Key takeaways:
- Refined screening criteria reduced the fibrosis screening pool from 60% to 76% of U.S. adults to 22%.
- Those who met the new criteria had sixfold higher 10-year risk for cirrhosis and liver-related mortality.
Researchers have developed a targeted fibrosis screening strategy that reduces the number of adults flagged for testing, doubling case detection while maintaining low risk for future liver disease in those not eligible for screening.
Current guidelines from AGA, American Association for the Study of Liver Diseases and European Association for the Study of the Liver identified 60% to 76% of the U.S. population as eligible for fibrosis screening.
“The major issue with current recommendations is that they are overly broad,” lead study author Laurens A. van Kleef, MD, PhD, a postdoctoral researcher in the department of gastroenterology and hepatology at Erasmus University Medical Center, told Healio. “With limited resources, [near population-level screening] is unfeasible and also unnecessary as the actual risk in this population is still relatively low.”
The screening indicators van Kleef and colleagues developed and validated in a population-based study would reduce the recommended screening group to 19% to 22% of U.S. adults.
“We aimed at providing feasible strategies and with this suggested screening algorithm, we hope that people are more aware and will consider screening,” van Kleef said. “This is important, illustrated by the high prevalence of increased liver stiffness — a proxy of fibrosis — in those targeted for screening with our new indicators.”
Researchers evaluated existing guideline-based indicators for fibrosis screening, including diabetes, obesity, cardiometabolic risk factors and high alanine aminotransferase, as predictors of liver stiffness measurements (LSM) in a derivation cohort. The cohort consisted of National Health and Nutrition Examination Survey data from 5,904 individuals (mean age, 47 years; 49% men) between 2017 and 2020.
Van Kleef and colleagues included subgroups with a minimum 10% prevalence of LSM greater than or equal to 8 kPa.
Based on analysis of the derivation cohort, the researchers recommended screening for individuals with diabetes and either class I to III obesity or an ALT level of at least 30 IU/L.
They also recommended screening all individuals with class III obesity regardless of other risk factors; individuals with class II obesity and an ALT level greater than or equal to 30 IU/L, and; those with class I obesity, an ALT level of at least 30 IU/L and at least three metabolic risk factors.
Using these revised criteria, researchers targeted 22% of the population for screening, identifying 28% with LSM greater than or equal to 8 kPa. Prevalence was just 4% among those not eligible for screening.
Conversely, using current guidelines targeting 60% to 76% of the population, the prevalence of high LSM was only 11% to 14% and just 2% among those not eligible for screening.
The researchers then pooled data from NHANES 2021-2023, the Rotterdam study and the Barcelona cohort to create a validation group of 13,295 individuals (mean age, 60 years; 46.8% men).
In this pooled group, 14% met the revised criteria and prevalence of LSM greater than or equal to 8 kPa was 22% among screening-eligible individuals and 4% among noneligible individuals.
Finally, the researchers evaluated whether the revised criteria could identify people with long-term risk for serious liver outcomes using a prognosis cohort of 282,852 individuals (mean age, 57 years; 43.7% men) from the UK Biobank.
Researchers evaluated incidence of cirrhosis and other liver-related events over a 10-year period.
Screening-eligible individuals in the prognosis cohort had a nearly sixfold higher 10-year risk for incident cirrhosis than those who were not eligible — 0.99% vs. 0.18%. Similarly, the risk for liver-related death also was higher in the screening-eligible group (0.4% vs. 0.07%).
Limitations of the study included uncertainty about high LSM prevalence among smaller subgroups and the possibility of false-positive LSM values, which could be overcome by the availability of serial LSM data.
Future research is needed to validate these screening recommendations over time, according to van Kleef.
“Metabolic risk factors are not static, and screening strategies need to be dynamic as well,” van Kleef said.
For more information:
Laurens van Kleef, MD, PhD, can be reached at gastroenterology@healio.com.
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