Published online Nov 7, 2020. doi: 10.3748/wjg.v26.i41.6304
Peer-review started: August 3, 2020
First decision: September 12, 2020
Revised: September 30, 2020
Accepted: October 20, 2020
Article in press: October 20, 2020
Published online: November 7, 2020
Recent progress in our understanding of the pathways linked to progression from hepatic insult to cirrhosis has led to numerous novel therapies being investigated as potential cures and inhibitors of hepatic fibrogenesis. Liver cirrhosis is the final result of prolonged fibrosis, which is an intimate balance between fibrogenesis and fibrinolysis. A number of these complex mechanisms are shared across the various etiologies of liver disease. Thankfully, investigation has yielded some promising results in regard to reversal of fibrosis, particularly the indirect benefits associated with antiviral therapy for the treatment of hepatitis B and C and the farnesoid receptor agonist for the treatment of primary biliary cholangitis and metabolic associated fatty liver disease. A majority of current clinical research is focused on targeting metabolic associated fatty liver disease and its progression to metabolic steatohepatitis and ultimately cirrhosis, with some hope of potential standardized therapeutics in the near future. With our ever-evolving understanding of the underlying pathophysiology, these therapeutics focus on either controlling the primary disease (the initial trigger of fibrogenesis), interrupting receptor ligand interactions and other intracellular communications, inhibiting fibrogenesis, or even promoting resolution of fibrosis. It is imperative to thoroughly test these potential therapies with the rigorous standards of clinical therapeutic trials in order to ensure the highest standards of patient safety. In this article we will briefly review the key pathophysiological pathways that lead to liver fibrosis and present current clinical and experimental evidence that has shown reversibility of liver fibrosis and cirrhosis, while commenting on therapeutic safety.
Core Tip: A number of clinical trials have targeted various etiologies of liver fibrosis and cirrhosis. Some have been promising, particularly in metabolic associated fatty liver disease and viral hepatitis. Results from these studies have shown that there are safe treatments available, forming currently practiced therapeutic guidelines, and shining light on the potential reversibility of liver fibrosis and cirrhosis caused by a variety of etiologies.