Global study identifies patient risk groups
16 March 2017
A global study involving researchers in Birmingham has identified key risk groups of liver disease patients to indicate their survival estimates and likelihood of developing cancer.
The paper, co-first authored by Doctors Palak Trivedi, a Clinical Lecturer based at the University of Birmingham and Queen Elizabeth Hospital Birmingham (QEHB), and Tobias Weismuller (Bonn, Germany), focuses on a rare liver disease called primary sclerosing cholangitis (PSC).
Although very rare, PSC accounts for approximately 10 – 15% of UK liver transplant activity, and is the leading indication for liver transplantation in many European countries. Patients with PSC have an additional, independent risk of developing cancer of the bile ducts that is over 160 times greater than that of the background population.
Presently, there is no known medical therapy shown to slow PSC progression and more than 50% of patients progress to the point of needing liver transplantation at some point in their lifetime. In addition, a significant proportion (more than 70%) also develop concurrent inflammatory bowel disease (IBD) – either ulcerative colitis or Crohn’s disease. Until now, it has not been known how the presence of bowel inflammation impacts the clinical course of liver and bile duct disease in PSC.
One of the biggest challenges in designing clinical trials to test new therapies is the fact that not all patients display the same disease behaviour. Moreover, most centres see (at most) a few hundred patients, which is not large enough to discern differences in the rate of disease progression. The paper, published by the International PSC Study Group, represents a global collaborative effort with 17 countries pooling data over 30 years for more than 7,000 patients.
The large size of this study shows clear variation in the clinical course that patients experience, dependent upon the age at presentation, gender, bile duct phenotype, and subtype of concurrent IBD.
Dr Trivedi is based at QEHB, which is run by University Hospitals Birmingham NHS Foundation Trust (UHB), and hosts the largest solid organ transplantation programme in Europe. Describing the key findings of the study, Dr Trivedi said: “The results of the IPSCSG study may allow doctors to provide a more individualised assessment for patients in terms of the rate of disease progression; and also the risk of developing bile duct cancer, which has direct implications in evaluating future cancer surveillance strategies. Perhaps most striking, we found that the development of concomitant ulcerative colitis is a critical determinant of liver disease progression.”
Talking about the impact of the study findings on ongoing liver disease research, Dr Trivedi explained: “Additionally, our study could refine the way in which patients are studied in future clinical trials, as we can now clearly see different patterns of disease behaviour emerge.
“Historically, clinical trials may have failed to show consistent benefit of treatments because outcome data from all patients were analysed collectively. This study shows that distinct rates of disease progression exist in PSC, by classifying individuals at high risk (large bile duct disease with concurrent ulcerative colitis), an intermediate risk group (those with without gut inflammation, or who have Crohn’s disease), and a relatively low risk population (patients with only the small bile ducts in the liver involved). When evaluating the impact of new potential therapies in PSC, we must therefore be mindful that the rates of disease progression vary according to phenotype, and future analysis must be refined by individual patient groups.”