ABO compatibility and acute graft-versus-host disease following allogeneic bone marrow transplantation

If ABO antigens/antibodies play any role in the pathogenesis of acute graft-versus-host disease (GVHD), one would expect the highest incidence of GVHD in recipients of minor ABO-mismatched grafts, followed by ABO-matched grafts, and the lowest incidence in major ABO-mismatched transplants. To test this hypothesis 174 patients receiving an HLA-identical allogeneic bone marrow transplant (BMT) for aplastic anemia (n = 32) or leukemia (n = 142) were analyzed for factors associated with acute GVHD. Variables analyzed included diagnosis, sex, age, blood group of donor and recipient, ABO compatibility, Rhesus compatibility, sex compatibility, number of bone marrow cells given at BMT, year of transplant, day of engraftment, and GVHD prophylaxis. We first carried out an exploratory contingency table analysis: minor ABO incompatibility was associated with a significantly higher risk of severe acute GVHD when compared with ABO-matched and major-ABO mismatched pairs (P = 0.003): 14/9, 57/67, and 5/22 patients developed, respectively, 0-I/II-IV acute GVHD in ABO major-mismatched, matched, and minor-mismatched pairs. Donors of group 0, (P = 0.06), older recipient's age (P = 0.08), fast engraftment (P = 0.03), and older donor's age (0.08) were also associated with a higher risk of GVHD. Recipient's ABO group, diagnosis, year of transplant, Rhesus group of donor or recipient, Rhesus compatibility, sex of donor or recipient, sex compatibility, and type of GVHD prophylaxis were not predictive of GVHD. A Cox multifactorial proportional hazards analysis confirmed that ABO matching was the single most significant factor associated with GVHD (P = 0.006). The cumulative incidence of GVHD grade II+ was 39%, 54%, and 82% for ABO major-mismatched, matched, and minor-mismatched pairs (P = 0.01). This study suggests that ABO antigens may play a role in the development of acute GVHD.     

Increased incidence of chronic rejection in adult patients transplanted for autoimmune hepatitis: assessment of risk factors

BACKGROUND/AIM: It remains uncertain whether autoimmune hepatitis (AIH), as an original indication for orthotopic liver transplantation (OLTX), predisposes to the development of chronic rejection (CR) after surgery and published reports on heterogeneous groups of patients provided conflicting data. In this work we analyzed the incidence and risk factors for CR in a large cohort of adult patients transplanted for AIH in our unit. RESULTS: A total of 1190 adult patients received OLTX in our center between 1982 and 1998. A total of 77 patients (6.5%) were transplanted for AIH and 12 (15.6%) patients from this group developed clinical and histological features of CR within a median time of 3.5 months after OLTX. Patients with AIH who developed CR were younger than other AIH patients at OLTX (32 vs. 44.2 ys; P=0.015) and more often had histological features of moderate or severe acute rejection (83 vs. 34%; P=0.002) on early post-OLTX biopsies. The incidence of CR in AIH patients was significantly higher than in subjects transplanted for other indications such as primary biliary cirrhosis (8.2%; P<0.05), primary sclerosing cholangitis (5.2%; P<0.05) or alcoholic cirrhosis (2.0%; P<0.001). Also, we observed a tendency to decreased incidence of CR with time in all transplanted subjects. CONCLUSIONS: Apart from younger age at OLTX and higher incidence of severe acute rejection, patients with AIH who developed CR did not differ from other subjects transplanted for this indication. Unlike other studies, not stratified by diagnosis, recipient CMV negative status, young donor age, and HLA DR matching were not identified as risk factors for CR in AIH.     

