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Diagnostic performance of point share wave elastography (pSWE) in comparison with transient elastography performed by Fibroscan® (TE) and non-invasive scores of fibrosis in primary biliary cirrhosis (PBC)
Abstracts / Digestive and Liver Disease 48S (2016) e42–e64
had median diameter of 17 mm (range: 6–50; 78% < 30 mm diameter), in 84% was diagnosed by imaging, 93% BCLC 0 or A, 95% within Milan criteria, 3% with neoplastic portal thrombosis. As initial treatment, patients received RFA (38%), surgical resection (28%) and TACE (21%). During 27 months of follow-up, 12% died of HCC progression while 24% successfully underwent liver transplantation within 6 months (2-77) from HCC diagnosis. Conclusions: A majority of HCC developing in Caucasian patients with compensated HBV under long-term NUC are small single tumors, within Milan criteria, BCLC 0/A, with normal AFP levels and therefore amenable to curative therapies. http://dx.doi.org/10.1016/j.dld.2015.12.112 F-15 DIAGNOSTIC PERFORMANCE OF POINT SHARE WAVE ELASTOGRAPHY (PSWE) IN COMPARISON WITH TRANSIENT ELASTOGRAPHY PERFORMED BY FIBROSCAN® (TE) AND NON-INVASIVE SCORES OF FIBROSIS IN PRIMARY BILIARY CIRRHOSIS (PBC) F. Saffioti 1,2 , D. Roccarina 1,3 , M. Rosselli 1 , M. Pinzani 1 , A. Marshall 1 , D. Thorburn 1 1
Sheila Sherlock Liver Centre, Royal Free London, NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College London, London, United Kingdom 2 Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy 3 Institute of Medical Pathology, Division of Internal Medicine and Gastroenterology, Università Cattolica del Sacro Cuore, Rome, Italy Introduction: The reliability of Fibroscan in the assessment of liver fibrosis is well established. The newer pSWE has been successfully applied in viral hepatitis and non-alcoholic liver disease. pSWE performance in PBC has been evaluated only once and a direct comparison with Fibroscan in PBC has never been investigated. Aim: To evaluate the performance of pSWE and its correlations with TE and the current scores of fibrosis in PBC. Methods: We prospectively collected demographics, biochemistry, clinical and ultrasonographic data from 50 PBC patients. Three (6%) male, mean age 57 ± 13 y, 38 (81%) AMA+ve, 3 (6%) autoimmune-overlap, 17 (30%) cirrhosis. TE (Fibroscan® , Echosens, IQR < 30%, SR > 60%), pSWE (ElastoPQ technique, Philips Affiniti70G, median kPa) and the most common clinical scores of fibrosis were obtained on visit date. Correlations of TE and pSWE with scores and clinical variables were investigated. Liver biopsy was not available for most patients. TE was used as surrogate of histological fibrosis, adopting the validated cutoffs in PBC (7.1, 8.8, 10.7 and 16.9 kPa for fibrosis stages F1, F2, F3, and F4, respectively). AUROCs were performed in order to define optimal cutoffs for pSWE. Results: TE and pSWE correlated significantly (p < 0.0001). LS obtained with both the techniques correlated with cirrhosis, portal hypertension, inflammation, cholestasis, APRI, FIB-4, Fibroindex, GUCI and King’s score (p < 0.0001), Lok index (p < 0.01) but not with AST/ALT and MELD score. AUROCs (95%CI) for pSWE were 0.91(0.80–1.0), 0.91(0.80–1.0), 0.97(0.92–1) for fibrosis stage ≥1, ≥2, ≥3, respectively. Optimal cutoff values were 6.5 (90% sensibility, 88% specificity), 8.8 (93% sensibility, 93% specificity), 13.5 (100% sensibility, 97%
e49
specificity) for mild, moderate and severe fibrosis/cirrhosis, respectively. Conclusions: In our cohort pSWE correlated with TE and noninvasive scores of liver fibrosis. These preliminary data suggest a role for pSWE in staging fibrosis in PBC, identifiying an optimal sensitivity and specificity in detecting significant fibrosis with a cutoff of 13.5 kPa. http://dx.doi.org/10.1016/j.dld.2015.12.113 F-16 DPPIV/CD26 AND SERPINB3 INTERACTION AFFECTS METABOLISM AND CLINICAL OUTCOME IN HEPATOCELLULAR CARCINOMA M. Ruvoletto 1 , S. Fasolato 1 , E. Trevellin 1 , M. Granzotto 1 , G. Zanus 2 , E. Babetto 3 , L. Terrin 1 , M. Battocchio 1 , F. Ciscato 4 , C. Turato 1 , U. Cillo 2 , P. Pontisso 1 , R. Vettor 1 1 Dept of Medicine, Internal Medicine and Hepatology, Regional Center for Hepatology (RCH), Italy 2 Unit of Hepatobiliary Surgery and Liver Transplantation, Italy 3 Department of Laboratory Medicine, University of Padua, Padua, Italy 4 Department of Biomedical Science, University of Padua, Padua, Italy
