Methods: Liver stiffness was measured by transient elastography for 157 patients with viral hepatitis, along with various other parameters potentially associated with HCC. HCC was initially present in 41 patients and absent in 116 patients, of whom 106 patients were followed prospectively for HCC development. Diagnostic performances of liver stiffness and other clinical parameters in predicting presence of HCC were evaluated using receiver operating characteristic (ROC) curves and Neratinib area under the ROC curve
(AUROC). Results: Liver stiffness was significantly higher in patients with HCC (24.9 ± 19.5 kPa) than in patients without HCC (10.9 ± 8.4 kPa; P < 0.0001). Age (P < 0.0001), platelet cell count (P = 0.0001), prothrombin activity (P = 0.0009), alpha fetoprotein (P = 0.0091), and des-gamma-carboxy prothrombin (DCP) (P = 0.0099) also differed significantly between patients with and without HCC. The largest AUROC was for liver stiffness. Differences between liver stiffness and age, platelet cell count, prothrombin activity, and DCP were not significant, but the AUROC of liver stiffness was superior to that of alpha fetoprotein
(P = 0.03850). Using a cut-off liver stiffness of 12.5 kPa, development of HCC was identified in 10 of the 106 patients followed. Multivariate analysis identified liver stiffness ≥12.5 kPa, age ≥60 years, and serum total bilirubin ≥1.0 mg/dL as significantly correlated with development of HCC. Conclusions: Liver stiffness as measured by transient elastography is a predictor of HCC development LY294002 price in viral hepatitis. “
“RNA-binding proteins (RBPs) play a major role in the control of messenger RNA (mRNA) turnover and translation rates. We examined the role of the RBP, human antigen R (HuR), during cholestatic liver injury and hepatic stellate cell (HSC) activation. HuR silencing attenuated fibrosis development in vivo after BDL, reducing liver damage, oxidative stress, inflammation, and collagen
and alpha smooth muscle actin (α-SMA) expression. HuR expression increased in activated HSCs from bile duct ligation mice and during HSC activation in vitro, and HuR silencing markedly reduced HSC activation. HuR regulated platelet-derived growth factor (PDGF)-induced proliferation and migration and controlled the expression MCE公司 of several mRNAs involved in these processes (e.g., Actin, matrix metalloproteinase 9, and cyclin D1 and B1). These functions of HuR were linked to its abundance and cytoplasmic localization, controlled by PDGF, by extracellular signal-regulated kinases (ERK) and phosphatidylinositol 3-kinase activation as well as ERK/LKB1 (liver kinase B1) activation, respectively. More important, we identified the tumor suppressor, LKB1, as a novel downstream target of PDGF-induced ERK activation in HSCs. HuR also controlled transforming growth factor beta (TGF-β)-induced profibrogenic actions by regulating the expression of TGF-β, α-SMA, and p21.