Long‐term medical and psycho‐social evaluation of patients undergoing orthotopic liver transplantation for alcoholic liver disease

Abstract The major concern in transplanting patients with alcoholic liver disease (ALD) is the high rate of alcohol recidivism. Our aim was to assess the long‐term outcome of liver transplantation (OLT) in a group of ALD patients in terms of post‐OLT alcohol recidivism and its relationship with pre‐OLT psychosocial variables and medical follow up. Fifty‐one ALD patients underwent strict medical and psychosocial evaluation before and after OLT. Alcohol abuse was recorded in 60% and alcohol dependence in 40% of patients before OLT. The 5‐year survival was similar to the one observed in non‐ALD transplanted patients (64 vs 56%). Alcohol recidivism was observed in 33 % of transplanted patients, 64 % of whom were occasional and 36 % were heavy drinkers. The admission of alcoholism by the patient and his/her family prior to OLT significantly predicted abstinence after OLT. A multidisciplinary approach evaluating medical and psycho‐social variables before OLT and a close follow up after OLT are mandatory for ALD patients.     

Long-term follow-up after liver transplantation for alcoholic liver disease under tacrolimus

BACKGROUND: Liver transplantation (LTx) for alcohol-related liver disease (ALD) is an accepted modality of treatment and is one of the most common indications for LTx in the United States. The present report examines the long-term patient survival, graft survival, rates of recidivism, and development of de novo cancers in this group, and compares these results with a contemporaneous group of patients who were transplanted for non-ALD indications. METHODS: Between August 1989 and December 1992, 185 adults received LTx for ALD (group I). During the same time interval, 649 adults received LTx for non-ALD (group II). The mean follow-up time was 94+/-10.7 months for group I vs. 92+/-11 months for group II. Kaplan-Meier survival estimates and the incidence of cancers using Surveillance Epidemiologic End Result data were compared in both groups. RESULTS: At 5 years after orthotopic LTx, the overall patient survival and graft survival for group I were 72.0% and 66.5% vs. 66.5% and 60.3% for group II, respectively. After 5 years, the patient survival and graft survival for the alcoholic group were significantly lower (P=0.001) compared to the non-alcoholic group. The rate of de novo oropharyngeal cancer and lung cancer was 25.5 times and 3.7 times higher, respectively, in ALD group compared with the general population matched for age, sex, and length of follow-up (P=0.001), whereas this was not higher in the non-ALD group. Prior pretransplant length of sobriety and alcohol rehabilitation was not associated with the rate of post-LTx rate of recidivism, which was 20%. Out of 79 deaths in group I, only 1 was attributed to recidivism and 3 to noncompliance with recidivism. The other deaths occurred from de novo cancer (n=13), posttransplant lymphoproliferative disorder (n=5), age-related complications (n=23), and other infection or miscellaneous causes (n=34). CONCLUSIONS: Patient and graft survival past 5 years after orthotopic LTx is significantly lower for ALD for a variety of reasons (P=0.001). The rate of upper airway malignances was significantly higher in ALD patients than for non-ALD post-LTx patients and the general public. Graft loss/death related to recidivism or chronic rejection was extremely low. More attention is needed for early diagnosis of de novo cancer and prevention of cardiorespiratory and cerebrovascular complications.     

De novo malignancies following liver transplantation: a case-control study with long-term follow-up

BACKGROUND: Long-term survival data on de novo malignancy are limited following orthotopic liver transplantation (OLT) when compared with controls without malignancies. METHODS: Over a 12 yr period at our institution, 50 of 1043 patients (4.8%) who underwent OLT were identified to have 53 de novo malignancies. The clinical characteristics and survival of these patients were retrospectively reviewed and compared with a control cohort of 50 OLT recipients without malignancy matched with the incidence cases by age, year of OLT, sex, and type of liver disease. RESULTS: Chronic hepatitis C, alcohol and primary sclerosing cholangitis were the three leading causes of liver disease. Skin cancer was the most common malignancy (32%), followed by gastrointestinal (21%), including five small bowel tumors, and hematologic malignancies (17%). The cases and controls were not significantly different in the immunosuppressive regimen (p = 0.42) or the number of rejection episodes (p = 0.92). The five- and 10-year Kaplan-Meier survival rates for the cases were 77% and 34%, respectively, vs. 84% and 70%, respectively, for the controls (p = 0.02 by log-rank test). Patients with skin cancers had survival similar to the controls, but significantly better than non-skin cancers (p = 0.0001). The prognosis for patients with gastrointestinal tumors was poor, with a median survival of 8.5 months after the diagnosis. CONCLUSION: In this single institutional study, de novo malignancies after OLT were uncommon. Patients with non-skin cancer after OLT had diminished long-term survival compared with the controls. Our results differ from other reports in the high incidence of gastrointestinal malignancies with attendant poor prognosis.     

