Belgian Week of Gastroenterology 2019 http://www.bwge.be Belgian Association for the Study of the Liver (BASL) / Belgian Liver Intestine Committee (BLIC) A01 The sPDGFR-beta containing PRTA-score is a novel diagnostic algorithm for significant liver fibrosis in patients with viral, alcoholic, and metabolic liver disease J. LAMBRECHT (1), S. VERHULST (1), I. MANNAERTS (1), J. SOWA (2), J. BEST (2), A. CANBAY (2), H. REYNAERT (1), L. VAN GRUNSVEN (1) / [1] Vrije Universiteit Brussel (VUB), Jette, Belgium, Department of Basic Biomedical Sciences, Liver Cell Biology Laboratory, [2] University Hospital Magdeburg, , Germany, Department of Gastroenterology, Hepatology and Infectious Diseases Introduction: Diagnosis of liver fibrosis onset and regression remains a controversial subject in the current clinical setting, as the gold standard remains the invasive liver biopsy. Multiple novel non-invasive markers have been proposed but lack sufficient sensitivity and specificity for diagnosis of early stage liver fibrosis. Platelet Derived Growth Factor Receptor beta (PDGFRβ) has been associated to hepatic stellate cell activation and has been the target of multiple therapeutic studies. However, little is known concerning its use as a diagnostic agent. Aim: In this study, we analysed the diagnostic potential of PDGFRβ for liver fibrosis in a heterogenous patient population. Methods: The study cohort consisted of 148 patients with liver fibrosis/cirrhosis due to various causes of liver injury (metabolic, alcoholic, viral), and 14 healthy individuals as control population. A validation cohort of 57 patients with metabolic liver disease, who underwent liver biopsy to stage fibrosis, were gathered. Circulating soluble PDGFRβ (sPDGFRβ) levels were determined using a commercial ELISA kit. The diagnostic performance of sPDGFRβ as individual parameter, or in combination with other biochemical and metabolic factors was evaluated, and values were compared to those obtained by the clinical diagnostic algorithms Fib-4, APRI, and AST/ALT ratio. Results: In the total patient population, sPDGFRβ levels were progressively augmented with increasing fibrosis stage. Circulating sPDGFRβ levels were elevated (p < 0.0001) in patients with significant fibrosis (F ≥ 2), compared to no or mild fibrosis (F0/1), with a discriminative capacity, as quantified by AUC, of 0.7303, which was shown to be higher for this cohort than the AUCs of Fib-4, APRI, and AST/ALT ratio. The accuracy of sPDGFRβ could be increased by combining it with albumin levels and platelet counts into a novel diagnostic algorithm, which we termed the PRTA-score. Using a cut-off value of 7.804; a sensitivity of 77.11% and a specificity of 73.17% could be obtained for the diagnosis of significant fibrosis (F ≥ 2). AUC values for the prediction of advanced liver fibrosis (F ≥ 3) and cirrhosis (F = 4) were respectively 0.7470 and 0.7995; values which are slightly better, or comparable to Fib-4, APRI, and AST/ALT ratio. The diagnostic value of sPDGFRβ levels and the PRTA score were confirmed in an independent patient cohort, suffering from metabolic liver disease, which were staged for fibrosis by liver biopsy. Conclusions: We put forth the PRTA score as an easy applicable, low cost and accurate scoring for significant liver fibrosis. With validation in larger patient cohorts, this serological test could become an important tool in future non-invasive clinical assessment of liver fibrosis. A02 A longitudinal study of skeletal muscle alterations in NAFLD M. NACHIT (1), M. DE RUDDER (1), Y. HORSMANS (2), G. VANDE VELDE (3), I. LECLERCQ (1) / [1] Institut de Recherche Expérimentale et Clinique (IREC), Catholic University of Louvain (UCL), , Belgium, Pôle d'Hépato-gastro-entérologie (GAEN), [2] Saint-Luc University Hospital, Brussel, Belgium, Service D’Hépato-Gastro Entérologie, [3] KU Leuven, , Belgium, Department of Imaging and Pathology Introduction: Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disease ranging from benign steatosis to non-alcoholic steatohepatitis (NASH). Unlike simple steatosis, hepatocellular injury and inflammation in NASH likely promote fibrosis and evolution to end-stage liver disease. Skeletal muscle, the largest body compartment, has mechanical, metabolic and endocrine functions. Cross-sectional studies clearly linked low muscularity (sarcopenia) to risk of having NAFLD and to severity of NASH- associated fibrosis. Yet it is still not clear whether low muscle mass is a cause, an aggravating factor, a consequence of the ongoing disease or an epiphenomenon reflecting general alteration in NAFLD. Aim: To longitudinally evaluate changes in muscle compartment according to liver pathology in NAFLD mouse models. Methods: For over 26 weeks, we followed WT mice fed a standard chow as controls (Ctl), WT mice fed a high fat (HF) diet (60% fat) as a model of simple