Much of what is known about the clinical course of HCV infection comes from retrospective studies of patients with acquired NANB PTH and from prospective studies of those who were acutely exposed to HCV (Prince et al., 1974; Alter et al., 1975; Feinstone et al., 1975; Knodell et al., 1975; Esteban et al., 1990; Tremolada et al., 1991). Overall, the clinical presentation of acute hepatitis is similar in patients infected with HAV, HBV or HCV, although acute HCV infection tends to be milder than acute HBV infection. In fact, 70–95% of HCV-infected people do not recall an episode of acute hepatitis, suggesting a subclinical course is very common (Meyers et al., 1977; Koretz et al., 1993b; Hoofnagle, 1997). Apart from the fact that the average incubation period for acute HCV infection (Seeff, 1991; Koretz et al., 1993b) is between that of HAV and HBV (Table 1.1), acute cases of symptomatic HCV infection are indistinguishable from severe acute HBV or HAV infections. Symptoms of acute HCV infection, which vary in duration and intensity, span 2–12 weeks (Ch. 4) and often include malaise, nausea, and upper right quadrant pain, followed by jaundice and dark urine (Hoofnagle, 1997). Loss of appetite may also occur (CDC, 1998). These symptoms occur weeks after the appearance of HCV RNA in blood and overlap in time with the elevation of transaminases (Fig. 4.1). ALT elevations often reach a peak 10-fold or more above normal, independent of whether patients develop symptoms.