Dysregulated Neurovascular Control Underlies Declining Microvascular Functionality in People With Non-alcoholic Fatty Liver Disease (NAFLD) at Risk of Liver Fibrosis

Abstract

Background/Aims: Increasing evidence shows that non-alcoholic fatty liver disease (NAFLD) is associated with dysregulation of microvascular perfusion independently of established cardio-metabolic risk factors. We investigated whether hepatic manifestations of NAFLD such as liver fibrosis and liver fat are associated with microvascular hemodynamics through dysregulation of neurovascular control. Methods: Microvascular dilator (post-occlusive reactive hyperemia) and sympathetically mediated constrictor (deep inspiratory breath-hold) responses were measured at the forearm and finger, respectively, using laser Doppler fluximetry. Non-linear complexitybased analysis was used to assess the information content and variability of the resting blood flux (BF) signals, attributable to oscillatory flow-motion activity, and over multiple sampling frequencies. Results: Measurements were made in 189 adults (113 men) with NAFLD, with (n = 65) and without (n = 124) type 2 diabetes mellitus (T2DM), age = 50.9 ± 11.7 years (mean ± SD). Microvascular dilator and constrictor capacity were both negatively associated with age (r = −0.178, p = 0.014, and r = −0.201, p = 0.007, respectively) and enhanced liver fibrosis (ELF) score (r = −0.155, p = 0.038 and r = −0.418, p < 0.0001, respectively). There was no association with measures of liver fat, obesity or T2DM. Lempel-Ziv complexity (LZC) and sample entropy (SE) of the BF signal measured at the two skin sites were associated negatively with age (p < 0.01 and p < 0.001) and positively with ELF score (p < 0.05 and p < 0.0001). In individuals with an ELF score

Risk of Heart Failure in Patients With Nonalcoholic Fatty Liver Disease

“…In another study of 496 individuals, Liu et al reported that HRV measures, as detected by 5-min resting electrocardiograms, were lower in individuals with ultrasounddetected NAFLD than in those without NAFLD (16). Similarly, Clough et al found that dysregulated neurovascular control underlined declining microvascular functionality in 189 patients with radiological or biopsy-proven NAFLD (17). A strong association between NAFLD (on ultrasonography) and impaired cardiac sympathetic/parasympathetic balance, regardless of the presence or absence of T2D and other cardiometabolic risk factors, was also recently confirmed in the Cooperative Health Research in South Tyrol-NAFLD substudy (n=356 individuals included) (18).…”

Association between non-alcoholic fatty liver disease and impaired cardiac sympathetic/parasympathetic balance in subjects with and without type 2 diabetes—The Cooperative Health Research in South Tyrol (CHRIS)-NAFLD sub-study

“…In a study including 46 UK patients with NAFLD, 16 patients with hepatic steatosis and excessive alcohol intake (i.e., having a dual aetiology fatty liver disease, DAFLD) and 34 control subjects, Houghton et al reported that both individuals with NAFLD and those with DAFLD had impaired CANS function (assessed by HRV measures using power spectral analysis) when compared to control subjects [20]. Similarly, in a study of 189 subjects with biopsy-proven NAFLD, it has been shown that dysregulated neurovascular control underlies declining microvascular functionality in adults with NAFLD, suggesting a mechanistic role for dysregulated neurovascular control of the vasculature in NAFLD [37]. Some small studies have also reported the presence of impaired heart recovery index after exercise (treadmill test) in individuals with NAFLD [38,39].…”

Energy Dynamics in the Metabolic Syndrome: Underpinnings of an Evolving Global Catastrophe

“…NAFLD composes a spectrum ranging from accumulation of fat in hepatocytes to progressive fibrosis, cirrhosis and liver failure [212][213][214][215][216][217]. Underlying dynamic causes are microvascular dysfunction [218][219][220][221][222][223][224][225][226][227][228][229][230], IR [231][232][233][234][235][236][237][238][239], mitochondrial dysfunction [240][241][242][243][244][245][246][247] and inflammation [248][249][250][251][252][253][254][255][256].…”