- Email: [email protected]
21 NON INVASIVE DIAGNOSIS OF STEATOSIS USING CAP BY FIBROSCAN®. A PROSPECTIVE STUDY
ORAL PRESENTATIONS increase in GIR (+0.4 mg/min/kg, p = 0.049), while A did not change it. S addition significantly increased GIR in both L (+1.3 mg/min/kg, p < 0.01) and in A group (+0.5 mg/min/kg, p < 0.05). Hs-CRP was significantly reduced by L (−0.4, p < 0.05), but not by A (−0.2, ns). S addition ameliorated Hs-CRP reduction in L (−0.6, p < 0.041) and also in A group (−0.5, p < 0.05). The SD changes showed a significant relationship with both GIR (r = −0.35, p < 0.05), and Hs-CRP (r = 0.36, p < 0.05) changes; also the VAT changes were correlated to GIR (r = −0.37, p < 0.05), and to Hs-CRP (r= 0.31, p < 0.05) changes. Conclusions: L/S combination improved the hepatic SD and VAT diameter more than A/S combination. Although a possible explanation might be the greater improvement in insulin resistance, it is possible the contribution of some other mechanism of the L/S combination, which yet needs to be clarified. 21 NON INVASIVE DIAGNOSIS OF STEATOSIS USING CAP BY FIBROSCAN® . A PROSPECTIVE STUDY V. de Ledinghen1,2 , B. Le Bail3 , J. Vergniol4 , J. Foucher1 , W. Merrouche1 , C. Fournier5 , L. Sandrin5 , V. Miette5 , M. Sasso5 . 1 CHU Bordeaux, Pessac, 2 INSERM U889, Universit´e Bordeaux 2, 3 CHU Bordeaux, Bordeaux, 4 CHU Besancon, ¸ Pessac, 5 Echosens, Paris, France E-mail: [email protected] Introduction: Recently, a retrospective study showed that CAP (Controlled Attenuation Parameter), based on Fibroscan® principle, could efficiently separate several steatosis grades [1]. The aim of this study was to prospectively evaluate the performance of CAP for the diagnosis of steatosis in patients with chronic liver disease and to compare it with another non-invasive method (steatotest). Patients and Methods: From June 2009 to June 2010, consecutive patients with chronic liver disease had steatosis diagnosis using CAP, blood sample for steatotest and liver biopsy the same day. All liver biopsies were analysed by one expert anatomopathologist. Fibrosis was assessed using Metavir or Brunt score depending on the aetiology. Steatosis was quantified as follows: S0 ≤ 10%, S1: 11–33%, S2: 34–66%, S3: ≥67%. Correlation was assessed using Spearman coefficient. Performance of CAP was appraised using ROC curves. Results: Characteristic of the 112 patients included were: 49% male, age 55 years, BMI 25 kg/m2 , HCV 36%, HBV 5%, NAFLD/ALD 15%. Steatosis repartition was: S0 53%, S1 18%, S2 14%, S3 15%. Fibrosis staging was F0F1 54%, F2 18%, F3 21%, F4 7%. CAP was significantly correlated to steatosis grade (r = 0.49 p < 0.0001), fibrosis (r = 0.16, p = 0.02) but not to liver stiffness. In bivariate analysis including steatosis grade and fibrosis, stage CAP was only related to steatosis (OR = 4.26 05%CI 3.14–5.78). AUROCS for the diagnosis of steatosis are indicated in the table. Table: AUROCs for the diagnosis of steatosis.
CAP SteatoTest
S>0
S>1
S>2
0.82 (0.74–0.90) 0.68 (0.58–0.78)
0.86 (0.78–0.95) 0.72 (0.61–0.83)
0.92 (0.83–1.0) 0.76 (0.62–0.90)
With Youden index, performances of CAP were: S > 0 cutoff 233 dB/m, sensitivity 0.85, specificity 0.68, positive predictive value 0.70, negative predictive value 0.83; S > 1 cutoff 266 dB/m, sensitivity 0.85, specificity 0.76, positive predictive value 0.60, negative predictive value 0.92; S > 2 cutoff 318 dB/m, sensitivity 0.82, specificity 0.89, positive predictive value 0.58, negative predictive value 0.97. Conclusion: CAP is very efficient to detect even minimal steatosis (10%). CAP being implemented on Fibroscan® , both steatosis and fibrosis can be evaluated simultaneously, enlarging the spectrum of non invasive techniques for chronic liver disease management. Reference(s) [1] Sasso et al. UMB2010;36:1825–35. S10
Parallel Session: CHOLESTATIC AND AUTOIMMUNE
22 ELECTROSTATIC MODIFICATIONS OF THE HLA-DR P9 PEPTIDE-BINDING POCKET AND SUSCEPTIBILITY TO PRIMARY SCLEROSING CHOLANGITIS J.R. Hov1,2,3 , V. Kosmoliaptsis4,5 , J.A. Traherne6 , M. Olsson7 , K.M. Boberg8 , A. Bergquist9 , E. Schrumpf3,8 , J.A. Bradley5 , C.J. Taylor4 , B.A. Lie10 , J. Trowsdale6 , T.H. Karlsen8 . 1 Norwegian PSC Research Center, Clinic for Specialized Medicine and Surgery, Oslo University Hospital Rikshospitalet, 2 Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, 3 Faculty of Medicine, University of Oslo, Oslo, Norway; 4 Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, 5 Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, 6 Division of Immunology, Department of Pathology, University of Cambridge and Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; 7 Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden; 8 Norwegian PSC research center, Clinic for Specialized Medicine and Surgery, Oslo University Hospital Rikshospitalet, Oslo, Norway; 9 Department of Gastroenterology and Hepatology, Karolinska University Hospital Huddinge, Stockholm, Sweden; 10 Institute of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway E-mail: [email protected] Background and Aims: Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts with unknown aetiology. Genome-wide association studies have shown that the HLA complex at chromosome 6p21 harbors the most important genetic risk factors. Genetic associations in autoimmune diseases implicating HLA class II are likely related to polymorphisms affecting antigen presentation to T lymphocytes, which subsequently shape disease-causing immune responses. The aim of this study was to analyse the role of the structure and electrostatic properties of the HLA-DR molecule in relation to PSC associated amino acid variation in HLA-DRb1. Methods: A total of 356 Scandinavian PSC patients (71% male, 81% with concomitant inflammatory bowel disease) and 366 healthy controls (70% male) were included. HLA-DRB1 genotyping to fourdigit resolution was performed with sequencing-based methods. