Spontaneous clearance after acute HCV infection occurs in 20%–25% of individuals. Predictors of spontaneous clearance include jaundice, elevated ALT level, female sex, younger age and host genetic polymorphisms (including IFNL3), although none of these factors can be used to predict clearance at the individual level. In most cases, clearance occurs within the first 6 months after infection, although late clearance has been demonstrated in a small proportion of individuals. Fluctuating viraemia is common in the first few months after infection, with variable patterns. A single HCV RNA test result below the limit of detection should not be taken as an indication of clearance; at least two undetectable HCV RNA test results, a minimum of 1 month apart, are required before clearance can be confirmed. Conversely, indicators of likely chronicity include a failure of reduction in HCV viral load of > 1 log10 IU/mL at 4 weeks, or a detectable HCV RNA test result at 12 weeks after initial presentation.