Genkyotex announced the publication of data in Clinics and Research in Hepatology and Gastroenterology showing that its anti-fibrotic drug candidate GKT831, prevents multiple complications of portal hypertension in a preclinical model. Portal hypertension, the major complication of cirrhosis, develops when advanced liver fibrosis restricts blood flow through the liver. In the face of increased intra-hepatic vascular resistance, portal venous pressure increases and blood flow coming from the bowel and spleen is redirected to the heart through a network of existing and newly formed collateral vessels. This process, called portal-systemic shunting, leads to the development of esophageal varices, enlarged veins prone to bleeding, and also increases cardiac burden. Critically, portal hypertension drives the transition from compensated to decompensated cirrhosis and is responsible for most cirrhosis-related deaths. Previous preclinical and clinical data indicated that GKT831 has the potential to attenuate portal hypertension by reversing fibrotic remodeling and reducing intrahepatic endothelial dysfunction, which are respectively the structural and dynamic components of portal hypertension. The published studies were conducted by Wensheng Deng and his colleagues at the Fudan and Jiao Tong Universities in Shanghai. GKT831 administered at 30mg/kg for 14 days following the surgical induction of portal hypertension, was able to prevent the development of complications, including splanchnic angiogenesis, cardiac overload and portal-systemic shunting. The results further demonstrate that NOX1/4 inhibition with GKT831 targets multiple pathways and pathogenic processes underlying progressive liver disease. These beneficial effects of GKT831 correlated with a marked reduction in NOX enzyme activity and reactive oxygen species production.