Impact of donor age and year of transplantation on graft and patient survival following liver transplantation for hepatitis C virus

BACKGROUND: Hepatitis C virus (HCV) infection has become the most common indication for liver transplantation (LT). Graft and patient survival are adversely affected by recurrent infection of the graft. Recent publications have described an inferior outcome for recently transplanted HCV patients and have highlighted the impact of advancing donor age on severity of recurrent HCV. The donor age at which a measurable impact on graft and patient outcome can be observed has not clearly been defined. In addition, the impact of donor age on graft and patient survival for non-HCV patients needs to be examined. METHODS: We have examined a large European liver transplant database to define the impact of transplantation date and donor age on graft and patient survival for HCV patients (n = 4,736) and the impact for a comparison group of transplanted alcoholic liver disease patients (ALD, n = 5,406). RESULTS: For the entire cohorts, graft and patient survival of HCV patients was inferior to ALD patients. Since 1987, there has been a steady and ongoing improvement in the outcome of transplanted ALD patients, an improvement not observed for HCV patients. Every year since 1989, there has been an increase in liver donor age. Graft and patient survival for both ALD and HCV cohorts was adversely affected by advancing donor age. Comparison of graft and patient survival for HCV and ALD cohorts was made according to donor age (donor age subgrouped <20, 20-30, 30-40, 40-50, 50-60 and >60 years of age). For donors younger than 40 years of age, HCV and ALD recipient graft and patient survival are not significantly different. For donors older than 40, HCV recipient graft survival is inferior to ALD graft survival, an inferiority that increases for each advancing decade of donor age. For donors older than 50 years, HCV recipient patient survival is inferior to ALD patient survival, an inferiority that increases when the donor age is greater than 60 years. CONCLUSION: The results of liver transplantation for European HCV patients is inferior to a comparison group of ALD patients, and have not improved during the past 15 years. Liver donor age has increased significantly during that period. Advancing donor age has an adverse influence on graft and patient survival for ALD and HCV patients, but a significantly greater impact is observed for HCV patients when the donor is older than 40 years.     

Risk factors for acute graft-versus-host disease in histocompatible donor bone marrow transplantation

We have analyzed factors associated with acute graft-versus-host disease following allogeneic bone marrow transplantation in 469 patients with histocompatible sibling donors between 1979 and 1987. Overall, 46 +/- 5% (95% confidence interval) developed clinical grade II-IV acute GVHD following transplantation. In univariate analysis, patient or donor age greater than or equal to 18 years was significantly associated with increased GVHD risks (greater than or equal to 18, 63 +/- 6% grade II-IV GVHD vs. less than 18, 27 +/- 6%, P less than .0001), without incremental risk in older adults. Univariate analysis showed that donor:recipient sex match and female:female transplants were associated with less-frequent GVHD. More frequent GVHD was associated with chronic myelogenous leukemia, cytomegalovirus seropositivity, and prior donor alloimmunity (pregnancy or transfusion). Additionally, the allele HLA-A26 was associated with increased risk of GVHD (72%, P = .005) while HLA-DR3 was associated with less GVHD (31%, P = .03). Stepwise multivariate analysis confirmed the increased GVHD risks associated with older recipient age, HLA-A26 and donor:recipient gender (not female:female) and the protective effect of HLA-DR3. Similar results were found using the different analytic technique of recursive partition analysis, which identified within the adult population the lowest GVHD risk in female recipients with nonalloimmunized female donors (20%), while other gender combinations had 68% acute GVHD, regardless of donor alloimmunity. In children (less than 18 years), lower GVHD risk accompanied donor:recipient sex-matched (18%) versus mismatched (33%) BMT. Clinical trials undertaken to lessen the hazards of GVHD must be designed with appropriate attention to these reproducibly identified clinical variables associated with different GVHD risks.     

A European multicenter study of chronic graft-versus-host disease. The role of cytomegalovirus serology in recipients and donors--acute graft-versus-host disease, and splenectomy

A group of 466 leukemic bone marrow transplanted patients were reported from 17 European bone marrow transplantation teams. Of these, 285 survived more than 3 months and could be evaluated for chronic GVHD. The cumulative incidence of chronic GVHD was 32% two years after BMT. The following factors were statistically significantly associated with chronic GVHD in bivariate analysis: high donor and recipient age, splenecacute GVHD, pretransplant seropositivity to CMV among the recipients and the donors, and donor seropositivity to 3 or 4 different herpesviruses, compared with 0-2, prior to BMT. In multivariate analysis pretransplant recipient CMV seropositivity in combination with donor CMV seropositivity prior to BMT (P = 0.0006), a previous grade II-IV acute GVHD (P = 0.001), and splenectomy (P = 0.01) were significantly associated with chronic GVHD. Thus, in addition to acute GVHD, CMV immune donor cells may be triggered by latent CMV in the recipient, which may play a role in the triggering of chronic GVHD. The possible role of splenectomy in GVHD is also discussed.     

