Influence of donor/recipient HLA-matching on outcome and recurrence of hepatitis C after liver transplantation.

The aim of this study was to analyze the effect of human leukocyte antigen (HLA) matching on outcome, severity of recurrent hepatitis C and risk of rejection in hepatitis C positive patients after liver transplantation (LT). In a retrospective analysis, 165 liver transplants in patients positive for hepatitis C virus (HCV) with complete donor/recipient HLA typing were reviewed for recurrence of HCV and outcome. Follow-up ranged from 1 to 158 months (median, 74.5 months). Immunosuppression consisted of either cyclosporine-A- or tacrolimus-based quadruple induction therapy including or an interleukin 2-receptor antagonist. Protocol liver biopsies were performed after 1, 3, 5, 7, and 10 years and staged according to the Scheuer scoring system. The overall 1-, 5-, and 10-year graft survival figures were 81.8%, 69.11 and 62%, respectively. There was no correlation in the study population between number of HLA mismatches and graft survival. The number of rejection episodes increased significantly in patients with more HLA mismatches (P < 0.05). In contrast to this, the fibrosis progression was significantly faster in patients with 0-5 HLA mismatches compared to patients with a complete HLA mismatch. In conclusion, HLA matching did not influence graft survival in patients after LT for end-stage HCV infection, however, despite less rejection episodes, the fibrosis progression increased in patients with less HLA mismatches within the first year after LT.     

Rapidly progressive liver injury and fatal alcoholic hepatitis occurring after liver transplantation in alcoholic patients.

Alcohol-related liver disease (ALD) is a common indication for orthotopic liver transplantation (OLT) in adults. Although return to 'heavy drinking' post-OLT is believed to be uncommon, the prevalence and severity of alcohol-related liver injury in such patients is not well characterized. We retrospectively reviewed the records of 68 adult patients who underwent OLT for ALD to determine the incidence of return to heavy drinking and to assess their clinical outcome. Follow-up ranged from 8-99 months (mean 42) post-OLT; 54 patients were followed for > or = 12 months. Ten patients (15%) had evidence of coexisting viral hepatitis (hepatitis C in 9 and hepatitis B in 1) before OLT. Six of 68 patients (8%) returned to heavy drinking post-OLT, and three of those died of alcoholic hepatitis at nine months, 2.5 and 3.5 years after OLT. In two of these three patients, premortem liver biopsy showed histologic features of alcoholic hepatitis in addition to bridging fibrosis or cirrhosis. None of the three patients who died of ALD had coexisting viral hepatitis. Of the 57 patients surviving for > or = 3 months post-OLT, 4 of 8 patients (50%) with steatosis and Mallory bodies in their native livers returned to heavy drinking compared to only 2/49 (4%) without these histologic findings (P<0.05). In conclusion, the incidence of heavy drinking post-OLT was uncommon, however, it was associated with fatal alcoholic hepatitis in 50% of patients. Rapidly progressive alcohol-related liver injury was seen even in the absence of coexisting viral hepatitis. The presence of steatosis and Mallory bodies in the native liver, which suggests recent or ongoing alcohol-related liver injury, predicted a return to heavy drinking post-OLT.     

The impact of recipient cytokine genotype on acute rejection after renal transplantation

BACKGROUND: Acute allograft rejection remains an important cause of morbidity after kidney transplantation, and has been shown to be a crucial determinant of long-term graft function. As cytokines are major regulators of the immune system, genetic variation in cytokine production or activity may influence susceptibility to acute rejection. This study sought to determine the impact of recipient cytokine and cytokine receptor polymorphisms on acute rejection after renal transplantation. METHODS: A total of 209 cadaveric renal transplant recipients were selected for analysis according to the presence or absence of graft rejection in the first 30 days after transplantation. DNA was genotyped for 22 polymorphisms in 11 cytokine and cytokine receptor genes using the polymerase chain reaction with sequence specific primers. Results were stratified by incidence and severity of rejection, and by HLA-DR mismatching. RESULTS: No association between any polymorphism and the incidence or severity of acute rejection was detected. In particular, no association was seen with tumor necrosis factor or interleukin-10 genotype, either alone or in combination. CONCLUSIONS: We have failed to demonstrate any association between recipient cytokine genotype and acute rejection after cadaveric renal transplantation. Although more extensive studies may disprove these findings, it would seem premature to use recipient cytokine genotyping to predict transplant outcome, or to guide immunosuppressive therapy after transplantation.     

