Abstract
BACKGROUND: There is no consensus scoring system for staging and prognosis in hepatocellular carcinoma (HCC), which is the fourth leading cause of cancer-related mortality worldwide. Commonly used systems include the albumin-bilirubin (ALBI) score, the Barcelona staging classification (Barcelona Clinic Liver Cancer, BCLC), the Model for End-Stage Liver Disease (MELD), and the model to estimate survival in ambulatory HCC patients (MESIAH). Liver secretion of pseudocholinesterase (PCHE) has been linked to liver function but is poorly studied in the natural history of HCC. We evaluated whether serum PCHE level predicts HCC mortality and whether it enhances existing scoring systems. METHODS: We conducted a retrospective cohort study of individuals diagnosed with HCC. We collected variables including PCHE level, clinical data used in scoring systems, and time to mortality or liver transplant. We then analyzed the association between these variables and survival using Kaplan-Meier curves, Cox proportional hazards regression models, receiver operating characteristic (ROC) curves, and area under the curve (AUC) calculations. RESULTS: We identified 420 individuals with HCC who were tested for PCHE levels, with a follow-up time of more than 20 years. There was a strong inverse relationship between PCHE level and overall survival, with the lowest quartile having high mortality and poor outcomes. Low PCHE level was associated with hepatitis C virus (HCV) infection, vascular invasion, poor liver function, and a high likelihood of liver transplant. In contrast, the highest quartile was associated with metabolic dysfunction-associated steatotic liver disease (MASLD) as the underlying cause. Compared with validated scoring systems, ALBI, BCLC, MELD 3.0, and MESIAH, the PCHE level was an independent predictor of mortality. PCHE levels could predict 3-month survival as well as or better than the other scoring systems, with an AUC of 0.74. PCHE level could also predict mortality related to hepatectomy. The addition of PCHE level to MESIAH and ALBI scoring systems could further improve the ability to predict overall mortality in HCC. CONCLUSIONS: PCHE is a reliable stand-alone biomarker of HCC prognosis. It is an independent predictor of mortality and can improve the accuracy of existing scoring systems. Improved risk stratification could improve outcomes by informing treatment decisions regarding hepatectomy or other interventions.