TY - JOUR
T1 - Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis
AU - El-Serag, Hashem
AU - Kanwal, Fasiha
AU - Ning, Jing
AU - Powell, Hannah
AU - Khaderi, Saira
AU - Singal, Amit G.
AU - Asrani, Sumeet
AU - Marrero, Jorge A.
AU - Amos, Christopher I.
AU - Thrift, Aaron P.
AU - Luster, Michelle
AU - Alsarraj, Abeer
AU - Olivares, Luis
AU - Skapura, Darlene
AU - Deng, Jenny
AU - Salem, Emad
AU - Najjar, Omar
AU - Yu, Xian
AU - Duong, Hao
AU - Scheurer, Michael E.
AU - Ballantyne, Christie M.
AU - Kaochar, Salma
N1 - Publisher Copyright:
© 2024 Author(s) (or their employer(s)).
PY - 2024
Y1 - 2024
N2 - Background: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. Methods: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). 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. 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. Results: We 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. Adding P9 to our clinical model with 10 factors including AFP improved 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. Conclusions: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors.
AB - Background: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. Methods: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). 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. 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. Results: We 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. Adding P9 to our clinical model with 10 factors including AFP improved 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. Conclusions: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors.
KW - ALCOHOL
KW - EPIDEMIOLOGY
KW - HEPATITIS C
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U2 - 10.1136/gutjnl-2024-332034
DO - 10.1136/gutjnl-2024-332034
M3 - Article
C2 - 38365278
AN - SCOPUS:85185971893
SN - 0017-5749
JO - Gut
JF - Gut
M1 - gutjnl-2024-332034
ER -