CIRRHOSIS AND LIVER FAILURE Fatigue and pruritus at onset identify a more aggressive subset of primary biliary cirrhosis Chiara Quarneti, Paolo Muratori, Claudine Lalanne, Angela Fabbri, Rita Menichella, Alessandro Granito, Chiara Masi, Marco Lenzi, Fabio Cassani, Georgios Pappas and Luigi Muratori Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Azienda Ospedaliera Universitaria Sant’Orsola- Malpighi, Bologna Italy Keywords antimitochondrial antibodies – biliary – cirrhosis – symptomatic – therapy Correspondence Luigi Muratori MD, PhD Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Azienda Ospedaliera Universitaria Sant’Orsola-Malpighi, via Massarenti 9, 40138 Bologna, Italy Tel: +39-51-6363868; +39-51-6363631 Fax: ++39-51-340877 e-mail: luigi.muratori@unibo.it Received 7 January 2014 Accepted 28 March 2014 DOI:10.1111/liv.12560 Abstract Background & Aims: In recent years, primary biliary cirrhosis is mostly diagnosed in patients who are asymptomatic; however, a proportion of cases still present with typical complaints such as fatigue and/or pruritus. We compared biochemical, histological and immunological features of patients with or without fatigue and/or pruritus at onset to see whether the different clinical presentation may eventually impact on disease pro- gression. Methods: We analysed the Bologna cohort of 216 patients with pri- mary biliary cirrhosis referred to our Centre between 1997 and 2007, according to symptomatic (fatigue and/or pruritus) or asymptomatic presen- tation. Clinical, biochemical, histological and immunological feature at diag- nosis, response to ursodeoxycholic acid and progression of the disorder were compared after a mean follow-up of 81 ± 75 months. Results: At diagnosis, symptomatic patients were significantly more often women (98.6% vs. 87.2%, P = 0.004), younger (mean age 49 ± 12 vs. 55 ± 12 years, P = 0.003) and with more pronounced biochemical activity, as indicated by higher alka- line phosphatase (mean 2.93 ± 2 vs. 2.12, P = 0.002) and aminotransferase (mean 1.92 ± 1 vs. 1.47 ± 1.27, P = 0.014) levels, whereas histological stage and autoantibody profile were similar. Symptomatic patients were less likely to respond to ursodeoxycholic acid therapy (63% vs. 81%, P = 0.006) and developed more often cirrhosis and its complications (31% vs. 13%, P = 0.004). Conclusions: Fatigue and/or pruritus at onset identify a subset of patients with primary biliary cirrhosis who preferentially are women, younger, with a particularly active disease, less responsive to ursodeoxy- cholic acid treatment, and more inclined to evolve to cirrhosis and its complications. Primary biliary cirrhosis (PBC) is an autoimmune liver disease affecting the intrahepatic small bile ducts, eventually leading to bile duct destruction, cirrhosis, liver failure and death (1, 2). In patients with intrahepatic cholestasis, the detection of antimi- tochondrial antibodies (AMA), the main serological marker of the disease, allows early diagnosis (3). Given the widespread availability of testing for AMA using both conventional indirect immunofluorescence and second-level assays with recombinant mitochon- drial antigens (4), more and more often PBC patients are being identified during the initial stage of the disease. The prompt initiation of treatment with ursodeoxycholic acid (UDCA) appears to delay or even ‘freeze’ disease progression, hence improving the natural history and the overall prognosis of the disease (5). A consistent proportion of PBC patients, however, still presents with typical symptoms such as pruritus and/or fatigue of unexplained origin. To evaluate whether the different presentation pat- terns of PBC are possibly associated with different modalities of progression, in this study, we analysed the Bologna cohort of Italian PBC patients, divided accord- ing to the clinical manifestations – or lack thereof – at the time of diagnosis. PBC patients presenting with symptoms such as pruritus and/or fatigue were com- pared to asymptomatic PBC patients referred to our Centre during the same time frame for the occasional detection of intrahepatic cholestasis. Clinical, biochemi- cal, histological and immunological features, response to treatment and evolution of the disease were analysed and compared between patients with symptomatic or asymptomatic onset. Liver International (2014) © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 1 Liver International ISSN 1478-3223