## 5 Steatohepatitic Hepatocellular Carcinoma (SH-HCC)  
The introduction of immunotherapy has been a major breakthrough in the treatment of HCC. However, recent data suggest that this is not universally true. According to meta-analyses and reviews of clinical statistics, non-viral HCC--particularly metabolic-associated stenotic liver disease-related HCC (MASLD-HCC)--may demonstrate limited efficacy to immunotherapy, especially ICIs. Nonetheless, these findings remain inconsistent, and the level of evidence is low. This inconsistency arises from the insufficient characterization and subclassification of non-viral HCC groups (e.g., MASLD, autoimmune conditions) in many studies, making it difficult to draw definitive conclusions. The underlying reasons for the observed reduced efficacy of immunotherapy in MASLD-HCC are unclear. This is particularly puzzling since immune system dysregulation is a common feature of both chronic liver disease and the neoplastic process. One potential approach to addressing this question involves a more detailed analysis of the relationship between the type of chronic liver disease and HCC characteristics. Although current treatment protocols for HCC are largely uniform, regardless of the underlying liver disease, it is plausible that the tumor biology of HCC may vary depending on its etiology. Could there be distinct subtypes of HCC that differ subtly based on their underlying causes? The 2019 5 th edition of the _WHO Classification of Digestive System Tumors_ identifies a subtype of HCC known as steatohepatitis hepatocellular carcinoma (SH-HCC). This subtype, which accounts for 5-20% of cases [136], has been linked to various etiologies, including chronic viral hepatitis. Specifically, studies by [PERSON] et al. [137] found that SH-HCC was frequently associated with HCV, while its association with HBV infection was significantly lower, consistent with findings by [PERSON] et al. [138]. However, there is growing evidence of an increased incidence of SH-HCC in NAFLD and NASH, suggesting a strong connection to metabolic syndrome [139; 140]. SH-HCC is defined by unique histological features, including large-droplet steatosis in tumor cells, ballooning of malignant hepatocytes, inflammation, Mallory-Denk bodies (eosinophilic inclusions from destroyed intermediate filaments), and pericellular fibrosis [141]. From a diagnostic imaging perspective, SH-HCCs are typically smaller than other HCC subtypes and are characterized by intralesional fat in the context of hepatic parenchymal steatosis. On ultrasonography, SH-HCC often appears as a hyperechoic lesion with acoustic shadowing. On MRI, prominent fatty deposits are evident, appearing as intralesional signal loss on opposed-phase images [142]. On dynamic CT, SH-HCCs are often classified as LR-5 (i.e., definitively HCC) in high-risk patients [143], showing hyperenhancement in the arterial phase, washout in the portal venous phase, and hypointensity in the hepatobiliary phase [144]. However, in unenhanced imaging, SH-HCCs may be challenging to differentiate from the surrounding steatotic liver parenchyma or other fat-containing liver lesions, such as angiomyolipoma or clear-cell HCC. According to the International Consensus Group for Hepatocellular Neoplasia, intralesional fat is typically found in early-stage HCCs but decreases as tumors progress. Early-stage HCCs rely on a portal venous blood supply, whereas more advanced HCCs shift toward an arterial supply. This transition can cause transient ischemia and hypoxia, potentially inducing fatty metamorphosis in hepatocytes. Intratumoral steatosis is commonly observed in HCCs smaller than 1.5 cm but becomes less frequent and more focal as tumor size and histological grade increase [145]. However, SH-HCCs are an exception, as they exhibit significant intralesional fat at both early and advanced stages [146]. This persistence of fat can complicate the diagnosis of SH-HCC, as early-stage HCCs with intratumoral fat might be misclassified [147].