Primary biliary cholangitis

PBC is a slowly progressive condition in the majority of patients. Given the age of presentation with the disease, many patients die of other causes before reaching end-stage liver disease. Epidemiological studies suggest that mortality overall is significantly increased in patients with PBC (standardised mortality ratio of 2.8 in northeast England).[70]Prince M, Chetwynd A, Newman W, et al. Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28 years. Gastroenterology. 2002 Oct;123(4):1044-51. http://www.ncbi.nlm.nih.gov/pubmed/12360466?tool=bestpractice.com This increase in overall mortality results from increases in both liver-related and, non-liver-related deaths. 

Liver-related mortality

There is approximately a doubling of risk of liver-related death in patients with PBC compared with in relevant comparator populations.[70]Prince M, Chetwynd A, Newman W, et al. Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28 years. Gastroenterology. 2002 Oct;123(4):1044-51. http://www.ncbi.nlm.nih.gov/pubmed/12360466?tool=bestpractice.com However, there has been a trend towards reduction in liver-related mortality as a consequence of the diagnosis of milder forms of the disease, which may have been missed previously (and which are associated with a lower risk of liver-related death), and the effects of treatment (in particular with ursodeoxycholic acid but also, where advanced liver disease develops, with transplantation). The long-term nature of ursodeoxycholic acid treatment means that changes in population mortality rate related to liver disease will take a long time to emerge. Liver-related mortality results from the development of the complications of cirrhosis (particularly portal hypertension with variceal bleeding), the development of advanced liver disease with hepatocellular failure and its associated complications, or hepatocellular carcinoma.[71]Gores GJ, Wiesner RH, Dickson ER, et al. Prospective evaluation of esophageal varices in primary biliary cirrhosis: development, natural history, and influence on survival. Gastroenterology. 1989 Jun;96(6):1552-9. http://www.ncbi.nlm.nih.gov/pubmed/2785470?tool=bestpractice.com [72]Jones DE, Metcalf JV, Collier JD, et al. Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes. Hepatology. 1997 Nov;26(5):1138-42. http://www.ncbi.nlm.nih.gov/pubmed/9362353?tool=bestpractice.com

Non-liver-related mortality

It is becoming clear from epidemiological studies that the risk of non-liver-related mortality is approximately doubled in patients with PBC, contributing to the overall increased risk to life.[70]Prince M, Chetwynd A, Newman W, et al. Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28 years. Gastroenterology. 2002 Oct;123(4):1044-51. http://www.ncbi.nlm.nih.gov/pubmed/12360466?tool=bestpractice.com This risk appears to be non-specific (the specific risk of malignant and cardiovascular disease has been addressed in detail, with no substantial PBC-associated risk being identified). One possibility is that this mortality increase is due to frailty associated with chronic inflammation. Specific preventative measures are difficult to recommend given the lack of a clear mechanism. Good clinical practice would suggest, however, that a comprehensive review of risk factors for important diseases where preventative lifestyle modification could be of benefit is appropriate in PBC.

Quality of life

The major factors contributing to impairment of quality of life in PBC are itch, fatigue, and the clinical features associated with advanced disease.[36]Newton JL, Bhala N, Burt J, et al. Characterisation of the associations and impact of symptoms in primary biliary cirrhosis using a disease specific quality of life measure. J Hepatol. 2006 Apr;44(4):776-83. http://www.ncbi.nlm.nih.gov/pubmed/16487619?tool=bestpractice.com [39]Crowe J, Christensen E, Doniach D, et al. Early features of primary biliary cirrhosis: an analysis of 85 patients. Am J Gastroenterol. 1985 Jun;80(6):466-8. http://www.ncbi.nlm.nih.gov/pubmed/4003376?tool=bestpractice.com ​​[40]Goldblatt J, Taylor PJ, Lipman T, et al. The true impact of fatigue in primary biliary cirrhosis: a population study. Gastroenterology. 2002 May;122(5):1235-41. http://www.ncbi.nlm.nih.gov/pubmed/11984509?tool=bestpractice.com ​​[73]Jacoby A, Rannard A, Buck D, et al. Development, validation, and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis. Gut. 2005 Nov;54(11):1622-9. http://www.ncbi.nlm.nih.gov/pubmed/15961522?tool=bestpractice.com [74]Poupon RE, Chretien Y, Chazouilleres O, et al. Quality of life in patients with primary biliary cirrhosis. Hepatology. 2004 Aug;40(2):489-94. http://onlinelibrary.wiley.com/doi/10.1002/hep.20276/full http://www.ncbi.nlm.nih.gov/pubmed/15368455?tool=bestpractice.com Itch is typically a symptom of the middle stages of the disease, normally being absent from patients with the earliest disease stage (although exceptions are seen), with improvement occasionally being seen in the end stages of disease. Fatigue, in contrast, shows no association with disease severity and, indeed, appears stable over time.[74]Poupon RE, Chretien Y, Chazouilleres O, et al. Quality of life in patients with primary biliary cirrhosis. Hepatology. 2004 Aug;40(2):489-94. http://onlinelibrary.wiley.com/doi/10.1002/hep.20276/full http://www.ncbi.nlm.nih.gov/pubmed/15368455?tool=bestpractice.com The implication of this observation is that patients who experience significant fatigue with PBC are unlikely to improve spontaneously. Patients not experiencing significant fatigue at presentation are unlikely to develop profound fatigue over relatively short follow-up periods.