serum markers of hepatocyte death and apoptosis are non invasive biomarkers of severe fibrosis in patients with alcoholic liver disease血清肝细胞死亡和凋亡的标志是严重纤维化非侵入性标志物在酒精性肝病患者.pdfVIP

Serum Markers of Hepatocyte Death and Apoptosis Are Non Invasive Biomarkers of Severe Fibrosis in Patients with Alcoholic Liver Disease 1,2,3. ´ 1,3. ´ 1,2,4 Vanessa Jeannette Lavallard , Stephanie Bonnafous , Stephanie Patouraux , Marie-Christine 1,2,4 ´ 1,2 1,2,3 1,2,3 Saint-Paul , Deborah Rousseau , Rodolphe Anty , Yannick Le Marchand-Brustel , Albert Tran1,2,3, Philippe Gual1,2,3* 1Team 8, %Hepatic complications of obesity, INSERM, U895, Nice, France, 2 Faculty of Medicine, University of Nice-Sophia-Antipolis, Nice, France, 3 Digestive Center, Centre Hospitalier Universitaire of Nice, Nice, France, 4 Biological Center, Centre Hospitalier Universitaire of Nice, Nice, France Abstract Background: Quantification of hepatotocyte death is useful to evaluate the progression of alcoholic liver diseases. Our aims were to quantify and correlate the circulating levels of Cytokeratin 18 (CK18) and its caspases-generated fragment to disease severity in heavy alcoholics. Methodology/Principal Findings: CK18 and CK18-fragment were evaluated in the serum of 143 heavy alcoholics. Serum levels of markers of hepatocyte death (CK18), apoptosis (CK18 fragment) and necrosis (CK18 -CK18 fragment) increased in patients with severe fibrosis compared to patients with mild fibrosis. These markers strongly correlated with Mallory-Denk bodies, hepatocyte ballooning, fibrosis and with hepatic TNFa and TGFb assessed in the liver of 24 patients. Elevated levels of serum hepatocyte death and apoptotic markers were independent risk factors in predicting seve