Fatty liver or steatosis is a common finding in several liver diseases, most notably non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) but is also seen more frequently in chronic hepatitis C virus (HCV) related liver disease than would be predicted by simple concurrence of the two diseases.¹ Several mechanisms have been proposed to explain why steatosis might develop in chronic viral infection, including direct effects of the virus on lipid metabolism, but none of these is entirely convincing. Furthermore, steatosis is not a benign lesion but one that contributes to the progression of fibrosis, not only in NAFLD and ALD but also in HCV, in part by increasing the sensitivity of the liver to oxidative stress and cytokine mediated injury.² The paper by Mundt and colleagues³ in this issue of Gut provides novel mechanistic insights into why steatosis develops in HCV and how it might accentuate liver injury (see page 1590). They have concentrated their efforts on a member of the tumour necrosis factor (TNF) superfamily called TRAIL or TNF related apoptosis inducing ligand. TRAIL is known to induce apoptosis in transformed cells and this group have previously shown TRAIL, acting through one of its receptors called TRAIL-DR5 or TRAIL-2, mediates hepatocyte apoptosis in viral hepatitis. What they now show is that this receptor-ligand pair can also mediate hepatic steatosis in both viral hepatitis and in response to alcohol.

The authors start with the observation that expression of TRAIL is increased in the livers of patients with HCV associated steatosis and they then proceed …