITH SORAFENIB IS ASSOCIATED WITH IMPROVED SURVIVAL OUTCOMES M.X. Ma1 , L. Adams1 , G. Garas1 , G. Macquillan1 , M. O’dea1 , S. Samuelson2 , J. Tibballs2 , R. Mac Nicholas1 . 1 Hepatology, 2 Radiology, Sir Charles Gairdner Hospital, Perth, WA, Australia E-mail:
[email protected]
P431 BRAF AND FHIT EXPRESSION IN HCV RELATED CIRRHOSIS AND HEPATOCELLULAR CARCINOMA AND THEIR ASSOCIATION WITH PROGNOSTIC ANATOMOPATHOLOGICAL FEATURES P.V.T. Vidigal1 , P.P. Garcia1 , F.M.F. Osorio ´ 2 , C.A. Couto2 , P.A.S. do Carmo1 , L.A.C. de Marco3 . 1 Pathology, 2 Clinical, 3 Surgery, UFMG/Faculdade de Medicina, Belo Horizonte, Brazil E-mail:
[email protected]
Background and Aims: SIRT and Sorafenib are used in treatment of HCC. The impact on survival of combining both treatments is unknown. Methods: A retrospective study of consecutive patients undergoing SIRT in our centre between November 2007 and October 2013 was conducted by electronic database and medical notes review. SIRT was performed if: PVT was present, large HCC (>8 cm) or multifocal disease (≥4 tumour nodules), or disease progression with TACE. Three monthly liver MRI was performed following SIRT. Results: 37 patients (34 male, 3 female) with BCLC stage B/C HCC and mean age of 57 years (range 42–79) received SIRT during the study period. Median MELD score was 8 (range 6–14). Median follow up was 7 months (range 0–39). 18 patients had tumour PVT, and 1 patient had bland PVT. 18 patients commenced Sorafenib (3 prior to SIRT). Median overall survival following SIRT was 16 months (95% CI 8.5–23.5).
Background and Aims: Hepatocarcinogenesis is a multistep process initiated by different external stimuli that lead to genetic changes in hepatocytes resulting in neoplasia. However, the mechanisms of malignant transformation seem to differ widely. To know carcinogenesis mechanisms is essential to develop new treatment and prevention methods. The aim of this study is to analyze BRAF and FHIT imunoexpression in HCV related cirrhosis and hepatocellular carcinoma (HCC) and to associate their expression with some prognostic pathological features. Methods: 36 patients with HCV related cirrhosis and HCC that underwent liver transplantation at Clinical Hospital – UFMG and 25 normal livers from the Hospital necropsy archives. Tumors were classified according to: number and diameter of nodules, vascular invasion and differentiation grade. BRAF and FHIT expression were determined by immunohistochemistry in tumor and their cirrhotic adjacent parenchyma and in normal livers.
Journal of Hepatology 2014 vol. 60 | S67–S214
S211
POSTERS Results: Braf was strongly expressed in the cytoplasm of hepatocytes of 17.1% of the cirrhotic livers and in 62.9% of the HCC samples (p < 0.001, RR = 3.67). Fhit was strongly expressed in the cytoplasm of hepatocytes of 19.4% of the cirrhotic livers and in 44.4% of the HCC samples (p = 0.04, RR = 2.27). There was no significant association among FHIT and BRAF scores and tumor differentiation grade, number and size nor with microvascular invasion. There was an association between high grade tumors and the presence of vascular invasion (p = 0.014, RR = 7.27). Conclusions: This data suggests that BRAF may play an important role in HCC carcinogenesis. Larger studies are needed to validate these observations. P432 TRADITIONAL INDIAN MEDICINAL PLANTS HAVE PHYTOCHEMICALS WITH POTENT ANTI-HBV ACTIVITY N. Mittal1 , P. Katyal1 , A. Vyas1 , P. Tulsiani1 , A. Singh1 , N. Trehanpati1 , S. Sharma1 , S.K. Sarin2 . 1 Research, 2 Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India E-mail:
[email protected] Background and Aims: Phyllanthus amarus, Sillybum marianum and Andrographis paniculata have been employed as treatment for hepatitis in Indian systems of medicine. We wanted to determine if specific phytochemicals from these species have anti-HBV potential. Methods: 1×106 HepG2.2.15 cells were exposed to andrographolide, neoandrographolide, phyllanthin, sylimarin at 100, 250, 500 or 1000 mg/ml and Adefovir, Tenfovir, Lamivudine, Entecavir (<3.25mM). HBsAg/HBeAg levels were determined by ELISA. DNA fragmentation/apoptosis were investigated by Hoechst33342/western blotting and HBV replicative intermediates (cccDNA, pre-genomic-, pre-core RNA) by rtPCR. Results: Andrographolide and neoandrographolide significantly reduced HBsAg/HBeAg concentrations (>2-fold) than phyllanthin or sylimarin, while inducing significantly less (p < 0.05) cellular DNA damage than all other drugs. Bclxl , Cdc2 and p53 expression was increased by andrographolide. Proapoptotic proteins Bax and Bak were suppressed (~75%) by andrographolide/tenefovir/adefovir in contrast to other drugs, which enhanced these levels (p < 0.05). Phyllanthin inhibited cell cycle by upregulation of Cdc2. Andrographolide and tenefovir significantly enhanced p53 