Fatigue and Pruritus in Patients with Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: The Impact on Patient‐Reported Outcomes

Fatigue and pruritus are common in patients with chronic liver diseases of all etiologies, but clinical awareness is mostly restricted to those with cholestatic liver diseases. We assessed the impact of fatigue and pruritus on patient-reported outcomes (PROs) of patients with advanced nonalcoholic steatohepatitis (NASH). Specifically, PROs (Short Form-36, Chronic Liver Disease Questionnaire-NASH, Euro-Qol 5 Dimension, and Work Productivity and Activity Impairment instruments) were assessed at baseline in patients with histologically confirmed bridging fibrosis (F3) or compensated cirrhosis (F4) due to NASH enrolled in STELLAR 3 and 4. Presence of fatigue and pruritus were indicated by a score of 4 or less on the respective items of the Chronic Liver Disease Questionnaire-NASH (scale range, 1-7). Among the included 1,669 patients with advanced NASH (mean age = 58 ± 9 years, 48% F3, 42% with psychiatric comorbidities), 33% and 27% had fatigue and pruritus, respectively. Patients with NASH with fatigue were younger, more likely to be female, cirrhotic, and diabetic, and had higher body mass index and more comorbidities (all P < 0.05). All PRO scores of patients with fatigue were significantly impaired (mean up to -31% of a PRO range size in comparison to patients without fatigue). In multivariate analysis, predictors of fatigue included diabetes, history of depression or nervous system comorbidities, and lower serum albumin (P < 0.05). Patients with pruritus had demographic characteristics similar to those with fatigue, but a higher prevalence of dermatologic comorbidities. All PROs were impaired (by up to -19% of a range size, all P < 0.01) in patients with NASH with pruritus. Female gender, lower serum albumin, and a history of depression, nervous system, and dermatologic comorbidities were associated with increased risk of pruritus (P < 0.05). Conclusion: Clinically significant fatigue and pruritus are common in patients with advanced NASH, and these symptoms negatively affect PROs.