Intrahepatic CD4+ Cell Depletion in Hepatitis C Virus/HIV???Coinfected Patients

Abstract

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.

Preservation of Intrahepatic Hepatitis C Virus (HCV)–Specific CD4+T Cell Responses despite Global Loss of CD4+T Cells in HCV/HIV Coinfection

“…We therefore considered whether the decreased CD4 + T cell percentages found in HCV/HIV-coinfected [21]. Thus, the present study confirms that these differences are found using a completely different approach.…”

“…Possible obstacles to identifying a relationship between these 2 parameters include inadequate sample size, the need to expand liver lymphocytes, and sampling error inherent in liver biopsies. It should be noted, however, that Canchis et al also found no association between liver CD4 + T cell frequencies enumerated in situ and liver disease stage in 38 HCV/HIV-coinfected subjects [21].…”

Liver disease: the effects of HIV and antiretroviral therapy and the implications for early antiretroviral therapy initiation

“…Tuyama et al [38 ] recently were able to demonstrate the possibility of HIV to directly infect hepatic stellate cells and induce enhanced collagen production in an in-vitro model. Immunostaining of liver biopsies demonstrated that HIV might enhance hepatocyte apoptosis [39] and proliferation [40], which could add to the higher risk for fibrosis progression in HIV/HCV-coinfected individuals. Interesting data on intrahepatic mRNA levels of cytokines and cellular markers that compares liver biopsies of HCV/HIV-coinfected patients with HCVmonoinfected ones was recently published [41].…”

Pathogenesis of HIV-HCV coinfection

“…One study that examined the global infiltrate of lymphocytes within the liver but not virus-specific T cells demonstrated a depletion of total intrahepatic portal CD4 T cells out of proportion to declines in peripheral counts [47]. This finding indicated that the inflammatory infiltrate in the liver is missing a key component of an effective T-cell response.…”