steatosis (WT HF) and foz/foz mice fed a HF diet as a model of progressive NASH (FOZ HF). We performed monthly micro-computed tomography to monitor changes in body composition, skeletal muscle and liver fatty infiltration (expressed as muscle or liver density to spleen density ratio). We used grip strength test to follow muscle functionality and analyzed liver histology at monthly intervals. Results: Ctl had normal liver histology, WT HF developed obesity and isolated mild steatosis, FOZ HF exhibited obesity and fatty changes at 4 and 8 weeks and histologically proven NASH (NAS>5) from 12 weeks up to NAS=8 from week 20 on. Muscle strength was similar in all groups up to week 8, but significantly decreased starting from week 12 in mice with NASH (Ctl : 244±4g; WT HF : 251.9±6g vs FOZ HF : 228.6±4g) and further worsened with time (188.67±8g at 26W in FOZ HF) while it remained stable in other groups. Muscle density was significantly lower in FOZ HF as early as 4 week (0.79±0.02) than in Ctl (0.91±0.02); reached a minimum at 12W (0.37±0.05 in FOZ HF vs 0.85±0.02 and 0.75±0.02 in Ctl and WT HF), then plateaued. Over the study period, liver density remained stable in Ctl [0.74-0.92], gently decreased in WT HF from 0.92 to 0.40±0.11 at 26W and followed a V-shaped curve in FOZ HF (0.89±0.02 at 0W; -0.07±0.05 at 26W), with minimal density at 12 week (-1.37±0.14). Liver density correlated with biochemical quantification of liver lipid content (r²=0.92, p<0.0001). Conclusions: Our results show remarkable skeletal muscle alterations concurrently to NASH onset and independently of body weight change, inviting to explore the pathophysiological role of muscle-liver axis in NASH pathogenesis and progression. A03 Non-alcoholic steatohepatitis significantly decreases microsomal liver function in the absence of fibrosis allowing the use of the 13C-aminopyrine breath test for its non-invasive detection E. VAN MIEGHEM (1), L. DEPAUW (1), W. VERLINDEN (2), J. WEYLER (3), P. MICHIELSEN (3), L. VONGHIA (3), T. VANWOLLEGHEM (3), E. DIRINCK (4), L. VAN GAAL (4), S. FRANCQUE (3) / [1] University of Antwerp, Antwerp, Belgium, Laboratory of experimental medicine and pediatrics, [2] AZ Nikolaas, Sint-Niklaas, Belgium, Gastroenterology and hepatology, [3] Antwerp University Hospital, Edegem, Belgium, Gastroenterology and Hepatology, [4] Antwerp University Hospital, Edegem, Belgium, Endocrinology, Diabetology and Metabolism Introduction: Non-alcoholic fatty liver disease (NAFLD) has become the most frequent cause of chronic liver disease in Western countries, with an increasing prevalence. The presence of non-alcoholic steatohepatitis (NASH) can lead to a more aggressive clinical course with fibrosis progression and hepatocellular carcinoma, which necessitates early NASH detection. Currently, the diagnosis of NASH is based on histology, though with the high prevalence of NAFLD, a non-invasive method is needed. The 13C-aminopyrine breath test (ABT) evaluates the function of the cytochrome P450 enzymes of the liver (microsomal liver function) and could be a potential candidate. Aim: We aimed to firstly, evaluate a potential change in liver microsomal function in NASH patients; and secondly, to evaluate the diagnostic power of ABT to detect both NASH and fibrotic NASH (NASH-F2-4). Methods: A retrospective analysis was performed on consecutive patients suspected of NAFLD who underwent a liver biopsy and ABT between 2002 and 2018 at the Antwerp University Hospital. Subgroups were created for patients without NASH (noNASH), patients with NASH but without significant fibrosis (NASH-noF) and patients with NASH and significant fibrosis (NASH-F). Results: 421 patients were included (37.8 % noNASH and 62.2% NASH with 41.8% NASH- noF and 20.4% NASH-F). A significant difference in ABT was found between noNASH and NASH-noF (p=0.011) and between NASH-noF and NASH-F (p<0.001) with a cumulative excretion of 14.5 ± 6.65, 12.8 ± 5.35 and 9.8 ± 5.16 %dose, respectively. The cumulative excretion (cABT) proved a better predictor of NASH and fibrosis than peak excretion. The predictive power of cABT as a single test was low for NASH and NASH-F with AUROCs of 0.620 and 0.650, respectively. A predictive model was created adding ALT, C-peptide and age to cABT, which increased the AUROC to 0.775 to detect NASH. A model adding AST to cABT increased the AUROC to 0.796 to detect NASH-F. Cut-off values were determined for optimal accuracy, 90% sensitivity and 90% specificity to predict both NASH (PPV 0.732 and NPV 0.668; PPV 0.603 and NPV 0.806; PPV 0.831 and NPV 0.628, respectively) and NASH-F (PPV 0.753 and NPV 0.693; PPV 0.601 and NPV 0.810; PPV 0.838 and NPV 0.649, respectively). Conclusions: The microsomal liver function of patients with NASH is significantly decreased even in the absence of fibrosis highlighting the sole impact of steatohepatitis on patients' health.