NEWS & VIEWS PRIMARY BILIARY CIRRHOSIS
Renaming primary biliary cirrhosis—clarity or confusion? Palak J. Trivedi and Gideon M. Hirschfield Refers to Beuers, U. et al. Changing nomenclature for PBC: from ‘cirrhosis’ to ‘cholangitis’. Hepatology http://dx.doi.org/10.1002/hep.28140
What is in a name; and why does the nomenclature of one disease, primary biliary cirrhosis, cause such contention that a proposed name change by those deeply committed to the advancement of its understanding and management stimulate huge debate? histological examinations as part of efficacy assessment, indicate that >25% of patients do in fact progress to cirrhosis at 4 years after treatment.6 These early findings are supported by more contemporary studies with improved risk-stratification,7 illustrating that the cumulative incidence of cirrhosis over a 10-year observation period is in the order of 40% (Figure 1). Cirrhosis development is therefore hardly inconsequential for our patients, and its use in medical language has an understandable basis in describing the potentially very substantial risks of living with PBC. 60 Cumulative incidence of cirrhosis (%)
Disease names are important because they need to readily identify distinct diseases and drive timely management. Thus, proposed changes to disease nosology inevitably provokes discussion and debate. Addison and Gull made the first clinical depiction of nonobstructive biliary cirrhosis, but nearly a century of percolating through terminology was needed before the condition became known universally as primary biliary cirrhosis (PBC). Pleasingly, clinical recognition has improved so much so that patients are increasingly diagnosed earlier, and have a low individual probability of having cirrhosis at presentation,1–3 relative to those individuals reported in more historical studies.4 Clarity has been further aided by well-conductednational and international patient registries encompassing >1,000 patient-years of follow-up data, which collectively suggest ~15% of patients have evidence of advanced disease at the time of diagnosis.1–3 To this effect, a thoughtful initiative has been put forward by Beuers and colleagues,5 who advocate avoidance of the term ‘cirrhosis’ in favour of the term ‘cholangitis,’ to address patient concerns about stigma and a description of the severity of disease. Given the slowly progressive nature of PBC, the term cirrhosis receives criticism because of concern that it might not capture the current clinical manifestations of the condition.5 However, with a single bile-acid-based therapy as the only medical option, development of cirrhosis and all its associated complications, continues to loom large in the modern era. Indeed, data from the original clinical trials of ursodeoxycholic acid in PBC, which employed paired serial
Patients and those committed to liver disease management are readily aware of the gaps in knowledge between general and specialist clinical practice, particularly relating to the causes and importance surrounding rare conditions such as PBC. Ideally, names should not confer stigma to a disease, but stigma surrounding liver disease is often a double-edged sword. For instance, patients with PBC can feel disappointed by repeated discussion of alcohol intake when not rele vant to aetiology, an experience shared by many patients with autoimmune liver disease. Conversely, by removing cirrhosis from the name, potential hazards in undervaluing overall clinical effect will arise by inadvertently offering false reassurance to nonspecialists that PBC no longer imposes a risk of progressive liver disease. Stigma is often driven by ignorance, and the many efforts to challenge it in the context of liver disease are welcomed.8 Although the hepatology community recognizes the varied causes of liver disease, general physicians might automatically (and incorrectly) ascribe aetiology to lifestyle; something that can be challenged with stridency via improved patient and public engagement. Equally, clinicians need to highlight lifestyle
40
20
0
Patients at risk
1.0
2.5 5.0 Time since PBC diagnosis (years)
7.5
10.0
511
412
115
14
249
Figure 1 | Development of liver cirrhosis as part of the natural history in PBC. Kaplan–Meier Nature Reviews | Gastroenterology & Hepatology estimates illustrating the rate of progression to cirrhosis across a multicentre registry encompassing patients diagnosed with PBC between 2000 and 2012. Data is extrapolated from the cohort presented by Trivedi et al.1 Follow-up is from point of PBC diagnosis until first identification of cirrhosis (or censor [transplantation, death or loss of follow-up]). Patients who presented with, or developed cirrhosis in the first 12 months of diagnosis have been excluded. Abbreviation: PBC, primary biliary cirrhosis.
