Aims: Hepatoprotective medications (HPMs) are commonly used in patients with chronic liver disease, especially across Asia. The phase 3 ONYX-I and ONYX-II studies evaluated the safety and efficacy of the 3-DAA regimen of ombitasvir and paritaprevir/ritonavir (OBV/PTV/r) plus dasabuvir (DSV) ± ribavirin (RBV) in an exclusively HCV GT1b-infected Asian population. This post-hoc analysis evaluated the impact of HPM use in patients treated with OBV/PTV/r + DSV ± RBV in these studies. Methods: ONYX-I and ONYX-II enrolled patients in China, South Korea and Taiwan. SVR12, treatment-emergent adverse events (AEs), and alanine transaminase (ALT) normalization, as well as mean changes in ALT over time were assessed in patients using vs not using HPMs. HPM use defined as all medications administered during any treatment period. Results: Overall, 11% (36/325) of non-cirrhotic and 57% (59/104) of cirrhotic patients were receiving HPMs, with ursodeoxycholic acid being the most commonly used in both non-cirrhotic (5.2% [17/325]) and cirrhotic (14.4% [15/104]) patients. SVR12 rates were high (99.7- 100%) in both non-cirrhotic and cirrhotic patients irrespective of HPM use. The regimen was generally well tolerated, with low rates of SAEs and AEs leading to treatment discontinuation (Table). Of patients with ALT above normal at baseline (BL), 100% vs 95% of non-cirrhotic and 98% vs 89% of cirrhotic patients using or not using HPMs, respectively, had normal ALT values at end of treatment (EOT). Mean ALT levels during treatment declined rapidly and similarly with and without HPM use; mean changes from BL to EOT were -38.8 and -37.0 U/L, respectively, in non-cirrhotic and -54.2 and -66.6 U/L, respectively, in cirrhotic patients. Conclusions: OBV/PTV/r + DSV ± RBV achieved high SVR12 and was generally well tolerated regardless of HPM use. HPM use had no impact on the safety profile of OBV/PTV/r + DSV therapy in Asian HCV infected subjects.