Favourable outcome of adefovir-dipivoxil treatment in acute de novo hepatitis B after liver transplantation

Adefovir-dipivoxil has been shown to be effective against lamivudine-resistant mutants in immunocompetent patients and in a small number of liver transplant recipients with recurrent hepatitis B virus (HBV) infection. The therapeutic role of adefovir-dipivoxil in acute de novo HBV infection after transplantation is uncertain. We describe a case of acute de novo HBV infection that occurred after liver transplantation and that was treated with lamivudine followed (when viral escape mutants emerged) by adefovir-dipivoxil rescue. Treatment outcome was excellent, with complete viral clearance and development of a protective titer of antibodies to anti-hepatitis B surface antigen. Because the donor was vaccinated against HBV, it is conceivable that clearance of HBV infection in the recipient might have been favored by adoptive transfer of immunity to HBV. The immune status of the donor might be a factor to consider when determining the treatment options for de novo hepatitis B.     

The impact of donor variables on the outcome of orthotopic liver transplantation for hepatitis C

Morphologic characteristics of the graft have been proposed as a major contributor to the long-term outcomes in orthotopic liver transplantation (OLT). Our objective was to determine the impact of donor variables, including donor age, donor-recipient HLA match, and type of donation (DCD vs donation after brain death [DBD]), on the outcome of OLT in 192 patients with hepatitis C virus (HCV). Fourteen patients underwent OLT from donation after cardiac death (DCD) donors and 188 from DBD donors. Mean donor age, warm ischemia time at recovery, and cold ischemia time were similar between the groups. Overall graft survival rate at 1 year (55% DCD vs 85% DBD) and 5 years (46% DCD vs 78% DBD) was significantly lower in the DCD group (P = .0003). Similarly, patient survival rate at 1 year (62% DCD vs 93% DBD) and 5 years (62% DCD vs 82% DBD) was significantly lower in the DCD group (P = .0295). Incidences of hepatic artery thrombosis, portal vein thrombosis, and primary nonfunction were similar between the DCD and DBD groups. The incidence of liver abscess with ischemic-type biliary stricture was higher in recipients from DCD as compared with DBD (42% vs 2%). A trend toward lower graft survival was noted in recipients from donors older than 60 years of age in the HCV population (P = .07), with statistically lower patient survival (P = .02). Donor- recipient HLA matching did not appear to correlate with OLT outcome in patients with HCV. DCD donors and donors older than 60 years of age significantly impact patient and graft survival. Lower graft and patient survival in recipients from DCD donors does not appear to be related to early disease recurrence.     

The impact of donor race on recurrent hepatitis C after liver transplantation

Background

Several studies have demonstrated mixed results regarding the influence of donor race on patient and graft survival in patients infected with hepatitis C virus (HCV) after liver transplant. However, few studies have looked at the impact of donor race on recurrent HCV. This study is a retrospective analysis of the influence of patient and donor race on the severity of recurrent HCV at a single center.

