What Have We Learned About Primary Liver Transplantation Under Tacrolimus Immunosuppression?

Abstract

Long-term patient and graft survival rates are excellent under tacrolimus immunosuppression. Pediatric patients have a better long-term outcome than adults, in part because of the limited recurrence of the original disease, which was the most common cause of late graft loss (other than patient death, most commonly the result of late de novo malignancies and cardiovascular events). Graft loss from late rejection was rare.

Incidence of de novo cancer and lymphoproliferative disorders after liver transplantation in relation to age and duration of follow-up

“…This incidence increased when the longitudinal follow-up was extended to 8199 person years in December 2002. 14 At that time point, there were 87 cases of de novo nonlymphoid malignancies (10.62 cases per 100 person years of follow-up). They consisted of 33 nonmelanoma, non-Kaposi's skin cancers and 54 other malignancies ( Table 1).…”

“…12 Currently, long-term graft loss and death are not commonly related to rejection but are often due to age-related complications, such as cardiovascular disease and de novo cancers. 13,14 The rate of de novo cancers after LTx has been reported to range from 3% to 26%, [15][16][17][18] and the variation is partly due to the length of follow-up, different ways of reporting, and geographic variations in de novo malignancies. Although registry data of de novo cancers provide a valuable source for accounting for the various types of malignancies; these registries do not include the denominator of the population at risk.…”

Predictors of Success in Conversion from Calcineurin Inhibitor to Sirolimus in Chronic Allograft Dysfunction

“…CNI toxicity is the most common identifiable factor contributing to CAD, affecting 18% of patients with failing grafts (2,3). In addition, CNI-induced renal insufficiency of native kidneys is an important problem in other solid organ transplant recipients (4,5). Therefore, the use of antiproliferative drugs in combination with a reduction or withdrawal of CNI has become an interesting concept in treating CNI toxicity, leading to deterioration of renal allograft function.…”

Influence of hepatic ischemia-reperfusion injury on tacrolimus acute renal toxicity in pigs

“…Tacrolimus, an immunosuppressive macrolid that belongs to the family of the calcineurin inhibitors, has been shown to display greater immunosuppressive potency than cyclosporine a, with a lower incidence of episodes of rejection [1][2][3][4][5] and a high degree of efficacy for the treatment of nonductopenic steroid-resistant rejection. 10 However, tacrolimus does have toxic features common to this group of drugs: neurotoxicity, hyperglycemia, hypertrophy, development of lymphoid and skin tumors, and nephrotoxicity.…”

“…The precipitating causes of acute nephrotoxicity (ANT), which may affect 35% to 45% of liver transplant patients are uncertain, 5-8 but possibly include early graft malfunction, a phenomenon related to ischemia and reperfusion injuries, which result at least in part from shortcomings in the organ preservation. [5][6][7][8][9] To shed light on the relationship between ischemic liver injury and ANT caused by tacrolimus, we designed a comparative experimental study of the kidney damage generated in two experimental models of hepatic ischemia-reperfusion injury: non-heart-beating donor and an ischemia-reperfusion model with the organ in situ. …”