Background and aim: The regulatory protease dipeptidylpeptidase IV (DPPIV/CD26), that also possesses proapoptotic properties, has been found abnormally regulated in different tumors, including hepatocellular carcinoma (HCC) but the pathogenetic mechanisms remain still unclear. The rotease inhibitor SerpinB3 has anti-apoptotic activity and it has been recently associated with poor rognosis in HCC. The aim of this study was to investigate the relationship between these two molecules in HCC and in experimental models. Material and methods: mRNA and protein expression of DPPIV/CD26 and SerpinB3 was analyzed in liver specimens of 60 patients with HCC. Cultured HepG2 cells over-expressing SerpinB3 (HepG2/SB3) and control HepG2 cells were used to assess biological and metabolic modifications induced by this serpin on DPPIV/CD26 activity. Results: DPPIV/CD26 and SerpinB3 expression was higher in tumor tissue than in the adjacent liver specimens. High expression of DPPIV/CD26 in HCCs was significantly associated with better survival rate, independently of SerpinB3 expression. The up-regulation of DPPIV/CD26 in vitro was affected by the antiprotease activity of SerpinB3. HepG2/SB3 cells displayed decreased oxygen consumption, increased mitochondrial polarization, higher levels of lipid accumulation and lower glycogen storage, compared to controls. Treatment of HepG2 cells overexpressing SerpinB3 with a DPPIV/CD26 inhibitor induced further up-regulation of DPPIV/CD26 and a dose-dependent increase of cell viability and these findings were not observed in control cells. Conclusions: DPPIV/CD26 and SerpinB3 interplay in hepatoma cells is involved in the regulation of apoptosis/antiapoptosis signaling and in metabolic profile. Diabetes treatment with DPPIV/CD26 inhibitors should be carefully evaluated in patients with HCC. http://dx.doi.org/10.1016/j.dld.2015.12.114
had median diameter of 17 mm (range: 6–50; 78% < 30 mm diameter), in 84% was diagnosed by imaging, 93% BCLC 0 or A, 95% within Milan criteria, 3% with neoplastic portal thrombosis. As initial treatment, patients received RFA (38%), surgical resection (28%) and TACE (21%). During 27 months of follow-up, 12% died of HCC progression while 24% successfully underwent liver transplantation within 6 months (2-77) from HCC diagnosis. Conclusions: A majority of HCC developing in Caucasian patients with compensated HBV under long-term NUC are small single tumors, within Milan criteria, BCLC 0/A, with normal AFP levels and therefore amenable to curative therapies. http://dx.doi.org/10.1016/j.dld.2015.12.112 F-15 DIAGNOSTIC PERFORMANCE OF POINT SHARE WAVE ELASTOGRAPHY (PSWE) IN COMPARISON WITH TRANSIENT ELASTOGRAPHY PERFORMED BY FIBROSCAN® (TE) AND NON-INVASIVE SCORES OF FIBROSIS IN PRIMARY BILIARY CIRRHOSIS (PBC) F. Saffioti 1,2 , D. Roccarina 1,3 , M. Rosselli 1 , M. Pinzani 1 , A. Marshall 1 , D. Thorburn 1 1
Sheila Sherlock Liver Centre, Royal Free London, NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College London, London, United Kingdom 2 Department of Clinical and Experimental Medicine, Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy 3 Institute of Medical Pathology, Division of Internal Medicine and Gastroenterology, Università Cattolica del Sacro Cuore, Rome, Italy Introduction: The reliability of Fibroscan in the assessment of liver fibrosis is well established. The newer pSWE has been successfully applied in viral hepatitis and non-alcoholic liver disease. pSWE performance in PBC has been evaluated only once and a direct comparison with Fibroscan in PBC has never been investigated. Aim: To evaluate the performance of pSWE and its correlations with TE and the current scores of fibrosis in PBC. Methods: We prospectively collected demographics, biochemistry, clinical and ultrasonographic