Non-cirrhotic Non-alcoholic Fatty Liver Disease Research Articles

Altered clot kinetics in patients with non-alcoholic fatty liver disease

Background. Emerging evidence has linked the presence of non-alcoholic fatty liver disease (NAFLD) with an increased risk for cardiovascular events. We hypothesised that altered clot kinetics and platelet function may contribute to this increased risk. This study compared whole blood clotting kinetics in patients with 1) non-cirrhotic NAFLD (n = 28) and 2) healthy control subjects (n = 22).Methods. Clotting kinetics were assessed in whole blood using thromboelastography (TEG) and assessed for correlations with cardiovascular risk factors.Results. Clot kinetics in patients with NAFLD showed significantly stronger clot development (maximum amplitude (MA); 58.3 ± 6.3 mm vs. 52.0 ± 10.1 mm, p = 0.01) and reduced clot lysis in the presence of thrombin (35 ± 307 vs. 51 ± 267 clot lysis 30 minutes after MA, p = 0.03) compared to control subjects. Clot strength was independently positively associated with body mass index in NAFLD, but not in control subjects. There was a greater platelet contribution to clot strength in patients with NAFLD compared to controls despite similar platelet counts. There was no association between clot kinetics and features of the metabolic syndrome or presence of type 2 diabetes.Conclusion. Patients with NAFLD have disturbances in ex-vivo clot kinetics including increased clot strength and clots that are more resistant to thrombin-stimulated lysis.

Fatigue and autonomic dysfunction in non-alcoholic fatty liver disease

Fatigue is a significant symptom in nonalcoholic 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 +/- SD age 54 +/- 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 +/- 4 vs. 1 +/- 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.