Periportal CD4+ Cell Infiltration Increases in HIV/Hepatitis C Virus-Coinfected Patients Commencing ART, Whereas CD8+ Cells Clear From the Liver

Abstract

Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common in Asia, but the effects of antiretroviral therapy (ART) are unclear. Histopathological changes in the liver are described in a prospective study of HCV-seropositive HIV-infected patients at Cipto Mangunkusomo Hospital (Jakarta, Indonesia). Liver biopsy specimens were collected at baseline (n = 48) and 48 weeks (n = 34). Ishak scores showed mild but detectable inflammation and/or fibrosis. Levels of portal inflammation declined during ART (P = .03), whereas fibrosis remained (P = .11). Portal infiltration of CD4(+) cells increased during ART (P < .0001), whereas infiltration of CD8(+) cells subsided. Numbers of CD4(+) cells in the liver at baseline correlated with circulating CD4(+) T-cell counts (P = .03-.05). Numbers of liver-infiltrating CD4(+) and CD8(+) cells at baseline were not associates with subsequent experience of an immune restoration disease, which is defined by a rise in alanine transaminase levels during ART.

CD56+ lymphocyte counts remain low in the livers of human immunodeficiency virus/hepatitis C virus patients commencing ART

“…Similar CD56 + lymphocyte numbers in patients with and without HCV IRD is consistent with the lack of any association between IRD and hepatic CD4 + and CD8 + cells in this cohort. 9 This study showed that CD56 + lymphocytes were rare or absent in the livers of HIV/HCV co-infected patients and their numbers did not rise during ART. NK and NKT cells can produce IFN-γ and inhibit fibrogenesis.…”

“…7 Two reports of a prospective cohort of HIV/HCV patients treated in Jakarta, Indonesia, examined the effects ART and IRD. 8,9 Yunihastuti et al 8 showed that a plasma marker of T-cell activation (soluble CD26) rose during HCV IRD. Gani et al 9 showed that intrahepatic CD4 + cells increased while CD8 + cells diminished after ART, but these were not predictive of IRD.…”

“…8,9 Yunihastuti et al 8 showed that a plasma marker of T-cell activation (soluble CD26) rose during HCV IRD. Gani et al 9 showed that intrahepatic CD4 + cells increased while CD8 + cells diminished after ART, but these were not predictive of IRD. Here we quantitate CD56 + NK/NKT cells in liver biopsies of the same patients.…”

“…Liver biopsy was accepted by all patients at baseline and 34 patients at week 48. 8,9 Embedded tissues were retained, but 9 baseline samples and 8 samples from week 48 contained insufficient tissue for further immunostaining. Antiretroviral drugs comprised two nucleoside reverse trancriptase inhibitors (NRTI) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (zidovudine, stavudine, lamivudine, nevirapine, efavirenz).…”

“…However, there was no clear effect of ART on CD56 + lymphocytes whilst numbers of CD4 + cells in the liver increased on ART. 9 Hence, there is no clear role for CD56 + lymphocytes in the evolution of HCV disease on ART.…”