We observed that only the activity of the NAD+-dependent sirtuins (silent mating type information regulation 2 homolog/SIRT) differed between the MMH-D3 and HBV-Met cells, suggesting that particularly these class III HDACs could be involved in the HBV-driven histone hypoacetylation, which appeared to be an early pre-HCC event in hepatitis B. Our results indicate slightly elevated mRNA levels for SIRT1, SIRT2, SIRT5 and SIRT7 in HBV-Met cells when compared to MMH-D3, although the biological relevance of this observation remains undisclosed. This evidence concerns the gene SIRT2 and hepatitis B virus infection.