OBJECTIVES: To map resource use and associated costs of managing chronic hepatitis C (CHC) in Greece across all disease stages and discuss simeprevir (SMV) in combination with pegylated-interferon + ribavirin (PR) as a potential treatment option in the early stages. METHODS: An expert panel of 8 leading hepatologists determined local resource use for CHC. Unit costs were obtained from officially published sources. Direct costs (medical, hospital, lab and imaging tests, and pharmaceutical care excluding anti-viral treatment) were estimated for each of the following health states of the disease: non-cirrhotic CHC, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation. Productivity losses were also included in the analysis. The perspective was that of the Social Insurance Fund (SIF) and the cost base year was 2014. RESULTS: The costs associated with non-cirrhotic CHC and compensated cirrhosis were estimated at €84.65 and €128.85, respectively, consisting mainly of lab and imaging tests. Medical follow up for CHC patients across all stages is performed through public hospital outpatient units, without entailing costs for SIFs. The annual per patient costs for decompensated cirrhosis, HCC and liver transplant were estimated at €3,170.20, €8,513.22 and €129,412, respectively and consisted mainly of hospitalization costs. Indirect costs were estimated at €1,009 for both non-cirrhotic and compensated cirrhosis stages, and at €4,539 for decompensated cirrhosis. CONCLUSIONS: Costs of managing CHC increase dramatically with disease severity. A recent publication from the UK supports the cost-effectiveness of SMV+PR against PR, with an ICER of £9,725/ QALY for treatment-naïve and £7,819/ QALY for treatment-experienced patients. Therefore and under the current cost containment environment in Greece, SMV+PR could be a cost-effective treatment option for treating patients earlier to prevent high costs at later stages.