Pinyol R, Torrecilla S, Wang H, et al. - Researchers investigated unique molecular traits characterizing non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) vs other HCC aetiologies. For this purpose, 80 NASH-HCC and 125 NASH samples were used. They also used NASH-HCC mouse models. TERT, CTNNB1, TP53 and Activin A Receptor Type 2 A (ACVR2A) were revealed as the most-frequently mutated genes in NASH-HCC. Higher ACVR2A mutation rates were found in NASH-HCC vs in other HCC aetiologies. A novel mutational signature (MutSig-NASH-HCC) significantly linked with NASH-HCC was discovered. More prevalence of Wnt/TGF-β proliferation subclass was identified in NASH-HCC vs in HCCs of other aetiologies. A significantly higher prevalence of an immunosuppressive pro-carcinogenic cancer field was exhibited by NASH-HCC. Overall, unique molecular characteristics were shown by NASH-HCCs, including higher rates of ACVR2A mutations as well as the presence of a newly detected mutational signature.