Risk Factors for Posttransplant Lymphoproliferative Disorder in Pediatric Liver Transplant Recipients With Cytomegalovirus Antigenemia

Epstein-Barr virus (EBV) infections, associated with posttransplant lymphoproliferative disorder (PTLD) are known to develop in cytomegalovirus (CMV)-infected transplant recipients due to the indirect effects of CMV. This study evaluated risk factors for PTLD among pediatric liver transplant recipients with CMV infections. We reviewed the medical records of 119 patients ≤18 years old who underwent liver transplantation between September 1996 and April 2009. Sixty-six subjects (55.5%) displayed CMV antigenemia during the study period; 15 (12.6%) developed PTLD. Of these, 10 developed PTLD after CMV antigenemia. The other patients (n = 5) were excluded due to negative CMV antigenemia. The incidence of PTLD influenced by CMV infection was not significantly different from the incidence of PTLD without underlying CMV (P = .258). There were no differences in age, gender, antiviral prophylaxis, type of liver transplantation, or acute rejection episodes in the incidence of between patients with versus without PTLD. EBV but not CMV high-risk groups were a predictor for the development of PTLD (P = .035). CMV syndrome, tissue-invasive CMV disease, and CMV peak titer were not associated with an increased risk of PTLD. The primary risk factor for PTLD was EBV high-risk patients (donor positive/recipient negative). CMV disease was not associated with PTLD in pediatric liver transplant recipients with CMV infections.     

Characteristics of liver transplant candidates delisted following recompensation and predictors of such delisting in alcohol‐related liver disease: a case–control study

Whether and when recovery beyond the need for transplant may occur in patients listed for decompensation remains unclear. This study aimed to investigate the characteristics of patients delisted following recompensation. Seventy‐seven patients who were listed between 2005 and 2015 for decompensation, but later delisted following recompensation were included. Alcohol‐related liver disease (ALD) was the underlying etiology in the majority (n = 47, 61%). Listing characteristics of these patients were compared with those of decompensated ALD patients who either underwent deceased donor liver transplantation or died on the waiting list. The model for end‐stage liver disease (MELD) score <20 and serum albumin ≥32 g/l at listing were the only independent predictors of recompensation/delisting in ALD. The probability of recompensation was 70% when both factors were present at listing. Interestingly, about a tenth of decompensated ALD patients who died on the waiting list (median duration on waiting list 11 months) and a quarter of decompensated ALD patients who underwent living donor liver transplantation (median duration on waiting list 2 months) also had both factors at listing. In conclusion, ALD seems to be the most favorable etiology for recompensation beyond the need for transplantation. Both MELD and serum albumin at listing independently predict recompensation/delisting in ALD. It seems advisable to implement a period of observation for ALD patients with both favorable factors, before embarking on living donor liver transplantation.     

Recurrence of autoimmune hepatitis after liver transplantation.

BACKGROUND: The literature data on the recurrence of autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLTX) is scanty. METHODS: We analyzed the frequency of recurrent AIH in 47 patients who had been transplanted for AIH and survived at least 1 year after surgery. The following criteria were applied to diagnose recurrence: (1) positive autoantibodies in the titer> or =1:40; (2) hypertransaminasemia; (3) histological features of chronic hepatitis; (4) need of reintroduction or significant increase of steroids; and (5) lack of serum markers of viral hepatitis. RESULTS: A total of 13 patients (1 male/12 females) developed recurrent AIH after an interval of 6-63 months after OLTX (mean 29 months). Mean AST level at recurrence was 542+/-129 U/L. Three patients from this group needed regrafting. Mismatch of DR3+ recipient and DR3- donor was not more common in the recurrent disease group (37%) compared to the nonrecurrence group (31%) (P=NS). CONCLUSIONS: Recurrence of AIH after OLTX was diagnosed in a high proportion of patients and some of them required regrafting. DR3+ patients are not particularly prone to develop recurrence.     

