Hepatocellular carcinoma in patients without cirrhosis

Table 5 Summary of available clinical trials on systemic therapy in individuals with hepatocellular carcinoma

Clinical trials	Treatment	Child-Pugh score	Cirrhosis status reported?	Key notes
SHARP[113]	Sorafenib vs placebo	Only A	Not mentioned, but approximately 95% with cirrhosis	First trial to show OS benefit with systemic therapy in advanced HCC
REFLECT[115]	Lenvatinib vs sorafenib	Only A	Reported, but not explained	Individuals with more than 50% liver involvement or main portal vein invasion were excluded
IMBRAVE150[116]	Atezolizumab + bevacizumab vs sorafenib	Only A	Not mentioned, but primarily cirrhotic	Untreated high-risk variceal individuals were excluded
HIMALAYA[117]	Durvalumab +/- tremelimumab vs sorafenib	Only A	Not specified	Primarily MASLD or viral causes, without subclassifying for cirrhosis
CARES-310[118]	Camrelizumab + rivoceranib vs sorafenib	Only A (A5 & A6)	Most had cirrhosis	Excluded patients at high risk for GI bleeding, including varices

CARES-310: Camrelizumab plus rivoceranib as first-line therapy for unresectable hepatocellular carcinoma; GI: Gastrointestinal; HCC: Hepatocellular carcinoma; MASLD: Metabolic dysfunction-associated steatotic liver disease; OS: Overall survival; SHARP: Sorafenib hepatocellular carcinoma assessment randomized protocol.