Liver fibrosis -from research to treatment- Current and future perspective

Liver Fibrosis is a consequence of chronic liver inflammation and characterized by excessive deposition of extracellular matrix, which can progress to cirrhosis. Cirrhosis is associated with significant liver dysfunction, portal hypertension, ascites, and the development of hepatocellular carcinoma. Recent reports show that some patients with liver fibrosis reduce liver fibrosis grades by treating the underlying liver disease conditions, such as hepatitis B and C, via direct antiviral agents. However, the reduction rate of fibrosis is still unsatisfactory when fibrosis is advanced. Also, clinical trials for treating fibrosis caused by non-alcoholic fatty liver disease are currently very active. However, several clinical trials have discontinued. Therefore, we still have to consider developing additional effective anti-fibrotics to treat liver fibrosis. The presentation will discuss recent advancements in the molecular mechanism of liver fibrosis, focusing on inflammatory and fibrotic signals, including our recent discovery of the regulation of the production of extracellular matrix hyaluronan, as potential targets for the treatment of liver fibrosis. Hepatic stellate cells are the primary cells producing extracellular matrix, but other immune cells, such as Kupffer cells also contribute to the activation of hepatic stellate cells, allowing these cells to be a more fibrotic phenotype. Additionally, hepatocytes have recently been recognized more to contribute to inflammation and fibrosis by producing pro-inflammatory and fibrotic factors. We will also discuss the contribution of different liver cell types as therapeutic targets for liver fibrosis.