The Potential Role of Fatigue in Identifying Patients With NASH and Advanced Fibrosis Who Experience Disease Progression

ABSTRACT

Background

/Aim: Fatigue is common in patients with advanced liver disease. We investigated fatigue and clinical outcomes among patients with advanced NASH.

Methods

In this study, patients with biopsy confirmed NASH and bridging fibrosis (F3) or compensated cirrhosis (F4) were followed for up to two years. The CLDQ-NASH fatigue domain at baseline (range 1-7, lower score indicating worse fatigue) quantified fatigue. Cox proportional hazard model was used to study time to liver-related clinical events (progression to histologic cirrhosis or hepatic decompensation in F3, hepatic decompensation in F4).

Results

Of the 1679 NASH patients with fibrosis, 802 had F3; 877 had F4 (age 58±9 years, 40% male, 74% type 2 diabetes). During median follow-up of 16 months (IQR 14-18), 15% (n=123) of NASH F3 patients experienced liver-related events and 3.5% (n=31) of NASH F4 patients experienced hepatic decompensation. Mean baseline CLDQ-NASH fatigue score in F3 patients was 4.77±1.36; NASH F3 patients who experienced liver-related events had lower baseline scores: 4.47±1.36 vs. 4.83±1.35 (p=0.0091). The mean fatigue score in F4 was 4.56±1.44; these scores were lower in patients who decompensated in follow-up: 3.74±1.31 vs. 4.59±1.43 (p=0.0011). The association of lower fatigue scores and risk of liver-related or decompensation events was significant after adjustment for confounders: adjusted hazard ratio (aHR) 0.85 (0.74-0.97), p=0.02, per 1 point in fatigue score in F3; aHR=0.62 (0.48-0.81), p=0.0004, in F4.

Conclusion

Worse fatigue at baseline is associated with a higher risk of adverse clinical events in patients with NASH-related advanced fibrosis and cirrhosis.