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.

Jwa EK, et al. Ann Hepatobiliary Pancreat Surg. 2019 May;23(2):122-127. https://doi.org/10.14701/ahbps.2019.23.2.122

This study evaluated the prognostic value of metabolic parameters based on the standardized uptake value (SUV) normalized by total body weight (bwSUV) and by lean body mass (SUL) measured on ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for predicting tumor recurrence after primary living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC) without transplantation locoregional therapy. This retrospective study enrolled 49 patients with HCC. The maximum tumor bwSUV (T-bwSUVmax) and SUL (T-SULmax) were measured on PET. The maximum bwSUV (L-bwSUVmax), mean bwSUV (L-bwSUVmean), maximum SUL (L-SULmax), and mean SUL (L-SULmean) were measured in the liver. All metabolic parameters were evaluated using survival analyses and compared to clinicopathological factors. Tumor recurrence occurred in 16/49 patients. Kaplan–Meier analysis revealed that all metabolic parameters were significant (p < 0.05). Univariate analysis revealed that prothrombin-induced by vitamin K absence or antagonist-II; T-stage; tumor number; tumor size; microvascular invasion; the Milan criteria, University of California, San Francisco (UCSF), and up-to-seven criteria; T-bwSUVmax/L-bwSUVmean; T-SULmax; T-SULmax/L-SULmax; and T-SULmax/L-SULmean were significant predictors. Multivariate analysis revealed that the T-SULmax/L-SULmean (hazard ratio = 115.6; p = 0.001; cut-off, 1.81) and UCSF criteria (hazard ratio = 172.1; p = 0.010) were independent predictors of tumor recurrence. SUL-based metabolic parameters, especially T-SULmax/L-SULmean, were significant, independent predictors of HCC recurrence post-LDLT.