The availability of oral direct-acting antiviral (DAAs) has altered the hepatitis C virus (HCV) treatment paradigm for both pre- and post-liver transplant (LT) patients. There is a perceived trade-off between pre- versus post-LT treatment of HCV—treatment may improve liver function but potentially decrease the likelihood of a necessary LT. Our objective was to identify LT-eligible patients with decompensated cirrhosis who would benefit (and not benefit) from pre-LT treatment based on their MELD scores. We simulated a virtual trial comparing long-term outcomes of pre- versus post-LT HCV treatment with oral DAAs for patients having MELD scores between 10 and 40. We developed a Markov-based microsimulation model, SIM-LT (simulation of liver transplant candidates), which simulated the life course of patients on the transplant waiting list and after LT. SIM-LT integrated data from recent trials of oral DAAs (SOLAR 1 and 2), United Network for Organ Sharing (UNOS), and other studies. The outcomes of the model included life expectancy, 1-year and 5-year patient survival, and mortality. Model-predicted patient-survival was validated with UNOS data. We found that, at the national level, treating HCV before LT increased life expectancy if MELD ≤ 27, but could decrease life expectancy at higher MELD scores. Depending on the UNOS region, the threshold MELD score to treat HCV pre-LT varied between 23 and 27, and was lower for UNOS regions 3, 10 and 11, and higher for regions 1, 2, 4, 5, 8 and 9. Sensitivity analysis showed that the thresholds were stable. Conclusions Our findings suggest that the optimal MELD threshold below which decompensated cirrhotic patients should receive HCV treatment while awaiting LT is between 23–27, depending on the UNOS region.

For cirrhotic patients awaiting LT, pre-LT HCV treatment with DAAs is cost effective/saving in patients with MELD scores of 21 or lower, whereas post-LT HCV treatment is cost effective/saving in patients with MELD scores of 22 or higher.