Cell Stress Mechanisms in Liver Disease Identified

A new prognostic factor for primary sclerosing cholangitis (PSC) from liver biopsies has been identified by researchers. This is so-called cellular ER stress. Primary sclerosing cholangitis (PSC) is a rare, chronic, inflammatory //disease of the bile ducts and is difficult to treat, since its causes have not yet been adequately researched.

PSC is a rare disease with a poor prognosis and can lead to cirrhosis of the liver or bile duct cancer. It affects 0.01% of the population but, even though it is rare, PSC is responsible for more than 10% of all liver transplants, making it the third most common indication on liver transplant waiting lists in Europe. In the recent study, which has now been published in the leading journal Hepatology, the researchers were able to identify a molecular signature for ER stress both in the liver cells (hepatocytes) and also in the bile duct epithelium - and notably as a stand-alone factor that is independent of the disease stage or degree of liver fibrosis (laying down of scar tissue) as a precursor to possible liver cirrhosis.

"Using transcriptional analysis, we were able to identify a personalised molecular signature of primary sclerosing cholangitis, which shows that patients with an impaired response to ER stress have a poorer prognosis with a higher incidence of complications," explains Trauner. "This discovery also opens up new treatment options, since ER stress can be counteracted with drugs."

Since the build-up of potentially toxic bile acids in cholestasis results in ER stress, it is now being attempted to restore this balance pharmacologically using the new bile acid therapeutics that are available. Beneficial effects can reportedly be expected from drugs already in clinically testing - however, more research has already been initiated to explore this further.

Source-Eurekalert