The second limitation is the ethnic homogeneity of the Japanese population. Because the baseline incidence of HCC development differs among population groups, longer-term longitudinal studies in larger cohorts with various population subgroups are required to verify the generality of our results. With the development of potent direct-acting antiviral agents combinations, IFN-free therapy is likely to be approved in the near future. This raises the question of whether posttreatment ALT and/or AFP levels will remain a significant predictor of HCC risk. Moreover, it

is uncertain whether the suppressive effect of viral eradication by IFN-free regimens on hepatocarcinogenesis will be identical to that obtained by IFN-based regimens. Therefore, it is extremely interesting to prove these issues in future studies. In conclusion, RG-7204 post-IFN treatment ALT and AFP levels are strictly associated with hepatocarcinogenesis risk in patients with CHC. Measurement of these values is useful for predicting future HCC risk in IFN-treated patients. Suppression of these values after IFN therapy reduces HCC risk even in patients without HCV eradication, while SVRs with increased ALT and/or AFP levels are at risk for HCC development. The present results have potentially important clinical implications for physicians and may influence their decisions regarding check details treatment strategy and HCC surveillance

for individual patients. Additional Supporting Information may be found in the online version of this article. “
“Background and Aims:  The effects of an EP4 agonist/antagonist on the healing of lesions produced by indomethacin in the small intestine were examined in rats, especially in relation to the expression of vascular endothelial growth factor (VEGF) and angiogenesis. Methods:  Animals were given indomethacin (10 mg/kg s.c.) and killed at various

time points. To impair the healing of these lesions, a small dose of indomethacin (2 mg/kg p.o.) or AE3-208 (EP4 antagonist: 3 mg/kg i.p.) was given once daily for 6 days after the ulceration was induced, with or without Tobramycin the co-administration of AE1-329 (EP4 agonist: 0.1 mg/kg i.p.). Results:  Indomethacin (10 mg/kg) caused severe damage in the small intestine, but the lesions healed rapidly decreasing to approximately one-fifth of their initial size within 7 days. The healing process was significantly impaired by indomethacin (2 mg/kg) given once daily for 6 days after the ulceration. This effect of indomethacin was mimicked by the EP4 antagonist and reversed by co-administration of the EP4 agonist. Mucosal VEGF expression was upregulated after the ulceration, reaching a peak on day 3 followed by a decrease. The changes in VEGF expression paralleled those in mucosal cyclooxygenase-2 expression, as well as prostaglandin E2 (PGE2) content.