OBJECTIVES: To estimate the costs and consequences of long-term antiviral treatment options on mortality, morbidity and associated costs in nucleoside-naïve CHB patients in Belgium and compare effects between antiviral (AV) treatments with low (entecavir; ETV) versus high probability of resistance (lamivudine; LVD). METHODS: A decision-tree model simulated morbidity, mortality and cost for a cohort of 1000 nucleoside-naïve CHB eAg-negative patients under three scenarios: no treatment, ETV 0,5mg, LVD 100mg. Morbidity was measured as the estimated number of compensated cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma (HCC) predicted to occur depending on viral load (VL) levels. Life expectancy impact was estimated using the DEALE method and life tables. Efficacy data were from published trials. Baseline VL was used as proxy to model no treatment option. Relative-risk estimations were derived from the R.E.V.E.A.L.-HBV Study. Direct medical costs include management cost of liver complications. Annual costs of liver complications were estimated from IMS hospital data. Numbers of liver complications, Life Years Lost (LYL) and costs were estimated over a 10-year time period. The Belgian health care payer perspective was applied. Costs and benefits were discounted as per Belgian guidelines. RESULTS: If untreated, 329 and 163 patients are predicted to develop cirrhosis and HCC within 10 years, respectively. Mortality due to liver complications and associated lifetime costs are estimated at approximately 5.25LYL and €60,767, respectively. If patients are started on ETV, morbidity is reduced to 38 cirrhotic and 13 HCC events, mortality to 0.40LYL, and costs to €6,951. If started on LVD, outcomes are 107 cirrhotic and 47 HCC events, 1.47LYL and lifetime costs of €19,829. CONCLUSIONS: Morbidity, mortality and costs are higher if CHB eAg-negative patients remain untreated. Treatment with antiviral therapy will have a major effect on these outcomes, especially if entecavir 0,5mg, an antiviral with very low probability of resistance, is used.