G. Paone

Role of lamivudine in the posttransplant prophylaxis of chronic hepatitis B virus and hepatitis delta virus coinfection.

Background. Posttransplant combined lamivudine (LAM) and immunoglobulin (HBIg) prophylaxis is the gold standard in the case of single hepatitis B virus (HBV), but is still not recommended in the case of patients coinfected with hepatitis delta virus (HDV). Methods. We compared two consecutive groups of chronic HDV carriers who survived >6 months after liver transplantation of the risk of recurrence, survival and HBIg requirements: 21 received passive prophylaxis (HBIg group) and 25 were treated with combined prophylaxis (LAM+HBIg group). The immunoprophylaxis schedule was the same in both groups: intramuscular HBIg targeted to maintain anti-HBs levels of >500 IU/L during the first 6 posttransplant months and >200 IU/L thereafter. Results. The mean length of follow-up in the two groups was significantly different (133 vs. 40 months; P<0.001). None of the patients in either group developed recurrent hepatitis, and the 3-year actuarial survival rate was 100% in both groups. During the first 6 months, HBIg requirement was 38% lower in the LAM+HBIg group although similar anti-HBs target levels were maintained, leading to significantly lower costs (&OV0556;5,000 in the first year and &OV0556;500 in the second). Conclusions. This is the first study of large and homogeneous cohort of long-term HDV coinfected liver transplant survivors showing the absence of HBV recurrence under combined prophylaxis. Although retrospective, our results suggest that combined anti-HBV prophylaxis should also be preferred to single immunoprophylaxis in patients with HDV coinfection because it allows significant cost savings in the first two posttransplant years.

Post‐hepatitis primary disease does not influence 6‐year survival after liver transplantation beyond 1 year

Abstract Orthotopic liver transplantation (OLT) is used as a definitive treatment for enD‐stage liver disease and prolonged posttransplant survival has already been reported. The incidence of late mortality and graft morbidity is, however, not well defined and the role of primary viral disease in the long‐term follow‐up results is not clear. Data of posttransplant follow‐up in 213 patients, 156 adults and 57 children, who survived at least 1 year were reviewed in order to define causes of graft dysfunction, graft loss and death. In 98 patients, 103 persistent graft dysfunctions were found. Thirty‐four grafts were later lost [28 deaths and 6 successful re‐transplantations (re‐OLT)]. The results were reviewed grouping patients according to their age and viral hepatitis status at the time of the transplantation. HBV‐positive patients (51) showed 4 re‐OLT (1 HBV), 3 liver‐related deaths (2 HBV), 24 graft dysfunctions (8 HBV, 5 HCV), and 85.2% 6‐year survival (based on 100% survival at 1 year). HCV‐positive adults (28) showed 1 re‐OLT, 3 HCV‐related deaths, 24 graft dysfunctions (19 HCV), and 68.8 % 6‐year survival. HBV‐HCV‐positive patients (14) showed no graft loss and death, 10 graft dysfunctions (7 HCV, 1 HBV, 2 HBV‐HCV), and 81.8 % 6‐year survival. HBV‐HCV‐negative adults (63) showed 3 non‐hepatitis‐related re‐OLT, 5 liver‐related deaths (2 HCV), 24 graft dysfunctions (6 HCV, 2 HBV), and 83.1 % 6‐year survival. HBV‐HCV‐negative children (49) showed no re‐OLT, 1 HCV‐related death, 14 graft dysfunctions (3 HCV), and 92.6% 6‐year survival. HCV‐positive children (8) showed 1 HCV‐related re‐OLT, 2 HCV‐related deaths, 4 graft dysfunctions (3 HCV), and 81.3% 6‐year survival. The main cause of graft dysfunction was hepatitis (45 HCV and 13 HBV), followed by technical complications (21), rejection (16), recurrent alcoholism (3), HIV infection (1), and unknown causes (4). In this long‐term post‐transplant follow‐up series, viral hepatitis led to graft dysfunction in 58/103 (56.3%) cases, late graft failure was viral hepatitis‐related in 11/20 (55 %) cases, and, as a total, HCV infection was present in 45/58 (77.5 %) cases of viral hepatitis‐related graft damage. Looking at the timing of hepatitis‐related graft failure, in 70% of cases death occurred after the 5th post‐transplant year. In our experience, the occurrence of hepatitis, particularly HCV induced, was common and led to abnormal graft function, but the 6‐year post‐transplant survival (based on 100% survival at 1 year) in patients surviving for at least 1 year did not differ on the basis of the pretransplant viral hepatitis status. This finding may be consistent with the slow progression of the viral damage and longer follow‐up results remain to be established. Nevertheless, data from the present study suggest that in long‐term liver transplant survivors, the risk of deteriorating liver damage and eventual failure after 5 years remains only in those patients experiencing a viral hepatitis infection.

Hepatitis B and C virus–induced diseases and acute rejection after liver transplantation

PREVIOUS reports outline that the rate of acute rejection (AR) after liver transplantation (LT) varies according to different primary diseases. In virus-related hepatic diseases, the graft reinfection after LT is a severe complication that may lead to the graft failure and retransplantation. Prevention of liver allograft rejection is not under discussion, but overimmunosuppression can be dangerous in virus hepatitis related primary diseases. The aim of this study is to verify if, among our patients, a difference exists in the rates of AR between virus-related hepatitis and unrelated primary hepatic diseases. A lower rate of AR in virus-related hepatic diseases after LT compared to other diseases could justify any attempt of therapies with a lower grade of immunosuppression.

Reduced acute rejection after liver transplantation with neoral-based double immunosuppression

CCYCLOSPORINE (CyA) is unequivocally a milestone in the development of organ transplantation. However, the wide interand intrapatient variability in gut absorption and the subsequent different bioavailability limited the exploitation of CyA in inducing immunosuppression without frequent blood monitoring. The clinical use of CyA in liver transplantation is further complicated by its bile-dependent absorption. These characteristics lead to fluctuations in the blood levels and to a potential higher incidence of acute rejection mainly in the early postoperative period. Recently, a new microemulsion formulation (Neoral) of CyA has been introduced in the clinical arena. The new formulation is better absorbed by the gastrointestinal tract, even in liver transplant patients with open external biliary drainage. Few open and randomized trials confirm the possibility of inducing immunosuppression by oral administration of CyA with a lower incidence of rejection in the Neoral arms. In this open, nonrandomized, retrospective study, we compare the incidence of acute rejection and nephrotoxicity during the first postoperative month and graft and patient survival rates at 1 year in 33 consecutive liver transplant adult patients: 17 patients treated with a Sandimmune-based double therapy and 16 patients treated with Neoral-based double therapy.

Long Term Outcome Of Right Split In Situ Liver Grafts In Adults

O28Aims:Split in situ liver transplantation (SSLT) in Italy was conceived to reduce the waiting list in pediatric liver transplantation (LT). Left grafts (II-III segments) are more often transplanted in pediatric patients (pts) whereas the right trisegments (IV,V-VIII) in adults. Pediatric waiting l