Optimizing living donor kidney graft function by donor-recipient pair selection

BACKGROUND: With the rising prevalence of living donor kidney transplantations (LDKT), we increasingly encounter transplant candidates who present with multiple potential living donors. For a given candidate, it can be unclear which donor offers the best opportunity for optimal posttransplant graft function. This study was undertaken to determine the relative contributions of individual donor demographic factors on graft function following LDKT. METHODS: All LDKT donor-recipient pairs between January 1, 1999 and December 31, 2002 entered into the Scientific Registry of Transplant Recipients (SRTR) were reviewed. Suboptimal one year graft function was defined as a serum creatinine (Cr) greater than 1.5 mg/dL. RESULTS: Of 20,528 adult LDKTs performed, 8,603 donor-recipient pairs had complete donor, recipient, and one year graft function data. Over one third (36%) of all LDKTs had suboptimal one year graft function. Logistic regression identified simple recipient and donor characteristics associated with suboptimal one year graft function. Four recipient factors (age, gender, race, and size), three donor factors (age, gender, and size) and recipient-donor relatedness were used to derive an equation that predicts the risk of suboptimal one year graft function posed by each potential living donor for a given transplant candidate. CONCLUSIONS: In the setting of multiple potential living kidney donors, this quantitative tool may facilitate the choice of the optimal donor.     

Multivariate analysis of factors affecting patient and graft survival after renal transplant

AIM: To evaluate factors affecting patient and kidney survival after renal transplant. PATIENT AND METHODS: Among 361 patients undergoing renal transplant: 52% (n = 189) were simultaneous with pancreas transplant (SPKT group) and 48% (n = 172), a kidney transplant alone (KT group). Out of 361 patients, 75% (n = 270) were diabetics. The patients were 220 (61%) men and 141 (39%) women of mean age 41 +/- 9 years. The mean time of dialysis was 42 +/- 21 months (range 0 to 126), and the mean duration of diabetes 24 +/- 7 years (range 5 to 51). A Cox regression analysis was done. RESULTS: The multivariate analysis revealed that in the final model diabetes and donor age were significant predictors of kidney graft survival; moreover, diabetes and recipient age were predictors of patient survival. Overall patient survival was significantly greater among nondiabetic patients (P = .002) or in diabetic patients who received SPKT, when compared with diabetics in whom only the kidney was transplanted (P = .001). CONCLUSIONS: Diabetes and donor age were independent prognostic factors affecting kidney graft survival after renal transplant, and recipient age and diabetes were prognostic factors affecting patient survival. Combined pancreas and kidney transplantation should be offered to patients with end-stage diabetic nephropathy.     

Natural history of unexplained chronic hepatitis after liver transplantation.

Unexplained chronic hepatitis (CH) in the adult liver allograft recipient is not uncommon, but its natural history and clinical significance is unknown. A retrospective study was undertaken of adult liver allograft recipients to determine the frequency and natural history of unexplained CH. We evaluated only those patients who had undergone >or=2 liver biopsies after 6 months and were grafted for indications where recurrent disease could be confidently excluded (alcoholic liver disease [ALD] in those who remained abstinent and fulminant hepatic failure [FHF] from drug reactions). Of 288 patients who were transplanted for ALD or FHF, 30 fulfilled the above criteria. CH was first diagnosed at a median of 15.25 months after transplantation. A total of 24 patients showed mild necroinflammatory changes, and 12 had mild or moderate fibrosis. Liver tests did not reflect the presence or degree of inflammation or fibrosis. After a median of 4 years, necroinflammatory scores were increased in 5; new or progressive fibrosis was noted in 13%; 3 had developed cirrhosis; and 5 developed clinical evidence of portal hypertension. Progressive fibrosis was associated with a high titer of anti-nuclear antibodies (>1:1600) and a portal tract plasma cell infiltrate. There was a trend for correlation between necroinflammatory activity and fibrosis stage, but this did not reach statistical significance (P = 0.06). Serum alkaline phosphatase (P = 0.012) and female gender of the donor (P = 0.033) were associated with progressive fibrosis. Unexplained CH is not uncommon in the liver allograft and may progress to established cirrhosis in a subgroup of patients transplanted for ALD or FHF. Standard liver tests do not reflect the extent of these changes, so protocol liver biopsies may be required to detect these changes. We recommend careful history and follow-up in these patients.     

