Gastroenterology

Gastroenterology

Volume 144, Issue 3, March 2013, Pages 560-569.e7
Gastroenterology

Original Research
Full Report: Clinical—Liver
Sex and Age Are Determinants of the Clinical Phenotype of Primary Biliary Cirrhosis and Response to Ursodeoxycholic Acid

https://doi.org/10.1053/j.gastro.2012.12.005Get rights and content

Background, & Aims

Studies of primary biliary cirrhosis (PBC) phenotypes largely have been performed using small and selected populations. Study size has precluded investigation of important disease subgroups, such as men and young patients. We used a national patient cohort to obtain a better picture of PBC phenotypes.

Methods

We performed a cross-sectional study using the United Kingdom-PBC, patient cohort. Comprehensive data were collected for 2353 patients on diagnosis reports, response to therapy with ursodeoxycholic acid (UDCA), laboratory results, and symptom impact (assessed using the PBC-40 and other related measures).

Results

Seventy-nine percent of the patients reported current UDCA, therapy, with 80% meeting Paris response criteria. Men were significantly less likely to have responded to UDCA than women (72% vs 80% response rate; P < .05); male sex was an independent predictor of nonresponse on multivariate analysis. Age at diagnosis was associated strongly and independently with response to UDCA; response rates ranged from 90% among patients who presented with PBC when they were older than age 70, to less than 50% for those younger than age 30 (P < .0001). Patients who presented at younger ages also were significantly more likely not to respond to UDCA therapy, based on alanine aminotransferase and aspartate aminotransferase response criteria, and more likely to report fatigue and pruritus. Women had mean fatigue scores 32% higher than men's (P < .0001). The increase in fatigue severity in women was related strongly (r = 0.58; P < .0001) to higher levels of autonomic symptoms (P < .0001).

Conclusions

Among patients with PBC, response to UDCA, treatment and symptoms are related to sex and age at presentation, with the lowest response rates and highest levels of symptoms in women presenting at younger than age 50. Increased severity of fatigue in women is related to increased autonomic symptoms, making dysautonomia a plausible therapeutic target.

Section snippets

Study Design and Subjects

This was an observational study of patients recruited to the UK-PBC Research Cohort.12 This cohort was established to undertake high-throughput genetic studies of PBC and its subphenotypes. The cohort consisted of patients, prevalent between the dates of January 1, 2008, and December 31, 2011, with a diagnosis of PBC based on established diagnostic criteria (two or more of the following criteria: cholestatic liver biochemistry, compatible or diagnostic liver histology, and antimitochondrial

Results

At the time of analysis data were available for 2402 nontransplanted PBC patients. Of these, 2353 returned analyzable measures and formed the study cohort. Included in this cohort were 221 male patients. Cross-validation of self-reported data with patient hospital record data available in the extended data subgroup of 1379 participants (59% of the whole cohort) suggested a high level of accuracy of patient self-reporting (Supplementary Figure 1). Based on these observations we were confident to

Discussion

The UK-PBC patient cohort provides a unique opportunity to undertake a detailed cross-sectional study of a substantial proportion of a national PBC patient population. The UK-PBC patient cohort includes patients from every hospital in the United Kingdom, and therefore is representative of PBC in the United Kingdom, avoiding potential specialist center bias. This was a large study of the phenotype and response to treatment of PBC and presented a unique opportunity to explore patterns of

Acknowledgments

The authors thank Dr Rachel Westbrook (Kings College Hospital, London), Dr Ashish Sinha (Frenchay Hospital, Bristol), Dr Elaine Robertson (NHS Lanarkshire), Dr Katie Clark (Wirral University Teaching Hospital), Dr Stephen Atkinson (Imperial College Healthcare NHS Trust), and Dr Giacomo Germani (Royal Free Hospital) for assistance with collection.

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    This article has an accompanying continuing medical education activity on page e14. Learning Objective: Upon completion of this CME exercise, successful learners will be able to identify PBC patients who are less likely to achieve a biochemical response to UDCA, who are therefore anticipated to have worse long-term prognosis. Successful learners will also be able to demonstrate their knowledge of the phenotypic variables that predict treatment response.

    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by the Wellcome Trust; Medical Research Council (MRC) Clinical Training Fellowship (G.F.M.); Borsa di Studio “Mario Coppo”, Associazione Italiana Studio Fegato (AISF) (M.C.); National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle-upon-Tyne Hospitals NHS Foundation Trust and Newcastle University; Isaac Newton Trust, University of Cambridge, and Addenbrooke's Charitable Trust (ACT), Cambridge University Hospitals NHS Foundation Trust. The UK PBC Project is a portfolio study of the NIHR Comprehensive Research Network (CRN). The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health.

    Authors share co-first authorship.

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