Primary Biliary Cholangitis (PBC which was previously known as
Primary Biliary Cirrhosis) is a long-term, auto-immune condition which
causes injury to bile ducts within the liver, causing fatigue, itchy
skin, poor memory and concentration. It can lead to liver fibrosis,
cirrhosis and liver failure.
Of patients with the condition, 70% respond to treatment, however
for the remaining 30% the tablets - Ursodeoxycholic acid - do not work
and this is not known until after a year of treatment.
‘The newly developed NanoString nCounter digital expression platform provides a reliable indicator of a primary biliary cholangitis patient's likelihood of failing to respond to the standard treatment.’
Newcastle scientists and medics have developed a promising new test
to identify patients with this rare liver disease who will not respond to
standard treatment, allowing earlier intervention with alternatives.
The new test has identified a gene signature related to the immune
response in the liver tissue of patients with high risk disease,
including the senescence marker p21WAF1/Cip.
Using the NanoString nCounter digital expression platform, standard
liver biopsies taken at diagnosis can be directly and rapidly screened
for this gene signature.
The team are looking to work with industry to develop this as a
companion diagnostic test which alongside a new treatment would
determine its applicability to a specific patient.
Publishing the work in e-biomedicine, lead author Dr Lucy Walker
from the Institute of Cellular Medicine at Newcastle University said,
"This NanoString test would be easy to introduce into a clinical setting
as it needs no separate samples. Our initial results show the technique provides a reliable
indicator of a patient's likelihood of failing to respond to the
standard treatment. This means medical teams could intervene earlier with alternative
treatments, increasing the chances of success and perhaps staving off
the need for a liver transplant."
In patients with PBC, the body thinks that the bile ducts within the
liver are foreign objects and tries to destroy the lining to these
ducts. These bile ducts are designed to allow the flow of bile from the
liver, so damage of these ducts leads to poor drainage of bile acids.
The bile acids then leak from the bile ducts, damaging surrounding
liver cells, which then causes inflammation and scarring in the liver.
PBC is relatively rare affecting up to one in 3-4,000 people and of those nine out of 10 are women.
While there is a genetic element to PBC, it is thought to be within
the auto-immune family of conditions and experts do not yet know what
causes PBC or what can cure it.
In the early stages of the disease, PBC often doesn't cause any
symptoms and many people are only diagnosed during tests carried out for
Developed at the NanoString facility within the Faculty of Medical
Sciences at Newcastle University, the test raises questions about PBC as
lead author, Dr Lucy Walker, explains: "As we have identified a
separate gene expression for those with high-risk PBC, it raises the
possibility that PBC may actually be two separate conditions with very
similar symptoms. This is something we will be examining further in
future, larger studies."
This study only examined samples from a small group of patients (13)
and a further study into a larger group to validate the results will
begin shortly. The work was funded by the Medical Research Council.
Dave Jones, Professor of Liver Immunology and co-author on the paper
said: "Currently patients with high-risk PBC may be offered
immunotherapies, however, these have mixed results and it may be that
often the aggressive nature of the condition in high-risk patients means
that even as the treatment starts the condition has created too much
damage in the liver. A test which could identify those who would benefit from treatment
and provide earlier intervention may increase the possibilities of
This test has emerged from the unique collaboration of healthcare
expertise and research excellence at the CRESTA clinics (Clinics for
Research and Service in Themed Assessment) which are led and managed by
the Newcastle Hospitals and bring in expertise from Newcastle University
and are supported by the NIHR Newcastle Biomedical Research Centre.
The CRESTA clinic provides enhanced care for patients with PBC
through a 'one-stop' multidisciplinary visit to better serve the needs
of a diverse patient population, ranging from young working mums to
older patients with complex needs. The clinic is also geared for
recruitment of such patients for participation in early phase trials -
Newcastle is one of the world's leading centers for trials of new
therapy in PBC.
This is part of the Newcastle Academic Health Partners, a
collaboration involving Newcastle Upon Tyne Hospitals NHS Foundation
Trust, Northumberland, Tyne and Wear NHS Foundation Trust and Newcastle
University. This partnership harnesses world-class expertise to ensure
patients benefit sooner from new treatments, diagnostics and prevention