Methods

Of patients transplanted at our center between 2000 and 2006, 222 were infected with HCV. Of these, 165 were eligible to be evaluated for recurrent HCV after transplant. We excluded those with patient and graft loss within 1 year that was not related to recurrent HCV, patients with advanced fibrosis from other causes, those who did not undergo posttransplant liver biopsy, and those lost to follow-up.Patients were given a recurrent HCV score of 1, 2, or 3. A score of 1 was assigned if the patient had no more than mild portal fibrosis at 1 year and no bridging fibrosis at any point. A score of 2 was defined as moderate portal fibrosis or focal bridging fibrosis at 1 year or bridging fibrosis or cirrhosis after 3 years. A score of 3 was defined as bridging fibrosis, cirrhosis, or graft loss from HCV within 3 years. Baseline characteristics including donor and recipient age, race, sex, body mass index, ischemia time, hypertension, and diabetes were recorded. Analysis was performed with ordinal multivariate logistic regression modeling.

Results

Of the 165 patients with a recurrent HCV score, 105 (64%) had a score of 1, 29 patients (17%) had a score of 2, and 31 patients (19%) had a score of 3. In all, 132 recipients (80%) had white donors, and 26 (16%) had African American donors, 115 patients (70%) were white and 40 (24%) were African American. The mean recurrent HCV scores for the patient donor and recipient race combinations are as follows: white donor and white recipient, 1.54; white donor and African American recipient, 1.89; African American donor and white recipient, 1.18; and African American donor and African American recipient, 1.23. Having a white donor also significantly associated with a higher recurrent HCV score regardless of recipient race (odds ratio 2.93, P = .044) in African American patients, having a white donor had an odds ratio of 4.62 (P = .046). After adjusting for donor age and sex and patient age and sex, having a white donor was still found to be associated with a higher recurrent HCV score (4.48, P = .0275) on multivariate analysis. For all 222 patients, donor race was not associated with overall patient and graft survival.

Conclusion

Patients receiving white donor grafts had significantly worse recurrent HCV than those receiving grafts from African American donors regardless of recipient race. This difference was especially marked in African American recipients and persisted on multivariate analysis. These data suggest a graft from a white donor is potentially one more important variable in identifying patients at risk for more aggressive recurrent HCV after orthotopic liver transplant.     

The impact of donor and recipient age on the outcome of kidney transplantation

BACKGROUND: As survival has improved in the general population over the last few decades, the age of patients participating in renal transplantation has also increased. This study sought to investigate the impact of donor and recipient age as predictors of long-term graft survival in renal transplantation. MATERIALS AND METHODS: We analyzed transplantation outcomes in 598 patients who received renal transplants from 1979 to 2002. Patients were divided into 4 groups according to their age at renal transplantation. Group A (donor age <50 years, recipient age >50 years, n = 19/3.2%); group B (donor age >50 years, recipient age <50 years, n = 153/25.5%); group C (donor age <50 years, recipient age >50 years, n = 69/11.6%), and group D (donor age <50 years, recipient age <50 years, n = 357/59.8%). Univariate analysis to assess the effect of donor and recipient age as predictor factors of graft outcome was complimented by Kaplan-Meier and log-rank methods to assess graft survival with P < 1.05 considered significant. RESULTS: In the elderly donor group, graft survival was 92.8% at 1 year and 85.6% at 3 years; in the younger donor group, they were 93.4% and 90.2%, respectively, a difference that was statistically significant (P = .02). Univariate analysis of age factors showed a significant reduction in graft survival among recipients who received kidneys transplants from donors older than 50 years, although recipient age >50 years was not found to be an independent risk factor. The incidence of acute rejection was 24.6% in the elderly donor group and 23.5% in the younger donor group (P = not significant). Among the 4 groups, the best result was group D with 1-year and 3-year graft survival rates of 93.3% and 90.5%, respectively, but this result was not statistically significant. CONCLUSIONS: These results may help the design for transplantation strategies for kidneys procured from elderly donors and for allocation to elderly recipients.     

