Does tacrolimus offer virtual freedom from chronic rejection after primary liver transplantation? Risk and prognostic factors in 1,048 liver transplantations with a mean follow-up of 6 years

Abstract

Tacrolimus has proven to be a potent immunosuppressive agent in liver transplantation (LT). Its introduction has led to significantly less frequent and severe acute rejection. Little is known about the rate of chronic rejection (CR) in primary LT using tacrolimus therapy. The aim of the present study is to examine the long-term incidence of CR, risk factors, prognostic factors, and outcome after CR. The present study evaluated the development of CR in 1,048 consecutive adult primary liver allograft recipients initiated and mostly maintained on tacrolimus-based immunosuppressive therapy. They were evaluated with a mean follow-up of 77.3 ؎ 14.7 months (range, 50.7 to 100.1 months). To assess the impact of primary diagnosis on the rate and outcome of CR, the population was divided into 3 groups. Group I included patients with hepatitis C virus (HCV)-or hepatitis B virus (HBV)-induced cirrhosis (n ‫؍‬ 312); group II included patients diagnosed with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), or autoimmune hepatitis (AIH; n ‫؍‬ 217); and group III included patients with all other diagnoses (n ‫؍‬ 519). Overall, 32 of 1,048 patients (3.1%) developed CR. This represented 13 (4.1%), 12 (5.5%), and 7 patients (1.3%) in groups I, II, and III, respectively. The relative risk for developing CR was 3.2 times greater for group I and 4.3 times greater for group II compared with group III. This difference was statistically significant (P ‫؍‬ .004). The incidence of acute rejection and total number of acute rejection episodes were significantly greater in patients who developed CR compared with those who did not (P < .0001). Similarly, the mean donor age for CR was significantly older than for patients without CR (43.0 v 36.2 years; P ‫؍‬ .02). Thirteen of the 32 patients (40.6%) who developed CR retained their original grafts for a mean period of 54 ؎ 25 months after diagnosis. Seven patients (21.9%) underwent re-LT, and 12 patients (38.3%) died. Serum bilirubin levels and the presence of arteriopathy, arterial loss, and duct loss on liver biopsy at the time of diagnosis of CR were significantly greater among the 3 groups of patients. In addition, patient and graft survival for group I were significantly worse compared with groups II and III. We conclude that CR occurred rarely among patients maintained long term on tacrolimus-based immunosuppressive therapy. When steroid use is controlled, the incidence of acute rejection, mean donor age, HBV-and/or HCV-induced cirrhosis, or a diagnosis of PBC, PSC, or AIH were found to be predictors of CR. Greater values for serum bilirubin level, duct loss, arteriopathy, arteriolar loss, and presence of HCV or HBV were found to be poor prognostic factors for the 3 groups; greater total serum bilirubin value (P ‫؍‬ .05) was the only factor found to be significant between patients who had graft loss versus those who recovered. (Liver Transpl 2001;7:623-630.)

Pediatric liver transplantation in 808 consecutive children: 20-years experience from a single center

“…4 Similar advantages of tacrolimus in pediatric transplantation have been published from our center and by others 5 --7 Nearly 80% of pediatric patients are now maintained on only low-dose tacrolimus. K The virtual absence of chronic rejection in adult liver transplant recipients following a review of over 5000 liver biopsies from more than 1200 patients with a mean follow-up of 6 years has been previously reported 9 Hepatitis Band C viruses, primary biliary cirrhosis, autoimmune hepatitis, and primary sclerosing cholangitis were found to be risk factors for the development of chronic rejection after liver transplantation. Fortunately, these liver diseases as indications for transplantation are extremely rare in the pediatric population.…”

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

“…[5][6][7] With the increasing success of liver transplantation (LTx) and fewer episodes of acute rejection with virtual freedom from chronic rejection, long-term survival rates have improved. [8][9][10][11] In addition, with an aging population, older recipients are also being considered for LTx. 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.…”

Histopathological Syndromes of Liver Allograft Rejection and Recurrent Disease

“…Recurrent disease, delayed manifestations of technical complications, such as vascular thrombosis or biliary sludge syndrome, and patient death are most commonly responsible for late (>1 year) graft failures [37,38]. Chronic rejection is uncommon as a cause of graft failure [37,39]. Recurrent HCV-induced cirrhosis is a leading cause for allograft failure that challenges organ allocation algorithms [40].…”

“…Early acute rejection episodes rarely lead to allograft failure or permanent damage [39,110], whereas episodes occurring late after transplantation more often produce permanent allograft damage, possibly because there is a delay in treatment [111][112][113][114]. The Banff classification for acute and chronic rejection was constructed on data generated by recognized experts in liver transplant pathology, hepatology, and surgery from many of the major hepatic transplant centers in North America, Europe, and Asia (Tables 82.2 and 82.3) [116].…”