OBJECTIVES: HCV patients with ALT-N have a slower progression to cirrhosis than patients with elevated transaminases (ALT-E). The use and impact of treatment on HCV progression are controversial in this population. We estimated the impact of antiviral treatment on the morbidity and mortality in patients with ALT-N, comparing with ALT-E, following different scenarios of treatment. METHODS: A Markov model of CHC with a twenty-year time horizon (2006-2025) was adapted to simulate ALT-N patients (30%) and ALT-E patients (70%) separately. The model takes into account: 1) The faster fibrosis progression rates for higher age, males and ALT-E; 2) The improvement of HCV screening and treatment; 3) The competitive mortality. The model is calibrated on reported HCC mortality (CepiDc). Antiviral treatment effects were incorporated by estimating the likelihood of being screened for HCV (InVS), of being treated (GERS) and of becoming sustained viral responders (literature review). We assumed that patients with ALT-N are treated 80% lower between 2002 and 2004 and 70% lower from 2005 than the ALT-E (HEPATYS). A sensitivity analysis has been assessed. RESULTS: The model showed that the antiviral treatment reduced by 36,000 cirrhosis (35%), 23,100 cirrhosis complications (26%) and 18,000 deaths (23%) on the total HCV population, including 3,000 cirrhosis (20%), 1,200 complications (14%) and 1,000 deaths (13%) in the ALT-N population, despite a probability to be treated 3 to 5 times lower in this population. Moreover, if ALT-N patients are treated in the same proportions than ALT-E, morbidity and mortality could be further reduced by 1,400 cirrhosis (12%), 600 complications (9%) and 500 deaths (8%). CONCLUSIONS: The treatment of CHC patients with ALT-N should have a long-term impact on morbidity and mortality, less important than in ALT-E patients. The sensitivity analysis showed that the proportion of ALT-N is the parameter having the most influence on the results.