Hepatocyte Cell Death in ACLF: Mechanism and Significance -An Immunohistochemical Study. P. Sakhuja 1 , A. Rastogi 2 , S. S Hissar 1 , A. Singh 1 , A. Kumar 2 , R. Gondal 1 , S.K. Sarin 1 1 GB Pant Hospital, 2 Institute of Liver and Biliary Sciences, New Delhi, India Background: Acute on chronic liver failure (ACLF) is defined as acute hepatic insult complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease. Caspases play an essential role in apoptosis. COX-2 is an inducible immediate early gene responsible for the release of prostaglandins during inflammatory response. We studied the immunohistochemical expression of COX-2 and caspase-1 in liver tissue to assess their role in pathophysiology and in predicting outcome of ACLF. Method: A retrospective analysis of 50 liver biopsies with clinical diagnosis of ACLF was undertaken. Patients were divided into two groups A and D based on clinical outcome (Alive/Died respectively). Immunohistochemical analysis for COX-2 and caspase was performed on 39 and 36 cases respectively and scored from 0-8 as per intensity and distribution. Score 6-8 indicated high intensity with focal to diffuse distribution, and was considered significant. Results: Etiology of acute liver failure was viral or alcoholic. Increased expression of Caspase was observed in 10/21 cases in group D and none of the cases in group A(n=15) (p=0.001). Increased expression of Cox-2 was observed in 4/21 cases in group D and none of the cases in group A (n=18) (p=0.052). Conclusion: Increased immunoreactivity of caspase in liver biopsies of patients of ACLF may indicate worse prognosis and its important role in the pathophysiology of ACLF. Immunostaining for caspase is useful for assessment of prognosis and possibility of anti-apoptotic and anti-fibrotic therapies in future.