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Logistic regression models based on the ratio models of plasma amino acids for diagnosis of hepatitis B associated hepatic fibrosis
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
Corresponding author. Palash Mandal. E-mail: [email protected]
LOGISTIC REGRESSION MODELS BASED ON THE RATIO MODELS OF PLASMA AMINO ACIDS FOR DIAGNOSIS OF HEPATITIS B ASSOCIATED HEPATIC FIBROSIS Zhan-qing Zhang, L. U. Wei, Yan-bing Wang, Xiao-fang Jia Shanghai Public Health Clinical Center of Fudan University, China
Background and Aims:To explore the efficacy of Logistic regression models based on age and the ratio models of plasma amino acids for diagnosis of hepatitis B associated hepatic fibrosis. Methods: One hundred and forty eight patients with chronic hepatitis B with pathological diagnoses of liver tissue were enrolled in present study. The pathological staging $S2, $S3, =S4 was defined as significant, severe, advanced fibrosis, respectively. Plasma molar concentrations of amino acids were determined by Agilent 1100 series high performance liquid chromatography. The ratio models of plasma amino acids were established by fraction function. The number of the ratio models based on all possible combinations of the partial variables was great, so the top six ratio models were selected and analyzed according to the correlation coefficients from big to small order, in which the ratio models were correlated significantly with the pathological staging. ROC curve methods were used for appraisement of the Logistic regression models based on age and the ratio models of plasma amino acids for diagnosis of different levels of hepatic fibrosis. Results: The Logistic regression model for diagnosis of significant fibrosis based on age and the ratio models of plasma amino acids could not be established. The area under ROC curve (AUROC) of predictive probabilities of the Logistic regression model for severe fibrosis (PPsev) for diagnosis of severe fibrosis was 0.722, and the 95% CI of the AUROC was 0.640-0.804; based on the optimal cutoff, the sensitivity, specificity, accuracy of the PPsev for diagnosis of severe fibrosis were 0.49, 0.85, 0.69. The AUROC of predictive probabilities of the Logistic regression models for advanced fibrosis (PPadv) for diagnosis of advanced fibrosis was 0.792, and the 95% CI of the AUROC was 0.7080.876; based on the optimal cutoff, the sensitivity, specific-
ity, accuracy of the PPadv for diagnosis of advanced fibrosis were 0.73, 0.76, 0.75. Conclusion: There could be diagnostic significance of the Logistic regression models based on age and the ratio models of plasma amino acids for severe and advanced fibrosis. Corresponding author. Zhan-qing Zhang. E-mail: [email protected]
CYLD-MEDIATED UPREGULATION OF HEPATOCYTE GROWTH FACTOR PREVENTS HEPATIC INJURY AND FIBROSIS Rajeswara Rao Pannem,1 Christoph Dorn,2 Claus Hellerbrand,2 Ramin Massoumi1 1 Department of Laboratory Medicine, Center for Molecular Pathology, Lund University, Malmo, Sweden, 2Department of Internal Medicine I, University Hospital Regensburg 93053 Regensburg, Germany
Hepatic fibrosis can be considered as physiologic woundhealing response to liver injury. This process also engages factors, including hepatocyte growth factor (HGF), that restrain hepatic injury and facilitate the reversibility of the fibrotic reaction in response to an acute insult. Chronic liver injury and sustained inflammation cause progressive fibrosis and ultimately organ dysfunction. The mechanisms that tip the balance from restoration to progressive liver tissue scaring are not well understood. In the present study we identify the mechanism that the tumor suppressor gene cylindromatosis (CYLD) protects from hepatocellular injury and fibrosis. Mice lacking CYLD were highly susceptible to acute and chronic liver injury compared to wild type animals through CYLD-mediated upregulation of HGF. Conversely, CYLD-deficient mice pre-treated with HGF eluded cell death, inflammation and fibrosis. The regulation of HGF levels occurred through interaction of CYLD with histone deacetylase 7 (HDAC7), which was independent of CYLD's deubiquitinating activity. Thus, by regulating the HGF level, CYLD is able to ameliorate hepatocellular damage and liver fibrogenesis. Pharmacological targeting of CYLD may be a therapeutic option in chronic liver disease. Corresponding author. Ramin Massoumi. E-mail: [email protected]
Journal of Clinical and Experimental Hepatology | March 2013 | Vol. 3 | No. 1S | S75–S77
S77
Liver Fibrosis
work, Western blot (VCAM-1, ICAM-1 and CD31), TUNEL and other enzymatic assays. Conclusion: Exploring the unknown novel relation between pro-angiogenic and pro-fibrotic effects mediated via adenosine signalling will provide pre-clinical data as to the efficacy of adenosine receptor blockade as a potential therapeutic approach for the treatment of fibrosis.
