Hepatocellular carcinoma in patients without cirrhosis

Table 4 Clinical comparison of individuals with and without cirrhosis with hepatocellular carcinoma in systemic therapy

	Cirrhotic	Non-cirrhotic
Liver function	Impaired (Child-Pugh A, B, C)	Preserved
Therapeutic flexibility	Limited	Higher freedom for the TKI and IO combination
Toxicity risk	High (decompensation, bleeding, and encephalopathy)	Low (better tolerance)
Clinical trial inclusion	Most Child-Pugh A (B or C are typically excluded)	No well-classified
TKI use	Reduced dose in Child-Pugh B, and avoided in Child-Pugh C	Full dose (according to guidelines)
IO	Can be used in Child-Pugh A, but has uncertain use in Child-Pugh B or C	Well tolerated (first-line treatment)
Treatment goals	Controlling the tumor while maintaining liver function	Aggressive tumor control; Potential cure
Liver transplant eligibility	Yes, it is within the criteria (e.g., Milan criteria)	Usually not applicable
Prognosis	Hepatic functional reserve is more critical than tumor stage	Determined by tumor size and stage

IO: Immunotherapy; TKI: Tyrosine kinase inhibitor.