Researchers have developed a risk score to identify hepatocellular carcinoma in adults without viral hepatitis or advanced fibrosis, according to a recent study.
In the Veterans Affairs (VA) cohort study, published in JAMA Network Open, the researchers introduced a hepatocellular carcinoma (HCC) risk score for adults without viral hepatitis or decompensated cirrhosis, leveraging data from 6.5 million veterans within the VA health system. Nearly 50% of HCC cases in the United States occur in patients without viral hepatitis, and this study addressed the need for effective screening tools tailored to metabolic- and lifestyle-related risk factors rather than advanced liver disease alone.
The researchers utilized routinely available clinical data—including age, sex, race/ethnicity, body mass index, diabetes status, smoking status, and alcohol use—combined with the Fibrosis-4 (FIB-4) Index to develop a risk score for assessing 10-year HCC risk. The score showed improved discrimination compared with FIB-4 alone (C-statistic, 0.83 vs 0.79) in identifying patients at higher risk without viral hepatitis or cirrhosis. The score performed consistently across various subgroups, including different racial and ethnic backgrounds.
Among the HCC cases, 69.5% of them occurred in participants with FIB-4 scores at or below 3.25, the commonly accepted threshold for advanced fibrosis, indicating a role of metabolic risk factors in HCC incidence. When using a risk score threshold of 58, the model identified 4.7% of the cohort as high risk with an improved balance of false positives compared with FIB-4 alone (23 vs 28 false positives per true positive).
The results indicated that this multivariable HCC risk score, based on routinely available clinical data, could help identify participants with modifiable risk factors, including obesity, diabetes, and alcohol use. Validation in non-VA populations would determine the score's applicability beyond the veteran population.
This study had limitations, including the need for further validation of the risk score outside the VA health system, particularly in settings where additional risk factors may influence HCC outcomes. The observational design also limited control over certain confounding factors, such as past alcohol consumption among abstainers, and the FIB-4 index may vary with age and overestimate fibrosis in some cases as a result of elevated liver enzyme levels.
Full disclosures can be found in the published study.
