Steatohepatitic Hepatocellular Carcinoma (SH-HCC)

Abstract

In explant livers with chronic hepatitis C (HCV-C) we have noted a distinctive histologic variant that we have termed steatohepatitic hepatocellular carcinoma (SH-HCC) with features resembling non-neoplastic steatohepatitis, including large droplet steatosis, ballooning of malignant hepatocytes, Mallory-Denk bodies, inflammation, and pericellular fibrosis. This study was undertaken to further describe the characteristics and prevalence of this histologic variant in HCV-C and any possible association with underlying risk factors for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We selected two 2-year periods (mid-2003 to mid-2005 and 2007 to 2008), from which selected explant livers with HCV-C and HCC were examined to determine the characteristics and frequency of SH-HCC. The underlying cirrhotic liver was also reassessed for steatosis and evidence of steatohepatitis. Clinical records were consulted for concomitant NAFLD and NASH risk factors. The SH-HCC variant was found in a total of 22 of 62 HCC cases (35.5%). Fourteen of the 22 patients with SH-HCC (63.6%) had at least one known risk factor for NAFLD/NASH including diabetes (6 of 22, 27.3%), obesity (6 of 22, 27.3%), hypertension (11 of 22, 50%), and hyperlipidemia (5 of 22, 27.8%). In 14 of the 22 cases (63.6%) of SH-HCC, the non-neoplastic liver showed changes of NAFLD/NASH superimposed on otherwise typical features of HCV-C. In conclusion, in our series of HCV-C explants, approximately one-third of HCCs show a distinctive histological variant termed SH-HCC. Underlying risk factors for NAFLD and for NASH were identified in 63.6% of our cases. Moreover, non-neoplastic tissue in HCV-C explants showed changes of NAFLD/NASH in 63.6% of cases. These results suggest a possible NAFLD/NASH pathway leading to SH-HCC in the setting of HCV-C which requires further investigation in the future.

Metabolic risk factors are associated with non‐hepatitis B non‐hepatitis C hepatocellular carcinoma in Taiwan, an endemic area of chronic hepatitis B

“…However, we only identified DM history to be significantly associated with SH‐HCC in the three groups of patients with HCC, while hypertension, high serum CHO, and TG levels were not. Thus, our data differ slightly from the two published reports 37, 38. Because SH‐HCC has not been found to be associated with prognosis, its clinical significance will need further study.…”

“…SH‐HCC has also been reported to be associated with metabolic syndrome,37, 38 which we confirmed in this study. However, we only identified DM history to be significantly associated with SH‐HCC in the three groups of patients with HCC, while hypertension, high serum CHO, and TG levels were not.…”

“…The criteria for the diagnosis of steatohepatitic HCC (SH‐HCC) included: 1) steatosis (>5% tumor cells with macrovesicular fatty change); 2) ballooning or Mallory‐Denk body formation is identified; 3) presence of interstitial fibrosis, and 4) presence of inflammatory infiltrate in the tumor 37, 38…”

Molecular classification of hepatocellular carcinoma: potential therapeutic implications

“…In fact, distinct histological variants, which often co-exist within a tumor nodule, are associated with specific molecular subclasses [66]. For example, steatohepatitic HCC, a recently identified variant [67], was associated with S1 subclass, macrotrabecular/compact pattern and clear cell variant were associated with S2 subclass and microtrabecular pattern was associated with S3 subclass. Single cell-level characterization may enable molecular subtyping at a finer resolution beyond histological variants in the future.…”

Efeito do sorafenibe na carcinogênese hepática experimental secundária à doença hepática gordurosa não alcoólica

“…O CHC tipo esteato-hepatítico é caracterizado por mais de 5% de esteatose intratumoral, presença de corpúsculos de Mallory-Denk, fibrose trabecular e pericelular, inflamação de linfócitos e polimorfonucleares, estando presente, na sua maioria, em pacientes com DHGNA (48,49) . (50) .…”