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We read with interest the paper by Amaddeo et al1 describing a comprehensive and integrative study to understand the molecular characteristics of HBV-related hepatocellular carcinoma (HCC). Chronic HBV infection is one of the most common causes of HCC. Although integration of viral gene into host genome has been implicated as an important oncogenic mechanism, a series of studies have reported that both direct and indirect hepatocarcinogenic actions of HBV infection exist. Amaddeo et al1 found a frequent inactivation of p53 and overexpression of stem cell-related genes in HBV-infected HCC tumours. Most importantly, TP53 mutations were shown to be associated with poor prognosis exclusively in HBV-related patients. This is probably an indirect oncogenic mechanism resulting from HBV infection.
In parallel, in a very recent Cancer Cell paper, …