Background: End stage liver disease in HIV-HCV co-infected patients is an emerging problem requiring to assess the benefit risk ratio of liver transplantation (LT). We started a prospective evaluation of LT in co-infected patients in December 1999 assessing  several parameters: impact on the immune system and HIV replication, drug interactions, mitochondrial toxicity and incidence of HCV relapse.

 Methods: Up to December 2002, eleven HIV-HCV co-infected patients without history of opportunistic infection, were transplanted. At time of LT all patients were exposed to HAART, HIV plasma viral load was < 400 copies/mL and the median CD4 lymphocyte count was 350 cells/mm³ (range: 103-659). Immunosuppression therapy consisted of steroids and Tacrolimus. Anti HCV viral therapy was used when necessary and its benefit risk ratio was prospectively evaluated. Lastly, mitochondrial toxicity on the graft was studied by spectrophotometric analyses of the respiratory chain complexes and molecular analysis of mitochondrial DNA (mtDNA).

Results:  At time of evaluation, the median follow-up is 18 months (range 3 to45): 3 patients died, 4, 11, and 19 months after LT. Seven patients are in good condition and one patient is in poor condition. None on the patients developed opportunistic infection. Drug interaction was under control, only one patient developed a transient renal insufficiency. HCV replication started promptly after LT in all patients. Seven patients began pegylated interferon (PEG-IFN) and ribavirin therapy. This treatment was stopped in three patients because of intolerance. One patient showed a virological response and another a biochemical response and a decrease of liver fibrosis. At last biopsy, METAVIR score was staged F4 in 2 patients, F3 in 1, F2 in 2. Microvesicular steatosis was observed in nearly all patients. The ratio mtDNA nuclear DNA was low in 4 patients. A significant defect on the activities of respiratory chain was noted in five patients.

Conclusions: Liver transplantation in HV/HCV co-infected patients is feasible in a very selected population. Our experience do not suggest a deterioration of immune deficiency. Drug interaction is not a limiting problem. The early and severe relapse of hepatitis C suggest to start promptly an association of PEG-IFN and ribavirin. LT requires a multidisciplinary partnership.

Keywords: Liver Transplantation; HIV-HCV co-infection; Mitochondrial Toxicity