Central nervous system dysfunction in primary biliary cirrhosis and its relationship to symptoms

McDonald, Claire; Newton, Julia L.; Lai, Hua; Baker, Stuart N.; Jones, David

doi:10.1016/j.jhep.2010.05.036

Cited by 47 publications

(52 citation statements)

References 23 publications

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“…Evidence in favor of an organic CNS process in PBC comes from brain imaging data and neurophysiology studies which suggest the presence of organic brain change. 24,28 In the current study autonomic symptoms associated strongly with cognitive symptoms, fatigue, and with sleep disturbance. The strong associations between autonomic dysfunction, fatigue, problems with cognition, and problems with sleep regulation all provide further support for at least some organic CNS element underpinning the symptom complex in PBC.…”

Section: Discussionsupporting

confidence: 49%

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

et al. 2013

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,4 and the UK-PBC Consortium 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. (HEPATOLOGY 2013;58:273-283)

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Section: Discussionsupporting

confidence: 49%

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

et al. 2013

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“…Paired-pulse trans-cranial magnetic stimulation showed, that PBC patients had a significantly lower central activation before fatiguing exercise and transplanted and non-transplanted patients show similar abnormalities [4]. This finding pointed to potentially irreversible and progressive brain impairment in PBC patients, and it was supported with the results of the other studies.…”

Section: Discussionsupporting

confidence: 78%

“…Fatigue affects between 60% and 80% of PBC patients, with impairment of their quality of life and their perception of their own mental health; it is not related to exercise, nor is it improved by rest [1][2][3]. The combination of fatigue, cognitive symptoms, and sleep disturbances points to central nervous system dysfunction as a contributing factors [4]. There are some evidences that fatigue in PBC is associated with abnormalities of autonomic function (e.g.…”

Section: Introductionmentioning

confidence: 99%

Brain Perfusion Scintigraphy in Evaluation of Pathogenesis of Fatigue in Patients with Primary Biliary Cholangitis (PBC) – A Pilot Study

Raszeja‐Wyszomirska¹,

Zorga²,

Kotulski³

et al. 2017

IJCEMS

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Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease characterized by a breakdown of immune tolerance to mitochondrial and nuclear antigens, causing injury to the biliary epithelial cells. Fatigue is the commonest reported symptom in PBC and has a negative impact on patients' perceived quality of life, often through social isolation. It is unrelated to the severity of liver disease and appears unresponsive to current therapies, including ursodeoxycholic acid and transplantation. Fatigue in PBC is complex, with numerous associated peripheral and central nervous system (CNS) features. Initially, cholestasis causes degenerative CNS change affecting areas of the brain regulating autonomic dysfunction and sleep, and these changes lead directly to some manifestations of fatigue and the associated cognitive impairment. The aim of the study was to examine global cerebral blood flow with brain perfusion scintigraphy SPECT in well-defined group of PBC Caucasian patients with verbally reported fatigue. Twenty consecutive PBC female patients (median age 58.9, ranges 38-80; 4 cirrhotic) with mean duration of the disease 3.3 years, were prospectively enrolled into the study. Fatigue Impact Scale (FIS) questionnaire was administered to every patients at the moment of brain examination. Brain perfusion scintigraphy SPECT was performed after intravenous injection of 760-800 MBq of technetium 99m labeled exametazime ( 99m Tc -HMPAO). Then patients were examined using double head gamma camera system, and data were analyzed with dedicated nuclear medicine software. In analyzed cohort the median FIS score was 70.5 points (ranges 21-160), which was higher than previously reported. There were no correlation between age of patients at the SPECT/FIS examination, duration of the disease, the presence of liver cirrhosis, Mayo Risk Score, and FIS domains: Cognitive, Physical and Social, as well as with brain blood flow. However, positive correlation between Cognitive dimension of FIS measure and right frontal lobe perfusion impairment assessed with SPECT technic (p<0.05) was found. The results of this study showed that right lobe perfusion impairment might impact brain function in PBC. Cognitive dimension was stage-independent symptom in analyzed cohort, and cognitive impairment might be, in turn, associated with functional brain lesion.

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“…This hypothesis is indeed supported by the increase in non-liver-related mortality reported in some population-based studies (26,28) and the growing evidence that patients with PBC may suffer from significant systemic dysfunctions. (29,30) The limitations of our study are inherent to its large-scale design mainly based on the goodwill of voluntary physicians and their declarative data. These include low rate of participation, incomplete exhaustiveness, frequent missing data, and residual uncertainties from unaudited data.…”

Section: Discussionmentioning

confidence: 99%

Large‐scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis

et al. 2017

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The prevalence, clinical characteristics, and outcomes of patients with antimitochondrial antibodies (AMAs), but no clinical evidence of primary biliary cholangitis (PBC), are largely unknown. A prospective study of AMA incidence was conducted through a nation-wide network of 63 French immunology laboratories. Clinical data from 720 of 1,318 AMApositive patients identified in 1 year were collected. Patients were categorized as either newly diagnosed with PBC (n 5 275), previously diagnosed with PBC (n 5 216), or with nonestablished diagnosis of PBC (n 5 229). The latter group was specifically evaluated. Follow-up data were collected for up to 7 years after detection of AMAs. Prevalence of AMApositive patients without evidence of PBC was 16.1 per 100,000. These patients had the following characteristics: 78% female; median age 58 years; median AMA titer 1:160; extrahepatic autoimmune disorders 46%; normal serum alkaline phosphatases (ALP) 74%; ALP above 1.5 times the upper limit of normal 13%; and cirrhosis 6%. Compared to those newly diagnosed with PBC, the patients were slightly younger, had lower AMA titers, and lower sex-ratio imbalance. Among the patients with normal ALP and no evidence of cirrhosis, the 5-year incidence rate of PBC was 16%. Whereas no patients died from PBC, the 5-year survival rate was 75%, as compared to 90% in a control, standardized population matched for age and sex (P < 0.05). Conclusion: Nearly half of the newly detected AMAs in clinical practice does not lead to a diagnosis of PBC. PBC is unrecognized in 13% of those cases. Only 1 in 6 patients with AMAs and normal ALP will develop PBC after 5 years. The mortality of AMA-positive patients without PBC is increased irrespective of the risk of PBC development. (HEPATOLOGY 2017;65:152-163).

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Central nervous system dysfunction in primary biliary cirrhosis and its relationship to symptoms

Cited by 47 publications

References 23 publications

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

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

Brain Perfusion Scintigraphy in Evaluation of Pathogenesis of Fatigue in Patients with Primary Biliary Cholangitis (PBC) – A Pilot Study

Large‐scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis

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