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

Received 1 December 2008; received in revised form 5 June 2009; accepted 25 June 2009. published online 14 September 2009.

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.

Associate Editor: P.-A. Clavien

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

1 Inserm, UMRS-945 Laboratoire d’Immunologie Cellulaire et Tissulaire, Centre Hospitalier Pitié-Salpêtrière, 83 Boulevard de l’hôpital, Bâtiment CERVI, 75013 Paris, France

2 UPMC Univ Paris 06, UMRS-945, Laboratoire d’Immunologie Cellulaire et Tissulaire, Paris, France

3 IFR113, Inserm, Laboratoire d’Immunologie Cellulaire et Tissulaire, Paris, France

4 AP-HP Hôpital Paul Brousse, Laboratoire de Virologie, Villejuif, France

5 Inserm, U785, Villejuif, France

6 Univ Paris-Sud, UMR-S785, Villejuif, France

7 AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France

8 AP-HP Hôpital Paul Brousse, Service Infectiologie, Villejuif, France

9 Inserm, CIC4, Nantes, France

10 AP-HP Hôpital Paul Brousse, Laboratoire d’Anatomo Pathologie, Villejuif, France

11 AP-HP Hôpital Pitié-Salpêtrière, Laboratoire d’Immunologie Cellulaire et Tissulaire, Paris, France

Corresponding author. Tel.: +33 1 42177481; fax: +33 1 42177490.

☆ The authors who have taken part in this study declared that they do not have anything to declare regarding funding from industries or conflict of interest with respect to this manuscript.

# Present address: First Faculty of Medicine, Charles University, Prague, Czech Republic.

PII: S0168-8278(09)00581-9

doi:10.1016/j.jhep.2009.06.031

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