Current therapies and novel approaches for biliary diseases

Abstract

Chronic liver diseases that inevitably lead to hepatic fibrosis, cirrhosis and/or hepatocellular carcinoma have become a major cause of illness and death worldwide. Among them, cholangiopathies or cholestatic liver diseases comprise a large group of conditions in which injury is primarily focused on the biliary system. These include congenital diseases (such as biliary atresia and cystic fibrosis), acquired diseases (such as primary sclerosing cholangitis and primary biliary cirrhosis), and those that arise from secondary damage to the biliary tree from obstruction, cholangitis or ischaemia. These conditions are associated with a specific pattern of chronic liver injury centered on damaged bile ducts that drive the development of peribiliary fibrosis and, ultimately, biliary cirrhosis and liver failure. For most, there is no established medical therapy and, hence, these diseases remain one of the most important indications for liver transplantation. As a result, there is a major need to develop new therapies that can prevent the development of chronic biliary injury and fibrosis. This mini-review briefly discusses the pathophysiology of liver fibrosis and its progression to cirrhosis. We make a special emphasis on biliary fibrosis and current therapeutic options, such as angiotensin converting enzyme-2 (known as ACE2) over-expression in the diseased liver as a novel potential therapy to treat this condition.

Keywords: Chronic liver disease; Biliary fibrosis; Current therapies for biliary fibrosis; Angiotensin converting enzyme-2; Gene therapy

Core tip: This mini-review focuses on the pathophysiology of chronic liver fibrosis, with a special emphasis on biliary fibrosis. We also attempted to provide information on current clinically available therapeutic options for biliary fibrosis and other potential therapeutic options that are in the preclinical stage of development, and discuss their advantages and disadvantages. In particular, work from the author’s laboratory described in this review indicates that liver-specific over-expression of angiotensin converting enzyme-2 (known as ACE2) of the alternate renin angiotensin system dramatically reduces biliary fibrosis in mouse models of biliary disease. This suggests that ACE2 gene therapy has the potential to treat patients with chronic biliary fibrosis.