A study of more than 40,000 people in Sweden found repeatedly measuring the fibrosis-4 (FIB-4) index in blood every few years can predict the risk of developing severe liver disease. However, the July 1 research in the Journal of Hepatology also found the sensitivity is comparatively low and improved tests are needed for general population screening.
The research team led by Dr. Hannes Hagstrom, a hepatologist at the Karolinska University Hospital and docent at Karolinska Institutet in Sweden, calculated FIB-4 at two time points within five years to determine whether doing so could predict the risk of cirrhosis. They found yes, it could: An increase of one unit in FIB-4 boosted the risk of severe liver disease (adjusted hazard ratio (aHR)=1.81, 95% confidence interval (CI) = 1.67-1.96).
"Based on these data, it seems likely that, in the general population, adding a second measurement of FIB-4 can enhance the identification of individuals at risk of severe liver disease later in life," the authors wrote.
Why measure FIB-4?
Advanced fibrosis is the major predictor of clinically significant outcomes; for instance, people with advanced fibrosis more frequently experience severe liver-related endpoints and have higher overall mortality. The gold standard to diagnose fibrosis is liver biopsy, but that's not a reasonable screening tool in larger populations, especially in a general population or primary care setting, Hagstrom and colleagues wrote.
Could there be a better noninvasive screening test? Several noninvasive scores already exist but their utility is modest, according to research. For the current study, Hagstrom and team sought to determine whether repeated measurements of the commonly used FIB-4 would improve the identification of individuals at risk of severe liver disease compared with a single measurement of FIB-4.
The researchers used data from the population-based Swedish Apolipoprotein Mortality Risk (AMORIS) cohort that underwent blood sampling between 1985 and 1996. The cohort includes 812,073 individuals who were either taking part in yearly routine health check-ups or outpatients in primary care referred for laboratory testing. No individuals were hospitalized at the time of blood sampling.
FIB-4 was calculated at two time points within five years. Incident severe liver disease was determined via Swedish national registers until 2011. After exclusions, the researchers used data from 40,729 people. They found 581 events of severe liver disease. An increase of one unit in FIB-4 was associated with an elevated risk of severe liver disease (aHR = 1.81, 95% CI = 1.67-1.96).
They also found transitioning from a low- or intermediate- to a high-risk group correlated with an increased risk of severe liver disease compared with those consistently in the low-risk group (aHR = 7.99 and 8.64). It wasn't as common to transition in the low-risk group at the first test (13.3%) versus the intermediate- (36.9%) and high-risk group (58.7%).
Hagstrom and colleagues also noticed increased risk in high-risk individuals at both tests (aHR = 17.04, 95% CI = 11.67-24.88), but almost half of all liver events occurred in those consistently in the low-risk group.
|FIB-4 in various risk groups|
|Intermediate at second test||40.6%||74.1%||73.7%|
|High at second test||21.1%||97.4%||96.4%|
|High at both tests||10.5%||99.2%||98.2%|
"A second measurement of FIB-4 within five years of the first was found to improve the identification of individuals at risk of future severe liver disease in this population-based, 27-year follow-up study of more than 40,000 persons," the authors wrote. "However, there were considerable changes in the risk classification over time, with one-third of the population being defined as at intermediate or high risk of having advanced fibrosis on at least one of the two tests."
Future research should evaluate the significance of a change in FIB-4 (or other scores) in other populations, Hagstrom and colleagues suggested.