Reduced plasma dehydroepiandrosterone sulfate levels are significantly correlated with fatigue severity in patients with primary biliary cirrhosis

Ahboucha, Samir; Pomier‐Layrargues, Gilles; Vincent, Catherine; Hassoun, Ziad; Tamaz, Raja; Baker, Glen B.; Butterworth, Roger F.

doi:10.1016/j.neuint.2007.06.002

Cited by 17 publications

(13 citation statements)

References 34 publications

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“…Neuroinhibition mediated via GABA‐A receptors was recently proposed by our group as a new pathophysiological mechanism of fatigue in patients with PBC following the findings of reduced levels of a GABA‐A receptor negative allosteric modulator dehydroepiandrosterone sulphate (DHEAS) 30 . Reduced levels of DHEAS (negative GABA‐A modulator), together with increased levels of 3α,5α‐THP and 3α,5β‐THP (positive GABA‐A modulators) would theoretically result in further inhibition through GABA‐A receptors, thus supporting the plausibility of such a mechanism of fatigue in PBC patients.…”

Section: Discussionmentioning

confidence: 99%

Neuroactive steroids and fatigue severity in patients with primary biliary cirrhosis and hepatitis C

Ahboucha

Butterworth

Pomier‐Layrargues

et al. 2008

Neurogastroenterology Motil

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Fatigue is one of the most common non-specific symptoms associated with several disease states including liver diseases. Recently, it was reported that levels of progesterone metabolites such as allopregnanolone (3alpha,5alpha-tetrahydroprogesterone; 3alpha,5alpha-THP) and isopregnanolone (3beta,5alpha-THP) were increased in plasma of patients with chronic fatigue syndrome. We hypothesize that THP metabolites might be associated with fatigue commonly observed in chronic liver diseases. We evaluated fatigue scores and plasma levels of five progesterone metabolites in 16 patients with primary biliary cirrhosis (PBC), 12 patients with chronic hepatitis C (CHC) and 11 age-matched controls. The fatigue impact scale (FIS) ratio was significantly increased (P < 0.01) in patients with PBC and CHC compared to controls. Plasma levels of 3alpha,5alpha-THP and pregnanolone (3alpha,5beta-THP) were significantly increased in PBC and CHC patients. The other progesterone metabolites, i.e. 3beta,5alpha-THP, 3beta,5beta-THP and 3alpha,5alpha-tetrahydrodeoxycorticosterone were either undetectable or detected only in some patients. Plasma levels of 3alpha,5alpha-THP and 3alpha,5beta-THP were found to be significantly higher in patients with fatigue (P < 0.05), while those of patients without fatigue were not significantly different from controls. Both 3alpha,5alpha-THP and 3alpha,5beta-THP are positive allosteric modulators of the gamma-aminobutyric acid type A (GABA-A) receptor and readily cross the blood-brain barrier. The present preliminary findings suggest that increased inhibition through GABA-A receptors due to the accumulation of neuroinhibitory steroids may represent an important pathophysiological mechanism of fatigue in chronic liver diseases.

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Section: Discussionmentioning

confidence: 99%

Neuroactive steroids and fatigue severity in patients with primary biliary cirrhosis and hepatitis C

Ahboucha

Butterworth

Pomier‐Layrargues

et al. 2008

Neurogastroenterology Motil

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“…Each item uses a 5-grade scale with higher scores denoting increased fatigue. Fatigue Impact Scale was applied in many studies regarding fatigue in PBC patients [1,10,[14][15][16][17][18][19][20][21][22][23].…”

Section: Fatigue Impact Scalementioning

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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“…67 reduced plasma levels of dehydro epiandrosterone sulfate are reported in patients with PBC and these levels correlate with the degree of fatigue. 68 therapy with dehydroepiandrosterone sulfate may improve fatigue symptoms experienced during the course of PBC but this hypothesis is untested. 68 human studies Different drugs, such as oral antioxidants, fluvoxamine, fluoxetine, ondansetron, colchicine, uDCa, ciclosporin, nalmefene, modafinil, and methotrexate have been evalu ated in clinical trials for the treatment of fatigue in patients with PBC.…”

Section: Treatment Of Fatiguementioning

confidence: 99%

“…68 therapy with dehydroepiandrosterone sulfate may improve fatigue symptoms experienced during the course of PBC but this hypothesis is untested. 68 human studies Different drugs, such as oral antioxidants, fluvoxamine, fluoxetine, ondansetron, colchicine, uDCa, ciclosporin, nalmefene, modafinil, and methotrexate have been evalu ated in clinical trials for the treatment of fatigue in patients with PBC. 30,69-75 most of these drugs have shown no bene ficial effects on fatigue except modafinil and methotrexate, which have both shown some favorable effects on reducing fatigue.…”

Section: Treatment Of Fatiguementioning

confidence: 99%

Fatigue in primary biliary cirrhosis

Abbas

Jorgensen

Lindor

2010

Nat Rev Gastroenterol Hepatol

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Primary biliary cirrhosis (PBC) is a chronic, autoimmune, cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis of the liver and may need liver transplantation in the late stage of disease. Fatigue and pruritus are the most common symptoms of PBC, but the majority of patients are asymptomatic at first presentation. There is no specific treatment for fatigue in PBC, but modafinil has shown some potential beneficial effects, such as increased energy levels and decreased total sleep time. This Review article discusses the natural history and the measurement of fatigue in patients with PBC. The central and the peripheral mechanisms that have been suggested for the pathogenesis of fatigue in PBC are also discussed and treatment options are reviewed.

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Reduced plasma dehydroepiandrosterone sulfate levels are significantly correlated with fatigue severity in patients with primary biliary cirrhosis

Cited by 17 publications

References 34 publications

Neuroactive steroids and fatigue severity in patients with primary biliary cirrhosis and hepatitis C

Neuroactive steroids and fatigue severity in patients with primary biliary cirrhosis and hepatitis C

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

Fatigue in primary biliary cirrhosis

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