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VOLUME 12 | DECEMBER 2015
NEWS & VIEWS management to all, including to patients with PBC, given evidence that disease severity is affected by smoking for example.9 If, however, ‘cirrhosis’ is substituted with ‘cholangitis’,5 then immediately a new concern arises given the common clinical association of cholangitis with infection of the bile ducts. Furthermore, in an era of easily accessible information from the internet, we have found that patients are already searching ‘primary’ and ‘cholangitis’ raising greater uncertainty as to whether the cholangitis they read about (associated with infection, IBD and substantial risk of hepatobiliary and colorectal cancer) applies to them or not. In addition, anxieties that disease boundaries are now less distinct have emerged, with patients as well as nonspecialist clinicians unnecessarily confused over diagnosis and management. Indeed, the suggested change has resulted in patient groups representing those with the distinct disease entity, primary sclerosing cholangitis, to register their concerns with the International Classification of Diseases about potential confusion.
‘‘
...what a name must not do is confuse or blur boundaries with other diseases...
’’
Medicine is as much art as it is science, thus for many diseases we must accept that historical terminology is inevitably crude and at times inaccurate. Most names for diseases represent insufficiently accurate descriptions and are idioms that require a deeper understanding of the meaning than is provided by the words alone. Nevertheless, what a disease name must do is accurately identify groups of patients who can be offered timely, appropriate treatment and follow-up by clinicians, together with recourse to interventions spanning the
DECEMBER 2015 | VOLUME 12
breadth of disease. Simultaneously, what a name must not do is confuse or blur boundaries with other diseases that might superficially seem similar, but for which clinical outcomes differ considerably.7 Nothing is ever as straightforward as we would like to believe, and the importance of a name spans many facets. However, in the tragedy of Romeo and Juliet, William Shakespeare reminds us not to forget that a name does not affect actual characteristics: Tis but thy name that is my enemy; Thou art thyself, though not a Montague. What’s Montague? It is nor hand, nor foot, Nor arm, nor face, nor any other part Belonging to a man. O, be some other name! What’s in a name? That which we call a rose, By any other name would smell as sweet. (William Shakespeare, c. 1595ad)
Since the Bard could recognize this point in 1595, we should arguably be less worried in 2015 about the name of our patients’ diagnosis and more focused on the unmet need for new therapies for PBC.10 Any proposed name change, however genuine in its intent for collaboration between patients and clin icians, must not confuse, divide, or blur the needs of all patients with liver disease that collectively we champion. At the same time as linguistic changes are discussed, we must ensure that the main focus remains on ending the days when patients with PBC can develop cirrhosis, by championing research and prioritizing recruitment to clinical trials of new therapies. National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, Institute of Immunology and Immunotherapy, University of Birmingham, Wolfson Drive, Birmingham B15 2TT, UK (P.J.T., G.M.H.). Correspondence to: G.M.H.
[email protected]
doi:10.1038/nrgastro.2015.187 Published online 10 November 2015 Acknowledgements P.J.T. has received funding from the NIHR Birmingham Liver Biomedical Research Unit and is in receipt of a Wellcome Trust funded Clinical Research Fellowship. G.M.H. has received funding from the NIHR Birmingham Liver Biomedical Research Unit and is a co-investigator for UK‑PBC supported by a Stratified Medicine Award from the UK Medical Research Council. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health. Competing interests The authors declare no competing interests. 1.
Trivedi, P. J. et al. Optimising risk stratification in primary biliary cirrhosis: AST/platelet ratio index predicts outcome independent of ursodeoxycholic acid response. J. Hepatol. 60, 1249–1258 (2014). 2. Lammers, W. J. et al. Development and validation of a scoring system to predict outcomes of patients with primary biliary cirrhosis receiving ursodeoxycholic acid therapy. Gastroenterology http://dx.doi.org/10.1053/j.gastro.2015.07.061. 3. Carbone, M. et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology 144, 560–569 (2013). 4. Sherlock, S. & Scheuer, P. J. The presentation and diagnosis of 100 patients with primary biliary cirrhosis. N. Engl. J. Med. 289, 674–678 (1973). 5. Beuers, U. et al. Changing nomenclature for PBC: from ‘cirrhosis’ to ‘cholangitis’. Hepatology http://dx.doi.org/10.1002/hep.28140. 6. Degott, C. et al. Histopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression. Hepatology 29, 1007–1012 (1999). 7. Trivedi, P. J., Corpechot, C., Pares, A. & Hirschfield, G. M. Risk Stratification in autoimmune cholestatic liver diseases: opportunities for clinicians and trialists. Hepatology http://dx.doi.org/10.1002/ hep.28128. 8. Hirschfield, G. M., Thain, C., Walmsley, M., Brownlee, A. & Jones, D. E. Liver disease in the UK. Lancet 385, 503 (2015). 9. Corpechot, C. et al. Smoking as an independent risk factor of liver fibrosis in primary biliary cirrhosis. J. Hepatol. 56, 218–224 (2012). 10. Hirschfield, G. M. et al. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology 148, 751–761 (2015).
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