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. Logistic regressions assuming both allele- and genotype-based models were performed to identify key residues. Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecular structure and electrostatic properties. Results: In logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P=1.2×10−32 and P=1.8×10−22 in single-residue models, respectively). Modeling showed that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the HLA-DR molecule. Asparagine at residue 37 (Asn37) conferred risk and largely induced a positive charge in pocket P9 (Figure 1), while tyrosine (Tyr37) was protective and induced a negative charge. Consistent with the statistical observations, variation at residue 86 did also influence the electrostatic properties of this pocket by determining the difference between DRB1*13:01 (PSC associated, positive P9 charge) and DRB1*13:02 (protective, negative P9 charge). Conclusions: The results suggest that in patients with PSC, the associated residues 37 and 86 of the HLA-DR b chain critically
Journal of Hepatology 2011 vol. 54 | S1–S24
CAP SteatoTest
S>0
S>1
S>2
0.82 (0.74–0.90) 0.68 (0.58–0.78)
0.86 (0.78–0.95) 0.72 (0.61–0.83)
0.92 (0.83–1.0) 0.76 (0.62–0.90)
With Youden index, performances of CAP were: S > 0 cutoff 233 dB/m, sensitivity 0.85, specificity 0.68, positive predictive value 0.70, negative predictive value 0.83; S > 1 cutoff 266 dB/m, sensitivity 0.85, specificity 0.76, positive predictive value 0.60, negative predictive value 0.92; S > 2 cutoff 318 dB/m, sensitivity 0.82, specificity 0.89, positive predictive value 0.58, negative predictive value 0.97. Conclusion: CAP is very efficient to detect even minimal steatosis (10%). CAP being implemented on Fibroscan® , both steatosis and fibrosis can be evaluated simultaneously, enlarging the spectrum of non invasive techniques for chronic liver disease management. Reference(s) [1] Sasso et al. UMB2010;36:1825–35. S10
Parallel Session: CHOLESTATIC AND AUTOIMMUNE
22 ELECTROSTATIC MODIFICATIONS OF THE HLA-DR P9 PEPTIDE-BINDING POCKET AND SUSCEPTIBILITY TO PRIMARY SCLEROSING CHOLANGITIS J.R. Hov1,2,3 , V. Kosmoliaptsis4,5 , J.A. Traherne6 , M. Olsson7 , K.M. Boberg8 , A. Bergquist9 , E. Schrumpf3,8 , J.A. Bradley5 , C.J. Taylor4 , B.A. Lie10 , J. Trowsdale6 , T.H. Karlsen8 . 1 Norwegian PSC Research Center, Clinic for Specialized Medicine and Surgery, Oslo University Hospital Rikshospitalet, 2 Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, 3 Faculty of Medicine, University of Oslo, Oslo, Norway; 4 Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, 5 Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, 6 Division of Immunology, Department of Pathology, University of Cambridge and Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; 7 Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden; 8 Norwegian PSC research center, Clinic for Specialized Medicine and Surgery, Oslo University Hospital Rikshospitalet, Oslo, Norway; 9 Department of Gastroenterology and Hepatology, Karolinska University Hospital Huddinge, Stockholm, Sweden; 10 Institute of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway E-mail: [email protected] Background and Aims: Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts with unknown aetiology. Genome-wide association studies have shown that the HLA complex at chromosome 6p21 harbors the most important genetic risk factors. Genetic associations in autoimmune diseases implicating HLA class II are likely related to polymorphisms affecting antigen presentation to T lymphocytes, which subsequently shape disease-causing immune responses. The aim of this study was to analyse the role of the structure and electrostatic properties of the HLA-DR molecule in relation to PSC associated amino acid variation in HLA-DRb1. Methods: A total of 356 Scandinavian PSC patients (71% male, 81% with concomitant inflammatory bowel disease) and 366 healthy controls (70% male) were included. HLA-DRB1 genotyping to fourdigit resolution was performed with sequencing-based methods. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. Logistic regressions assuming both allele- and genotype-based models were performed to identify key residues. Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecular structure and electrostatic properties. Results: In logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P=1.2×10−32 and P=1.8×10−22 in single-residue models, respectively). Modeling showed that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the HLA-DR molecule. Asparagine at residue 37 (Asn37) conferred risk and largely induced a positive charge in pocket P9 (Figure 1), while tyrosine (Tyr37) was protective and induced a negative charge. Consistent with the statistical observations, variation at residue 86 did also influence the electrostatic properties of this pocket by determining the difference between DRB1*13:01 (PSC associated, positive P9 charge) and DRB1*13:02 (protective, negative P9 charge). Conclusions: The results suggest that in patients with PSC, the associated residues 37 and 86 of the HLA-DR b chain critically
Journal of Hepatology 2011 vol. 54 | S1–S24