HOUSTON — It can be difficult to determine which patients with cirrhosis will go on to develop hepatocellular carcinoma (HCC).
Noting that “inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies,” a study team led by the Michael E. DeBakey VAMC and the Baylor College of Medicine, both in Houston, has developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study.
The researchers used data and banked serum from a prospective cohort of 2,266 adult patients with cirrhosis who were followed until 126 of them developed HCC. Their results were published in the journal Gut.1
“We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC,” the investigators explained. “We performed bootstrapping to evaluate the predictive performance using C-index and time-dependent area under the receiver operating characteristic curve (AUROC). We quantified the incremental predictive value of the biomarker panel when added to previously validated clinical models.”
Ultimately, the study identified a nine-biomarker panel (P9) with a C-index of 0.67 (95% CI 0.66 to 0.67), including:
- insulin growth factor-1,
- interleukin-10,
- transforming growth factor β1,
- adipsin,
- fetuin-A,
- interleukin-1 β,
- macrophage stimulating protein α chain,
- serum amyloid A and
- TNF-α.
The effort also added P9 to the clinical model with 10 factors including alpha-fetoprotein and improved prediction, indicated as AUROC, at 1 and 2 years by 4.8% and 2.7%, respectively. Adding P9 to aMAP score improved AUROC at 1 and 2 years by 14.2% and 7.6%, respectively. Adding AFP L-3 or DCP did not change the predictive ability of the P9 model, however, the researchers reported.
“We identified a panel of nine serum biomarkers that are independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors,” the study authors concluded.
- El-Serag H, Kanwal F, Ning J, Powell H, et. Al. Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis. Gut. 2024 Feb 16:gutjnl-2024-332034. doi: 10.1136/gutjnl-2024-332034. Epub ahead of print. PMID: 38365278.
