The challenge to reverse liver fibrosis in advanced liver disease

Progression of liver fibrosis often leads to liver cirrhosis (LC), and becomes a major global health problem. The annual number of death from LC is approximately 17,000 in Japan, 50,000 in USA, and over 1 million in the world. Ongoing fibrogenesis causes decompensation of liver function, and represents the major risk factor of hepatocellular carcinoma (HCC). Thus, liver fibrosis is an important determinant for prognosis in LC including non-alcoholic steatohepatitis as well as viral hepatitis. Recently, direct-acting antivirals (DAA) caused high rates of sustained virologic response (SVR) of hepatitis C virus (HCV). In many reports evaluating regression of liver fibrosis after SVR, one third to two thirds patients had some reduction in fibrosis, suggesting that elimination of causing agents has shown that liver fibrosis is reversible. However, reduction of liver fibrosis in LC patients seems to regress less than those with less severe fibrosis. Reversal of liver fibrosis occurs too slowly and not so frequently to improve the prognosis of LC. At present, no approved therapy exists for liver fibrosis, and an anti-fibrotic therapy is urgently required to solve this unmet medical need. In this symposium, I will talk cellular and molecular mechanisms of fibrogenesis and fibrolysis to develop anti-fibrotic therapies for liver fibrosis.