Hepatocellular Carcinoma Recurrence and Death Following Living and Deceased Donor Liver Transplantation

We examined mortality and recurrence of hepatocellular carcinoma (HCC) among 106 transplant candidates with cirrhosis and HCC who had a potential living donor evaluated between January 1998 and February 2003 at the nine centers participating in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Cox regression models were fitted to compare time from donor evaluation and time from transplant to death or HCC recurrence between 58 living donor liver transplant (LDLT) and 34 deceased donor liver transplant (DDLT) recipients. Mean age and calculated Model for End-Stage Liver Disease (MELD) scores at transplant were similar between LDLT and DDLT recipients (age: 55 vs. 52 years, p = 0.21; MELD: 13 vs. 15, p = 0.08). Relative to DDLT recipients, LDLT recipients had a shorter time from listing to transplant (mean 160 vs. 469 days, p < 0.0001) and a higher rate of HCC recurrence within 3 years than DDLT recipients (29% vs. 0%, p = 0.002), but there was no difference in mortality or the combined outcome of mortality or recurrence. LDLT recipients had lower relative mortality risk than patients who did not undergo LDLT after the center had more experience (p = 0.03). Enthusiasm for LDLT as HCC treatment is dampened by higher HCC recurrence compared to DDLT.     

AGMA Score: A Novel Prognostic Score for Patients Undergoing Liver Transplant for Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma (HCC) in cirrhosis represents one of the leading indications for liver transplant. In an effort to expand the listing criteria, a variety of scoring systems have been suggested, mainly based on the tumor number/size criterion. The objective of our study was to evaluate the feasibility of proposing a transplant score for HCC excluding the tumor number/size criterion.Patients and MethodsData corresponding to patients who received transplants because of HCC were reviewed for the purposes of this study. Deceased donor and living donor liver transplants were included. Demographic, clinical and tumor-related parameters were evaluated. Uni- and multivariate regression analyses and survival analysis were performed.ResultsOne hundred patients were included in the study. Fifty-five patients underwent deceased donor liver transplant, and 45 patients received living donor liver transplants. Tumor differentiation (G1/2 vs G3), alpha-fetoprotein levels (AFP), recipient age, and recipient laboratory Model for End-Stage Liver Disease Score (MELD) showed statistical significance. A scoring system was developed, with prognostic points assigned as follows: age 60 years or younger:age older than 60 years = 1:0 points, tumor grading well or moderate:tumor grading poor = 1:0 points, MELD score ≤22:MELD score >22 = 1:0 points, and AFP level ≤400 ng/mL:AFP level >400 ng/mL = 1:0 points. This stratification delineated 3 separate population samples corresponding to patients with scores of 4, 3, and 1 to 2, respectively. The calculated 5-year survival for scores 4, 3, and 1 to 2 was 76%, 47%, and 20%, respectively (P < .001).ConclusionThe AGMA score (age, grading, MELD, AFP) showed prognostic value in this single-center analysis and may find clinical implication avoiding the tumor number/size criterion.     

