248 The Korean Journal of Hepatology Vol. 17. No. 3, September 2011 advanced fibrosis (F3, F4) using α2-macroglobulin, apolipoprotein in clinical practice for noninvasive diagnosis of NASH as a A-I, haptoglobin, total bilirubin, GGT and ALT (positive simple, easy to measure, reproducible and reliable method. predictive value: 73%, negative predictive value: 90%).12 Further studies are needed to validate the accuracy of this Similarly, NAFLD fibrosis score was investigated for apoptosis panel for NASH diagnosis in each race and country. predicting advanced fibrosis using age, hyperglycemia, BMI, We need to investigate whether this apoptosis panel could be platelet count, albumin and aspartate aminotransferase (AST)/ used for assessment of treatment response and predicting ALT ratio (positive predictive value: 82%, negative predictive prognosis of NASH. value: 93%).13 Several inflammatory mediators are increased in NASH compared to simple hepatic steatosis such as tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), CC-chemokine ligand 2 (CCL-2), and hyaluronic acid.14-16 Deregulation of hepatocyte apoptosis is an important mechanism of liver injury and NASH development.17-19 Fas has a critical role in apoptosis pathway as a death receptor member of the TNF receptor family. Expression of this membrane protein is increased in NASH patients.17 Accumulation of free fatty acids in hepatocytes results in up-regulation of Fas in the cell membrane which increases the sensitivity to Fas mediated apoptosis.20 At the level of mitochondria, apoptosis pathway induces permiabilization of the mitochondrial outer membrane and release of multiple protein from the mitochondrial inner membrane space to cytoplasm.21 This results in activation of effector caspases (mainly caspase 3) which will cleave substrates in cytoplasm like cytokeratin 18 (CK-18), the major intermediate filament protein of liver, inducing the specific morphologic change of apoptosis.21 There are several reports showing that the quantification of this caspase generated CK-18 fragments is useful for diagnosis of NASH.22-25 In subject study, they investigated the apoptosis panel for non-invasive diagnosis of NASH using these two biomarkers, serum CK-18 fragments and soluble Fas (sFas). Compared to each single biomarker, the combination of two biomarkers, serum CK-18 fragments and sFas showed significantly higher area under curve (AUC) (0.86 in CK-18, 0.86 in sFas and 0.93 in CK-18 with sFas), sensitivity (88%), and specificity (89%) for diagnosis of NASH. The high AUC in the validation group (0.79) indicates the reproducibility of this apoptosis panel. This apoptosis panel for NASH diagnosis is non-invasive, simple, reproducible and reliable method which is needed in real clinical situation. Not only for diagnosis but also for assessment of treatment response and prognosis, this apoptosis panel with serum CK-18 fragments and sFas could be used after proper researches are done. In conclusion, this diagnostic apoptosis panel including serum CK-18 fragments and sFas for diagnosis of NASH is useful test REFERENCES 1. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. 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