Ask the author session with Prof. Quentin Anstee

For healthcare professionals managing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, and type 2 diabetes, identifying those at highest risk of adverse outcomes is crucial. The Fibrosis-4 Index (FIB-4) has long been a valuable, non-invasive tool for assessing the presence of advanced liver fibrosis. It’s easy to calculate using standard lab values: platelets, AST, ALT, and age. Known for its strong negative predictive value, FIB-4 is already incorporated into many clinical guidelines for diagnosing fibrosis.

However, recent research is exploring the potential of FIB-4 to go beyond just diagnosing fibrosis. Can it also predict future clinical events? This important question was the focus of a significant longitudinal cohort study recently published in “Lancet Regional Health Europe,” authored by Professor Quentin Anstee, a well-known investigator in the field of MASLD.

Professor Anstee and colleagues aimed to investigate the association between FIB-4 and subsequent liver events, cardiovascular events, and all-cause mortality in individuals with obesity and/or type 2 diabetes examined in routine general practice. This study moved beyond the traditional diagnostic application of FIB-4 to address its potential prognostic utility.

The study utilized a very large primary care database from the United Kingdom, the CPRD database, including 44,481 individuals with obesity and/or type 2 diabetes and at least one calculable FIB-4 score. Individuals with alcohol-related disorders or other chronic liver diseases (except non-alcoholic fatty liver disease) or those on drugs inducing liver disease were excluded. Over a 10-year follow-up period, the researchers tracked the occurrence of liver events, cardiovascular events, and all-cause mortality.

The findings revealed that a raised baseline FIB-4 is indeed prognostically useful for predicting long-term outcomes. During the 10 years of follow-up, there were 979 liver, 6002 cardiovascular, and 8971 mortality events.

Looking at baseline FIB-4 risk groups:

  • At 10 years, the cumulative incidence of liver events was 15% in the high-risk group (>2.67), compared to 3% in the indeterminate group (1.30–2.67) and 1% in the low-risk group (<1.30).
  • Age- and sex-adjusted hazard ratios (HRs) for liver events were significantly elevated in the high-risk (HR 16.46) and indeterminate (HR 2.45) groups compared to the low-risk group.
  • Similar significant associations were found for cardiovascular events and all-cause mortality.

Beyond a single baseline measurement, the study also explored the value of serial FIB-4 measurements. Among 20,433 individuals with at least two FIB-4 measurements, changes in the FIB-4 score over 12 months after baseline were directly associated with the risk of liver events.

Specifically:

  • Compared to individuals with low baseline FIB-4 and no change, those with high baseline FIB-4 saw their risk increase significantly with a one-unit increase in FIB-4 (adjusted HR 24.27).
  • Importantly, for those initially in the high-risk group, a one-unit decrease in FIB-4 was associated with a lower, but still elevated, adjusted HR (10.90) compared to those with high baseline FIB-4 and increasing score.
  • This demonstrates that factoring in the change (delta) in FIB-4 adds additional prognostic value. Serial measurements allow for refining prognostication over time.

These findings underscore the clinical utility of FIB-4 as a prognostic biomarker in addition to its established diagnostic value. Because FIB-4 is easy to deliver, requires standard tests, and is relatively cheap, sequential measurement provides a pragmatic, tractable monitoring biomarker.

While calculating FIB-4 automatically from disparate laboratory systems (like hematology and biochemistry) has historically been a challenge in some healthcare systems, there is a growing trend towards building automated FIB-4 calculation into electronic care records. As technology and interconnectivity advance, this will become increasingly feasible.

To delve deeper into these significant results and their implications for clinical practice, we encourage you to learn directly from Professor Quentin Anstee. He discussed this paper in an “Ask the Author” session. You can also explore the related publication here.
Understanding the prognostic power of FIB-4, especially through serial measurements, offers a valuable tool for risk stratification and monitoring in your patients with obesity and type 2 diabetes.

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