Worse fatigue at baseline among patients with nonalcohol steatohepatitis-related advanced fibrosis and cirrhosis correlated with a higher risk adverse clinical events, according to published results.

“Although generally considered asymptomatic, almost half of patients with NASH have clinically significant fatigue which, in turn, has a profound negative impact on the overall patient experience,” Zobair M. Younossi, MD, MPH, president of Inova Medicine Services and professor and chairman of the department of medicine at Inova Fairfax Medical Campus in Virginia, and colleagues wrote in Clinical Gastroenterology and Hepatology. “In this context, ongoing clinical trials aim at finding a drug-based therapy for NASH that may reverse fibrosis and could also potentially improve fatigue. Given that, patient-reported outcome instruments are now commonly included in these trials in order to provide a comprehensive assessment of the impact of the investigational drugs on patients and their experience.”

For 2 years, Younossi and colleagues followed 1,679 patients with biopsy-confirmed NASH, of whom 802 had bridging fibrosis (F3) and 877 had compensated cirrhosis (F4). Fatigue was quantified at baseline with the seven-point Chronic Liver Disease Questionnaire (CLDQ)- NASH fatigue domain, in which lower scores indicate worse fatigue. Time to liver-related clinical events, such as progression to histologic cirrhosis or hepatic decompensation in F3 or F4, was assessed with Cox proportional hazard model.

At a median follow-up of 16 months, investigators observed 15% (n = 123) of NASH F3 patients experienced liver-related events, mostly in progression to histologic cirrhosis, and 3.5% (n = 31) of NASH F4 patients experienced hepatic decompensation. Among F3 patients, the mean baseline CLDQ-NASH fatigue score was 4.77, with those who experienced liver-related events reporting lower baseline scores of 4.47 compared with 4.83. Among patients with F4, the mean fatigue score was 4.56, and in those who decompensated, the scores at follow-up were 3.74 compared with 4.59.

After adjusting for confounders, researchers observed a significant correlation between lower fatigue scores and risk for liver-related or decompensation events (adjusted HR = 0.85; 95% CI, 0.74-0.97, per 1 point in fatigue score in F3; aHR = 0.62; 95% CI, 0.48-0.81 in F4).

“This suggests that, in addition to commonly used clinical parameters, presence of clinically significant fatigue can identify NASH patients at risk for adverse events,” the authors wrote. “Since fatigue also negatively impacts patients [health-related quality of life] and work productivity, it adds to the disease burden related to NASH. Given the critical importance of fatigue in NASH, clinical trials of regimens for NASH should not only show improvement of surrogates of clinical endpoints, such as the stage of fibrosis or resolution of NASH, but also improvement in patient-reported endpoints, such as fatigue.”