22, 31 In our study, neither the AMA at diagnosis nor that at questionnaire was associated with fatigue (P > 0.05), hence not supporting this hypothesis. Using a backwards selection
procedure to perform multivariate analysis, with significance defined as P < 0.05, we identified calcium and vitamin D use, elevated BMI, stage of disease at diagnosis, presence of varices, clinically reported fatigue at questionnaire, and pruritus as the significant predictors of fatigue when evaluated formally in the PBC-40 questionnaire (Table 5). This broad modeling of our data reinforces the concept that fatigue in PBC is multifactoral. Within each variable it remains highly likely that there are related factors that we are unable to capture or define accurately that contribute to fatigue severity. The Toronto criteria for treatment response is derived from this clinic practice and predicts no histological progression Ixazomib at 10 3Methyladenine years if patients have ALP values less than 1.67 × upper limit of normal after 2 years of UDCA.30 Comparative criteria were also applied as per Pares (normalization of ALP or >40% reduction of ALP after 1 year of UDCA)28 and Corpechot
(ALP <3 × upper limit of normal and aspartate aminotransferase less than 2 × upper limit of normal and bilirubin less than 1 mg/dL after 1 year of UDCA).29 Student t tests were used to compare PBC-40 responses between treatment responders and nonresponders. Complete biochemistries for at least one treatment response were available in 261 patients. As demonstrated in Table 6, there were significantly lower symptom scores in all domains other than Fatigue and Cognition, if patients responded as per the Toronto definition. Thymidine kinase Applying the alternative definitions of treatment response also demonstrated significantly lower total PBC-40 scores in responders than
in nonresponders (range, 8.7-14.9 points lower; P < 0.05). Itch scores were significantly lower, absolute difference 1.1-1.9, according to the Toronto (P = 0.02) and Corpechot (P = 0.001) criteria, but not Pares (P = 0.71). Responders by any criteria scored lower values in the Social and Emotional domains; range 3.5-4.1 points lower; P < 0.05. Fatigue is a common but complex symptom that is poorly understood and lacks effective treatment. Up to 85% of patients with PBC will complain of fatigue, and it is often a symptom that negatively impacts on the quality of life of patients, as well as having been suggested to be associated with early mortality.32 In this study, we set out to explore and describe the frequency and severity of fatigue in patients with PBC, through the use of a multidomain disease-specific QOL tool, the PBC-40, and to specifically define the role of comorbidities in fatigue. We confirm the importance of this symptom for patients with PBC but clearly show the relevance of comorbidities in determining fatigue severity.