CLINICAL STUDIES A 35-year follow-up of a large cohort of patients with primary biliary cirrhosis seen at a single centre Annarosa Floreani 1 , Diego Caroli 1 , Angela Variola 1 , Erik Rosa Rizzotto 1 , Sara Antoniazzi 1 , Maria Chiaramonte 2 , Nora Cazzagon 1 , Chiara Brombin 3 , Luigi Salmaso 3 and Vincenzo Baldo 4 1 Department of Surgical and Gastroenterological Sciences, University of Padova, Padova, Italy 2 Sacro Cuore Hospital, Negrar, Italy 3 Department of Management and Engineering, University of Padova, Padova, Italy 4 Department of Hygiene and Public Health, University of Padova, Padova, Italy Keywords mortality – primary biliary cirrhosis – survival – ursodeoxycholic acid Correspondence Prof. Annarosa Floreani, Department of Surgical and Gastroenterological Sciences, University of Padova, Via Giustiniani 2, 35128 Padova, Italy Tel: 139 049 8212894 Fax: 139 049 8760820 e-mail: annarosa.Floreani@unipd.it Received 20 April 2010 Accepted 8 October 2010 DOI:10.1111/j.1478-3231.2010.02366.x Abstract Background: The natural history of primary biliary cirrhosis (PBC) is still debated. Aims: To evaluate: (i) long-term survival in a large cohort of PBC patients observed prospectively at a single centre and (ii) mortality in relation to baseline characteristics and ursodeoxycholic acid (UDCA) treatment. Methods: We considered all consecutive patients between 1973 and 2007 (327 subjects; 310 females, 17 males). Results: The mean follow-up was 9.1  7.7 years. The patients’ age at diagnosis for representative periods (1973–1980, 1981–1990, 1991–2000, 2001–2007) increased progressively from 47.7  1.5 to 53.2  1.2, to 65.2  2.1 and then 63.6  2.9 years. The proportion of asymptomatic patients at diagnosis increased from 30 to 48% in the last decade, while associated symptoms of extrahepatic autoimmunity remained unchanged. Eighty patients (24.4%) died, 74 of them because of liver failure (12 patients developed hepatocellular carcinoma); nine patients underwent liver transplantation. From 1988 onwards, all patients were treated with UDCA (n = 288). The mean age at death for the sample as a whole was 67.2  1.3 years. The survival probability at 20 years was 82% for patients with histological stages I–II at entry, 64% for those with stage III and 42% for those with stage IV (P = 0.0007). Mortality was significantly reduced in patients treated with UDCA (P = 0.012), whereas it was independently associated with oesophageal varices (P = 0.015).Patients treated with UDCA had a better prognosis than those untreated, irrespective of the histological stage. Early treated subjects with a good response to UDCA have an 85% chance of survival at 20 years. Conclusions: The clinical presentation of PBC has been changing over the years. Its early detection and early treatment improve the related survival rates. Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that progresses slowly to end-stage liver disease. The overall survival ranges between 10 and 15 years (1). Its natural history is still debated and depends on several variables and on the symptoms of liver disease in particular. In asymptomatic patients, survival is com- parable with the predictions for an age- and gender- matched control population, whereas it is shorter in those who develop symptoms (2). Another important factor is the age of onset of liver disease; in general, patients who are diagnosed in the symptomatic phases are sometimes younger than those who present in the asymptomatic phase (2, 3). The development of oesophageal varices has a huge impact on survival, whereas the 3-year survival in a prospective study of 256 patients was 59% after the development of this complication (4). More patients with asymptomatic PBC are now being diagnosed thanks to the routine use of biochemical screening (5). Moreover, the natural history of PBC is supposed to be changed in the ursodeoxycholic acid (UDCA) era (6). In fact, extended data from several studies indicate that UDCA improves the natural history of PBC, especially when administered in the early stages (7–9), although a recent meta-analysis on 16 randomized clinical trials and a total of 11 447 patients failed to demonstrate any benefit of UDCA on mortality and mortality or liver transplantation rates (10). Mortality data were reviewed recently in a large cohort of 930 PBC patients and 9202 controls drawn from the General Practice Research Database in the UK (11). This survey indicated that individuals with PBC have a three- fold higher mortality risk than the general population; this risk is somewhat reduced by regular treatment with Liver International (2011) c  2010 John Wiley & Sons A/S 361 Liver International ISSN 1478-3223