Significance of a T-lymphocytotoxic crossmatch in liver and combined liver-kidney transplantation

BACKGROUND: In contrast to kidney transplants a positive crossmatch is no contraindication for liver transplantation (OLT). In liver transplantation, antibody mediated rejections are rarely reported and a liver graft is suspected to have protective effects for kidney grafts when transplanted simultaneously. The aim of this study was to evaluate the effect of a positive crossmatch on outcome after OLT and combined liver and kidney transplantation (CLKTx). METHODS: We analyzed retrospectively the impact of a positive crossmatch on graft survival and rejection episodes after OLT (793pats) and CLKTx (18pats, 2.2%). Immunosuppression consisted of either Cyclosporine- or Tacrolimus-based regimens. RESULTS: A total of 50/811 (6%) of patients had a positive crossmatch, 45/793 (5.6%) with liver transplantation alone and 5/18 (28%) of patients with CLKTx. Follow-up ranged from 1 to 122.5 months (median 45.8 months). One- and 5-year graft survival rates of liver transplants alone with a positive crossmatch were 89.6% and 75.3%, respectively and were 88% and 77.5% in crossmatch negative recipients. Additionally, the incidence of acute and steroid-resistant rejection (44% and 15.5%) was not significantly increased in patients with a positive crossmatch when compared with patients with a negative crossmatch (38% and 19%). None of the patients with a positive crossmatch and CLKTx underwent a hyperacute-rejection episode after transplantation, and kidney graft survival 100%. CONCLUSIONS: In conclusion, a positive crossmatch is no contraindication for OLT and CLKTx. Furthermore, not having to wait for results of donor/recipient crossmatching can shorten cold ischemia time and may improve the clinical outcome.     

Primary adult liver transplantation under tacrolimus: more than 90 months actual follow-up survival and adverse events.

The introduction of tacrolimus has shown decreased rates of acute and steroid-resistant rejection after liver transplantation (LTx). The aim of the present study is to examine the long-term efficacy and safety of tacrolimus in primary liver transplant recipients. The first 121 consecutive adults (aged >16 years) who underwent primary LTx at a single center from August 1989 to February 1990 were followed up until August 1997. The mean follow-up was 93.2 +/- 1.2 months (range, 90.5 to 96.5 months). Patient survival, graft survival, rate of rejection, and adverse events were examined. The actual 7-year patient survival rate was 67.8%, and the graft survival rate was 63.6%. Infections, recurrence of disease, de novo malignancies, and cardiovascular events constituted the main causes of graft loss and death in the long term. Graft loss related to acute or chronic rejection was rare. The rate of acute rejection beyond 2 years was approximately 3% per year, and most rejections were steroid responsive. Approximately 70% of the patients received only tacrolimus after 1 year. Four patients developed end-stage renal disease, and 2 patients underwent kidney transplantation. Hyperkalemia and hypertension were observed in one third of the patients. New-onset insulin-dependent diabetes mellitus was observed in 9% and 13% of the patients at the 1-year and 7-year follow-up, respectively. Seven patients developed de novo malignancies, including two skin malignancies. Six patients developed posttransplantation lymphoproliferative disorder during the entire follow-up period. Actual patient and graft survival at 7 years was excellent, and few adverse events developed after the first year. Graft loss from acute or chronic rejection was rare under tacrolimus, and approximately 70% of the patients were steroid free on tacrolimus monotherapy after the first year after LTx.     

