Autonomic nervous system tone measured by baroreflex sensitivity is depressed in patients with end-stage liver disease

Barron, Hal V.; Alam, Imtiaz; Lesh, Michael D.; Strunk, A.; Bass, Nathan M.

doi:10.1016/s0002-9270(99)00055-6

Cited by 13 publications

(9 citation statements)

References 23 publications

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“…However, several potential mechanisms are known. Autonomic dysfunction, including cardiovascular instability, has been demonstrated to be associated with advanced liver disease in a number of settings, including in patients with PBC, and this undoubtedly will be found to contribute to the symptoms described in at least some of the patients 13–15, 35–39. It is most unlikely, however, that such features of advanced disease are responsible for a symptom complex present in almost three quarters of patients given the predominance of early‐stage disease and the very low prevalence of advanced liver disease and/or portal hypertension in the study population.…”

Section: Discussionmentioning

confidence: 94%

Population prevalence and symptom associations of autonomic dysfunction in primary biliary cirrhosis

et al. 2007

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Patients with primary biliary cirrhosis (PBC) frequently experience significant fatigue thought to result from as-yet-unidentified central nervous system (CNS)-mediated processes. Pilot studies have suggested that autonomic dysfunction is a frequent occurrence in PBC and may contribute to the pathogenesis of this fatigue. The degree to which autonomic dysfunction affects the PBC population as a whole, and its interrelationship with other symptoms experienced by PBC patients remains unstudied. In this study, we used a geographically defined, fully representative PBC patient cohort to study the prevalence of symptoms of autonomic dysfunction and its relationship with other symptoms of PBC. Symptoms of cardiovascular autonomic dysfunction (as assessed using the Orthostatic Grading Scale [OGS]) were significantly more frequently reported and significantly more severe in PBC patients than in both matched normal controls (40% versus 6% with moderate or worse orthostasis (P < .0001), mean OGS score 3.2 ؎ 3.4 versus 1.3 ؎ 1.9, P < .005) and in patients with primary sclerosing cholangitis and in severity were independently associated with severity of fatigue and cognitive symptoms (both r 2 ‫؍‬ 0.3, P < .0001). Thirteen of 20 patients with an OGS value > 4 (moderate severity and worse) had significant abnormality in autonomic regulation of blood pressure, which was identified on dynamic testing. Conclusion: Symptoms suggestive of autonomic dysfunction frequently occur in PBC patients and reflect dysregulation of actual blood pressure. Autonomic dysfunction is independently associated with both fatigue and, importantly, symptoms of cognitive dysfunction, suggesting the potential for significant organic sequelae. (HEPATOLOGY 2007;45:1496-1505.) P rimary biliary cirrhosis (PBC) is a chronic cholestatic liver disease affecting up to 1 in 700 women over the age of 40 in western European populations. 1 It has become widely accepted in the last few years that this condition is characterized by profound fatigue that can often significantly impair quality of life. [2][3][4][5][6] The severity of fatigue experienced by PBC patients appears to be unrelated to the degree of hepatocellular dysfunction. 3,4,6 Studies using animal models of cholestasis (exemplified by the bile duct ligated rodent) have suggested that fatigue results from a combination of the biochemical and inflammatory consequences of cholestasis development. 7-10 Studies using these animal models have further suggested that the processes responsible for fatigue pathogenesis are mediated in the central nervous system. More limited studies performed in human PBC patients have indicated the likelihood that central nervous system-mediated processes are similarly important in fatigue pathogenesis in human cholestatic subjects. 11,12 Despite increasing appreciation of the importance of fatigue in the experience of PBC patients and localization of key pathogenetic processes to the central nervous system, the understanding of the precise mechanisms responsible for fatigue ex...

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Section: Discussionmentioning

confidence: 94%

Population prevalence and symptom associations of autonomic dysfunction in primary biliary cirrhosis

et al. 2007

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“…Several studies have reported the presence of an autonomic neuropathy in cirrhosis, and most authors agree that the presence of autonomic dysfunction is related with the severity of liver disease, irrespective of its aetiology (15, 16, 18). A decrease in BRS in cirrhotic patients has been described both in experimental (13, 21, 22) and clinical studies (6, 23–26). In most human studies, the severity of cirrhosis was established according to clinical parameters and Child–Pugh score.…”

Section: Discussionmentioning

confidence: 96%

Baroreceptor sensitivity and baroreceptor effectiveness index in cirrhosis: the relevance of hepatic venous pressure gradient

Genovesi¹,

Pizzala²,

Pozzi³

et al. 2010

Liver International

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These data support the hypothesis that liver disease severity and particularly portal hypertension have an important role in the derangement of baroreceptor function. The aetiology of cirrhosis seems to be related to baroreceptor impairment as well. Mortality rate is higher in subjects with a more damaged autonomic system, strengthening the idea of a worse prognosis in cirrhotic patients with autonomic neuropathy.

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“…Brain cholinergic dysregulation has also been reported in patients with cirrhosis and in models of liver failure (183). Interestingly, alterations in brain cholinergic signaling parallel with lower vagal tone in patients with cirrhosis (184, 185). …”

Section: The Role Of the Central Nervous Systemmentioning

confidence: 99%

Molecular and Functional Neuroscience in Immunity

Pavlov

Chavan

Tracey

2018

Annu. Rev. Immunol.

334

320

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The nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines, and other immune molecules by sensory neurons generates immunoregulatory responses through efferent autonomic neuron signaling. The functional organization of this neural control is based on principles of reflex regulation. Reflexes involving the vagus nerve and other nerves have been therapeutically explored in models of inflammatory and autoimmune conditions, and recently in clinical settings. The brain integrates neuro-immune communication, and brain function is altered in diseases characterized by peripheral immune dysregulation and inflammation. Here we review the anatomical and molecular basis of the neural interface with immunity, focusing on peripheral neural control of immune functions and the role of the brain in the model of the immunological homunculus. Clinical advances stemming from this knowledge within the framework of bioelectronic medicine are also briefly outlined.

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Autonomic nervous system tone measured by baroreflex sensitivity is depressed in patients with end-stage liver disease

Abstract: Vagal tone, as assessed by BRS, is markedly depressed in cirrhotic patients awaiting liver transplantation.

Cited by 13 publications

References 23 publications

Population prevalence and symptom associations of autonomic dysfunction in primary biliary cirrhosis

Population prevalence and symptom associations of autonomic dysfunction in primary biliary cirrhosis

Baroreceptor sensitivity and baroreceptor effectiveness index in cirrhosis: the relevance of hepatic venous pressure gradient

Molecular and Functional Neuroscience in Immunity

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