Hepatocellular carcinoma in patients without cirrhosis

Figure 1 Geographic distribution of hepatocellular carcinoma in non-cirrhotic liver based on different etiologies. ALD: Alcohol-associated liver disease; HBV: Hepatitis B virus; HCV: Hepatitis C virus; MASLD: Metabolic dysfunction-associated steatotic liver disease. Created in BioRender (Supplementary material).

Figure 2 Summary of percentage by etiology of hepatocellular carcinoma in individuals without cirrhosis from studies conducted. A: North America; B: Europe; C: Summary of percentage by etiology of individuals with hepatocellular carcinoma (HCC) from studies conducted in South America; D: Asia. ¹Risk factor distribution was not mutually exclusive as many patients had more than one risk factor, and the percentage sum was more than 100%; ²Percentage of non-cirrhotic HCC by country: Peru 31%, Ecuador 28%, Chile 26%, Brazil 12%, Argentina 7%, Colombia 4%. Limitation of the study: The reported etiology was combined with that of individuals with cirrhosis; ³The data were inferred from the individuals with cirrhosis available status, but no confirmation of non-cirrhosis was reported in the study; ⁴Countries included in the analysis: Peru, Ecuador, Brazil, Argentina, Colombia, Uruguay. No data on the number of individuals without cirrhosis were available. The study’s limitation was that the reported etiology was combined with that of individuals with cirrhosis; ⁵Only data available on hepatitis B virus (HBV) infection in non-cirrhosis available. ALD: Alcohol-associated liver disease; HCV: Hepatitis C virus; MASLD: Metabolic dysfunction-associated steatotic liver disease.

Figure 3 Inflammatory mechanism in hepatic carcinogenesis and metastasis. IL: Interleukin; HBV: Hepatitis B virus; HCV: Hepatitis C virus; TNF-α: Tumor necrosis factor alpha. Created in BioRender (Supplementary material).

Figure 4 Hypothesis of the development of hepatocellular carcinoma in individuals with metabolic dysfunction-associated steatotic liver disease. Akt: Protein kinase B; IGF-1: Insulin-like growth factor-1; MAPK: Mitogen-activated protein kinase; mTOR: Mammalian target of rapamycin; PI3K: Phosphoinositide 3-kinase. Created in BioRender (Supplementary material).

Figure 5 Graphical abstract summarizing the etiology, treatments, and diagnosis of hepatocellular carcinoma in individuals without cirrhosis. MASLD: Metabolic dysfunction-associated steatotic liver disease. Created in BioRender (Supplementary material).