data from 50 PBC patients. Three (6%) male, mean age 57 ± 13 y, 38 (81%) AMA+ve, 3 (6%) autoimmune-overlap, 17 (30%) cirrhosis. TE (Fibroscan® , Echosens, IQR < 30%, SR > 60%), pSWE (ElastoPQ technique, Philips Affiniti70G, median kPa) and the most common clinical scores of fibrosis were obtained on visit date. Correlations of TE and pSWE with scores and clinical variables were investigated. Liver biopsy was not available for most patients. TE was used as surrogate of histological fibrosis, adopting the validated cutoffs in PBC (7.1, 8.8, 10.7 and 16.9 kPa for fibrosis stages F1, F2, F3, and F4, respectively). AUROCs were performed in order to define optimal cutoffs for pSWE. Results: TE and pSWE correlated significantly (p < 0.0001). LS obtained with both the techniques correlated with cirrhosis, portal hypertension, inflammation, cholestasis, APRI, FIB-4, Fibroindex, GUCI and King’s score (p < 0.0001), Lok index (p < 0.01) but not with AST/ALT and MELD score. AUROCs (95%CI) for pSWE were 0.91(0.80–1.0), 0.91(0.80–1.0), 0.97(0.92–1) for fibrosis stage ≥1, ≥2, ≥3, respectively. Optimal cutoff values were 6.5 (90% sensibility, 88% specificity), 8.8 (93% sensibility, 93% specificity), 13.5 (100% sensibility, 97%
e49
specificity) for mild, moderate and severe fibrosis/cirrhosis, respectively. Conclusions: In our cohort pSWE correlated with TE and noninvasive scores of liver fibrosis. These preliminary data suggest a role for pSWE in staging fibrosis in PBC, identifiying an optimal sensitivity and specificity in detecting significant fibrosis with a cutoff of 13.5 kPa. http://dx.doi.org/10.1016/j.dld.2015.12.113 F-16 DPPIV/CD26 AND SERPINB3 INTERACTION AFFECTS METABOLISM AND CLINICAL OUTCOME IN HEPATOCELLULAR CARCINOMA M. Ruvoletto 1 , S. Fasolato 1 , E. Trevellin 1 , M. Granzotto 1 , G. Zanus 2 , E. Babetto 3 , L. Terrin 1 , M. Battocchio 1 , F. Ciscato 4 , C. Turato 1 , U. Cillo 2 , P. Pontisso 1 , R. Vettor 1 1 Dept of Medicine, Internal Medicine and Hepatology, Regional Center for Hepatology (RCH), Italy 2 Unit of Hepatobiliary Surgery and Liver Transplantation, Italy 3 Department of Laboratory Medicine, University of Padua, Padua, Italy 4 Department of Biomedical Science, University of Padua, Padua, Italy
Background and aim: The regulatory protease dipeptidylpeptidase IV (DPPIV/CD26), that also possesses proapoptotic properties, has been found abnormally regulated in different tumors, including hepatocellular carcinoma (HCC) but the pathogenetic mechanisms remain still unclear. The rotease inhibitor SerpinB3 has anti-apoptotic activity and it has been recently associated with poor rognosis in HCC. The aim of this study was to investigate the relationship between these two molecules in HCC and in experimental models. Material and methods: mRNA and protein expression of DPPIV/CD26 and SerpinB3 was analyzed in liver specimens of 60 patients with HCC. Cultured HepG2 cells over-expressing SerpinB3 (HepG2/SB3) and control HepG2 cells were used to assess biological and metabolic modifications induced by this serpin on DPPIV/CD26 activity. Results: DPPIV/CD26 and SerpinB3 expression was higher in tumor tissue than in the adjacent liver specimens. High expression of DPPIV/CD26 in HCCs was significantly associated with better survival rate, independently of SerpinB3 expression. The up-regulation of DPPIV/CD26 in vitro was affected by the antiprotease activity of SerpinB3. HepG2/SB3 cells displayed decreased oxygen consumption, increased mitochondrial polarization, higher levels of lipid accumulation and lower glycogen storage, compared to controls. Treatment of HepG2 cells overexpressing SerpinB3 with a DPPIV/CD26 inhibitor induced further up-regulation of DPPIV/CD26 and a dose-dependent increase of cell viability and these findings were not observed in control cells. Conclusions: DPPIV/CD26 and SerpinB3 interplay in hepatoma cells is involved in the regulation of apoptosis/antiapoptosis signaling and in metabolic profile. Diabetes treatment with DPPIV/CD26 inhibitors should be carefully evaluated in patients with HCC. http://dx.doi.org/10.1016/j.dld.2015.12.114