expression (~1.5-fold, p < 0.05). Neoandrographolide was more effective than andrographolide in reducing (>2-fold) cccDNA, pregenomic RNA (~2.5 log values), while andrographolide reduced precore RNA (>4 log values) up to 72 hrs. Tenefovir also achieved similar values only upto 24 hrs, after which the DNA levels showed an increase (1.3-fold) in contrast to neoandrographolide or andrographolide (p < 0.05). Conclusions: These results suggest that andrographolide and neoandrographolide have potent activity against the HBV intermediates, specially the cccDNA and pgRNA. In combination with phyllanthin, the drugs may help provide anti-tumor activities by increasing p53 production. These phytochemicals could serve as potent antviral agents against HBV. P433 IS TIPS INDICATED IN CIRRHOTIC PATIENTS WITH CHILD–PUGH B SCORE AND ACTIVE VARICEAL BLEEDING? R. Sia1 , J. Scanzi2 , B. Pereira2 , R.A. Sombie´ 1 , A.K. Serme´ 1 , P.D. Ilboudo1 , S.H.M. Godonou1 , L. Poincloux2 , M. Dapoigny2 , G. Lamblin2 , G. Bommelaer2 , A. Abergel2 . 1 University Hospital of Yalgado Ouedraogo, Ouagadougou, Burkina Faso; 2 University Hospital of Clermont-Ferrand, Clermont-Ferrand, France E-mail:
[email protected]
Methods: We included retrospectively all consecutive cirrhotic patients admitted to our University Hospital for variceal bleeding between January 2007 and December 2011. The primary endpoint was the mortality at six-weeks. Results: 143 patients were included. Patients were classified in Child–Pugh A (18.2%), Child–Pugh B (39.2%) and Child–Pugh C (42.6%). Among Child–Pugh B patients (55), 12 had active bleeding at endoscopy (survival rate: 100%) and 43 had none (survival rate: 97.7%). Active bleeding during initial endoscopy was observed in 30 patients (24.1%). Endoscopic therapy was performed in 118 patients. Six patients underwent a TIPS placement including three in an early stage. A bleeding recurrence was observed in 27%. The sixweek mortality rate was 18.9% (27): Child A=0 (0%), Child B=1 (1.8%) and Child C=26 (42.6%). Child–Pugh C and early bleeding recurrence, were associated with an increased mortality at sixweeks (p < 0.001, p = 0.05). Active bleeding during initial endoscopy in Child B patients was not a risk factor of six-week mortality (p=1). Conclusions: The six-week mortality was 18.9%, which is in accordance with Baveno V (10–20%). This mortality rate could probably be decreased by a more frequent use of early TIPS, which should be considered in patients at high-risk of mortality (Child– Pugh C). In our study, like in the study of Thabut et al, active bleeding at endoscopy was not associated with a poor survival in Child B patients. P434 DESCRIPTIVE EPIDEMIOLOGY OF LIVER CANCER IN NIGER: RESULTS FROM THE NATIONAL CANCER REGISTRY S. Mamoudou Garba1,2 , H. Hami1 , H.M. Zaki2 , A. Soulaymani1 , H. Nouhou2 , A. Quyou1 . 1 Faculty of Sciences, Department of Biology, Laboratory of Genetics and Biometry, Ibn Tofail University, K´enitra, Morocco; 2 Faculty of Health Sciences, Abdou Moumouni University, Niamey, Niger E-mail:
[email protected] Background and Aims: Liver cancer is the fifth most common cancer and the third most common cause of cancer death worldwide. The incidence rate of liver cancer is higher in SubSaharan Africa, particularly in endemic areas of hepatitis B virus infection. The aims of this study are to estimate the incidence and determine the epidemiological characteristics of liver cancer in the population of Niger. Methods: This is a descriptive retrospective study of liver cancer cases, reported between 1992 and 2009 to the Niger Cancer Registry, established in 1992, in the Laboratory of Pathological Anatomy and Cytology at the Abdou Moumouni University in Niamey. Results: A total of 812 patients were diagnosed with liver cancer, representing 11.5% of all cancer cases reported during the study period. The incidence rate of liver cancer was 5.52 cases per 100 000 persons. More than two-thirds were males with a male-female ratio of 2.27 and 60.7% were farmers. The mean age at diagnosis of the patients was 48.06±14.12 years. The most common histological type was malignant tumor not otherwise specified with 92.9%of cases. Among all detected cases, 296 deaths were registered with a lethality rate of 36.45%. Conclusions: The absence of appropriate health policy prevents early detection of liver cancer and its management. This has a direct consequence on increasing in cancer incidence. Because of the seriousness of liver cancer in Niger; the health authorities should pay more attention to this pathology through efficient fight strategies.
Background and Aims: The indication of early TIPS in variceal bleeding is currently debated. We aimed to determine which subgroup of patients could take advantage of an early TIPS. S212
Journal of Hepatology 2014 vol. 60 | S67–S214