FIB-4 Index Misclassifies Many Patients

The Fibrosis-4 (FIB-4) index shows high discordance with liver stiffness measurement (LSM) via transient elastography, suggesting that many patients are misclassified, potentially impacting clinical decisions, according to investigators.

These findings call for a cautious interpretation of low-risk FIB-4 results among patients at greatest risk of misclassification, and/or use of alternative assessment strategies, reported Mazen Noureddin, MD, MHSc, of Houston Methodist Hospital, and coauthors.

swesabobogathobegeuecucheticrithucrufromocaphemaluclemulawromilokuswagucinobegitorilaspouaposididefrolowraprobeseswewrigivepr

“Currently, the AGA/AASLD Pathways recommends identifying patients at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), then using sequential testing with FIB-4 followed by FibroScan to risk-stratify patients,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Yet the performance of the FIB-4 index in this context remains unclear.

“Previous studies have shown FIB-4 to have low accuracy for screening liver fibrosis, especially among obese and diabetic patients,” the investigators wrote. “Thus, there is a concern that classifying patients with FIB-4 can lead to misclassification and missed diagnosis.”

To explore this concern, Dr. Noureddin and colleagues turned to data from the 2017-2020 National Health and Nutrition Examination Surveys, including 5285 subjects at risk for MASLD. Exclusions were made for those with excessive alcohol intake or other liver diseases, resulting in a final cohort of 3741 individuals.

All subjects were classified as low-, indeterminate-, or high-risk for advanced liver fibrosis based on FIB-4 scores. These scores were then compared with liver stiffness measurements (LSM) obtained through transient elastography (FibroScan).

Out of 2776 subjects classified as low-risk by FIB-4, 277 (10%) were reclassified as higher risk by LSM, including 75 (2.7%) who were found to be at high risk. Out of 879 subjects with indeterminate FIB-4 scores, 37 (4.2%) were at high risk according to LSM. Finally, among the 86 subjects classified as high risk by FIB-4, 68 (79.1%) were reclassified as lower risk by LSM, including 54 (62.8%) who were deemed low risk.

Subjects misclassified as low risk by FIB-4 were typically older and had higher waist circumferences, body mass indices, glycohemoglobin A1c levels, fasting glucose levels, liver enzyme levels, diastolic blood pressures, controlled attenuation parameter scores, white blood cell counts, and alkaline phosphatase levels, but lower high-density lipoprotein and albumin levels (all P less than .05). They were also more likely to have prediabetes or diabetes.

“[I]t is important to acknowledge that 10% of the subjects were misclassified as low risk by FIB-4,” Dr. Noureddin and colleagues wrote, including 2.7% of patients who were actually high risk. “This misclassification of high-risk patients can lead to missed diagnoses, delaying crucial medical treatments or lifestyle interventions.”

They therefore suggested cautious interpretation of low-risk FIB-4 results among patients with factors predicting misclassification, or even use of alternative diagnostic strategies.

“Some possible alternatives to FIB-4 include new serum tests such NIS-2+, MASEF, SAFE score, and machine learning methods,” Dr. Noureddin and colleagues wrote. “However, additional confirmatory and cost-effective studies are required to validate the effectiveness of these tests, including studies conducted on the general population.”

The investigators disclosed relationships with AbbVie, Corcept, Galectin, and others.

The Fibrosis-4 (FIB-4) index shows high discordance with liver stiffness measurement (LSM) via transient elastography, suggesting that many patients are misclassified, potentially impacting clinical decisions, according to investigators.

These findings call for a cautious interpretation of low-risk FIB-4 results among patients at greatest risk of misclassification, and/or use of alternative assessment strategies, reported Mazen Noureddin, MD, MHSc, of Houston Methodist Hospital, and coauthors.

swesabobogathobegeuecucheticrithucrufromocaphemaluclemulawromilokuswagucinobegitorilaspouaposididefrolowraprobeseswewrigivepr

“Currently, the AGA/AASLD Pathways recommends identifying patients at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), then using sequential testing with FIB-4 followed by FibroScan to risk-stratify patients,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Yet the performance of the FIB-4 index in this context remains unclear.

“Previous studies have shown FIB-4 to have low accuracy for screening liver fibrosis, especially among obese and diabetic patients,” the investigators wrote. “Thus, there is a concern that classifying patients with FIB-4 can lead to misclassification and missed diagnosis.”

To explore this concern, Dr. Noureddin and colleagues turned to data from the 2017-2020 National Health and Nutrition Examination Surveys, including 5285 subjects at risk for MASLD. Exclusions were made for those with excessive alcohol intake or other liver diseases, resulting in a final cohort of 3741 individuals.

All subjects were classified as low-, indeterminate-, or high-risk for advanced liver fibrosis based on FIB-4 scores. These scores were then compared with liver stiffness measurements (LSM) obtained through transient elastography (FibroScan).

