OBJECTIVES: Although the high cost burden of chronic hepatitis C (CHC) has been described in the literature, there is a lack of data on the assessment of characteristics associated with high healthcare utilizers. The purpose of this study was to identify demographics and clinical characteristics associated with high healthcare utilizers and liver disease progression among CHC patients. METHODS: Health insurance claims from 60 self-insured US companies were analyzed (01/2001-03/2013). Adult patients with ≥2 CHC claims (ICD-9-CM: 070.44 or 070.54), ≥6 months of continuous insurance coverage before the first CHC diagnosis and ≥36 months after were included. Patients with HIV were excluded. Demographics and baseline comorbidities including CHC- and non-CHC-related conditions were described. Generalized estimating equations with logit link for binary outcomes were used to identify the most predictive demographics and clinical characteristics of being in the 20% of patients with the highest healthcare resource utilization (HRU). Predictive factors of liver disease progression were also identified. RESULTS: The mean age of the study population (N=4,898) was 52.4 years and 39.4% were female. Compensated cirrhosis, ESLD and both CHC- and non CHC-related comorbidities were strong predictors of high healthcare costs, with odds ratios (ORs; 95%CI) for ESLD, ≥2 CHC-related, and ≥2 non CHC-related comorbidities of 3.31 (2.80-3.92), 2.78 (2.47-3.12), and 2.18 (1.75-2.71), respectively. CHC- and non CHC-related comorbidities were also strong predictors of liver disease progression with ORs (95%CI) for ≥2 CHC-related and ≥2 non CHC-related comorbidities of 2.18 (1.83-2.60) and 1.50 (1.14-1.97), respectively. CONCLUSIONS: This real-world study suggests that CHC patients with the highest HRU and costs had a high level of comorbidity at baseline and that non-CHC conditions are strong predictors of high healthcare costs. Liver disease severity alone does not fully predict high consumption of HRU, although when present it is a predictor of high HRU.