Fatigue and autonomic dysfunction in non-alcoholic fatty liver disease

Fatigue is a significant symptom in non-alcoholic fatty liver disease (NAFLD) that impacts upon quality of life and is unrelated to liver disease severity. We examined the relationship between parameters of blood pressure regulation with perception of fatigue in NAFLD. Thirty-four non-diabetic subjects with histologically proven, non-cirrhotic NAFLD (26 [77%] males and 8 [23%] females) (mean +/- A SD age 54 +/- A 11) and 34 age, sex and BMI matched non-diabetic controls underwent subjective and objective evaluation of cardiovascular autonomic function (24 h blood pressure and head up tilt testing). All subjects completed the fatigue impact scale. The NAFLD group had significantly higher autonomic symptom burden assessed using the orthostatic grading scale (OGS) compared to controls (4 +/- A 4 vs. 1 +/- A 2; p = 0.0003). Increasing orthostatic symptoms correlated with increasing fatigue (p = 0.006; r (2) = 0.3). Fatigue in NAFLD correlated inversely with 24 h measurement of systolic, diastolic and mean blood pressures (all p < 0.03; r (2) = 0.2). This relationship was predominantly related to lower blood pressure at night (p < 0.003; r (2) = 0.3). On head up tilt testing 57% of the NAFLD group had neurally-mediated hypotension (vasovagal syncope and/or orthostatic hypotension) (p = 0.006 compared to controls). The degree of blood pressure drop in response to standing correlated with fatigue severity (p = 0.008; r (2) = 0.3) and the autonomic symptom burden (OGS) (p = 0.03; r (2) = 0.2). Autonomic symptoms are prevalent in NAFLD and associate with objective measures of autonomic dysfunction. Fatigue in NAFLD is associated with lower blood pressure and autonomic dysfunction. Studies are needed to determine whether this is a potential therapeutic target for fatigue in NAFLD.