The joint impact of donor and recipient parameters on the outcome of heart transplantation in Germany after graft allocation

Organ shortage in heart transplantation (HTx) results in increased use of grafts from donors with substantial risk factors. It is discussed controversially which donor characteristics may be detrimental. Therefore, we evaluated the joint impact of donor‐ and patient‐related risk factors in HTx on patient survival by multiple analysis in a nationwide multicentre study after donor selection was carried out. The research database consists of data concerning hearts donated and transplanted in Germany between 2006 and 2008 as provided by Deutsche Stiftung Organtransplantation and the BQS Institute. Multiple Cox regression (significance level 5%, hazard ratio [95% CI]) was conducted (n = 774, recipient age ≥ 18 years). Survival was significantly decreased by donor age (1.021 [1.008–1.035] per year), nontraumatic cause of death (1.481 [1.079–2.034]), troponin >0.1 ng/ml (2.075 [1.473–2.921]), ischaemia time (1.197 [1.041–1.373] per hour), recipient age (1.017 [1.002–1.031] per year) and in recipients with pulmonary vascular resistance ≥320 dyn*s*cm^?5 (1.761 [1.115–2.781]), with ventilator dependency (3.174 [2.211–6.340]) or complex previous heart surgery (1.763 [1.270–2.449]). After donor selection had been conducted, multiple Cox regression revealed donor age, nontraumatic cause of death, troponin and ischaemia time as well as recipient age, pulmonary hypertension, ventilator dependency and previous complex heart surgery as limiting risk factors concerning patient survival.     

The influence of cytomegalovirus viraemia on the outcome of recurrent hepatitis C after liver transplantation

BACKGROUND: Several interrelated host and hepatitis C virus (HCV) associated factors have been proposed to explain the variable outcomes in HCV recurrence. Recent evidence suggests that cytomegalovirus (CMV) infection not only is co-factor in progression of HCV recurrence but may precipitate allograft rejection. We investigated whether short-term CMV viremia influences HCV recurrence, the number and grade of acute rejection episodes, and the histological course of HCV recurrence during the first year after orthotopic liver transplantation (OLT) for HCV-related cirrhosis. METHODS: A cohort of 39 patients transplanted for cirrhosis HCV-related was analyzed. Patients were evaluated twice weekly for CMV infection by a blood polymerase chain reaction (PCR) assay. Triple therapy with cyclosporine or tacrolimus, azathioprine and prednisolone was the initial immunosuppressive regimen. Preemptive treatment with ganciclovir was started when two consecutive PCRs for CMV were positive. Liver biopsies were performed on day 7 after OLT or when indicated. A 3-day IV 1 g methilprednisolone was given to patients with moderate or severe rejection. Ishak's score was used to grade inflammation and to stage fibrosis. RESULTS: Neither CMV viremia nor CMV disease after OLT for HCV-related cirrhosis adversely influenced the incidence and grade of acute rejection episodes nor the histological outcome of post transplant HCV recurrence, during the first year after liver transplantation. CONCLUSION: CMV viremia as detected by PCR does not affect the progression of HCV recurrence in liver grafts.     

大鼠受体性别对肝移植效果的影响

目的探讨大鼠性别对肝移植效果的影响。方法根据大鼠受体性别将实验动物分为2组：雄性（M）组和雌性（F）组，比较两组术后急性排斥反应（ACR）发生率、术后7d肝功及术后6周生存率。结果F组大鼠肝移植效果优于M组，两组术后急性排斥反应的发生率、术后7d ALT及AKP水平、术后6周生存率具有显著性差异（P〈0．05或0．01）。结论性别对大鼠肝移植的急性排斥反应、生存率及术后肝功能的恢复有重要的影响。     

The impact of wait list body mass index changes on the outcome after liver transplantation