An ‘alcohol contract’ has no significant effect on return to drinking after liver transplantation for alcoholic liver disease

Return to drinking after liver transplantation for alcoholic liver disease (ALD) remains a source of unease with varying reported rates of return to drinking and impact this has on graft function. In 2005, the UK Transplant liver advisory group recommended an ‘alcohol contract’ in which ALD patients listed for transplantation confirmed in writing their commitment to abstinence. We aimed to measure the rates and consequences of return to drinking alcohol in a UK transplant programme and assess the effect of the ‘alcohol contract’. Consecutive patients transplanted for ALD during 1996–2011 were included. Every patient listed after Feb 2007 signed up to the ‘alcohol contract’. We compared rates and pattern of return to drinking and survival before and after the introduction of the contract. Overall, 52 (37%) patients returned to drinking alcohol; 37 (39%) before and 15 (34%) after the contract. There was no significant difference in the rate of return or pattern of drinking. Median survival was 176 months (145–207 95% CI). There was no significant difference in survival, mortality rates, or in the causes of death in either group. We report high rates of return to drinking alcohol in a UK liver transplant programme. Despite this, the impact on patient and graft survival is low. There is no evidence that an ‘alcohol contract’ has had any effect on alcohol consumption.     

Heterotopic vs. orthotopic liver transplantation for chronic liver disease: a case-control comparison of short-term and long-term outcomes.

Between 1986 and 1990 we performed heterotopic liver transplantation (HLT) in 17 patients with chronic liver disease. In spite of theoretical advantages and favorable short-term results, we abandoned HLT because of doubts about the long-term outcome and the improved results of standard orthotopic liver transplantation (OLT). There are, however, no studies comparing the long-term survival after HLT and OLT for chronic liver disease. We performed a case-control study of HLT vs. OLT, with long-term patient and graft survival as the main outcome measures. Known confounders and differences in baseline characteristics between HLT and OLT patients were corrected for. At 1 year, 5 of the 17 HLT patients had died, compared with 9 of the 34 OLT patients (relative risk [RR], 1.15; 95% confidence interval [CI], 0.33-4.02; P = 0.83). After correction for confounders, the long-term risk of graft failure (RR, 18.0; 95% CI, 1.5-223.5; P = 0.02) and of death (RR, 5.2; 95% CI, 0.8-34.8; P = 0.09) was higher after HLT than after OLT. The main causes of graft loss and death at more than 1 year after HLT were de novo malignancies and a variety of biliary complications. In conclusion, our data, from 1 of the largest single-center series of HLTs available, showed no significant difference between HLT and OLT in 1-year survival. However, the long-term outcome of HLT was inferior. HLT cannot be recommended as an alternative to OLT for any of the indications we studied, even though only 1 of the late deaths was definitely related to the heterotopic technique.     

Donor‐specific anti‐HLA antibodies are not associated with nonanastomotic biliary strictures but both are independent risk factors for graft loss after liver transplantation

Donor‐specific alloantibodies (DSA) have been associated with rejection and shorter graft survival after orthotopic liver transplantation (OLT). We examined the role of DSA in nonanastomotic biliary strictures (NAS) after OLT. Patients receiving first OLT who developed NAS (n = 68) and a control group without NAS (n = 83), with pre‐OLT and 12 months post‐OLT serum samples, were included. DSA were specified using the Luminex single antigen test. Risk factors for NAS and graft survival were analyzed. The presence of preformed DSA was not significantly different between patients with NAS and controls (P = .89). After 12 months, 26.5% of NAS patients and 16.9% of controls had generated de novo DSA (P = .15). Neither de novo class I DSA nor de novo class II DSA were associated with NAS. De novo DSA generally developed after the diagnosis of NAS. Time‐dependent regression analysis identified both NAS (aHR 8.05, CI 3.28 – 19.77, P < .01) and de novo class II DSA (aHR 2.84, CI 1.38 – 5.82, P < .01) as independent risk factors for graft loss. Preformed or de novo DSA were not associated with the development of NAS. However, NAS as well as de novo class II DSA were independent risk factors for graft loss after OLT.     

Incidence and risk factors of development of lung tumors after liver transplantation

INTRODUCTION: Lung tumors have been related to tobacco and alcohol. The incidence increases after orthotopic liver transplantation (OLT) especially when it is performed because of alcoholic cirrhosis. PATIENTS AND METHODS: We analyzed the incidence and risk factors for de novo lung tumors among 701 patients who underwent OLT between April 1986 and July 2004, after exclusion of pediatric recipients and adults who died within 2 months after OLT. RESULTS: The incidence of de novo lung tumors was 15 patients (2.1%), including 12 (4.3%) who underwent OLT for alcoholic cirrhosis and 3 (0.7%) for nonalcoholic diseases. There were 14 men and 1 woman of mean age at OLT of 50.8 +/- 9.6 years. Mean time from OLT to lung tumor was 83 +/- 43 months (range, 10-184 months). Thirteen patients (86.6%) were heavy smokers before OLT and 8 (61.5%) continued after OLT; 12 patients (80%) were heavy drinkers before OLT. Ten patients were immunosuppressed with CyA and 5 with tacrolimus. Acute rejection episodes before tumor diagnosis occurred in 6 patients (40%). Two patients underwent thoracotomy, but only one was resected. The remaining 13 patients were unresectable because of locally advanced tumor or metastatic disease. Two unresectable patients received palliative chemotherapy. All patients died with a mean survival from tumor diagnosis, of 5.3 months (range, 3 days to 33 months). CONCLUSION: A significantly higher incidence of lung tumors was observed among patients who underwent OLT for alcoholic cirrhosis, usually diagnosed in advanced stages of poor prognosis and low survival.     

