OBJECTIVES: To provide real-world evaluations of newer direct-acting antivirals (DAAs) in CHC patients from large US payer perspectives. METHODS: Medical and pharmacy claims linked to lab data from the Humana Database were analyzed for Medicare Advantage or commercially-insured adults with ≥2 CHC claims (ICD-9 070.44; 070.54) who received therapy containing SMV and/or SOF through June 2014; those with HIV were excluded. Patients were grouped based on most common regimens in the data: SMV/SOF, SMV/SOF/ribavirin (RBV), SOF/RBV, or SOF/interferon (IFN)/RBV; <3% received other regimens. Baseline (BL) demographics and clinical characteristics (e.g., claims-based cirrhosis or end stage liver disease [ESLD], FIB-4 scores) were described and post-treatment time measured. Methods to control for treatment selection bias were not performed, and comparative analyses were not conducted. RESULTS: There were 715 CHC patients who received therapy with SMV/SOF (n=184), SMV/SOF/RBV (n=37), SOF/RBV (n=269) or SOF/IFN/RBV (n=225); mean age was between 60-62 years; 58%, 68%, 62% and 70% were male; most (85%, 78%, 81% and 80%) had Medicare. For SMV/SOF, SMV/SOF/RBV, SOF/RBV, and SOF/IFN/RBV groups, BL cirrhosis was present in 27%, 27%, 17%, and 24% of patients and ESLD in 48%, 38%, 27%, and 12% of patients, respectively. Slightly over half in each cohort had calculable FIB-4 scores, of which, 56%, 54%, 34% and 35%, respectively, had scores >3.25. Among those with genotype data, 100% (78/78) SMV/SOF, 94.7% (18/19) SMV/SOF/RBV, 24.4% (29/119) SOF/RBV and 95.8% (92/96) SOF/IFN/RBV were genotype 1. Using prior claims history, 10%, 19%, 12% and 17% of respective cohorts were treatment-experienced. Less than half of each cohort had post-treatment data ≥1 week. CONCLUSIONS: This analysis of CHC patients predominantly insured through Medicare found that the majority of those who received SMV/SOF +/- RBV had either cirrhosis or ESLD claims prior to therapy and, based on lab data, over half had FIB-4 scores >3.25.