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Unlabelled: Primary biliary cirrhosis (PBC) has a complex clinical phenotype, with debate about the extent and specificity of frequently described systemic symptoms such as fatigue. The aim of this study was to use a national patient cohort of 2,353 patients recruited from all clinical centers in the UK to explore the impact of disease on perceived life quality. Clinical data regarding diagnosis, therapy, and biochemical status were collected and have been reported previously. Detailed symptom phenotyping using recognized and validated symptom assessment tools including the PBC-40 was also undertaken and is reported here. Perception of poor quality of life and impaired health status was common in PBC patients (35% and 46%, respectively) and more common than in an age-matched and sex-matched community control group (6% and 15%, P < 0.0001 for both). Fatigue and symptoms of social dysfunction were associated with impaired perceived quality of life using multivariate analysis. Fatigue was the symptom with the greatest impact. Depression was a significant factor, but appeared to be a manifestation of complex symptom burden rather than a primary event. Fatigue had its greatest impact on perceived quality of life when accompanied by symptoms of social dysfunction, suggesting that maintenance of social networks is critical for minimizing the impact of fatigue., Conclusion: The symptom burden in PBC, which is unrelated to disease severity or ursodeoxycholic acid response, is significant and complex and results in significant quality of life deficit. The complexity of symptom burden, and its lack of relation to disease severity and treatment response, suggest that specific approaches to symptom management are warranted that address both symptom biology and social impact., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Unlabelled: The etiology of primary biliary cirrhosis (PBC) is far from clear. Both genetic and environmental factors are likely to be involved. We have previously reported evidence of space-time clustering, suggesting that a transient environmental agent may be involved in etiology. To further examine whether a seasonally varying environmental agent may contribute to the etiology of PBC, we have analyzed seasonal variation with respect to month of diagnosis using population-based data from northeast England over a defined period (1987-2003). Date of diagnosis was defined as the earliest date at which the patient was found to have fulfilled any two of three diagnostic criteria (i.e., antimitochondrial antibody-positive titer ≥1 in 40, cholestatic liver blood tests, diagnostic or compatible liver histology). Monthly expected (E) numbers of cases were calculated under an assumption of a uniform distribution throughout the year. Observed counts (O) were compared with the expected numbers. The chi-squared heterogeneity test was used to test for overall nonuniform variation and also for individual months. Poisson regression analysis was used to fit a sinusoidal (i.e., harmonic) model to the data, using month of diagnosis as a covariate in the model. There was a marked peak for diagnoses in the month of June (O = 115, E = 84.7, O/E = 1.36; P = 0.001). Furthermore, there was evidence of a sinusoidal pattern with a June peak (P = 0.012)., Conclusion: These highly novel results provide further evidence for the involvement of a seasonally varying environmental agent in the etiology of PBC., (Copyright © 2011 American Association for the Study of Liver Diseases.)

The cause of primary biliary cirrhosis (PBC) is unclear. Both genetic and environmental factors are likely to contribute. Some studies have suggested that one or more infectious agents may be involved. To examine whether infections may contribute to the cause of PBC, we have analyzed for space-time clustering using population-based data from northeast England over a defined period (1987-2003). Space-time clustering is observed when excess cases of a disease are found within limited geographical areas at limited periods of time. If present, it is suggestive of the involvement of one or more environmental components in the cause of a disease and is especially supportive of infections. A second-order procedure based on K-functions was used to test for global space-time clustering using residential addresses at the time of diagnosis. The Knox method determined the spatiotemporal range over which global clustering was strongest. K-function tests were repeated using nearest neighbor thresholds to adjust for variations in population density. Individual space-time clusters were identified using Kulldorff's scan statistic. Analysis of 1015 cases showed highly statistically significant space-time clustering (P < 0.001). Clustering was most marked for cases diagnosed within 1-4 months of one another. A number of specific space-time clusters were identified. In conclusion, these novel results suggest that transient environmental agents may play a role in the cause of PBC.