Long-term results after liver transplantation.

Liver transplantation (OLT) has become a successful surgical therapy for terminal liver failure. We here report about long-term results of OLT in a single center over a period of 15 years. Between 1988 and 2002, 1365 adult OLTs were performed. Mean follow-up was 103 +/- 56 months. Main indications for OLT were viral-induced cirrhosis (27.1%), alcoholic liver disease (21%), tumors (15.7%) and cholestatic liver disease (14.6%). Retransplantation was necessary in 120 (9.6%) patients because of initial nonfunction (26.9%), recurrence of underlying disease (20.2%), acute and chronic rejection (16.8%) or thrombosis of the hepatic artery (16.8%). 275 patients (22.1%) died. Causes of death included recurrence of disease (32.1%), infections (21.8%), de novo malignancies (13.5%) and cardiovascular disease (11.6%). Patient survival after OLT was 91.4%, 82.5%, 74.7% and 68.2% after 1, 5, 10 and 15 years, and graft survival was 85.8%, 75.3%, 67.3% and 61.7% after 1, 5, 10 and 15 years, respectively. Patient survival after retransplantation was 81.6%, 68.8% and 57.1% and 48.0% after 1, 5, 10 and 15 years. This analysis reveals excellent long-term results after OLT achieved in a single center.     

The impact of acute alcoholic hepatitis in the explanted recipient liver on outcome after liver transplantation.

Patients with clinical acute alcoholic hepatitis (AAH) are not considered suitable candidates for orthotopic liver transplantation (OLT). The histological correlates of AAH are often seen in the explanted liver at the time of transplantation. The importance of these findings remains inconclusive regarding their role as a prognostic marker for patient or allograft health. Our aim was to examine the explanted liver of patients with purely alcoholic liver disease (ALD) for findings of histologic AAH and to correlate these to patient and graft outcomes. We compared patients with and without histological AAH with patients transplanted for non-ALD. Of 1,097 liver transplant recipients, 148 had ALD and 125 were non-ALD control patients with similar demographics. Thirty-two of 148 ALD patients had histologic AAH, and 116 had bland alcoholic cirrhosis (BAC). Twenty-eight percent of the ALD patients reported <6 months abstinence, and 54% reported <12 months abstinence. There was a statistically significant relationship between the presence of histologic AAH and abstinence durations<12 months (P=0.009), but not <6 months. Overall, posttransplantation patient and graft survival between the ALD and non-ALD groups was not significantly different (P=0.53). Furthermore, patient and graft survival between ALD patients with histologic AAH and BAC were similar (P=0.13 and P=0.11, respectively). The rate of posttransplantation relapse among ALD patients was 16%; however, there was no increase in graft loss, nor was there decreased survival compared with controls. The patients with histologic AAH and those with BAC had no differences in posttransplantation relapse (P=0.13). In multivariate analysis, patient and graft survival was not influenced by pretransplantation abstinence or posttransplantation relapse. In conclusion, histological alcoholic hepatitis in the explant did not predict worse outcome regarding relapse, and allograft or patient survival for liver transplant recipients. Caution should be exercised when liver histology is used to discriminate among suitable candidates for OLT concerning alcoholic patients.     

Orthotopic liver transplantation for biliary atresia: the U.S. experience.

