Higher Mortality Rate for NAFLD Patients With Fatigue

Zobair M. Younossi, MD

Patients with non-alcohol fatty liver disease (NAFLD) who are fatigued are at an increased risk of a number of negative outcomes, including cardiovascular disease, poor sleep, and mortality.

A team, led by Zobair M. Younossi, MD, Betty and Guy Beatty Center for Integrated Research, Inova Health System, determined the prevalence of fatigue and its association with all-cause mortality in patients with NAFLD.

NAFLD and Fatigue

Patients with NAFLD who have fatigue could have worsened health-related quality of life and higher rates of mortality.

In the study, the investigators looked at data on mortality from NHANES 2005-2010 (n = 5,429, mean age 47.1 years, 49.7% male, 69.9% white) and 2017-2018 (n = 3,830, mean age 48.3 years, 48.6% male, 62.3% white).

The investigators defined NAFLD by the fatty liver index for NHANES 2005-2010 and by transient elastography for NHANES 2017-2018. They also assessed fatigue using Patient Health Questionnaires.

In the 2005-2010 cohort, 37.6% of the patient population were diagnosed with NAFLD. In this group, fatigue was more common in the NAFLD group compared to non-NAFLD control participants (8.35% vs 6.0%; P = 0.002).

The numbers were similar in the later cohort.

Here, 36.9% of the patient population was diagnosed with NAFLD.

In this group, fatigue was more pronounced than the non-NAFLD control group (8.7% vs 6.2%).

Negative Outcomes

NAFLD also resulted in a number of other negative outcomes, including sleep disturbance (34.0% vs 26.7%), cardiovascular disease (10.7% vs. 6.3%), significant hepatic fibrosis (liver stiffness > 8.0kPa, 17.9% vs 3.5%), and advanced hepatic fibrosis (> 13.1 kPa, 5.4% vs 0.9%) (all P <0.003).

In addition and outside of a NAFLD diagnosis, the presence of depression (OR, 11.52, 95% CI, 4.45-29.80, P <0.0001), cardiovascular disease (OR, 3.41, 95% CI, 1.02-11.34, P = 0.0462), and sleep disturbance (OR, 2.00; 95% CI, 1.00-3.98; P = 0.0491) were independently associated with fatigue.

On the other hand, good sleep quality (OR, 0.58; 95% CI, 0.35-0.96, P = 0.0366) had an inverse association.

After conducting a multivariable Cox model, the investigators found adults with NAFLD and fatigue had a 2.3-fold higher mortality rate than a cohort of patients with NAFLD without fatigue (HR, 2.31; 95% CI, 1.37-3.89; P = 0.002).

“Fatigue amongst those with NAFLD is associated with increased risk for mortality and is mainly driven by depression, sleep disturbance, and CVD,” the authors wrote. “These findings have important clinical implications.”

NAFLD Rates Worldwide

A new look at NAFLD data show the disease is increasing worldwide and remains especially high among men.

A team, led by Kiarash Riazi, MD, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, examined the burden of NAFLD by estimating the temporal trends of worldwide prevalence and incidence.

In the systematic review and meta-analysis, the investigators searched various databases between inception and May 25, 2021 for observational cross-sectional or longitudinal studies in patient populations representative of the general adult population for which NAFLD was diagnosed using an imaging method in absence of excessive alcohol consumption and viral hepatitis.

Overall, the prevalence of NAFLD worldwide was 32.4% (95% CI, 29.9-34.9%). However, the prevalence of the disease has significantly increased over time, from 25.5% (95% CI, 20.1-31.0%) in or before 2005 to 37.8% (95% CI, 32.4-43.3%) in 2016 or later (P = 0.013).

The prevalence of disease was also higher in men (39.7%; 95% CI, 36.6-42.8%) than it was in women (25.6%; 95% CI, 22.3-28.8) (P <0.0001).

The study, “The Impact of Fatigue on Mortality of Patients with Non-alcoholic Fatty Liver Disease (NAFLD): Data from National Health and Nutrition Examination Survey (NHANES) 2005-2010 and 2017-2018,” was published online in Liver International.