Steatohepatitic variant of hepatocellular carcinoma in the absence of metabolic syndrome or background steatosis: A clinical, pathological, and genetic study

Association between the steatohepatitic hepatocellular carcinoma (SH-HCC) and metabolic syndrome has been suggested. Most SH-HCC morphology appears to result from a typical HCC that retains the ability to respond to the metabolic syndrome and develops features of steatohepatitis. We aim to ask if this is true for all SH-HCC cases, or does the SH-HCC morphology in some cases reflect genetic changes inherent to the HCC itself, as opposed to wide tissue response in liver to the metabolic syndrome. Twelve SH-HCC cases occurring in individuals without metabolic syndrome were identified and examined pathologically. Genomic microarray analysis was performed in a subset. The SH-HCC in all cases showed diffuse moderate to marked fatty change, abundant balloon cells often containing Mallory-Denk bodies, and pericellular fibrosis. The background livers showed no significant fatty change in any cases. The background livers showed cirrhosis in seven cases and had no fibrosis in five cases. The underlying liver diseases were hepatitis C (n = 4) and no known (n = 8). The clinical and pathological characteristics of these cases did not differ significantly from the cases with the classical HCC morphology. Loss of 9q12-q31.1 was observed in a subset of cases, a finding that has not been previously reported in HCC. Our results indicate HCC can also develop steatohepatitic morphology outside the setting of fatty liver disease or metabolic syndrome. This SH-HCC is more likely to result from genetic changes to shared genes or metabolic pathways within the tumor and is an ideal subtype for future genetic studies. In this regard, potential genetic alterations include loss of 9q12-q31.1.