Corresponding author. Palash Mandal. E-mail: [email protected]
LOGISTIC REGRESSION MODELS BASED ON THE RATIO MODELS OF PLASMA AMINO ACIDS FOR DIAGNOSIS OF HEPATITIS B ASSOCIATED HEPATIC FIBROSIS Zhan-qing Zhang, L. U. Wei, Yan-bing Wang, Xiao-fang Jia Shanghai Public Health Clinical Center of Fudan University, China
Background and Aims:To explore the efficacy of Logistic regression models based on age and the ratio models of plasma amino acids for diagnosis of hepatitis B associated hepatic fibrosis. Methods: One hundred and forty eight patients with chronic hepatitis B with pathological diagnoses of liver tissue were enrolled in present study. The pathological staging $S2, $S3, =S4 was defined as significant, severe, advanced fibrosis, respectively. Plasma molar concentrations of amino acids were determined by Agilent 1100 series high performance liquid chromatography. The ratio models of plasma amino acids were established by fraction function. The number of the ratio models based on all possible combinations of the partial variables was great, so the top six ratio models were selected and analyzed according to the correlation coefficients from big to small order, in which the ratio models were correlated significantly with the pathological staging. ROC curve methods were used for appraisement of the Logistic regression models based on age and the ratio models of plasma amino acids for diagnosis of different levels of hepatic fibrosis. Results: The Logistic regression model for diagnosis of significant fibrosis based on age and the ratio models of plasma amino acids could not be established. The area under ROC curve (AUROC) of predictive probabilities of the Logistic regression model for severe fibrosis (PPsev) for diagnosis of severe fibrosis was 0.722, and the 95% CI of the AUROC was 0.640-0.804; based on the optimal cutoff, the sensitivity, specificity, accuracy of the PPsev for diagnosis of severe fibrosis were 0.49, 0.85, 0.69. The AUROC of predictive probabilities of the Logistic regression models for advanced fibrosis (PPadv) for diagnosis of advanced fibrosis was 0.792, and the 95% CI of the AUROC was 0.7080.876; based on the optimal cutoff, the sensitivity, specific-
ity, accuracy of the PPadv for diagnosis of advanced fibrosis were 0.73, 0.76, 0.75. Conclusion: There could be diagnostic significance of the Logistic regression models based on age and the ratio models of plasma amino acids for severe and advanced fibrosis. Corresponding author. Zhan-qing Zhang. E-mail: [email protected]
CYLD-MEDIATED UPREGULATION OF HEPATOCYTE GROWTH FACTOR PREVENTS HEPATIC INJURY AND FIBROSIS Rajeswara Rao Pannem,1 Christoph Dorn,2 Claus Hellerbrand,2 Ramin Massoumi1 1 Department of Laboratory Medicine, Center for Molecular Pathology, Lund University, Malmo, Sweden, 2Department of Internal Medicine I, University Hospital Regensburg 93053 Regensburg, Germany
Hepatic fibrosis can be considered as physiologic woundhealing response to liver injury. This process also engages factors, including hepatocyte growth factor (HGF), that restrain hepatic injury and facilitate the reversibility of the fibrotic reaction in response to an acute insult. Chronic liver injury and sustained inflammation cause progressive fibrosis and ultimately organ dysfunction. The mechanisms that tip the balance from restoration to progressive liver tissue scaring are not well understood. In the present study we identify the mechanism that the tumor suppressor gene cylindromatosis (CYLD) protects from hepatocellular injury and fibrosis. Mice lacking CYLD were highly susceptible to acute and chronic liver injury compared to wild type animals through CYLD-mediated upregulation of HGF. Conversely, CYLD-deficient mice pre-treated with HGF eluded cell death, inflammation and fibrosis. The regulation of HGF levels occurred through interaction of CYLD with histone deacetylase 7 (HDAC7), which was independent of CYLD's deubiquitinating activity. Thus, by regulating the HGF level, CYLD is able to ameliorate hepatocellular damage and liver fibrogenesis. Pharmacological targeting of CYLD may be a therapeutic option in chronic liver disease. Corresponding author. Ramin Massoumi. E-mail: [email protected]
Journal of Clinical and Experimental Hepatology | March 2013 | Vol. 3 | No. 1S | S75–S77
S77
Liver Fibrosis
work, Western blot (VCAM-1, ICAM-1 and CD31), TUNEL and other enzymatic assays. Conclusion: Exploring the unknown novel relation between pro-angiogenic and pro-fibrotic effects mediated via adenosine signalling will provide pre-clinical data as to the efficacy of adenosine receptor blockade as a potential therapeutic approach for the treatment of fibrosis.