A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma.

Sorafenib is currently a targeted agent widely used in the treatment of advanced hepatocellular carcinoma (aHCC). However, to date there is still a lack of a reliable marker capable of predicting sorafenib therapeutic responses. Here, we conducted a genome-wide association study (GWAS) to identify candidate single-nucleotide polymorphism outcome predictors in aHCC patients. A total of 74 real-world sorafenib-treated aHCC patients were enrolled for GWAS and outcome analysis. GWAS showed that rs1010816 (p = 2.2 × 10-7) was associated with sorafenib therapeutic response in aHCC patients. Kaplan-Meier analysis indicated that the "TT" genotype was significantly associated with a favorable therapeutic response but not significantly associated with overall survival (OS). Univariate followed by multivariate Cox proportional hazard analysis showed that ascites, main portal vein thrombosis, lower platelet count, lower total sorafenib doses, higher PALBI score in model A and higher ALBI grade in model B were significantly associated with a shorter OS. Subgroup analysis showed that only in alcoholic aHCC patients treated by sorafenib, rs1010816 "TT" genotype was significantly associated with longer OS (p = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 "TT" genotype.

Hepatoprotective effects of Ger-Gen-Chyn-Lian-Tang in thioacetamide-induced fibrosis in mice.

BACKGROUND: Many researchers have focused on developing traditional herbal medicines as pharmacological medicines to treat hepatic fibrosis. In this study, we evaluated the possible mechanism of Ger-Gen-Chyn-Lian-Tang (GGCLT) on thioacetamide (TAA)-induced hepatic injury in mice. METHODS: Hepatic fibrosis mice were established by intraperitoneal injection with TAA (100 mg/kg, 3 times/week), and treated with daily oral administration of 30 mg/kg, 100 mg/kg, and 300 mg/kg of GGCLT for 6 weeks. There were 40 mice randomly assigned to control, TAA and TAA+GGCLT groups. When the experiment was completed, Masson's trichrome staining was used to measure the degree of liver fibrosis. Hepatic fibrosis molecules were assessed by Western blot and real-time polymerase chain reaction. Hepatic glutathione levels, matrix metalloproteinase (MMP-2 and MMP-9), and hydroxyproline were also measured. RESULTS: Treatment with GGCLT significantly reduced the toxicity of TAA and exhibited effective hepatoprotective activity. The mechanism of the hepatoprotective effect of GGCLT is proposed to be by normalizing oxidative stress. Additionally, the data of fibrotic areas, expression of procollagen III, and MMP2 and 9 mRNA levels in the TAA+GGCLT group were much lower than those in the TAA group (p < 0.05). Furthermore, the upregulation of hepatic protein levels of nuclear factor-κB, transforming growth factor (TGF)-ß receptor-1, and smooth muscle α-actin induced by TAA was significantly inhibited after GGCLT treatment. CONCLUSION: GGCLT can efficiently ameliorate hepatic fibrosis by its inhibitory effects on the intrahepatic oxidative stress in TAA mice model. The antioxidant properties afforded by GGCLT may be attributed to its modulation on TGF-ß/TGFß receptor signaling through the downregulation of integrated signal pathways involving smooth muscle α-actin and lipid peroxidation.