peer reviewed ; Background: Hepatitis C virus genotype 4 (HCV-4) is the most prevalent genotype in Central Africa. A large population of Black African individuals, among whom HCV-4 infection is widespread, resides in Belgium. Aim: To compare epidemiology, clinical characteristics and any differences in receipt of HCV therapy in two populations of HCV-4 patients residing in Belgium. Methods: This retrospective multicenter study selected 473 patients from seven hospital databases and compared them according to ethnic origin, i.e., Black African (n=331) or not (n=142), for epidemiological, clinical, biological and histological characteristics. Interleukin 28B polymorphism (CC-genotype) was evaluated in a second cohort of 69 Black African and 30 non-Black African patients. Results: Compared to other patients, the Black African patients were more likely to be female and were older, more commonly overweight, more frequently had abnormal glucose metabolism and arterial hypertension; they were less likely to have dyslipidemia, a history of alcohol consumption or ALT elevation. The route of infection was more frequently unknown in Black African than in other patients. Black African patients had more HCV-4 subtypes, were less frequently of IL28B CC-genotype and had less severe liver fibrosis. The proportion of patients who received antiviral treatment was similar in the two groups. Conclusion: In this Belgian cohort, patients with HCV-4 infection were more frequently of Black African origin than of other origin. Infected Black African patients were more commonly female, older at diagnosis, and had more co-morbidities than other patients; they also had less advanced liver fibrosis than infected non-Black African patients and fewer had a CC genotype. The number of patients treated with antiviral therapy was similar in the two groups.