BACKGROUND: Caspase-cleaved cytokeratin 18 (CK18-Asp396) is released from hepatocytes during apoptosis. Recent studies have indicated that serum levels of CK18-Asp396 could be a clinically useful biomarker of chronic liver disease. To shed more light on the rate of hepatocyte loss by apoptosis in chronic liver disease, serum levels of CK18-Asp396 were examined in patients with nonalcoholic steatohepatitis (NASH) and chronic hepatitis C. MATERIAL/ METHODS: Apoptotic CK18-Asp396 levels were quantified in sera from 35 patients with nonalcoholic steatohepatitis (NASH), 21 patients with chronic hepatitis C (HCV), and 18 healthy controls. RESULTS: Analysis of serum CK18-Asp396 levels showed an increasing trend starting from healthy controls (median: 54.5 U/l), to HCV patients (80.1 U/l), to patients with NASH (144.1 U/l, Kruskall-Wallis test: P<0.001). Post hoc analyses revealed that CK18-Asp396 levels were significantly higher in the NASH patients than in both HCV patients (P=0.008) and healthy controls (P<0.001). Moreover, the levels were significantly higher in patients with HCV than in control individuals (P<0.05). In patients with chronic HCV infection there was a significant positive correlation between serum CK18-Asp396 levels and AST (r=0.442, P<0.05), the ultrasonographic grade of steatosis (r=0.446, P<0.05), and the histological steatosis score (r=0.759, P<0.001). CONCLUSIONS: Although subject to future confirmation, these pilot findings seem to indicate that serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) are higher in patients with NASH than in those with chronic HCV infection. These data suggest that NASH patients have an increased hepatocyte loss by apoptosis compared with chronic hepatitis C patients.
BACKGROUND: Caspase-cleaved cytokeratin 18 (CK18-Asp396) is released from hepatocytes during apoptosis. Recent studies have indicated that serum levels of CK18-Asp396 could be a clinically useful biomarker of chronic liver disease. To shed more light on the rate of hepatocyte loss by apoptosis in chronic liver disease, serum levels of CK18-Asp396 were examined in patients with nonalcoholic steatohepatitis (NASH) and chronic hepatitis C. MATERIAL/ METHODS: Apoptotic CK18-Asp396 levels were quantified in sera from 35 patients with nonalcoholic steatohepatitis (NASH), 21 patients with chronic hepatitis C (HCV), and 18 healthy controls. RESULTS: Analysis of serum CK18-Asp396 levels showed an increasing trend starting from healthy controls (median: 54.5 U/l), to HCV patients (80.1 U/l), to patients with NASH (144.1 U/l, Kruskall-Wallis test: P<0.001). Post hoc analyses revealed that CK18-Asp396 levels were significantly higher in the NASH patients than in both HCV patients (P=0.008) and healthy controls (P<0.001). Moreover, the levels were significantly higher in patients with HCV than in control individuals (P<0.05). In patients with chronic HCV infection there was a significant positive correlation between serum CK18-Asp396 levels and AST (r=0.442, P<0.05), the ultrasonographic grade of steatosis (r=0.446, P<0.05), and the histological steatosis score (r=0.759, P<0.001). CONCLUSIONS: Although subject to future confirmation, these pilot findings seem to indicate that serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) are higher in patients with NASH than in those with chronic HCV infection. These data suggest that NASH patients have an increased hepatocyte loss by apoptosis compared with chronic hepatitis Cpatients.
Authors: Raj Vuppalanchi; Ajay K Jain; Ross Deppe; Katherine Yates; Megan Comerford; Howard C Masuoka; Brent A Neuschwander-Tetri; Rohit Loomba; Elizabeth M Brunt; David E Kleiner; Jean P Molleston; Jeffrey B Schwimmer; Joel E Lavine; James Tonascia; Naga Chalasani Journal: Clin Gastroenterol Hepatol Date: 2014-05-17 Impact factor: 11.382
Authors: Bryan D Maliken; James E Nelson; Heather M Klintworth; Mary Beauchamp; Matthew M Yeh; Kris V Kowdley Journal: Hepatology Date: 2013-03-14 Impact factor: 17.425
Authors: Y Pan; R Xu; M Peach; C-P Huang; D Branstetter; W Novotny; R S Herbst; S G Eckhardt; P M Holland Journal: Br J Cancer Date: 2011-10-27 Impact factor: 7.640
Authors: Guadalupe Garcia-Tsao; Michael Fuchs; Mitchell Shiffman; Brian B Borg; Nikolaos Pyrsopoulos; Kirti Shetty; Juan F Gallegos-Orozco; K Rajender Reddy; Eyob Feyssa; Jean L Chan; Mason Yamashita; James M Robinson; Alfred P Spada; David T Hagerty; Jaime Bosch Journal: Hepatology Date: 2018-11-26 Impact factor: 17.425