Liver damage caused by various factors results in fibrosis and inflammation, leading to cirrhosis and cancer. Fibrosis results in the accumulation of extracellular matrix components. The role of STAT proteins in mediating liver inflammation and fibrosis has been well documented; however, approved therapies targeting STAT3 inhibition against liver disease are lacking. This study investigated the anti-fibrotic and anti-inflammatory effects of STAT3 decoy oligodeoxynucleotides (ODN) in hepatocytes and liver fibrosis mouse models. STAT3 decoy ODN were delivered into cells using liposomes and hydrodynamic tail vein injection into 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice in which liver injury was induced. STAT3 target gene expression changes were verified using qPCR and Western blotting. Liver tissue fibrosis and bile duct proliferation were assessed in animal experiments using staining techniques, and macrophage and inflammatory cytokine distribution was verified using immunohistochemistry. STAT3 decoy ODN reduced fibrosis and inflammatory factors in liver cancer cell lines and DDC-induced liver injury mouse model. These results suggest that STAT3 decoy ODN may effectively treat liver fibrosis and must be clinically investigated.

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett\'s test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in Cmax, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in Cmax and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

BACKGROUND: Extrahepatic biliary atresia is a progressive disorder characterised by fibroinflammatory obliteration or stenosis of the extrahepatic biliary tree leading to obstruction of bile flow and cholestatic jaundice. It is the most common cause for cholestasis in newborn. Histopathological criteria for diagnosing biliary atresia from liver biopsy have not been clearly defined.
OBJECTIVE: This study was undertaken to analyse the significance of the various histopathological features in diagnosis and prognosis of extrahepatic biliary atresia from liver biopsy specimens.
METHODS: This was a retrospective study of 43 cases of extra-hepatic biliary atresia diagnosed and treated at a tertiary care hospital between January 2010 to December 2014. Formalin fixed paraffin embedded liver biopsy tissues were processed by standard technique and the slides were stained with haematoxylin and eosin. All the slides were reviewed and graded by a semi-quantitative scoring system. Features such as increased age at kasai\'s portoenterostomy, portal fibrosis, bile duct proliferation, cholestasis, portal inflammation and duct plate malformation were studied. Statistical analysis was worked out using SPSS 17.0 (statistical package for the social science software). Chi-square test was used to find association between various parameters with respect to mortality and Kaplan-Meier estimator was used for survival analysis of the population under study.
RESULTS: In this study comprising of 43 cases, only 6 cases (13.95%) were alive at the end of 6 months follow-up. Twenty patients who died and the 17 cases with poor survival had greater degrees of fibrosis, bile duct proliferation and cholestasis. Majority of the cases with duct plate malformation expired inspite of earlier surgical intervention. Thus proving the association of fibrosis, bile duct proliferation, cholestasis and duct plate malformation with the survival and prognosis of biliary atresia cases. Age at surgery did not show any correlation with prognosis as cases operated even at <60 days had poor survival.
CONCLUSIONS: From this study it can be concluded that in extrahepatic biliary atresia patients, presence of duct plate malformation, greater degrees of fibrosis, bile duct proliferation and cholestasis were strongly associated with poor prognosis.

Pulmonary vascular dilation and angiogenesis underlie experimental hepatopulmonary syndrome (HPS) induced by common bile duct ligation (CBDL) and may respond to receptor tyrosine kinase (RTK) inhibition. Vascular endothelial growth factor-A (VEGF-A) expression occurs in proliferating cholangiocytes and pulmonary intravascular monocytes after CBDL, the latter contributing to angiogenesis. CBDL cholangiocytes also produce endothelin-1 (ET-1), which triggers lung vascular endothelin B receptor-mediated endothelial nitric oxide synthase (eNOS) activation and pulmonary intravascular monocyte accumulation. However, whether RTK pathway activation directly regulates cholangiocyte and pulmonary microvascular alterations in experimental HPS is not defined. We assessed RTK pathway activation in cholangiocytes and lung after CBDL and the effects of the type II RTK inhibitor sorafenib in experimental HPS. Cholangiocyte VEGF-A expression and ERK activation accompanied proliferation and increased hepatic and circulating ET-1 levels after CBDL. Sorafenib decreased each of these events and led to a reduction in lung eNOS activation and intravascular monocyte accumulation. Lung monocyte VEGF-A expression and microvascular Akt and ERK activation were also found in vivo after CBDL, and VEGF-A activated Akt and ERK and angiogenesis in rat pulmonary microvascular endothelial cells in vitro. Sorafenib inhibited VEGF-A-mediated signaling and angiogenesis in vivo and in vitro and improved arterial gas exchange and intrapulmonary shunting. RTK activation in experimental HPS upregulates cholangiocyte proliferation and ET-1 production, leading to pulmonary microvascular eNOS activation, intravascular monocyte accumulation, and VEGF-A-mediated angiogenic signaling pathways. These findings identify a novel mechanism in cholangiocytes through which RTK inhibition ameliorates experimental HPS.