The specificity of fatigue in primary biliary cirrhosis: Evaluation of a large clinic practice

Abstract

Quality of life is an important concern for patients with chronic liver disease. We sought to describe the frequency, severity, and associations of fatigue, in patients with primary biliary cirrhosis (PBC). We performed association testing between PBC-40 multidomain disease-specific quality of life responses and clinical findings. Three hundred twenty-seven patients from a single clinic with PBC (94% female, 92% AMA-positive) were evaluated. The average age was 57 years and average disease duration 7.2 years. Verbally reported fatigue was noted in 48% but present in the overwhelming majority on PBC-40 completion, with 44% having moderate or severe symptoms. Of those not complaining of fatigue clinically, 25% documented moderate or severe fatigue by questionnaire. Age had an inverse relationship with fatigue (P < 0.01), whereas body mass index (BMI) was positively associated (P < 0.01), as was the presence of pruritus (P < 0.001), sicca symptoms (P < 0.001), depression (P < 0.001), fibromyalgia (P < 0.004), and scleroderma (P < 0.05). For those with varices (P < 0.05) or cirrhosis clinically (P < 0.05), higher fatigue scores were noted, although those who initially presented with noncirrhotic disease had higher scores at the time of testing (P < 0.005). Fatigue was associated with greater use of prescription medication (P < 0.01), in particular for antipruritics (cholestyramine: P < 0.001; rifampin: P < 0.001), proton pump inhibitors (P < 0.002), beta-blockers (P < 0.02), and antidepressants (P < 0.001), whereas those taking calcium and vitamin D appeared less fatigued (P < 0.05). In a multivariate model, calcium and vitamin D use, BMI, stage of disease at diagnosis, as well as symptomatic fatigue or pruritus, were significant. Biochemical response to UDCA was not associated with lower fatigue scores. Conclusion: Attempts at defining the biological basis of fatigue in patients with PBC, and improving its treatment, must account for its multifactoral causes. (HEPATOLOGY 2010;52:562-570)

Impact of primary biliary cirrhosis on perceived quality of life: The UK-PBC national study

“…Taken together, these findings suggest that, whereas fatigue is a highly significant Control values are for an age-and sex-matched control population not preselected for symptom severity who completed a version of the PBC-40 (the PBC-40c) which was validated for completion by non-PBC patients for the purposes of this study and which was found to demonstrate construct validity (Supporting Table 1). In addition to the potentially generic symptom domains demonstrated in this figure, the impact of pruritus and general PBC symptoms was unsurprisingly greater in PBC patients than in matched controls (pruritus: PBC-40 pruritus domain score median 4 [interquartile range 0-9 in PBC patients versus 2 [0-3] in controls, P < 0.0001; general PBC symptoms 16 [12][13][14][15][16][17][18][19][20] versus 10 [8-13], P < 0.0001). Dotted lines for each symptom domain represent the cutoff for clinically significant symptoms (defined as mean value for normal subjects 12 SD).…”

“…Given the previous controversy regarding the impact of depression in the expression of fatigue in PBC, 12,22 we explored the interrelationship between fatigue severity and depression (defined by HADS-D 11 indicating "caseness" for depression). Although a correlation was seen between fatigue severity and HADS-D score (r 2 5 0.49, P < 0.0001) the interrelation between depression and fatigue was complex, involving other symptom sets (Fig.…”

“…Whereas reports of depression are common in the clinical records of patients, detailed psychiatric evaluation has failed to demonstrate major depressive illness. 12,22 This issue is of real importance to patients both in terms of management and perceptions of their illness (both their own and those of others). In the UK population depression, assessed in terms of percentage of patients meeting criteria for "caseness" using the HADS-D, a measure optimized for use in a chronic disease population, was rare as an isolated feature in both fatigued and nonfatigued patients (3% with severe fatigued and <1% with mild or none).…”

“…11 There is also significant debate as to whether these symptoms are a manifestation of the disease process itself, associated processes, or a reflection of the age, gender, and comorbidity of the selected PBC patient populations studied. 12,13 The uncertainty about the nature of the complex symptoms of PBC is compounded by the fact that studies addressing these issues have often been performed in small, selected study populations and in centers with a particular interest in such symptoms.…”

The pathogenesis of chronic fatigue in primary biliary cirrhosis

“…Stwierdzono w nim, że spośród 48% osób skarżących się na zespół przewlekłego zmęczenia aż 44% uznało je w badaniu kwestionariuszowym za objaw o natężeniu co najmniej średnim, ale co istotne -takie nasilenie zespołu przewlekłego zmęczenia podało także 25% badanych, którzy wcześniej nie zgłaszali tej dolegliwości. Pozytywnie z przewlekłym zmęczeniem korelowały wskaźnik masy ciała, świąd skóry, suchość błon śluzo-wych, fibromialgia i sklerodermia [9].…”