The rare liver disease primary sclerosing cholangitis (PSC) may impact just .01% of people, but the extremely pernicious disorder’s attacks on the liver mean bearers of the disorder account for 10% of liver transplants in Europe. This is because the inflammatory illness has historically not been given much time in the lab, and thus the little understood disease has no effective treatment options. For that reason, many PSC patients only hope is a transplant, making PSC the third most common reason Europeans have indicated for being added to the liver waiting list; a list too many never make it off of.
With success, the researchers identified a molecular signature that can be used as another diagnostic tool when assessing patients with the disease. Using RNA sequencing, they found a signature caused by stress on the cells that causes a cellular reaction known as ‘cellular ER stress.’ They found that patients with this ER stress signature were more likely to develop liver cirrhosis, regardless of the condition of their disease. However, there are steps patients can take to treat this.
Primary Sclerosing Cholangitis
Primary sclerosing cholangitis (PSC)
is a rare chronic inflammatory disorder that appears due to the build up of toxins due to inflammation or scarring to the bile ducts, which blocks up the passages. These blockages mean instead of aiding food digestion, bile gets trapped in the liver. The harsh acidic nature of the bile damages the liver cells, resulting in liver damage such as cirrhosis, fibrosis, and eventual liver failure. Patients may begin noticing itchiness and fatigue, before the disease advances to cause pain in the upper right abdomen, an enlarged liver, jaundice, fever, bile duct infections, and liver failure. While the cause is unknown, its believe to be associated with the immune system and 70% of patients are male. While there is no cure, various medications exist for treating infections and itching, and other patients get bile duct surgery or sign up for a liver transplant. Patients have a poor prognosis if they cannot get a liver transplant.
A Molecular Clue
In the study, the scientists found evidence of the cellular stress in the liver cells and bile duct epithelium through a molecular signature. The specific marking of the signature indicated the patient had ER stress in the liver, which is the cell’s response to stress due to the overabundance of a misfolded protein in the endoplasmic reticulum.
The presence of this signature that indicates ER stress can be used as an risk factor for liver cirrhosis, regardless of the stage or severity of their PSC. Rather, the presence of the ER stress can be understood as a stand alone factor in increasing the patient’s risk of toxic buildup and a liver transplant later down the road.
The Bad News, The Good News
The signature indicates that the person is prone towards other liver induced difficulties, introducing the burden of a potential slew of medical difficulties ahead. The head of the research project at MedUni Vienna’s Division of Gastroenterology and Hepatology, Michael Trauner said,
“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,”
But while the presence of the signature is glum news, recognizing the meaning of its presence is groundbreaking. Trauner continued,
“This discovery also opens up new treatment options, since ER stress can be counteracted with drugs.”
ER stress is the result of the accumulation of toxic bile acids, and with luck, doctors already have pharmaceutical tools and treatments to restore a healthier bile balance. They had already tested the drugs on patients in clinical trials and found benefits, that they expect more research is needed to confirm and explore treatment plans.
Any new understanding is good news in the world of rare disease research, and these scientists can be satisfied that their novel finding of this signature’s toxic nature will help alert PSC patients to take measures to get their intense but treatable needs addressed.