Hepatocellular carcinoma in patients without cirrhosis

Table 3 Summary of the scores and stage systems in individuals with non-cirrhotic hepatocellular carcinoma

	Controversies	Limitations	Research hotspots
Scores and stage systems
BCLC	New update in 2022, introducing more flexibility and personalized treatment decisions with no strictly stage-based approach could be advantageous for individuals without cirrhosis	Primarily focus on individuals with underlying chronic liver disease, especially with cirrhosis. Not validated in non-cirrhotic individuals	Studies validated the BCLC stage systems in non-cirrhotic individuals with HCC, which evaluate treatment options, long-term outcomes, and explicitly stratified categories for those individuals are needed
Child-Pugh	The use of ascites and encephalopathy may be underestimated due to the common presentation of preserved liver functions observed in individuals without cirrhosis	Designed to evaluate the severity and prognosis in individuals with cirrhosis. Not validated in non-cirrhotic individuals	Studies that validate the Child-Pugh score in individuals with HCC without cirrhosis are needed; Creating a new score potentially without ascites and encephalopathy is needed to compare if the individuals are being underestimated
TNM	It is a valuable staging system for anatomical tumor burden, but is not sufficient alone for accurate HCC treatment guidance or outcomes	Focus on anatomical staging; Best for post-operative prognosis	Studies redefining TNM, evaluating treatment responses, and long-term outcomes are needed
HKLC	Proposed more aggressive treatments with more curative therapy but with potential risk of over-treatment	Developed based on a population predominantly with hepatitis B; Not well validated with other etiologies	Studies validating the stage system in diverse populations with different background etiologies are needed; Studies evaluating treatment options and long-term outcomes are needed
LI-RADS	Only individuals with hepatitis B or cirrhosis benefit from this, but individuals outside these criteria may be leading to a missed diagnosis. No consensus on biopsy, follow-up time, or surveillance in intermediate categories	Designed for individuals with cirrhosis or with HCC-associated hepatitis B; Not well validated with other etiologies	Studies validating the diagnosis in populations with different background etiologies are needed; Studies integrating LI-RADS with biomarkers to improve early HCC detection are needed

BCLC: Barcelona Clinic Liver Cancer; HCC: Hepatocellular carcinoma; HKLC: Hong Kong liver cancer; LI-RADS: Liver imaging reporting and data system TNM: Tumor-node-metastasis.