Temporary Cessation of Immunosuppression for Infection May Contribute to the Development of Graft-vs-Host Disease After ABO-Incompatible Living Donor Liver Transplantation: A Case Report

Graft-vs-host disease (GVHD) after liver transplantation is a rare complication with a high mortality rate. A complex interplay between donor and recipient immunity plays a role in the development of GVHD. Infection following liver transplantation is one of the most common complications in a recipient of an organ transplant who is immunosuppressed. On clinical signs of infection, the immune reaction of the recipient can be reconstituted by withdrawal of immunosuppression in order to help combat infection. However, the discontinuation of immunosuppression could restore the donor’s immune activity rather than that of the recipient. There is little information available as to whether the discontinuation of immunosuppression for severe infection could contribute to the development of GVHD in a patient who underwent ABO-incompatible (ABO-I) living donor liver transplantation (LDLT). Herein, we present a unique case of GVHD following ABO-I LDLT, for which the cessation of immunosuppression could be responsible.     

Impact of evolving trends in recipient and donor characteristics on cytomegalovirus infection in liver transplant recipients

BACKGROUND: This study determines whether the recipient and donor characteristics that influence the cytomegalovirus (CMV) infection rate after liver transplantation have changed. METHODS: The recipient and donor characteristics that may affect the rate of CMV infection were assessed in 232 liver transplant recipients at our institution during a 14-year period (1989-2003). RESULTS: Since 1989, the age of recipients (P=0.0001) and donors (P=0.0001) has increased significantly. Pretransplant CMV seropositivity in recipients has decreased significantly (P=0.0001, 86.4% [1989-1992] to 53.7% [2000-2003]), whereas donor CMV seropositivity has remained unchanged (P>0.20). As a result, there has been a significant increase in the proportion of high-risk (CMV recipient-/donor+) patients (P=0.012); 10.6% of recipients from 1989 to 1992 versus 24.1% of recipients from 2000 to 2003 were CMV recipient-/donor+. The Child-Pugh scores of recipients have remained unchanged over time. However, the proportion of patients undergoing transplantation while being cared for in the intensive care unit has decreased significantly over time (P=0.0002). Despite an increase in the rate of CMV infection (P=0.09), the incidence of CMV disease has decreased significantly (P=0.0004). CONCLUSIONS: The proportion of high-risk patients (CMV recipient-/donor+) has increased significantly over time, attributable largely to a declining rate of CMV seropositivity in recipients before transplantation. These data have implications for guiding prophylactic practices and resource use after liver transplantation.     

D-MELD, a Simple Predictor of Post Liver Transplant Mortality for Optimization of Donor/Recipient Matching

Numerous donor and recipient risk factors interact to influence the probability of survival after liver transplantation. We developed a statistic, D-MELD, the product of donor age and preoperative MELD, calculated from laboratory values. Using the UNOS STAR national transplant data base, we analyzed survival for first liver transplant recipients with chronic liver failure from deceased after brain death donors. Preoperative D-MELD score effectively stratified posttransplant survival. Using a cutoff D-MELD score of 1600, we defined a subgroup of donor–recipient matches with significantly poorer short- and long-term outcomes as measured by survival and length of stay (LOS). Avoidance of D-MELD scores above 1600 improved results for subgroups of high-risk patients with donor age ≥60 and those with preoperative MELD ≥30. D-MELD ≥1600 accurately predicted worse outcome in recipients with and without hepatitis C. There is significant regional variation in average D-MELD scores at transplant, however, regions with larger numbers of high D-MELD matches do not have higher survival rates. D-MELD is a simple, highly predictive tool for estimating outcomes after liver transplantation. This statistic could assist surgeons and their patients in making organ acceptance decisions. Applying D-MELD to liver allocation could eliminate many donor/recipient matches likely to have inferior outcome.     

Clinical tolerance after allogeneic hematopoietic stem cell transplantation: a study of influencing factors