Obesity is associated with poor health outcomes in the general population, but the evidence surrounding the effect of body mass index (BMI) on postliver transplantation survival is contradictory. The aim of this study was to assess the impact of wait list BMI and BMI changes on the outcomes after liver transplantation. Using the Scientific Registry of Transplant Recipients, we compared survival among different BMI categories and examined the impact of wait list BMI changes on post‐transplantation mortality for patients undergoing liver transplantation. Cox proportional hazards multivariate regression was carried out to adjust for confounding factors. Among 38 194 recipients, underweight patients had a poorer survival compared with normal weight (HR = 1.3, 95% CI: 1.13–1.49). Conversely, overweight and mildly obese men experienced better survival rates compared with their lean counterparts (HR = 0.9, 95% CI: 0.84–0.96, and HR = 0.86, 95% CI: 0.79–0.93 respectively). Female patients gaining weight over 18.5 kg/m² while on the wait list showed improving outcomes (HR = 0.46, (95% CI: 0.28–0.76)) compared with those remaining underweight. This study supports the harmful impact of underweight on postliver transplant survival, and highlights the need for a specific monitoring and management of candidates with BMIs close to 18.5 kg/m². Obesity does not constitute an absolute contraindication to liver transplantation.     

Impact of recipient age on outcome of ABO-incompatible living-donor liver transplantation

BACKGROUND: Transplantation of hepatic grafts from ABO-incompatible donors is controversial because of the risk of hyperacute rejection mediated by preformed anti-ABO antibodies. The aim of the present study was to evaluate the outcome of liver transplants performed with ABO-incompatible living-donor livers and to detect risk factors for development of complications. METHODS: From June 1990 to February 2000, 66 patients, 10 months to 55 years old (median, 2 years old), received 68 ABO-incompatible living-donor liver grafts. The antibody titer and clinical course were followed prospectively during a period ranging from 3 to 11 years. RESULTS: The 5-year patient survival was 59%, 76%, and 80% for ABO-incompatible, ABO-compatible, and ABO-identical grafts, respectively (P<0.01). In patients <1 year old, > or =1 to <8, > or =8 to <16, and and > or =16 years old, 5-year survival was 76%, 68%, 53%, and 22%, respectively. The incidence of intrahepatic biliary complications and hepatic necrosis in ABO-incompatible living-related grafts (18% and 8%, respectively) was significantly (P<0.0001) greater than in ABO-compatible and ABO-identical grafts (both 0.6% and 0%, respectively). Predictive risk factors for increased mortality and morbidity were age greater than 1 year and elevated anti-ABO titers before transplantation. CONCLUSIONS: ABO-incompatible liver transplantation was carried out with relative safety in infants <1 year old but was not satisfactory in children >1 year in long-term follow-up. Patients aged >8 years remain at considerable risk of early fatal outcome because of hepatic necrosis, and new strategies to prevent antibody-mediated rejection are required.     

Highly urgent liver transplantation: possible impact of donor-recipient ABO matching on the outcome after transplantation

BACKGROUND: Survival after liver transplantation for fulminant hepatic failure has been reported to be less favorable than survival for patients with chronic liver diseases. METHODS: We have studied all patients (n=229) undergoing highly urgent liver transplantation from 1990 to 2001 in the Nordic countries. The impact of patient and donor characteristics, with emphasis on donor-recipient ABO matching (identical, compatible, incompatible), has been studied. RESULTS: One-year and 3-year patient survival rates were 73% and 70% for the total period and 86% and 78% for the last 4-year period. Patients receiving an ABO-compatible liver allograft had significantly lower patient survival rates than those receiving an ABO-identical donor organ (1-year patient survival rates 66% of vs. 79%, P=0.03). Graft survival rates varied less (1-year graft survival rates of 64% vs. 74%, P=0.09). Patients receiving an ABO-incompatible liver allograft had patient survival rates of 70% at 1 year and 60% at 3 years but low graft survival rates (40% and 30% at 1 and 3 years). In a multiple regression analysis, significant independent predictors of poor patient survival were early year of transplantation, ABO-compatible donor, high donor age, and waiting time more than 3 days and less than 9 days. CONCLUSION: Survival after highly urgent liver transplantation has improved and is comparable to that observed in patients receiving a liver allograft because of chronic liver disease. Patients receiving an ABO-identical donor organ had significantly higher patient survival rates compared with those receiving an ABO-compatible donor liver.