Successful treatment with tenofovir in a child C cirrhotic patient with lamivudine-resistant hepatitis B virus awaiting liver transplantation. Post-transplant results.

Antiviral treatment can be complex in decompensated hepatitis B virus (HBV) cirrhosis because of potential emergence of lamivudine-resistant mutants and worsening liver function, and to multifactorial nephrotoxicity. Negative HBV-DNA status by hybridization before liver transplantation is a favorable prognostic factor. We present the case of a 54-year-old HBV+ liver transplantation candidate who, after testing negative for HBV-DNA, developed YMDD lamivudine-resistant mutants resulting in a deteriorated clinical condition. After 8 months of adefovir plus lamivudine double therapy, only partial response was achieved. Tenofovir was added to this regimen, and an early decline of HBV-DNA was seen at 4 weeks without adverse events. The patient underwent transplantation. At 21-month postoperative follow-up, the patient's outcome was excellent. Post-transplantation HBV prophylaxis, taking into account the prior development of mutants, consists of hepatitis B immunoglobulin plus lamivudine and adefovir. Tenofovir was well tolerated and produced a fast antiviral response, suggesting its potential value in combined antiviral treatment for liver transplantation candidates.

Long-term immune response after liver transplantation in patients with spontaneous or post-treatment HCV-RNA clearance.

Recurrent HCV infection after liver transplantation is universal and sustained clearance of HCV-RNA rarely occurs. The aim of this study was to characterize cell-mediated immunity and cytokine production in HCV-infected patients after liver transplant. The study included 6 pretransplantation patients (PT) and 15 liver transplanted patients, including 5 with spontaneous HCV-RNA clearance (SC group), 5 with sustained virological response after antiviral treatment (SVR group), and 5 no response (NR group). The control group included 5 HCV-RNA negative, anti-HCV negative healthy individuals. This study examines proliferative T-cell response and cytokine production (gamma-interferon and IL-10) after HCV specific and phytohemagglutinin (PHA) stimulation in cultured peripheral blood mononuclear cells (PBMCs) from each group. Multispecific proliferative responses to HCV antigens (mean Stimulation Index; SI) were higher in the SVR group (mean SI 7.4 +/- 2) and SC group, as compared with the NR group (P <.05, vs SVR) and PT group (P <.05, vs SVR and SC). After PHA stimulation, gamma-interferon levels were similar to controls (4330 +/- 640 pg/ml) in the SC (4474 +/- 300 pg/mL) and SVR groups (3647 +/- 300 pg/mL), but were significantly lower than controls in the PT (401 +/- 331 pg/mL; P <.02) and NR groups (546 +/- 360 pg/mL; P <.01). IL-10 production after PHA stimulation was similar in SC, SVR, and controls (647 +/- 279 pg/mL, 674 +/- 310 pg/mL and 841 +/- 294 pg/mL, respectively), but was lower in PT patients (232 +/- 94 pg/mL). The NR group showed high basal IL-10 production with little increase after stimulation. In conclusion, liver post-transplantation patients with spontaneous clearance of HCV-RNA and those with sustained viral response after therapy showed an immune response despite immunosuppression that might have contributed to their favorable outcome.