Fibrosis-4 May Be Effective Tool for Diagnosing Advanced Liver Diseases


It remains a challenge to understand how to stratify risk of liver diseases before they have reached the advanced stage.

The Fibrosis-4 (FIB-4) index may not be a useful indicator of non-alcoholic fatty liver disease (NAFLD); however, it was found to effectively predict chronic hepatitis or cirrhosis in healthy individuals, according to a study published by Scientific Reports.

“We…clarified the usefulness of a high FIB-4 index in predicting the future development of chronic hepatitis or liver cirrhosis in a health checkup setting for the general population,” the study authors wrote.

Worldwide, NAFLD is the most common subset of chronic liver disease and can result in fibrosis that can lead to the development of more severe conditions, including cirrhosis, liver failure, or liver cancer. A liver biopsy is the gold standard prognostic tool for diagnosing liver fibrosis stage. Most experts also use the FIB-4 index, which scores liver fibrosis stage, according to the study. Investigators are now looking at FIB-4 as a tool to predict the development of an advancing liver disease, which is historically challenging to determine.

For the study, the authors compiled 30 years of data on alcohol intake and body mass index (BMI) of generally healthy individuals, evaluating the FIB-4 index’s ability to predict NAFLD, and advanced liver diseases, including chronic hepatitis and liver cirrhosis. Participants were classified by alcohol intake, which includes non-light drinkers (0 to 3 times per month), moderate drinkers (1 to 5 drinks/week), and heavy drinkers (6 to 7 drinks/week), and BMI, including underweight (18.5 or less), normal weight (18.75 to 25), overweight (25 to less than 30), and obese (30 or higher).

The researchers administered abdominal ultrasounds to confirm the presence of fatty liver, chronic hepatitis, or liver cirrhosis over the study period. They found that the scoring system could predict advanced liver diseases more than NAFLD and diseases that had not yet progressed to the advanced stages.

The data showed no significant change in BMI during the study period, despite fatty liver being associated with BMI, so “[FIB-4] was suggested to be more useful…in predicting the future development of chronic hepatitis or liver cirrhosis in a health checkup setting for the general population… than the diagnosis of fatty liver,“ the study authors wrote.

The study includes some limitations, including that the researchers used ultrasound to define chronic hepatitis and cirrhosis, however, ultrasound only detects more advanced forms of these conditions. Additionally, patients dropped out of the long-term follow up, so the results may be underestimated.

Fatty liver disease incidence has dramatically increased over the past 3 decades—cases rose from 21.9% in the 1990s to 35.5% during the 2010s.

“Categorization based on the FIB-4 index value is a much more useful indicator for the future development of chronic hepatitis and liver cirrhosis than the diagnosis of fatty liver,” the study authors wrote. “The importance of the FIB-4 index, which can predict liver fibrosis and the future development of advanced liver diseases, might be greatly increasing.”


Yamamichi, Nobutake, Shimamoto, Takeshi, Okushin, Kazuya, et al. Fibrosis-4 index efficiently predicts chronic hepatitis and liver cirrhosis development based on a large-scale data of general population in Japan. Sci Rep 12, 20357 (2022).

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