SIRT6 and alcoholic liver diseases: Furthermore, Sirtuin 6 (SIRT6), a NAD-dependent histone deacetylase which is a critical epigenetic regulator in alcoholic liver disease (64), deacetylates Smad family member 3 (Smad3) and attenuates its expression induced by transforming growth factor β (TGF-β) in the activated HSCs (65).