Biliary atresia is the most common indication for orthotopic liver transplantation (OLT) in the pediatric population. The outcomes of liver transplantation for biliary atresia, however, have not been formally examined on a national scale. The objective of this study was to identify pretransplant variables that predict patient survival after primary liver transplantation for biliary atresia. A cohort of 1,976 pediatric patients undergoing primary liver transplantation for biliary atresia between 1/1988 to 12/2003 was enrolled from the United Network for Organ Sharing database after excluding patients with a history of multiorgan transplant or previous liver transplant. Follow-up data up to 16 years post-OLT was available. The 5- and 10-year actuarial survival rates of patients that underwent liver transplantation for biliary atresia in the United States are 87.2% and 85.8%, respectively, and the 5- and 10-year graft actuarial survival rates are 76.2% and 72.7%, respectively. Early deaths (< or =90 days post-OLT) were more often caused by graft failure (P = 0.01), whereas late deaths (>90 days post-OLT) were more often due to malignancy (P < 0.01). An analysis of outcomes over time demonstrated a decrease in post-OLT survival and an increase in the number of OLTs done for biliary atresia at an increasing number of centers. A multivariate analysis revealed that cadaveric partial/reduced liver grafts, a history of life support at the time of OLT, and decreased age were independent predictors of increased post-OLT mortality. In conclusion, OLT is an effective treatment for biliary atresia. Certain pretransplant variables may help predict patient survival following liver transplantation for biliary atresia.     

New era of liver transplantation for hepatitis B: a 17-year single-center experience

OBJECTIVE: To evaluate the variables affecting orthotopic liver transplantation (OLT) outcome for hepatitis B virus (HBV) in a large patient cohort over a 17-year period. SUMMARY BACKGROUND DATA: Historically, OLT for chronic HBV infection has been associated with aggressive reinfection and poor survival results. More recently, OLT outcome has been improved with the routine use of antiviral therapy with either hepatitis B immune globulin (HBIg) or lamivudine; however, HBV recurrence remains common. The authors studied the factors affecting HBV recurrence and outcome of transplantation, including the effects of combination viral prophylaxis with HBIg and lamivudine. METHODS: A retrospective review of 166 OLT recipients for chronic HBV over a 17-year period at a single center was performed. Median follow-up was 29 months. HBV recurrence was defined by HBsAg seropositivity after OLT. HBIg monotherapy was used in 28 (17%) patients, lamivudine monotherapy in 20 (12%), and HBIg and lamivudine combination in 89 (54%); 29 (17%) did not receive any HBV prophylaxis. Hepatocellular carcinoma (HCC) was present in 43 patients (26%) and urgent United Network for Organ Sharing (UNOS) status was assigned to 27 patients (16%). Univariate and multivariate analyses were performed to identify factors that affected OLT outcome. RESULTS: Overall 1-, 3-, and 5-year patient survival rates were 85.8%, 73.6%, and 71.8%, respectively. As expected, HBV recurrence-free survival rates were significantly lower than overall survival rates (76.4%, 58.7%, and 48.3%). When compared with a nontreated cohort, OLT recipients receiving combination viral prophylaxis with HBIg and lamivudine showed markedly reduced HBV recurrence rates and significantly improved 1- and 3-year recurrence-free survival rates. By univariate estimates, patient survival was reduced in the presence of HCC, in the Asian population, and urgent candidates by UNOS classification. Graft loss rates were significantly increased in urgent OLT candidates, Asians, patients with pretransplant positive DNA, and in the presence of HCC. Factors that were significant by univariate analysis or thought to be clinically relevant were subjected to multivariate analysis. By multivariate estimates, urgent UNOS or presence of HCC adversely affected patient and graft survival rates, whereas combination prophylactic therapy strongly predicted improved patient and graft survival rates as well as recurrence-free survival rates. CONCLUSIONS: Orthotopic liver transplantation for HBV under combination viral prophylaxis results in survival rates equivalent to other indications. Pretransplant viral replication, UNOS status, and the presence of HCC are all sensitive markers for posttransplantation outcome. Viral prophylactic therapy has effectively reduced HBV recurrence and prolonged survival outcomes. The combination of HBIg and lamivudine is the prophylactic regimen of choice.     

