38 Aberrant induction of FoxM1 following PHx and the associated defects in the expression of cell cycle factors (delayed induction of cyclin B1 and Cdc25C combined with sustained expression of p21) found in regenerating

c-rel−/− livers resembles the phenotype described in mice with hepatocyte-targeted disruption of foxm1.38 We conclude that c-Rel is required for appropriate timing of the induction of FoxM1 and exerts a regulatory influence on hepatocyte DNA synthesis during the regenerative response. Recent work provides conflicting data for the effects of hepatocyte-targeted blockade of NF-κB on proliferative responses to Selleckchem XL765 injury and PHx.39-41 These studies employed inducible hepatocyte-selective transgenic expression of a degradation-resistant IκBα transgene or hepatocyte-targeted deletion of IKK2, both of which lead to inhibition of the canonical (RelA/p50) NF-κB pathway. However, functions for IKK2 are emerging outside of the NF-κB system, including influences of proteins intimately selleck associated with cell cycle control.42 Further investigation of distinct NF-κB subunit-specific functions

may help better define the role of the NF-κB system in liver homeostasis and regeneration. In summary, c-Rel may now be considered an important regulator of hepatic wound-healing. Moreover, the potential for c-Rel activities to influence pathological features of the chronic injured liver—including hepatitis, fibrosis, and hepatocellular carcinoma—should be explored. Additional Supporting Information may be found in the online version of this article. “
“Liver fibrosis is a risk factor for hepatocellular carcinoma (HCC), but at what fibrotic stage the risk for HCC is increased has been poorly investigated quantitatively. This study aimed to determine the appropriate cut-off value of liver stiffness for HCC concurrence by FibroScan,

and its clinical significance in hepatitis B virus (HBV), hepatitis C virus (HCV) and non-B, non-C (NBNC) liver disease. Subjects comprised 1002 cases (246 with HCC and 756 without HCC) with chronic liver disease (HBV, 104; HCV, 722; and NBNC, 176). Liver stiffness was significantly greater in all groups with HCC, medchemexpress and the determined cut-off value for HCC concurrence was more than 12.0 kPa in those with HCV, more than 8.5 kPa in those with HBV and more than 12.0 kPa in those with NBNC. Liver stiffness of more than 12.0 kPa was an independent risk factor for new HCC development in HCV. For HCV, risk factors for HCC concurrence were old age, male sex, low albumin, low platelets and liver stiffness, while for HBV they were old age, low platelets and liver stiffness, and for NBNC they were old age, elevated α-fetoprotein and liver stiffness. Liver stiffness cut-off values and their association with HCC concurrence were different depending on the etiology. In HCV, liver stiffness of more than 12.