Moreover, overexpression of both NR1D1 and ApoA5 via AAV8 did not reverse severe hyperlipidemia and NASH in ApoA5-/- hamsters and fed an HFD (data not shown), raising a concern of gene therapy applied to patients with severe HTG due to ApoA5. Here, APOA5 is linked to metabolic dysfunction-associated steatohepatitis.