The impact of fatigue on mortality of patients with non‐alcoholic fatty liver disease: Data from National Health and nutrition examination survey 2005–2010 and 2017–2018

Abstract Objective Fatigue among patients with NAFLD may negatively impact their health‐related quality of life and clinical outcomes (mortality). We determined fatigue prevalence and its association with all‐cause mortality among patients with NAFLD. Design NHANES 2005–2010 and 2017–2018 data were used with linked mortality data. NAFLD was defined by fatty liver index for NHANES 2005–2010 and by transient elastography for NHANES 2017–2018. Fatigue was assessed by Patient Health Questionnaire. Results NHANES 2005–2010 cohort ( n = 5429, mean age 47.1 years, 49.7% male, 69.9% white), 37.6% had NAFLD. Compared to non‐NAFLD controls, fatigue was more common in NAFLD (8.35% vs 6.0%, p = .002). Among NHANES 2017–2018 cohort ( n = 3830, mean age 48.3 years, 48.6% male, 62.3% white), 36.9% had NAFLD. Compared to non‐NAFLD controls, fatigue was more common among NAFLD (8.7% vs 6.2%). NAFLD had more sleep disturbance (34.0% vs 26.7%), cardiovascular disease (CVD) (10.7% vs. 6.3%), significant hepatic fibrosis (liver stiffness>8.0 kPa, 17.9% vs 3.5%) and advanced hepatic fibrosis (>13.1 kPa, 5.4% vs 0.9%; all p < .003). The presence of depression (OR: 11.52, 95% CI: 4.45–29.80, p < .0001), CVD (OR: 3.41, 95% CI: 1.02–11.34, p = .0462) and sleep disturbance (OR: 2.00, 95% CI: 1.00–3.98, p = .0491) was independently associated with fatigue; good sleep quality (OR: 0.58, 95% CI: 0.35–0.96, p = .0366) had an inverse association. By multivariable Cox model, NAFLD adults with fatigue experienced 2.3‐fold higher mortality than NAFLD without fatigue (HR: 2.31, 95% CI: 1.37–3.89, p = .002). Conclusions Fatigue among those with NAFLD is associated with increased risk for mortality and is mainly driven by depression, sleep disturbance and CVD. These findings have important clinical implications.