- Email: [email protected]
P1007 SOLUBLE CD163, A MACROPHAGE ACTIVATION MARKER, IS INDEPENDENTLY ASSOCIATED WITH FIBROSIS IN PATIENTS WITH CHRONIC VIRAL HEPATITIS B AND C
POSTERS be determined as cirrhosis or non-cirrhosis and obviating liver biopsies, which was significantly superior to TE alone (81.8%). Conclusions: By integrating TE, ultrasonic images of liver, serum albumin, platelet count and INR, liver biopsies may be completely substituted by TEBaCS for detecting compensated HBRC. P1006 ARTIFICIAL NEURAL NETWORK: AN ACCURATE AND CHEAP METHOD FOR NONINVASIVE ASSESSMENT OF CHRONIC HEPATITIS B RELATED LIVER FIBROSIS N.N. Salkic, P. Jovanovic, E. Alibegovic, M. Brcic, N. Krizic, S. Iljazovic-Topcic. Department of Gastroenterology and Hepatology, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina E-mail: [email protected] Background and Aims: We aimed to asses the diagnostic accuracy of artificial neural network (ANN) model based on routinely used biochemical and ultrasound parameters in the assessment of chronic hepatitis B (CHB) related liver fibrosis and to and compare it against other noninvasive scores. Methods: We included 270 patients. Age, platelets count, AST, ALT, GGT, LDH, albumin, cholesterol level, INR, portal vein and longitudinal spleen diameters were used to devise an ANN model and compare it against liver histology. Results: There were 154 (57.0%) of patients having significant fibrosis (>F2) and 34 (12.6%) having cirrhosis (F4). The AUC for significant fibrosis and cirrhosis for ANN model were 0.89 (95% CI 0.85–0.93) and 0.94 (%95 CI 0.91–0.98), respectively. ANN probability scores (range 0–1.0) <0.20 and >0.90 had negative and positive predictive values of 97% and 92%. Restricting the liver biopsy in patients with intermediate scores may prevent liver biopsy in 39% of patients with >95% accuracy. The areas under the ROC curve for significant fibrosis for AAR, APRI, GUCI, FORNS, HALT-C, HUI and FIB-4 scores were 0.67, 0.87, 0.84, 0.80, 0.80, 0.78 and 0.84 respectively. Correspondingly, AUCs for cirrhosis or AAR, APRI, GUCI, FORNS, HALT-C, HUI and FIB-4 scores were 0.75, 0.84, 0.86, 0.80, 0.85, 0.79 and 0.87. Conclusions: ANN model based on routinely available biochemical and ultrasound parameters is an accurate and cheap option for prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B with favorable diagnostic accuracy in comparison with other free noninvasive scores. P1007 SOLUBLE CD163, A MACROPHAGE ACTIVATION MARKER, IS INDEPENDENTLY ASSOCIATED WITH FIBROSIS IN PATIENTS WITH CHRONIC VIRAL HEPATITIS B AND C K. Kazankov1 , F. Barrera2 , H.J. Møller3 , B.M. Bibby4 , H. Vilstrup1 , J. George2 , H. Grønbæk1 . 1 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 2 The Storr Liver Unit, Westmead Millenium Institute, University of Sydney and Westmead Hospital, Westmead, NSW, Australia; 3 Department of Clinical Biochemistry, Aarhus University Hospital, 4 Department of Biostatistics, Aarhus University, Aarhus, Denmark E-mail: [email protected] Background and Aims: Macrophages are involved in inflammation and liver fibrosis. Soluble (s)CD163 is a specific marker of activated macrophages. Methods: We investigated associations between sCD163 and biochemical and histological parameters of inflammatory activity and fibrosis in 556 patients with chronic hepatitis C virus (HCV) and 208 patients with chronic hepatitis B virus (HBV) before anti-viral treatment. Scheuer histological scores of activity and fibrosis were obtained. Clinical, biochemical, and metabolic parameters were recorded. We measured sCD163 by enzyme-linked immunosorbent assay (ELISA). Results: Soluble CD163 was higher in patients with HCV compared to HBV [3.7 (interquartile range (IQR) 2.5–5.5) vs. 2.4 (IQR S410
1.8–3.6) mg/L, p < 0.001). sCD163 was associated with fibrosis stages, with highest levels in patients with advanced fibrosis (F ≥ 3) [5.7 (IQR 3.9–6.9) mg/L] and cirrhosis (F = 4) [6.2 (IQR 5.0–6.9) mg/L]. sCD163 was a marker of fibrosis independent of other biochemical parameters and known risk factors. A sCD163-based Fibrosis Score, CD163-FS, had an area under the Receiver Operating Characteristics curve (AUROC) of 0.87 (95% CI: 0.82–0.92) for cirrhosis, 0.84 (95% CI: 0.80–0.88) for advanced fibrosis, and 0.78 (95% CI: 0.74–0.81) for significant fibrosis. Compared to existing fibrosis scores, CD163-FS was superior to the AST to platelet ratio index (APRI) for all fibrosis stages and to FIB-4 for significant fibrosis. Conclusions: sCD163 levels are increased in patients with chronic viral hepatitis, reflecting macrophage activation. Increased sCD163 is associated with the severity of disease and predicts fibrosis. A sCD163-based fibrosis score, CD163-FS, is superior to APRI and FIB-4 for the diagnosis of significant fibrosis. P1008 A 5.9 kDa SERUM FRAGMENT OF FIBRINOGEN a-CHAIN IS A SPECIFIC SURROGATE MARKER OF ACTIVE FIBROGENESIS IN PATIENTS WITH LIVER DISEASE S. Marfa1 , G. Crespo2 , V. Reichenbach1 , X. Forns2 , G. Casals1 , 1,3 1 M. Morales-Ruiz1 , M. Navasa2 , W. Jimenez ´ . Biochemistry and Molecular Genetics Service, 2 Liver Unit, Hospital