Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review

Abstract

The most common primary liver cancer is hepatocellular carcinoma (HCC), and its mortality rate is increasing globally. The overall 5-year survival of patients with liver cancer is currently 10–20%. Moreover, because early diagnosis can significantly improve prognosis, which is highly correlated with tumor stage, early detection of HCC is critical. International guidelines advise using α-FP biomarker with/without ultrasonography for HCC surveillance in patients with advanced liver disease. However, traditional biomarkers are sub-optimal for risk stratification of HCC development in high-risk populations, early diagnosis, prognostication, and treatment response prediction. Since about 20% of HCCs do not produce α-FP due to its biological diversity, combining α-FP with novel biomarkers can enhance HCC detection sensitivity. There is a chance to offer promising cancer management methods in high-risk populations by utilizing HCC screening strategies derived from new tumor biomarkers and prognostic scores created by combining biomarkers with distinct clinical parameters. Despite numerous efforts to identify molecules as potential biomarkers, there is no single ideal marker in HCC. When combined with other clinical parameters, the detection of some biomarkers has higher sensitivity and specificity in comparison with a single biomarker. Therefore, newer biomarkers and models, such as the Lens culinaris agglutinin-reactive fraction of Alpha-fetoprotein (α-FP), α-FP-L3, Des-γ-carboxy-prothrombin (DCP or PIVKA-II), and the GALAD score, are being used more frequently in the diagnosis and prognosis of HCC. Notably, the GALAD algorithm was effective in HCC prevention, particularly for cirrhotic patients, regardless of the cause of their liver disease. Although the role of these biomarkers in surveillance is still being researched, they may provide a more practical alternative to traditional imaging-based surveillance. Finally, looking for new diagnostic/surveillance tools may help improve patients’ survival. This review discusses the current roles of the most used biomarkers and prognostic scores that may aid in the clinical management of HCC patients.

Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

“…It has also been implicated in the development and progression of HCC along with drug resistance in HCC cells[ 49 ]. However, only 60%–70% of HCC cases show elevated AFP levels, while 30%–40% of patients have normal values[ 50 , 51 ]. Newer biomarkers and models such as lens culinaris agglutinin-reactive fraction of AFP, des-carboxy-prothrombin, and GALAD scores (gender, age, AFP-L3, AFP, and DCP) are being increasingly used by various centers around the world[ 52 , 53 ].…”

Diagnostic and Prognostic Nomograms for Hepatocellular Carcinoma Based on PIVKA-II and Serum Biomarkers

“…The occurrence and development of HCC involves a multi-step evolutionary process from the molecular to the clinical level, characterized by marked abnormalities in liver function, including liver enzymes, metabolism, and protein synthesis function [ 38 ]. Emerging evidence suggests that the imbalance of tumor and blood coagulation disorders promotes tumor growth, invasion, and metastasis [ 39 , 40 ].…”

Exploring predictive markers for liver failure post-hepatectomy in hepatocellular carcinoma patients

“…The use of a large sample size and the division of patients into modeling and validation cohorts strengthens the study's validity. The high concordance between predicted and actual events in the study emphasizes the potential of these markers as tools for better clinical decision-making[ 2 ].…”