Changing the way Primary Sclerosing Cholangitis (PSC) is viewed and treated
Imagine you discovered a complete paradigm shift in the way a rare life-threatening condition could be treated but first, you had to convince your colleagues and your peers of its validity.
That was precisely the task ahead of PA Hospital (PAH) based Dr Ayesha Shah when she discovered that contrary to popular consensus, patients with the rare liver and colon disease Primary Sclerosing Cholangitis (PSC), who are treated by antibiotic Vancomycin on an ongoing basis see the disease regress.
Dr Ayesha Shah
PSC among the medical community had always been viewed as an autoimmune disease that couldn't be treated long term by antibiotics, until recently, when Dr Shah reviewed a PSC patient who also had inflammatory bowel disease (IBD).
Amazed by what she saw, she took the case to her colleague and mentor at PAH Professor Gerald Holtmann, and once convinced both researchers set about validating their findings on a greater scale.
"She was a very well-educated patient who had read all about the condition because the disease was out of control and she was going to have a colectomy. Her disease was that bad, there was also some talk about her requiring in the future a liver transplant as well," Dr Shah said.
"We realised that that antibiotic treatment controlled the disease but as soon as the treatment was stopped, the colitis flared up again. With antibiotic treatment a complete remission could be achieved. We traced back the images from when she was at the Children's Hospital, and it was well-confirmed colitis, very active disease, all confirmed on history, and in histology as well.
"Since then she has been on vancomycin, absolutely asymptomatic, but on numerous occasions flared up when the antibiotic therapy was discontinued. While this single case was an eye-opener, more evidence was needed. Thus, we conducted a systematic review and meta-analysis of antimicrobial therapy in patients with PSC and published these data. However, what is lacking is the placebo-controlled clinical trial in larger cohorts to define the changes of the microbes colonising the gastrointestinal tract of PSC patients and establish the efficacy of the antimicrobial therapy as the routine clinical practice," Prof Holtmann said.
Though other studies on PSC were not up to Australian standards for research, the duo went ahead and published their findings, such was their belief in the treatment pathway's benefit for patients, and had their work published in respected international journal Seminars of Liver Disease.
Dr Shah alongside her colleague Professor Holtmann
After studying the microbiome of more patients to confirm their findings Dr Shah and Professor Holtmann pushed on, joined forces with gastroenterologists and hepatologists across Queensland knowing they are about to establish a radical change how this disease is treated. Instead of prescribing immunosuppressant in PSC patients with IBD, the aim now is to modify the microbes that colonise the gastrointestinal tract to potentially cure this disease.
With more patients showing a positive response, Dr Shah and Professor Holtman have now attracted National Health and Medical Research Council funding for a randomised trial to prove their findings, and hopefully convince more hepatologists and members of the wider medical community that PSC should be treated with ongoing antibiotics.
Though rare, PSC is a pre-malignant condition that can lead to liver failure, colon cancer, bowel cancer, and bilatry cancer and largely affects young men in the prime of their lives, reinforcing the importance of the trial which will start recruiting patients soon from right across Queensland.
Helping to drive the research trial, which may also benefit patients with irritable bowel disease and ulcerative colitis, and identify potential genetic and environmental links, will be the PA Research Foundation funded biobank.
"We will take from those patients the microbes, the mucosa-associated microbiome, and it goes into the biobank, we can then test these microbes and find out can we more specifically modulate them? are there helpful chemicals, or is there a herbal combination that can do something? all this research is enabled with a biobank," Prof Holtmann said.
"Without the biobank, that PA Research Foundation funded we couldn't do it. The biobank enables us to have live bacteria to work with.
"It's a rare disease so we have involved all major gastroenterology departments in the state. It's a state-wide network. Essentially every patient in the state has an opportunity to be involved in this trial. Therefore, what we have been driving here at PA Hospital is not just for the small community in Metro South, it has impacts and benefits for everybody in the state."