Out of 2776 subjects classified as low-risk by FIB-4, 277 (10%) were reclassified as higher risk by LSM, including 75 (2.7%) who were found to be at high risk. Out of 879 subjects with indeterminate FIB-4 scores, 37 (4.2%) were at high risk according to LSM. Finally, among the 86 subjects classified as high risk by FIB-4, 68 (79.1%) were reclassified as lower risk by LSM, including 54 (62.8%) who were deemed low risk.

Subjects misclassified as low risk by FIB-4 were typically older and had higher waist circumferences, body mass indices, glycohemoglobin A1c levels, fasting glucose levels, liver enzyme levels, diastolic blood pressures, controlled attenuation parameter scores, white blood cell counts, and alkaline phosphatase levels, but lower high-density lipoprotein and albumin levels (all P less than .05). They were also more likely to have prediabetes or diabetes.

“[I]t is important to acknowledge that 10% of the subjects were misclassified as low risk by FIB-4,” Dr. Noureddin and colleagues wrote, including 2.7% of patients who were actually high risk. “This misclassification of high-risk patients can lead to missed diagnoses, delaying crucial medical treatments or lifestyle interventions.”

They therefore suggested cautious interpretation of low-risk FIB-4 results among patients with factors predicting misclassification, or even use of alternative diagnostic strategies.

“Some possible alternatives to FIB-4 include new serum tests such NIS-2+, MASEF, SAFE score, and machine learning methods,” Dr. Noureddin and colleagues wrote. “However, additional confirmatory and cost-effective studies are required to validate the effectiveness of these tests, including studies conducted on the general population.”

The investigators disclosed relationships with AbbVie, Corcept, Galectin, and others.

The Fibrosis-4 (FIB-4) index shows high discordance with liver stiffness measurement (LSM) via transient elastography, suggesting that many patients are misclassified, potentially impacting clinical decisions, according to investigators.

These findings call for a cautious interpretation of low-risk FIB-4 results among patients at greatest risk of misclassification, and/or use of alternative assessment strategies, reported Mazen Noureddin, MD, MHSc, of Houston Methodist Hospital, and coauthors.

swesabobogathobegeuecucheticrithucrufromocaphemaluclemulawromilokuswagucinobegitorilaspouaposididefrolowraprobeseswewrigivepr

“Currently, the AGA/AASLD Pathways recommends identifying patients at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), then using sequential testing with FIB-4 followed by FibroScan to risk-stratify patients,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Yet the performance of the FIB-4 index in this context remains unclear.

“Previous studies have shown FIB-4 to have low accuracy for screening liver fibrosis, especially among obese and diabetic patients,” the investigators wrote. “Thus, there is a concern that classifying patients with FIB-4 can lead to misclassification and missed diagnosis.”

To explore this concern, Dr. Noureddin and colleagues turned to data from the 2017-2020 National Health and Nutrition Examination Surveys, including 5285 subjects at risk for MASLD. Exclusions were made for those with excessive alcohol intake or other liver diseases, resulting in a final cohort of 3741 individuals.

All subjects were classified as low-, indeterminate-, or high-risk for advanced liver fibrosis based on FIB-4 scores. These scores were then compared with liver stiffness measurements (LSM) obtained through transient elastography (FibroScan).

Out of 2776 subjects classified as low-risk by FIB-4, 277 (10%) were reclassified as higher risk by LSM, including 75 (2.7%) who were found to be at high risk. Out of 879 subjects with indeterminate FIB-4 scores, 37 (4.2%) were at high risk according to LSM. Finally, among the 86 subjects classified as high risk by FIB-4, 68 (79.1%) were reclassified as lower risk by LSM, including 54 (62.8%) who were deemed low risk.

Subjects misclassified as low risk by FIB-4 were typically older and had higher waist circumferences, body mass indices, glycohemoglobin A1c levels, fasting glucose levels, liver enzyme levels, diastolic blood pressures, controlled attenuation parameter scores, white blood cell counts, and alkaline phosphatase levels, but lower high-density lipoprotein and albumin levels (all P less than .05). They were also more likely to have prediabetes or diabetes.

“[I]t is important to acknowledge that 10% of the subjects were misclassified as low risk by FIB-4,” Dr. Noureddin and colleagues wrote, including 2.7% of patients who were actually high risk. “This misclassification of high-risk patients can lead to missed diagnoses, delaying crucial medical treatments or lifestyle interventions.”

They therefore suggested cautious interpretation of low-risk FIB-4 results among patients with factors predicting misclassification, or even use of alternative diagnostic strategies.

“Some possible alternatives to FIB-4 include new serum tests such NIS-2+, MASEF, SAFE score, and machine learning methods,” Dr. Noureddin and colleagues wrote. “However, additional confirmatory and cost-effective studies are required to validate the effectiveness of these tests, including studies conducted on the general population.”

The investigators disclosed relationships with AbbVie, Corcept, Galectin, and others.