Patient-reported outcomes (PROs) of quality of life and function were significantly lower in patients with non-alcoholic steatohepatitis (NASH) with advanced fibrosis compared to the general population, data from the two STELLAR clinical trials revealed.
Among the over 1,600 NASH patients with available PRO data, F4 fibrosis led to score reductions of 4.4% to 12.9% in six out of eight Short Form-36 (SF-36) domains, while F3 fibrosis was tied to score reductions of 3.9% to 11.7% in four of eight domains (P<0.01), Zobair M. Younossi, MD, MPH, of Inova Health Systems in Falls Church, Virginia, and colleagues reported.
“Treatment of patients with NASH should focus on improving not only clinical outcomes but also quantifiable symptom burden and health-related quality of life,” the authors wrote in Clinical Gastroenterology and Hepatology.
They explained that fibrosis is the only histologic feature of NASH associated with long-term outcomes, including impairment of health-related quality of life.
“Most physicians think that NASH is an asymptomatic disease,” Younossi told MedPage Today. This study suggests, however, that NASH patients have significant impairment of their quality of life and as the stage of fibrosis increases, quality of life worsens. “Therefore, as new treatment regimens for NASH are developed, it is important they address patient-reported outcomes, which are surrogates of patients’ experience with their disease,” he said.
The two phase III STELLAR trials (NCT03053050 and NCT03053063) evaluated selonsertib, an investigational small-molecule inhibitor of ASK1, a pro-inflammatory protein that promotes apoptosis and fibrosis in settings of oxidative stress such as NASH. The trials were launched in 2017-18 in 27 countries in North and South America, Europe, Asia, Australia, and New Zealand, with an anticipated total duration of approximately 7 years and up to 240 weeks of treatment.
Of 1,679 biopsy-confirmed NASH patients enrolled, 1,667 had available pre-treatment PRO data based on SF-36, EuroQol’s EQ-5D, the Chronic Liver Disease Questionnaire (CLDQ)-NASH, and the Work Productivity and Activity Impairment: Specific Health Problem.
The cohort comprised 870 patients with NASH plus cirrhosis and 797 with NASH and bridging fibrosis. Patients were an average age of 58 years, and the cohort was 40% male, 73% white, 22% Asian, and 55% U.S.-enrolled. The mean body mass index (BMI) was 33.5, 74% were diabetic, and 49% were employed. In addition, 52% had cirrhosis and 74% had diabetes.
Compared with patients who had F3 stage fibrosis, a higher proportion of patients with F4 stage were female and white, and more had hematologic and gastrointestinal comorbidities and type 2 diabetes (P≤0.01).
In comparison with F3 fibrosis patients, those with F4 fibrosis had lower scores on CLDQ-NASH, EQ-5D, and the SF-36’s role in physical, bodily pain, and social functioning domains (P≤0.01).
Factors independently associated with lower PRO scores included cirrhosis, female sex, higher BMI, and history of smoking and diabetes or other comorbidities such as psychiatric problems (P<0.01). The impact of these factors on PROs was similar to that reported earlier by Younossi's group for chronic hepatitis C.
The authors stressed that their current results need verification in broader and more diverse patient populations.
Commenting on the findings, Po-Hung (Victor) Chen, MD, of Johns Hopkins Medicine in Baltimore, who was not involved in the research, commended the authors for using the patient data from the STELLAR trials to go beyond clinical outcomes and focus on quality of life: “This analysis is important because there’s not a lot of concrete data in this area,” he said.
“In a way, the findings support what we already see in clinical practice, that patients with advanced fibrosis have not just poor clinical outcomes but also poor quality of life. If you can quantify that phenomenon with actual numbers, you can go beyond practice and use the data for health economics, resource allocation, and health policy decisions. We need the actual numbers to make impactful healthcare changes,” Chen said.
Study limitations, the researchers said, included the highly selected study population and the lack of non-NASH controls or patients with less advanced stages of NASH. In addition, the clinical trial source of the data limits generalizability of results to real-world practice. Furthermore, NASH patients with significant comorbidities and on certain medications were excluded, and the study’s use of several PRO instruments could theoretically increase the risk of false-positive findings. Finally, these ongoing trials could not provide longitudinal data relating progression or regression of NASH and fibrosis to changes in PRO scores, Younossi and co-authors stated.