Intrahepatic CD4⁺ cell depletion in hepatitis C virus/HIV-coinfected patients

Coinfection with HIV and hepatitis C virus (HCV)-specific immune responses, increases hepatic inflammation, accelerates hepatic fibrosis, and is associated with deceased treatment responses. We quantified intrahepatic lymphocyte and hepatocyte phenotypes in HCV-infected patients with (n = 38) and without (n = 41) HIV infection. A single pathologist counted positive cells in 5 portal and 5 lobular areas. Coinfected patients had 6.81 ± 1.9 fewer CD4⁺ cells per portal field (10.58 ± 1.12 vs. 4.97 ± 1.09 cells/high-power field [HPF]; P < 0.001) and 0.48 ± 0.15 more apoptotic lymphocytes per lobular field (0.16 ± 0.06 vs. 0.64 ± 0.15 cell/HPF; P = 0.002) than monoinfected patients. The number of portal CD4⁺ cells was not associated with the peripheral CD4⁺ cell number. Portal and lobular CD8⁺ cells did not differ between the 2 groups. Portal proliferative hepatocytes were increased in coinfected patients with HIV RNA levels of >400 copies/mL (1.13 ± 0.32 cells/HPF; P = 0.01) compared with those with undetectable HIV RNA (0.46 ± 0.09 cell/HPF) and monoinfected patients (0.45 ± 0.08 cell/HPF). In conclusion, HIV coinfection is associated with fewer portal CD4⁺ cells and increased lobular lymphocyte apoptosis that may impact on the natural history of HCV infection.