Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging

Grover, V. P. B.; Southern, Louise; Dyson, Jessica; Kim, J. U.; Crossey, Mary M.E.; Wylezinska-Arridge, Marzena; Patel, Neeral; Fitzpatrick, Julie; Bak-Bol, Aluel; Waldman, Adam D.; Alexander, Graeme; Mells, George; Chapman, Roger W.; Jones, David; Taylor-Robinson, Simon D

doi:10.1111/apt.13797

Cited by 31 publications

(22 citation statements)

References 44 publications

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“…Magnetic resonance spectroscopy and positron emission tomography studies prove neuroinflammation in HCV‐afflicted patients . Similar MRS studies of the brain comparing controls to HBV or PBC patients found no difference, though in very small patient groups . So far, similar studies are missing for AIH.…”

Section: Discussionmentioning

confidence: 90%

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Neuropsychiatric symptoms in hepatitis C patients resemble those of patients with autoimmune liver disease but are different from those in hepatitis B patients

Dirks

Haag

Pflugrad

et al. 2019

Journal of Viral Hepatitis

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Chronic fatigue, mood alterations and cognitive impairment are frequent accessory symptoms of HCV-infection. Fatigue and mood alterations have also been observed in autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but not in hepatitis B virus (HBV)-infection, thus indicating an autoimmune response as possible cause of HCV-infection associated encephalopathy. Data, however, are sparse. This study aims to prove that HCV patients feature similar to those with autoimmune liver disease but contrary to HBV patients regarding neuropsychiatric symptoms. 132 non-cirrhotic patients (HCV: 46, HBV: 22, AIH: 27, PBC: 29, AIH/PBC: 8) completed questionnaires addressing the domains mentioned above. Eighty-eight underwent a comprehensive neuropsychological assessment. Patient groups were compared among each other and to 33 healthy controls. Fatigue, anxiety and depression scores were significantly increased, and the SF-36 mental score significantly decreased in all patient groups compared to controls. Fatigue was significantly more pronounced in HCV than in HBV patients. HCV patients scored significantly worse than HBV patients but not AIH and PBC patients in the SF-36. HCV, AIH and PBC but not HBV patients did significantly worse than controls in word learning. Recognition of words was impaired in HCV, AIH and PBC patients and recognition of figures in HCV patients, exclusively (p≤0.002). HCV patients did also worse than controls and HBV patients concerning alertness and working memory (p≤ 0.001). The neuropsychiatric profiles of HCV patients are similar to those of AIH and PBC patients but differ from those of HBV patients, suggesting an autoimmune response as a possible cause for these differences. This article is protected by copyright. All rights reserved.

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Section: Discussionmentioning

confidence: 90%

“…38,39,41,42 Similar MRS studies of the brain comparing controls to HBV or PBC patients found no difference, though in very small patient groups. 43,44 So far, similar studies are missing for AIH.…”

Section: Discussionmentioning

confidence: 99%

Neuropsychiatric symptoms in hepatitis C patients resemble those of patients with autoimmune liver disease but are different from those in hepatitis B patients

Dirks

Haag

Pflugrad

et al. 2019

Journal of Viral Hepatitis

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“…The basal ganglia changes mirror those seen in cirrhosis of all aetiologies, but in PBC are seen in noncirrhotic patients. Indeed, MR changes are seen in PBC in patients within 6 months of diagnosis . The nature of the relationship of early brain change in PBC and similar change in cirrhotic disease is not clear.…”

Section: Fatigue In Liver Diseasementioning

confidence: 99%

Fatigue in chronic liver disease: New insights and therapeutic approaches

Swain

Jones

2018

Liver International

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The management of fatigue associated with chronic liver disease is a complex and major clinical challenge. Although fatigue can complicate many chronic diseases, it is particularly common in diseases with an inflammatory component. Fatigue can have both peripheral (i.e., neuromuscular) and central (i.e., resulting from changes in neurotransmission within the brain) causes. However, fatigue in chronic liver disease has strong social/contextual components and is often associated with behavioural alterations including depression and anxiety. Given the increasing awareness of patient-reported outcomes as important components of treatment outcomes and clinical research, there is a growing need to better understand and manage this poorly understood yet debilitating symptom. Although several pathophysiological mechanisms for explaining the development of fatigue have been generated, our understanding of fatigue in patients with chronic liver disease remains incomplete. A better understanding of the pathways and neurotransmitter systems involved may provide specific directed therapies. Currently, the management of fatigue in chronic liver disease can involve a combined use of methods to beneficially alter behavioural components and pharmacological interventions, of which several treatments have potential for the improved management of fatigue in chronic liver disease. However, evidence and consensus are lacking on the best approach and the most appropriate biochemical target(s) whilst clinical trials to address this issue have been few and limited by small sample size. In this review, we outline current understanding of the impact of fatigue and related symptoms in chronic liver disease, discuss theories of pathogenesis, and examine current and emerging approaches to its treatment.

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“…It is postulated that chronic cholestasis and inflammation impact autonomic centers in central nervous system leading to cognitive impairments and sleep disturbances. The neuroimaging abnormalities suggest that the brain changes seen in PBC occur early in the pathological process, even before significant liver damage has occurred [24,25]. Cognitive impairment in PBC patients was previously reported by groups of Raszeja-Wyszomirska et al [26] and Newton et al [27] as the symptom independent of liver disease severity and associated with poorer performance on objective cognitive testing.…”

Section: Discussionmentioning

confidence: 53%

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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Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging

Cited by 31 publications

References 44 publications

Neuropsychiatric symptoms in hepatitis C patients resemble those of patients with autoimmune liver disease but are different from those in hepatitis B patients

Neuropsychiatric symptoms in hepatitis C patients resemble those of patients with autoimmune liver disease but are different from those in hepatitis B patients

Fatigue in chronic liver disease: New insights and therapeutic approaches

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

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