BACKGROUND: Clinical tolerance, defined as discontinuation of immunosuppression without immunological events, is often achieved after allogeneic hematopoietic stem cell transplantation, unlike after organ transplantation. However, this phenomenon has rarely been studied. METHODS: Between September 1977 and December 1997, we evaluated 354 allogeneic hematopoietic stem cell recipients who had had more than 1 year of relapse-free survival, regarding time to discontinuation of immunosuppression. Factors such as patient age, donor age, donor sex, immunosuppressive protocols, cell dose, and graft-versus-host-disease (GVHD) were studied. RESULTS: Patients who did not develop GVHD had discontinued immunosuppression according to the protocols, within 1 year for malignant diseases and within 2 years for nonmalignant diseases. Patients given methotrexate as a single drug were off immunosuppression faster than those given cyclosporine alone (P=0.05). Children (<18 years) discontinued immunosuppression faster than adults (P=0.05). Low donor age was of greater importance than low recipient age for early discontinuation (P=0.003). Male recipients of stem cells from immunized female donors needed a longer time to discontinuation (P<0.001). Patients without acute GVHD had a shorter time to discontinuation than patients with any grade of GVHD (P=0.02). Thirteen months after hematopoietic stem cell transplantation, 54% of HLA-identical sibling marrow recipients and 36% of unrelated marrow recipients with malignant disease had discontinued immunosuppression (P=0.002). Twenty-five months after hematopoietic stem cell transplantation, the corresponding figures were 69% and 75% in the two groups, respectively. CONCLUSION: In multivariate analysis, high donor age, immunized female donor to male recipient, and grades II-IV acute GVHD were significantly associated with a longer time to clinical tolerance.     

Predictive factors for cytomegalovirus infection after orthotopic liver transplantation using an ultrasensitive polymerase chain reaction assay

The predictive factors for cytomegalovirus (CMV) infection in de novo liver transplant patients were determined at 3 months posttransplantation. We included all consecutive patients except those who died or who had lost their graft within 1 month posttransplant. We recorded both donor (D) and recipient (R) data. Immunosuppression utilized tacrolimus, steroids, with or without mycophenolate mofetil, and/or induction therapy with anti-CD25 monoclonal antibodies. CMV prophylaxis was administered only to those at high risk of CMV infection, namely, D+/R- patients. These cases received intravenous ganciclovir at 500 mg/d for the first 2 weeks followed by oral ganciclovir at 500 mg for the following 3 months. The median time to CMV infection was 1 month. The significant predictive factors for CMV infection were D/R CMV status, (P = .002): D+/R+ versus other patients (P = .01), D-/R- versus other patients (P = .002), D+ versus D- (P = .009). In addition infection was associated with the original liver disease (hepatitis C virus infection or alcohol-related cirrhosis; P = .03), R+ vs. R- (P = .03), donor age (<45 or >45 years; P = .01), lymphocyte count at M2 (< or >1300/mm(3); P = .02), hemoglobin levels at 1 and 3 months, and platelet and white blood cell counts at day 7. The independent predictive factors were recipient CMV sero-status (R+ vs R-; odds ratio = 10.2), donor age >45 years (odds ratio = 11.4) and lymphocyte count at M2 <1300/mm(3) (odds ratio = 7.33). This study showed that the major factors associated with CMV infection were recipient CMV status, donor age, and lymphocyte count.     

Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation.

With improved cytomegalovirus (CMV) prophylaxis, CMV disease after liver transplantation has decreased dramatically, and patient and graft survival have improved. We examined the impact of CMV prophylaxis on biopsy proven rejection after orthotopic liver transplantation by analyzing data on 192 liver recipients over 5 years (1994-1999). Risk factors assessed for biopsy proven rejection including donor and recipient age, CMV serostatus; CMV prophylaxis; immunosuppression; bacteremia and blood product use were examined over a 2-year follow-up. Multivariate analysis of risk factors for rejection showed that bacteremia (HR 3.57, 95% CI 1.39-9.36, P=0.008), donor age (HR 1.20, 95% CI 1.06-1.36, per 10 year increase, P=0.004), and use of cyclosporine as initial immunosuppression compared to tacrolimus (HR 1.98, 95% CI 1.27-3.09, P=0.003) were associated with increased risk; ganciclovir prophylaxis for 3 months (HR 0.51, 95% CI 0.33 to 0.79, P=0.003) and recipient age (HR 0.78; 95% CI 0.63-0.96, for each 10 year increase, P=0.03) were associated with decreased risk. We conclude that, the use of CMV prophylaxis with ganciclovir significantly reduces the incidence of biopsy proven rejection in liver transplant recipients.