Factors associated with spontaneous clearance of chronic hepatitis C virus infection

Background & Aims Spontaneous clearance of chronic hepatitis C virus (HCV) infection (CHC) is rare. We conducted a retrospective case-control study to identify rates and factors associated with spontaneous clearance of CHC. Methods We defined cases as individuals who spontaneously resolved CHC, and controls as individuals who remained chronically infected. We used data obtained on HCV testing between 1994 and 2013 in the West of Scotland to infer case/control status. Specifically, untreated patients with ⩾2 sequential samples positive for HCV RNA ⩾6 months apart followed by ⩾1 negative test, and those with ⩾2 positive samples ⩾6 months apart with no subsequent negative samples were identified. Control patients were randomly selected from the second group (4/patient of interest). Case notes were reviewed and patient characteristics obtained. Results 25,113 samples were positive for HCV RNA, relating to 10,318 patients. 50 cases of late spontaneous clearance were identified, contributing 241 person-years follow-up. 2,518 untreated, chronically infected controls were identified, contributing 13,766 person-years follow-up, from whom 200 controls were randomly selected. The incidence rate of spontaneous clearance was 0.36/100 person-years follow-up, occurring after a median 50 months’ infection. Spontaneous clearance was positively associated with female gender, younger age at infection, lower HCV RNA load and co-infection with hepatitis B virus. It was negatively associated with current intravenous drug use. Conclusions Spontaneous clearance of CHC occurs infrequently but is associated with identifiable host and viral factors. More frequent HCV RNA monitoring may be appropriate in selected patient groups. Lay summary Clearance of hepatitis C virus infection without treatment occurs rarely once chronic infection has been established. We interrogated a large Scottish patient cohort and found that it was more common in females, patients infected at a younger age or with lower levels of HCV in the blood, and patients co-infected with hepatitis B virus. Patients who injected drugs were less likely to spontaneously clear chronic infection.