title: Systemic symptoms in non-alcoholic fatty liver disease.
abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in the Western world and the incidence of the disease is constantly increasing. Most patients with NAFLD do not present with symptoms directly attributable to their underlying liver disease. It is increasingly recognized, however, that those with NAFLD describe a range of non-specific symptoms, which include fatigue and daytime sleepiness, may be the presenting problem and can impact dramatically upon quality of life in this patient group. The recognition of systemic symptoms in NAFLD has important implications for patients as many are potentially modifiable with targeted interventions. Fatigue appears to be a significant problem in NAFLD and the severity of fatigue is not associated with severity of NAFLD or any parameters of liver damage. Instead, fatigue in these patients shows a strong relationship with the symptom of daytime sleepiness and autonomic dysfunction. Daytime sleepiness can frequently be associated with obstructive sleep apnoea in those with NAFLD and is therefore treatable with evidence-based interventions. Recent studies have confirmed the presence of autonomic nervous system dysfunction in those with early stages of NAFLD. The presence of autonomic nervous system dysfunction leads to symptoms such as postural dizziness and syncope and is also associated with a number of clinical consequences in hepatic and non-hepatic diseases such as cognitive dysfunction, falls and fall-related injuries. On direct questioning, problems with memory and concentration are frequently described by those with NAFLD, with our studies confirming that 50% of NAFLD patients experience mild cognitive symptoms and up to 46% moderate or severe cognitive impairment. There were no positive correlations between cognitive symptoms and biochemical or histological markers of liver damage severity, confirming that cognitive impairment in early-stage NAFLD is not related to hepatic encephalopathy. Falls are also considered a direct consequence of autonomic nervous system dysfunction, and our work suggests that a history of falls is common in NAFLD (43%). The proportion of recurrent fallers is significantly higher in a NAFLD cohort compared to controls (p = 0.001), with injuries (p = 0.009), emergency medical attention (p < 0.001), fracture rates (p < 0.001) and hospital admission (p < 0.001) all significantly more common in the NAFLD group. Falls and the aforementioned associations were unrelated to the presence of diabetes or the severity of liver disease. A range of systemic symptoms appear to affect those with NAFLD, the severity of which is unrelated to the underlying liver disease severity. The presence of autonomic dysfunction may provide a unifying mechanism for these symptoms and a therapeutic target. Consideration of these symptoms affecting patients with NAFLD and, where possible, effective treatment will lead to improvements in quality of life and enhance the ability of those with NAFLD to function in their daily lives.
authors.affiliation: Biomedical Research Centre in Ageing-Liver Theme, Newcastle University, Newcastle, UK. julia.newton@nuth.nhs.uk
authors.forename: Julia L
authors.initials: JL
authors.lastname: Newton
mesh_terms: D000058:Accidental Falls; D001342:Autonomic Nervous System Diseases / Q000209:etiology; D003072:Cognition Disorders / Q000209:etiology; D005221:Fatigue / Q000209:etiology; D005234:Fatty Liver / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D007024:Hypotension, Orthostatic / Q000209:etiology; D011788:Quality of Life; D012894:Sleep Stages; D013575:Syncope / Q000209:etiology