Non-liver-related mortality can be higher in NAFLD ‘depending on age, fibrosis stage’
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A patient outcomes simulator found that non-liver-related mortality could surpass liver-related mortality in patients with nonalcoholic fatty liver disease, depending on age and fibrosis stage at diagnosis, noted data in JAMA Network Open.
“NAFLD is a slowly progressive disease, therefore ongoing clinical trials evaluating NAFLD and NASH treatments use surrogate markers as primary end points,” Jagpreet Chhatwal, PhD, director of the Institute for Technology Assessment at Massachusetts General Hospital and assistant professor at Harvard Medical School, told Healio. “It is important that patients and providers understand the relationship between surrogate endpoints and long-term adverse outcomes.”
![“Depending on age and fibrosis stage, non-liver-related mortality can be higher than liver-related mortality in NAFLD patients. [For example,] in 65-year-old patients, 10-year non–liver-related mortality is higher than liver-related mortality in all fibrosis stages.” Jagpreet Chhatwal, PhD](/~/media/slack-news/gastroenterology/misc/infographics/2022/1022/hgi0922chhatwal_graphic_01.jpg?w=800)
To estimate long-term outcomes in NAFLD, Chhatwal and colleagues developed a mathematical model using individual state-transition simulation analysis. They also created an interactive online tool, the NAFLD Simulator, which simulates the natural history of NAFLD by age and fibrosis stage at the time of diagnosis and could be used for patient education.
Using this microsimulation model, a patient may transition between different health states which included NAFL, NAFLD-related stages of fibrosis (F0-F4), decompensated cirrhosis, hepatocellular carcinoma and liver transplant. Researchers accounted for three causes of mortality in the model: liver-related, non-liver-related and background mortality.
Chhatwal
The model included 1,000,000 simulated patients (66% women, mean age at baseline, 49 years), all of whom shared similar characteristics with individuals in the NASH Clinical Research Network Study.
According to study results, life expectancy among those aged 49 years at the time of diagnosis was 25.3 years (95% CI, 20.1-29.8) for those with NAFLD-related fibrosis stage F0, 25.1 years (95% CI, 20.1-29.4) for those with F1, 23.6 years (95% CI, 18.3-28.2) for those with F2, 21.1 years (95% CI, 15.6-26.3) for those with F3 and 13.8 years (95% CI, 10.3-17.6) for those with F4.
They further estimated that the 10-year liver-related mortality was 0.1% (95% uncertainty interval [UI], <0.1-0.2), 0.2% (95% UI, 0.1-0.4), 1% (95% UI, 0.6-1.7), 4% (95% UI, 2.5-5.9) and 29.3% (95% UI, 21.8-35.9) for stages F0 to F4, respectively.
The estimated 10-year non-liver-related mortality was 1.8% (95% UI, 0.6-5), 2.4% (95% UI, 0.8-6.3), 5.2% (95% UI, 2-11.9), 9.7% (95% UI, 4.3-18.1) and 15.6% (95% UI, 10.1-21.7) for stages F0 to F4, respectively. Of note, 10-year liver-related and non-liver-related mortality in stage F4 was 7.3-fold and 1.6-fold higher, respectively, than in stage F3.
“Depending on age and fibrosis stage, non-liver-related mortality can be higher than liver-related mortality in NAFLD patients,” Chhatwal added. “For example, in 50-year-old patients with cirrhosis, the 10-year liver-related mortality is higher than non-liver-related mortality. However, in 65-year-old patients, 10-year non-liver-related mortality is higher than liver-related mortality in all fibrosis stages.”
Researchers further reported that cumulative incidence of decompensated cirrhosis and HCC at 10 years was 0.08% (95% UI, 0.05-0.1) and 0.03% (95% UI, 0.02-0.05), respectively, in stage F0; 0.15% (95% UI, 0.1-0.25) and 0.06% (95% UI, 0.03-0.09) in F1; 0.7% (95% UI, 0.5-1) and 0.29% (95% UI, 0.19-0.4) in F2; 2.7% (95% UI, 2.1-3.4) and 1.12% (95% UI, 0.88-1.37) in F3; and 17.2% (95% UI, 15.9-18.6) and 7.88% (95% UI, 7.41-8.67) in F4.
“By translating surrogate marker outcomes into clinical outcomes easily understood by patients and providers, the NAFLD Simulator can be used as an educational tool to increase awareness of the health consequences of NAFLD among patients and medical providers,” Chhatwal said.
He added, “Future research should evaluate outcomes in patients by different comorbidities, such as diabetes and obesity. As more data become available, our model could be extended to evaluate long-term outcomes associated with noninvasive tests, including emerging imaging and serum-based biomarkers.”
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