The development of HCC was independently associated with PNPLA3 rs738409 (OR<sub>adjusted</sub> 1.84 [95% CI 1.55-2.18], p = 1.85 × 10<sup>-12</sup>) and TM6SF2 rs58542926 (OR<sub>adjusted</sub> 1.66 [1.30-2.13], p = 5.13 × 10<sup>-05</sup>), using an additive model, and controlling the sex, age, body mass index, and type 2 diabetes mellitus; the risk associated with carriage of MBOAT7 rs641738 (OR<sub>adjusted</sub> 1.04 [0.88-1.24], p = 0.61) was not significant.
As variants in PNPLA3 (I148M) and TM6SF2 (E167K) are associated with nonalcoholic fatty liver disease, we assessed these variants in type 2 diabetes (T2D) patients randomized to receive BIL (n=1822) or GL (n=1270) in three phase 3 trials.