Adding factors to FIB-4 improves early identification of patients with risk of HCC

A risk score developed using routinely available clinical data outperformed the Fibrosis-4 Index (FIB-4) at identifying patients at risk of hepatocellular cancer (HCC) who didn't have viral hepatitis or cirrhosis, a cohort study found.

Researchers analyzed Veterans Affairs data on 6,509,288 patients (92.9% male; median age, 65 years) to develop the score, which took into account age, sex, race and ethnicity, body mass index, diabetes status, smoking status, alcohol use, and FIB-4 score. All included patients were between the ages of 30 and 95 years and were followed until HCC diagnosis, death, or Dec. 31, 2021. Any patient with hepatitis B or C virus infection, hepatic decompensation, or prevalent HCC at baseline was excluded. Outpatient visits between October 2007 and March 2020 were used as index dates, and patients were divided into development (5,119,775 patients) and validation (1,389,513 patients) samples. Findings were published by JAMA Network Open on Nov. 6.

A total of 15,142 patients (0.2%) developed HCC, 69.5% of whom had a FIB-4 score of 3.25 or lower at baseline. In the development sample, discrimination of the model was better than FIB-4 alone (C statistic, 0.83 [95% CI, 0.82 to 0.85] vs. 0.79 [95% CI, 0.77 to 0.80]). The new model performed consistently well in the validation sample and all subgroups, with FIB-4 being the most important variable, followed by diabetes status and age. Researchers found that a FIB-4 threshold of 3.25 would identify 5% of the cohort at a cost of 28 false positives for every true positive. A model risk score of 58 would identify 4.7% of the cohort at a cost of 23 false positives for every true positive. Obesity and diabetes were independently associated with HCC, and patients who identified as Hispanic had the greatest risk for HCC, especially those with a FIB-4 score higher than 3.25.

Researchers were unable to identify confounding variables not routinely collected in the electronic health record, such as past alcohol consumption among current abstainers, among other limitations.

“Screening for HCC could serve both primary and secondary prevention goals if conducted when major risk factors remain modifiable and if it detects HCC at a point when curative treatment remains an option,” the researchers wrote. They concluded that “As the incidence of HCC continues to increase in tandem with the burden of obesity, the use of algorithms to stratify patients by HCC risk can guide patient-centered care.”