Preservation of immune function and anti-hepatitis C virus (HCV) immune responses after liver transplantation in HIV–HCV coinfected patients (ANRS-HC08 “THEVIC” trial)☆

Background/Aims

Liver transplantation (LT) in immune-suppressed human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected patients is feasible but raises questions regarding the severity of HCV recurrence on the liver graft and preservation of immune function. We investigated whether LT is deleterious to the immune system.

Methods

Fourteen HIV–HCV coinfected patients (HIV viral load [VL] <50copies/ml; median CD4 count of 276/mm³ pretransplantation) were grafted for HCV–cirrhosis and followed over 2years. Nine patients received anti-HCV therapy post-transplantation. HCV and HIV VLs and degree of acute and chronic hepatitis were monitored. Peripheral blood T-cell phenotypes and interferon-γ (IFN-γ) immune responses against opportunistic pathogens, HCV, and HIV-1 p24 were evaluated.

Results

Median HCV VLs, CD4 counts, T-cell subsets, and IFN-γ–producing T-cell frequencies against opportunistic pathogens and HIV-1 p24 did not change over time. HCV-specific T cells were observed ex vivo in two patients pretransplantation and in two others post-transplantation. HCV-specific in vitro amplification enabled the detection of HCV-specific IFN-γ-producing responses in three further patients post-transplantation. Anti-HCV responses were observed independently of anti-HCV therapy and were undetectable in patients with severe hepatitis or liver fibrosis.

Conclusions

These results demonstrate that LT in HIV–HCV coinfected patients is not deleterious to the immune system and does not alter immune responses directed against HCV, HIV, or opportunistic pathogens.

Abbreviations: AIDS, acquired immunodeficiency syndrome, HCV, hepatitis C virus, HIV, human immunodeficiency virus, LT, liver transplantation, HAART, highly active antiretroviral therapy, PBMC, peripheral blood mononuclear cells, VL, viral load, PI, protease inhibitors, NNRTI, non-nucleoside reverse transcriptase inhibitors, IFN, interferon, CMV, cytomegalovirus, SFC, spot forming cells, SD, standard deviation, BCR, biochemical response, Th, T helper type, TDF, tenofovir, NFV, nelfinavir, SQV, saquinavir, LPV, lopinavir, 3TC, lamivudine, d4T, stavudine, ABC, abacavir, RTV, ritonavir, ATV, atazanavir, NVP, nevirapine, ZDV, zidovudine, ddI, didanosine, EFV, efavirenz, PegIFN, pegylated interferon alpha, RBV, ribavirin, FTC, emtricitabine, T20, fuzeon, MMF, mycophenolate mofetil, Tcr, tacrolimus

Keywords: HIV–HCV coinfection, HCV recurrence, Anti-HCV immune response, Anti-HCV therapy, Liver transplantation