(A) Acute hepatitis C followed by clinical recovery. The incubation phase occurs during the first 2–3 months after infection. The acute phase is marked by increased ALT levels in most patients, although only about 20%–30% develop clinical symptoms such as jaundice. ALT elevations coincide with the onset of HCV-specific T cell responses in the liver, and these responses are detectable in the blood by proliferation and cytokine assays. HCV-specific antibodies are detectable by enzyme immunoassay (EIA) at this time, but the presence of transient, strain-specific neutralizing antibodies is still controversial. After clearance of HCV, antibody titers decrease and may eventually become undetectable. HCV-specific T cells remain detectable in the blood, and in vitro recall responses to HCV antigens remain indicators of previous infection and recovery. (B) Chronically evolving acute hepatitis C. Chronic HCV infection is characterized by relatively stable HCV RNA levels, which are about 2–3 log₁₀ lower than in the acute phase and do not vary by more than 1 log₁₀ during the chronic phase. The titers of HCV-specific antibodies, including those of neutralizing antibodies against multiple HCV strains, increase during chronic hepatitis. HCV-specific T cell reactivity decreases over time, and in vitro recall responses to HCV antigens are typically weak to undetectable. Figure modified with permission from Seminars in Liver Disease (S24).