Cl´ınic, IDIBAPS, CIBEREHD, 3 Departament de Ciencies Fisiologiques I, University of Barcelona, Barcelona, Spain E-mail: [email protected] Background and Aims: Early detection of fibrosis progression is of major relevance for the diagnosis and management of patients with liver disease. This study was designed to find noninvasive biomarkers of fibrosis in a clinical context in which this process occurs rapidly, HCV-positive patients undergoing liver transplantation (LT). Methods: We analyzed 93 LT patients with HCV recurrence, 17 non-LT patients with liver disease and 9 LT patients without HCV recurrence who received antiviral treatment before LT, as the control group. Blood obtained from 5 healthy subjects was also analyzed. Serum samples were fractionated by ion exchange chromatography and their proteomic profile was assessed by SELDITOF-MS. Results: Marked differences were observed between the serum proteome profile of LT patients with early fibrosis recurrence and non-recurrent LT patients. A robust peak intensity located at 5905 m/z was the distinguishing feature of non-recurrent LT patients. However, the same peak was barely detected in recurrent LT patients. Similar results were found when comparing samples of healthy subjects with those of non-LT fibrotic patients, indicating that our findings were not related to either LT or HCV infection. Using tandem mass-spectrometry, we identified the protein peak as a C-terminal fragment of the fibrinogen a chain. Cell culture experiments demonstrated that TGF-b reduces a-fibrinogen mRNA expression and 5905 m/z peak intensity in HepG2 cells, suggesting that TGF-b activity regulates the circulating levels of this protein fragment. Conclusions: In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as an early serum biomarker of fibrogenesis in patients with liver disease.
Journal of Hepatology 2014 vol. 60 | S361–S522
1.8–3.6) mg/L, p < 0.001). sCD163 was associated with fibrosis stages, with highest levels in patients with advanced fibrosis (F ≥ 3) [5.7 (IQR 3.9–6.9) mg/L] and cirrhosis (F = 4) [6.2 (IQR 5.0–6.9) mg/L]. sCD163 was a marker of fibrosis independent of other biochemical parameters and known risk factors. A sCD163-based Fibrosis Score, CD163-FS, had an area under the Receiver Operating Characteristics curve (AUROC) of 0.87 (95% CI: 0.82–0.92) for cirrhosis, 0.84 (95% CI: 0.80–0.88) for advanced fibrosis, and 0.78 (95% CI: 0.74–0.81) for significant fibrosis. Compared to existing fibrosis scores, CD163-FS was superior to the AST to platelet ratio index (APRI) for all fibrosis stages and to FIB-4 for significant fibrosis. Conclusions: sCD163 levels are increased in patients with chronic viral hepatitis, reflecting macrophage activation. Increased sCD163 is associated with the severity of disease and predicts fibrosis. A sCD163-based fibrosis score, CD163-FS, is superior to APRI and FIB-4 for the diagnosis of significant fibrosis. P1008 A 5.9 kDa SERUM FRAGMENT OF FIBRINOGEN a-CHAIN IS A SPECIFIC SURROGATE MARKER OF ACTIVE FIBROGENESIS IN PATIENTS WITH LIVER DISEASE S. Marfa1 , G. Crespo2 , V. Reichenbach1 , X. Forns2 , G. Casals1 , 1,3 1 M. Morales-Ruiz1 , M. Navasa2 , W. Jimenez ´ . Biochemistry and Molecular Genetics Service, 2 Liver Unit, Hospital Cl´ınic, IDIBAPS, CIBEREHD, 3 Departament de Ciencies Fisiologiques I, University of Barcelona, Barcelona, Spain E-mail: [email protected] Background and Aims: Early detection of fibrosis progression is of major relevance for the diagnosis and management of patients with liver disease. This study was designed to find noninvasive biomarkers of fibrosis in a clinical context in which this process occurs rapidly, HCV-positive patients undergoing liver transplantation (LT). Methods: We analyzed 93 LT patients with HCV recurrence, 17 non-LT patients with liver disease and 9 LT patients without HCV recurrence who received antiviral treatment before LT, as the control group. Blood obtained from 5 healthy subjects was also analyzed. Serum samples were fractionated by ion exchange chromatography and their proteomic profile was assessed by SELDITOF-MS. Results: Marked differences were observed between the serum proteome profile of LT patients with early fibrosis recurrence and non-recurrent LT patients. A robust peak intensity located at 5905 m/z was the distinguishing feature of non-recurrent LT patients. However, the same peak was barely detected in recurrent LT patients. Similar results were found when comparing samples of healthy subjects with those of non-LT fibrotic patients, indicating that our findings were not related to either LT or HCV infection. Using tandem mass-spectrometry, we identified the protein peak as a C-terminal fragment of the fibrinogen a chain. Cell culture experiments demonstrated that TGF-b reduces a-fibrinogen mRNA expression and 5905 m/z peak intensity in HepG2 cells, suggesting that TGF-b activity regulates the circulating levels of this protein fragment. Conclusions: In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as an early serum biomarker of fibrogenesis in patients with liver disease.
Journal of Hepatology 2014 vol. 60 | S361–S522