Experience of a successful pediatric liver transplant program in Mexico

Orthotopic liver transplantation (OLT) has been very difficult to develop in Mexico and for many years its occurrence was anecdotal. This report presents the results of a pediatric liver transplant program, analyzing the variables that affect outcomes. Between June 1998 and March 2004, 35 OLT were performed in 34 recipients including 80% cadaveric whole-organ grafts and 20% segmental grafts, with 11% from cadaveric and 9% from living donors. Most of the recipients were infants or toddlers weighing less than 15 kg. There was only 1 case of arterial thrombosis (2.8%); the graft was saved with a Kasai procedure. Biliary complications were present in 22% of cases, all resolved with reoperations. Posttransplant cytomegalovirus infection or reactivation (28%), acute rejection (25%), or posttransplant lymphoproliferative disorders (5.7%) were not a cause of graft or patient loss. Overall, 1- and 5-year patient survival rates are 77.1% and 74.2%, respectively; however, when the 1998-2000 cohort was compared with the 2001-2004 cohort, there was a significant difference in survival (P = .004). The 1-year patient survival for the later group is 91.6%. We performed the first successful living donor liver transplantation and the first simultaneous liver-kidney transplantation in a child in our country. Our results demonstrate that pediatric liver transplantation is a feasible undertaking in Mexico, with survival rates comparable to those of foreign centers.     

De novo malignancies after kidney and liver transplantations: experience on 582 consecutive cases

De novo malignancies after transplantation are a growing problem of solid organ transplant recipients, due to longer survival follow-up under chronic immunosuppression. The aim of this study was to analyze a population of 582 consecutive kidney (n = 382) and liver (n = 202) transplant recipients, who survived at least 12 months after transplantation, at a single transplant center for the development of de novo cancers. The incidence of de novo malignancies was 7% after both renal and liver transplantation. The median elapsed time from transplant to the diagnosis of de novo malignancy was 45 months (range 3 to 220) months for kidney and 37 months (range 12 to 101 months) for liver transplants. Skin cancers were the most common within renal recipients, while gastroenteric cancers were more frequently encountered in liver transplants. Oropharyngeal and upper digestive tract tumors were always associated with a history of chronic alcohol consumption in liver recipients. Liver transplant recipients treated for acute rejection had a worse cancer prognosis than patients without rejection 1- and 2-year survivals 83% and 63% versus 36% and 17% (P = .026). The estimated 1- and 2-year survival rates for all types of de novo malignancies were 79% and 66%, including 64% and 51% for solid organ tumors versus 89% and 89% for skin cancers and posttransplant lymphoproliferative disorder (PTLD) (P = .17) in renal transplants and 70% and 42%, including 57% and 28% for solid organ tumors versus 85% and 64% for skin cancers and PTLD (P = .43) in liver transplants respectively.     

Transplantation for alcoholic cirrhosis: How does recurrence of disease harm the graft?

Abstract Many transplant centres are reluctant to accept alcoholic patients because of their supposed potential for alcoholic recidivism, resulting in graft failure and recurrence of alcoholic liver cirrhosis. From May 1982 to January 1993 80 patients received orthotopic liver transplantation (OLT) at our institution either for alcoholic cirrhosis exclusively ( n = 58) or for a hepatoma in an alcoholic cirrhosis ( n = 22). The outcome of these patients was analysed with particular attention to recurrence of liver disease. Overall survival in this group was 67% and 49% at 1 and 5 years, respectively, with a median follow-up' of 45 months. Actuarial survival of patients transplanted since January 1989 ( n = 46) and 84% and 82% at 1 and 2 years (median follow-up 31 months). Non-fatal clinical endpoints were analysed in those patients surviving for at least 3 months ( n = 61). Return to alcohol abuse was documented in 16 patients at routine short-term out patient check-ups. All patients except one admitted to taking alcohol and showed changes in their laboratory test results. A specific pattern of liver function test values related to alcohol abuse was not detected and at the end of a relapse the liver function values usually returned to pre-event values. Only in one case was toxic injury of the liver related to alcoholic recidivism diagnosed on percutaneous liver needle biopsy or post-mortem examination. Com-plicance with the required immunosuppressive regimen and social rehabilitation after OLT were excellent. Unwillingness to offer OLT to individuals with alcoholic liver disease because of failure to demonstrate 100% long-term abstinence appears difficult to defend in the face of results showing good survival, compliance and social rehabilittion. The hypothesis of a higher sensitivity of the transplanted liver to a drinking episode and the redevelopment of alcoholic diesease in the new liver was not confirmed in our study population.     

Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post‐transplant year

Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long‐term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post‐transplant year (p = 0.655) but worse during the five subsequent years among the five‐yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post‐transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post‐transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non‐ALD recipients up to the fifth post‐transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre‐transplant diagnosis of ALD yields negative effects on post‐transplant outcomes beyond the fifth post‐transplant year, not attributable to recidivism.     

