Alpha-fetoprotein and carbohydrate antigen 19-9 as prognostic biomarkers in acute liver failure: A retrospective study

Abstract

ObjectiveTo investigate the clinical significance of alpha-fetoprotein and carbohydrate antigen 19-9 as potential predictors of outcomes in patients with acute liver failure.MethodsWe conducted a retrospective analysis of 208 patients with acute liver failure admitted to the intensive care unit between 2009 and 2023. Serum alpha-fetoprotein and carbohydrate antigen 19-9 levels were measured on Days 1 and 3, and their prognostic value was evaluated using logistic regression and receiver operating characteristic curve analyses. Patients were stratified by etiologies to assess biomarker performance across different causes of acute liver failure.ResultsNonsurvivors had significantly lower alpha-fetoprotein levels and higher carbohydrate antigen 19-9 levels than survivors on Days 1 and 3 (all p < 0.05). Alpha-fetoprotein levels increased over time in both groups, whereas carbohydrate antigen 19-9 levels increased in nonsurvivors and decreased in survivors. The combination of carbohydrate antigen 19-9 with the Model for End-Stage Liver Disease score significantly improved prognostic accuracy, with an area under the curve value of 0.828, compared with 0.784 for alpha-fetoprotein combined with Model for End-Stage Liver Disease score. Etiology-specific analysis revealed that carbohydrate antigen 19-9 showed the best predictive performance in acetaminophen-induced acute liver failure (area under the curve value = 0.885), whereas alpha-fetoprotein showed better predictive performance in viral hepatitis-associated acute liver failure (area under the curve value = 0.880).ConclusionsAlpha-fetoprotein is a protective prognostic factor, whereas carbohydrate antigen 19-9 enhances outcome prediction, particularly when combined with Model for End-Stage Liver Disease score. Etiology-specific biomarker performance supports tailored prognostic approaches in the management of acute liver failure.

Keywords: Acute liver failure; alpha-fetoprotein; carbohydrate antigen 19-9; prognostic biomarkers; retrospective analysis; survival prediction.

Figure 1.

Flow diagram of the participants analyzed. AFP: alpha-fetoprotein; ALF: acute liver failure; CA19-9: carbohydrate antigen 19-9.

Figure 2.

Analysis of AFP and CA199 levels at admission as predictors of outcomes in patients with ALF. (a) AFP levels at admission were significantly higher in the survival group (p = 0.03) and (b) CA199 levels at admission were significantly different between the survival and nonsurvival groups. The nonsurvival group had higher CA199 levels (p < 0.01). AFP: alpha-fetoprotein; CA19-9: carbohydrate antigen 19-9; ALF: acute liver failure.

Figure 3.

CA19-9 and AFP levels on Days 1 and 3 in the survival and nonsurvival groups. (a) Serum AFP levels and (b) serum CA19-9 levels. *p-value <0.05, **p-value <0.01. CA19-9: carbohydrate antigen 19-9; AFP: alpha-fetoprotein.

Figure 4.

The ROC curve of serum AFP and CA19-9 levels at ICU admission, MELD scores, and their combination for predicting 28-day mortality. (a) Serum AFP levels, MELD scores, and their combination and (b) serum CA19-9 levels, MELD scores, and their combination. ROC: receiver operating characteristic; AFP: alpha-fetoprotein; CA19-9: carbohydrate antigen 19-9; MELD: Model for End-Stage Liver Disease.

Figure 5.

The ROC curve of serum AFP and CA19-9 levels for assessment of the risk level of 28-day mortality in different etiologies. (a) AFP in APAP-induced ALF (n = 67); (b) CA19-9 in APAP-induced ALF (n = 67); (c) AFP in viral hepatitis-associated ALF (n = 48); (d) CA19-9 in viral hepatitis-associated ALF (n = 48); (e) AFP in TCM-induced ALF (n = 46) and (f) CA19-9 in TCM-induced ALF (n = 46). ROC: receiver operating characteristic; AFP: alpha-fetoprotein; CA19-9: carbohydrate antigen 19-9; APAP: acetaminophen; ALF: acute liver failure; TCM: traditional Chinese medicine.