Prognostic value of vascular endothelial growth factor in both conventional and drug eluting beads transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma in HCV patients.

OBJECTIVES: This work aimed to measure serum vascular endothelial growth factor (VEGF) levels before and after Conventional transarterial chemoembolization (cTACE) versus drug-eluting beads (DEB)-TACE and evaluate its efficacy in predicting response to therapy and tumor recurrence. METHODS: 114 patients with unresectable hepatocellular carcinoma complicating hepatitis C virus-related cirrhosis were included. They underwent cTACE (58) or DEB-TACE (56). VEGF serum levels were measured before and on days 1 and 30 after TACE. Patients with complete response (CR) after TACE were followed-up for one year. Statistical analysis was done. RESULTS: VEGF level was higher than baseline after cTACE (P < 0.001), and DEB-TACE (P = 0.004). It was also significantly higher in patients with progressive disease (P < 0.001). VEGF level at cut off values of 97.3, 149.8, and 104.1 pg/ml could discriminate disease progression from treatment success with area under ROC curves of 0.806, 0.775, and 0.771, respectively. The sensitivity was 88.9%, 88.9%, and 77.8% and specificity was 62.5%, 64.6 and 66.7%, respectively. However, no relation to tumor recurrence in CR group could be detected after one year. CONCLUSION: VEGF serum levels may predict response to therapy in patients treated by DEB-TACE or cTACE but it has no relation to tumor recurrence.

Toll-like receptor 4 blocker as potential therapy for acetaminophen-induced organ failure in mice.

Acetaminophen (APAP, 4-hydroxyacetanilide) is the most common cause of acute liver failure in the United States. In addition to exhibiting hepatotoxicity, APAP exerts a nephrotoxic effect may be independent of the induced liver damage. Toll-like receptors (TLRs) have been suggested as a potential class of novel therapeutic targets. The aim of the present study was to investigate the potential of the TLR-4 blocker TAK-242 in the prevention of APAP-induced hepato-renal failure. Four groups of C57BL mice were studied: Vehicle-treated/control (VEH), APAP-treated (APAP), N-acetyl cysteine (NAC)-pretreated plus APAP (APAP + NAC) and TAK-242-pretreated plus APAP (APAP + TAK) groups. Mice were clinically assessed then perfused 4 h later. Liver and kidney tissues were collected and examined histologically using basic hematoxylin and eosin staining to detect signs of necrosis and inflammation. Plasma samples were collected to measure the levels of alanine transaminase, aspartate transaminase and serum creatinine. In addition, liver and kidney tissues were assayed to determine the levels of reduced glutathione. The results of the present study indicate the potential role of TLR-4 in APAP-induced organ toxicity. In the APAP + TAK and APAP + NAC groups, histopathological examination indicated that pretreatment with TAK-242 or NAC afforded protection against APAP-induced injury. However, this protective effect was more clinically evident in the APAP + TAK group compared with the APAP + NAC group. The various biochemical parameters (serum enzymes and reduced glutathione) revealed no significant protection in either of the pretreated groups. Therefore, the present study indicated that the TLR-4 blocker had protective effects against acute APAP toxicity in liver and kidney tissues. These effects were identified clinically, histologically and biochemically. Furthermore, the TLR-4 blocker TAK-242 exhibited antioxidant properties in addition to anti-inflammatory effects.