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Liver Transplant Do Not Impair Immune Response in HIV/HCV Coinfected Patients

HIV/HCV coinfected patients who undergo liver transplantation do not lose immune responses to hepatitis C virus (HCV), HIV, or opportunistic infections, according to an analysis reported in the December 2009 Journal of Hepatology. This study adds to the evidence that appropriately selected coinfected individuals can be suitable candidates for liver transplants.

In recent years, a growing body of data has shown that HIV positive people can have nearly as good outcomes as HIV negative people after liver transplantation, assuming they have well-maintained immune function (CD4 count of at least 200 cells/mm3) and achieved HIV suppression with antiretroviral therapy (ART) -- or are expected to do so, if they are currently not on ART due to liver disease.

However, people with HCV do not fare as well as those who require liver transplants for other reasons, and this holds true for HIV/HCV coinfected as well as HIV negative recipients.

Preservation of immune function after liver transplantation has not been well studied -- an issue addressed by Assia Samri and fellow investigators with the French ANRS-HC08 "THEVIC" trial. The researchers aimed to determine whether liver transplantation is detrimental to the immune system, and in particular how this affects severity of HCV recurrence in the liver graft.

The study included 14 HIV/HCV coinfected patients receiving transplants due to HCV-related liver cirrhosis. Prior to transplantation they had HIV viral load < 50 copies/mL and a median CD4 count of 276 cells/mm3. Of these patients, 9 received interferon-based hepatitis C therapy after transplantation.

Participants were followed for more than 2 years. HIV and HCV viral load were monitored, as well as degree of acute and chronic hepatitis. The investigators also assessed peripheral blood T-cell phenotypes and interferon-gamma (IFN-gamma) immune responses against the HIV-1 p-24 core protein, HCV, and various opportunistic pathogens.

Results

• Median HCV RNA viral load, CD4 counts, T-cell subsets, and number of IFN-gamma-producing T-cells responsive to HIV p24 and opportunistic pathogens did not change over time after transplantation.
• HCV-specific T-cells were observed in samples from 2 patients prior to transplantation and in 2 others post-transplantation.
• After in vitro amplification, HCV-specific IFN-gamma-producing T-cell responses were detected in 3 more patients post-transplantation.
• Anti-HCV responses were independent of hepatitis C therapy.
• Anti-HCV responses were undetectable, however, in patients with severe hepatitis or liver fibrosis.

Based on these findings, the study authors concluded, "These results demonstrate that liver transplantation 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."

Inserm, UMRS-945 Laboratoire d'Immunologie Cellulaire et Tissulaire, Centre Hospitalier Pitié-Salpêtrière, Paris, France; UPMC Univ Paris 06, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France; IFR113, Inserm, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France; Inserm, U785, Villejuif, France; Univ Paris-Sud, UMR-S785, Villejuif, France; AP-HP Hôpital Paul Brousse, Laboratoire de Virologie, Centre Hépato-Biliaire, Service Infectiologie & Laboratoire d'Anatomo Pathologie, Villejuif, France; Inserm, CIC4, Nantes, France; AP-HP Hôpital Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France.

1/15/10

Reference

A Samri, AM Roque-Afonso, O Beran, and others. Preservation of immune function and anti-hepatitis C virus (HCV) immune responses after liver transplantation in HIV-HCV coinfected patients (ANRS-HC08 "THEVIC" trial). Journal of Hepatology 51(6): 1000-1009 (Abstract). December 2009.