Little is known about Primary Sclerosing Cholangitis (PSC).
PSC is a chronic liver disease, is a disease that affects the liver and bile ducts, which causes inflammation and the scarring of the bile ducts (both inside and outside the liver) eventually growing narrow or blocked.
Affecting 1 in 100,000, this rare disease seems to target males (2:1 male to female ratio) in the prime of their life at a mean age of onset of approximately 40 years. Currently there is no cure for PSC which is often progressive, leading to end stage liver disease. About 60-80% of patients with PSC have an associated colitis (often ulcerative colitis). Moreover, patients with PSC face a high cancer burden and are at an increased risk of developing colonic, bile duct or liver cancer. Moreover, in patients with PSC cancer-related deaths significantly outnumber those caused by end-stage liver disease.
Currently, there is no cure for PSC, and liver transplantation is the only available option, with recurrence occurring in about one-third of transplanted patients. Even though a liver transplant, which is a huge intervention, can preserve their liver function for some time, they are still at a greater risk of developing these cancers. Sadly, even after a transplant, a significant portion may still pass away from these cancers.
However, Dr Ayesha Shah and Professor Gerald Holtmann are working hard to understand and potentially treat PSC with an associated colitis and find an alternative treatment or potentially a cure. The strong association between PSC and colitis suggests that the bidirectional gut-liver axis and the gastrointestinal microbiome play a crucial role in the development and progression of PSC.
“Our goal is to stop the progression or even cure a currently incurable disease for which there are currently no effective treatment options besides liver transplantation for advanced stages of PSC and colectomy for the poorly controlled colitis associated with PSC,” Dr Shah said.
Currently, PSC associated with or without colitis is being treated with oral antibiotic called vancomycin, in a clinical trial which is currently underway at several hospitals across Queensland.
“Our clinical experience suggests that treatment with non-absorbable antibiotic like oral Vancomycin is often associated with significant improvemnt in the inflammation in the colon that is associated with PSC. This itself is a breakthrough, however, some people would argue that we shouldn’t treat patients for a prolonged period with antibiotics,” Professor Holtmann said.
It is well known that long-term use of antibiotics is associated with side effects, including drug resistance. Therefore, through their research, kindly funded by the PA Research Foundation's generous donors, Dr Shah and Professor Holtmann are seeking to find alternatives that can be used instead of antibiotics.
“We aim to use other non-antibiotic antimicrobial therapies that specifically target the altered microbial composition that plays a crucial role in pathophysiology of PSC associated with or without colitis,” Ayesha said.
While PSC is believed to be an immune mediated disease, Dr Shah and Professor Holtmann’s interest in composition of the microbes colonizing the gastrointestinal tract comes from their belief that there could be potentially infective trigger leading to the onset of the disease.
“It is a rare disease, one in 100,000, yet we have one household where a stepdaughter and a stepfather both have the disease. Given the prevalence of PSC, how likely is it that two people living in one household, who are not related, have this condition at the same time? It is virtually impossible.
“Essentially, we believe that there are, potentially, changes in the microbes colonizing the gastrointestinal tract act as a trigger in the genetically predisposed individual, which can potentially trigger an immune response leading to onset of PSC” Gerald and Ayesha said.
Dr Shah and Professor Holtmann will use samples collected from an earlier pilot study to look at the mucosa-associated microbiome of patients with PSC and associated colitis and test whether various antimicrobial (non-antibiotic) agents can be potentially be an alternative treatment option..
Ayesha mentioned, “We will be working with the basic scientists from the labs at the Translational Research Institute to test antifoaming agents, which are routinely used in endoscpopy like simethicone
“These agents are readily available, and our preliminary in vitro studies have shown potential to suppress microbial activity.. If proven effective, this treatment would be a much safer, cheaper and more effective option that doesn’t pose the threat of antibiotic resistance.”
Dr Shah and Professor Holtmann are continuing to add to the growing number of scientific literature about PSC and their work has worldwide implications.
“The information that we generate from our research is not just advancing healthcare in by transforming practices related to PSC treatment, but we also hope to promotes improved access to the healthcare services required to manage PSC.
“Many health insurances currently don’t cover the cost of oral vancomycin since large clinical trials are lacking since it is an orphan disease and subsequently management guidelines for PSC do not include this treatment option. This creates a significant barrier, making it challenging for many patients to access the treatment due to out-of-pocket costs.
“We hope that our studies persuades insurances to implement updated reimbursement policies for the treatment and management of PSC,” Professor Holtmann said.
Dr Shah and Professor Holtmann would like to thank the PA Research Foundations donors because their donations are making an impact on the global scale.
