AIM: Hepatitis C virus (HCV) infection is very common among end-stage kidney disease patients on hemodialysis, but its natural history is not known.METHODS: In this study, 189 dialysis patients (case)positive for HCV antibodies who were followed up for more than 4 years were compared with twice as many sex/age matched controls with chronic hepatitis C who were diagnosed in the same month as the case and followed up for comparable periods. The longest follow-up was 23 years in dialysis cases.The disease activities were graded into asymptomatic if ALT was less than 40 (35 in cases) IU/L, low activities if ALT was 40 (35)-79 IU/L, and high activities if ALT was above 80 IU/L during the last or latest 4 year period.RESULTS: All 25 dialysis cases who were followed up for more than 15 years were asymptomatic and 15 of them were negative for HCV RNA. Of the 50 controls followed up for more than 15 years, 34 had high activities, and none cleared HCV RNA. There were 60 controls who were asymptomatic,but they were all positive for HCV RNA, while 22.3% of asymptomatic dialysis cases were RNA negative. No dialysis patients with chronic hepatitis C progressed to cirrhosis,whereas the disease progressed to cirrhosis in more than one quarter of the controls. These differences were highly significant (P＜0.0001).CONCLUSION: Chronic hepatitic C among hemodialysis patients is mild in disease activity, and is not progressive,perhaps due to immunological abnormalities in these patients.Hepatic C virus is frequently cleared in asymptomatic dialysis patients during a long course. A possible mechanism for viral clearance is viral particle destruction on the surface of the dialyzer membrane.