肝移植治疗原发性胆汁性肝硬化的远期效果观察

目的 观察肝移植治疗原发性胆汁性肝硬化(PBC)的远期效果.方法 对15例接受了肝移植的终末期PBC患者进行长期随访,中位随访时间为70个月(38～86个月),记录并总结随访期间患者的相关资料,分析肝移植术后患者的预后、新发疾病以及术后远期存活率.结果 15例PBC患者共接受原位肝移植16例次,其中1例因原发性移植肝无功能进行了2次肝移植.术后患者均采用环孢素A(或他克莫司)+霉酚酸酯+激素的三联免疫抑制方案,部分患者使用了熊去氧胆酸.术后2周时,患者肝功能指标基本恢复正常,乏力、皮肤瘙痒及黄疸等症状缓解,患者的生存质量明显改善.术后有4例患者出现新发疾病(26.7%),1例为乙型肝炎病毒感染,2例为自身免疫性肝炎,1例为结肠癌,经治疗后2例好转,2例治疗无效死亡.肝移植术后,患者无PBC复发,1、2和5年的存活率分别为100%、100%和86.7%.结论 肝移植可提高终末期PBC患者的生存质量和存活率,但一些少见的新发疾病对患者的远期存活率影响较大.     

Multicentric outcome analysis of sirolimus‐based immunosuppression in 252 liver transplant recipients

The use of sirolimus (SRL) in orthotopic liver transplantation (OLT) has been controversial after experimental data suggested an increased risk of hepatic artery thrombosis (HAT). To assess the safety and efficacy of SRL as de novo immunosuppression in OLT recipients. Outcomes of 252 OLT patients who received SRL were compared with outcomes of 291 OLT recipients who received calcineurin inhibitor in a retrospective study. Primary outcomes of this study were: patient‐ and graft survivals, vascular, biliary, wound complications and rejection rates. Secondary outcomes were: postoperative infection rate, bone marrow and renal function and changes of lipid levels. Patient‐ and graft survivals, rejection and infection rates were similar. In the SRL group, HAT occurred in 1.2%, biliary complications in 19.4%, and incisional hernias in 9.1%. In the control group the incidence of HAT was 5.8% (P = 0.004), biliary complications 18.5% (P = NS) and incisional hernias 7.2% (P = NS). Patients on SRL experienced significantly higher levels of serum triglycerides but fewer acute cellular rejections. Bone marrow and renal functions were similar in both the groups. Our findings would suggest that SRL is safe and effective for very selected OLT recipients. Randomized controlled trials are necessary to confirm our results.     

Impact of surgical and immunological parameters in pediatric liver transplantation: a multivariate analysis in 500 consecutive recipients of primary grafts

OBJECTIVE: To assess the respective impact of surgical and immunologic factors on patient/graft outcome and rejection after pediatric liver transplantation. SUMMARY BACKGROUND DATA: Orthotopic liver transplantation (OLT) constitutes a validated therapeutic modality for acute liver failure and end-stage liver disease in children. Only a few large studies of factors influencing outcome of pediatric OLT are available in the literature. Studies considering the impact of rejection on graft outcome are scarce in adult OLT and are not even available for pediatric recipients. METHODS: Five hundred consecutive pediatric recipients (<15 years) of a primary OLT performed between March 1984 and July 2000 were retrospectively reviewed. The main indication was biliary atresia (n = 328). A living related donor graft was used from July 1993 onwards in 82 children (16%). Survival was calculated and multivariate analysis was performed. RESULTS: Actuarial survival rates at 1, 5, and 10 years were 85%, 81%, and 79% for patients, and 76%, 71%, and 70% for grafts, respectively. At the multivariate analysis, only 3 factors were found to be independently correlated with better patient survival: year of transplantation (P = 0.001), pretransplant diagnosis (P < 0.001, worst results for liver tumors), and ABO matching (P < 0.001, worst results for ABO incompatibility). Similarly, 3 factors were independently correlated with better rejection-free graft survival: tacrolimus as primary immunosuppressant (P < 0.001), a negative T-cell crossmatch (P = 0.016), and younger age of the donor (P < 0.001). CONCLUSIONS: Pediatric OLT constitutes a complex undertaking with multifactorial impact on results: (1). a strong learning curve effect was shown to impact on overall results; (2). pediatric liver tumors still represent a challenging indication for OLT; (3). primary immunoprophylaxis with tacrolimus provided a lower rejection incidence; (4). the younger donor age effect deserves further immunologic investigations.