BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are up-regulated in hepatocellular carcinoma (HCC). To investigate the levels of COX-2 and VEGF expression in chronic hepatitis (CH), cirrhosis, and HCC. METHODS: The immunohistochemical expressions of COX-2 and VEGF were evaluated in tissues from patients with CH (n=95), cirrhosis (n=38), low-grade HCC (LG-HCC; n=6), and high-grade HCC (HG-HCC; n=29). RESULTS: The COX-2 expression scores in CH, cirrhosis, LG-HCC, and HG-HCC were 3.3+/-1.9 (mean+/-SD), 4.2+/-1.7, 5.5+/-1.0, and 3.4+/-2.4, respectively (CH vs. cirrhosis, P=0.016; CH vs. LG-HCC, P=0.008; LG-HCC vs. HG-HCC, P=0.004), and the corresponding VEGF expression scores were 0.9+/-0.8, 1.5+/-0.7, 1.8+/-0.9, and 1.6+/-1.1 (CH vs. cirrhosis, P<0.001; CH vs. LG-HCC, P=0.011; LG-HCC vs. HG-HCC, P=0.075). Both factors were correlated with the fibrosis stage in CH and cirrhosis (COX-2: r=0.427, P<0.001; VEGF: r=0.491, P<0.001). There was a significant correlation between COX-2 and VEGF in all of the tissue samples (r=0.648, P<0.001), and between high COX-2 and VEGF expression scores and survival (COX-2: P=0.001; VEGF: P<0.001). CONCLUSIONS: The expressions of both COX-2 and VEGF are significantly higher in cirrhosis and LG-HCC than in CH. High COX-2 and high VEGF expressions are associated with a high survival rate.
Adult ; Aged ; Carcinoma, Hepatocellular/*metabolism/mortality/pathology ; Cyclooxygenase 2/*metabolism ; Female ; Hepatitis, Chronic/*metabolism/mortality/pathology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Cirrhosis/*metabolism/mortality/pathology ; Liver Neoplasms/*metabolism/mortality/pathology ; Male ; Middle Aged ; Vascular Endothelial Growth Factor A/*metabolism

Patients with cirrhosis who are hospitalized for an acute decompensation (AD) and also have organ failure(s) are at high risk of short-term death. These patients have a syndrome called Acute-on-Chronic Liver Failure (ACLF). ACLF is now considered as a new syndrome that it is distinct from "mere" AD not only because of the presence of organ failure(s) and high short-term mortality but also because of younger age, higher prevalence of alcoholic etiology of cirrhosis, higher prevalence of some precipitants (such as bacterial infections, active alcoholism), and more intense systemic inflammatory response. ACLF is a new syndrome also because severe sepsis or severe alcoholic hepatitis do not account for 100% of the observed cases; in fact, almost 50% of the cases are of "unknown" origin. In other words, severe sepsis, severe alcoholic hepatitis and ACLF of "unknown origin" are subcategories of the syndrome.
Acute-On-Chronic Liver Failure/complications/mortality/*pathology ; Age Factors ; Cytokines/metabolism ; Hepatitis, Alcoholic/complications ; Humans ; Liver Cirrhosis/*complications/diagnosis ; Sepsis/complications ; Severity of Illness Index ; Survival Rate