Long-term survival after liver transplantation in 4,000 consecutive patients at a single center

OBJECTIVE: To evaluate the long-term survival outcomes of a large cohort of liver transplant recipients and to identify static and changing factors that influenced these outcomes over time. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, with continual improvements in patient survival as a result of advances in immunosuppression and medical management, technical achievements, and improvements in procurement and preservation. Although many reports, including registry data, have delineated short-term factors that influence survival, few reports have examined factors that affect long-term survival after liver transplantation. METHODS: Four thousand consecutive patients who underwent liver transplantation between February 1981 and April 1998 were included in this analysis and were followed up to March 2000. The effect of donor and recipient age at the time of transplantation, recipient gender, diagnosis, and year of transplantation were compared. Rates of retransplantation, causes of retransplantation, and cause of death were also examined. RESULTS: The overall patient survival for the entire cohort was 59%; the actuarial 18-year survival was 48%. Patient survival was significantly better in children, in female recipients, and in patients who received transplants after 1990. The rates of retransplantation for acute or chronic rejection were significantly lower with tacrolimus-based immunosuppression. The risk of graft failure and death was relatively stable after the first year, with recurrence of disease, malignancies, and age-related complications being the major factors for loss. CONCLUSION: Significantly improved patient and graft survival has been observed over time, and graft loss from acute or chronic rejection has emerged as a rarity. Age-related and disease-related causes of graft loss represent the greatest threat to long-term survival.     

影响肝移植术后生存率因素的单中心研究分析

目的 探讨目前影响肝移植术后患者生存率的原因。方法 回顾性分析解放军总医院2007年1月-2010年12月232例肝移植患者的临床资料,并对随访过程中死亡患者的资料进行分析.结果 肝移植患者的1年生存率已达73.6％,2年生存率为69.6％,其中原发病是良性疾病的患者长期生存率要高于恶性肿瘤患者。肿瘤复发已成为导致患者死亡的首要因素,达35.8％,术后出血占第2位,达到24.7％。结论 肿瘤复发以及术后出血是影响肝移植术后生存率的重要因素。     

Biliary tract complications after liver transplantation in a single center

Biliary tract complications, which occur in 5.8% to 24.5% of adult liver transplant recipients, remain one of the most common problems following transplantation. The aim of this study was to determine the incidence of biliary complications and analyze methods of treatment. From 1993 to 2004, 14 cases (10%) among 140 patients who had undergone liver transplantation developed biliary complications, third to respiratory and neurologic complications. In addition to biliary leakage in six cases, obstruction/stenosis occurred in three cases. One case of biliary fistula and one vanishing bile duct syndrome were observed. There was no death or need for retransplantation; all cases were treated surgically without recurrence. Biliary complications remain an important problem in liver transplantation. Endoscopic and radiologic management are effective in the majority of cases. Surgical intervention is obligatory and safe in selected cases.     

Pediatric liver transplantation for hepatoblastoma: a single center experience

The objective of this study was to review our experience with liver transplantation (OLT) for hepatoblastoma (HB) patients. We evaluated retrospectively clinical features of seven pediatric patients with HB who underwent OLT at our institute from 2007 to February 2011. We investigated pretreatment extent of disease (PRETEXT) stage at diagnosis, type of procedure, complications, changes in serum alpha-fetoprotein (AFP) level, recurrences and metastases. The median age at surgery was 47 months (range, 11 months to 10.3 years). OLT was performed for PRETEXT stage III with a central location (n = 2) and for PRETEXT stage IV cases (n = 5). Five children underwent live donor OLT (LDLT) and two deceased donor OLT including one split deceased donor OLT. One patient received a hepatic vein stent insertion due to stenosis and another experienced biliary leakage which was treated with percutaneous drainage and conservative management. Postoperative serum AFP level remained below 20 ng/mL during follow-up period in six patients who were free of recurrences or metastases. Postoperative serum AFP levels in one patient with pulmonary metastasis were never below 20 ng/mL and increased gradually thereafter. A Pulmonary metastasis was discovered in the 2^nd month post-operative. The other 6 patients are free of tumor recurrences with 29.9 month median follow-up.Although the number of cases is small without long term follow-up data, OLT for unresectable HB confined to the liver following chemotherapy seemed to show good clinical results. The role of post transplantation serum AFP levels needs further investigation.     

Steroid withdrawal in adult liver transplantation: occurrence at a single center

Backgrounds

Steroids are the predominant immunosuppressive agent used after liver transplantation even though patients may experience steroid-related side effects.

Aims

The objective of this study was to determine whether steroid use influenced the outcomes of liver transplantations.

Methods

Three hundred forty-four adult patients underwent liver transplantation between May 2002 and December 2007. We reviewed the medical records of these patients, excluding those younger than 18 years old or those who died within the first month. The protocol withdrawal group (group 1) ceased steroid use within 5 months after transplantation, while the late withdrawal group (group 2) continued steroid use beyond this 5-month posttransplantation period.

Results

All patients were classified according to the onset of steroid withdrawal (group 1: n = 243; group 2: n = 99). The incidences of biopsy-confirmed and treated acute rejection episodes (ARE) at 12 and 24 months posttransplantation were 7.8% and 12.3% in group 1, but 25.3% and 27.3% in group 2, respectively (P = .001). The incidence of hepatitis B virus (HBV) recurrence in group 2 was higher than that in group 1 (P = .007). The HBV-free survival rates at 1 and 2 years posttransplantation were 99.0% and 97.1% in group 1 and 96.1% and 92.1% in group 2, respectively. New-onset diabetes, avascular necrosis of the femoral head, corticosteroid-resistant ARE, hepatocellular carcinoma recurrence, as well as graft and patient survivals did not differ between the two groups.

Conclusions

Acute rejection episodes and HBV recurrence occurred less frequently when steroids were discontinued within 5 months after liver transplantation.     

Results of liver transplantation: analysis of 140 cases at a single center

The Shiraz Organ Transplant Center in southern Iran has been performing all liver transplantations in Iran and certain neighboring countries for 12 years. This study evaluated the 140 operations performed from April 1993 through November 2004. Sixty-one percent of the recipients were men and 39% were women. The average recipient age was 29.9 +/- 14.0 years. One hundred twenty-eight patients has a full-size cadaveric transplant. Most frequent causes of cirrhosis were cryptogenic and viral. An acute rejection episode occurred in 47.5% of cases, and two episodes in 8%. Most frequent short-term complications included respiratory, neurologic, and biliary problems. The 1-, 2-, and 3-year patient survival rates were 92%, 89%, and 85%, respectively. The experience that the Shiraz Organ Transplant Center has had with liver transplantation indicated success comparable to that noted in other reports. The calculated trend suggests that a goal of 100 transplantations for 2005 is within reach.     

Living-donor liver transplantation: results of a single center

In the absence of cadaveric donor liver transplantation, living-donor liver transplantation (LDLT) is an alternative option for patients with end-stage liver disease. The objective of this study was to evaluate the outcome of LDLT at a single medical center in Turkey. We retrospectively analyzed the results of 101 LDLTs in 99 recipients with end-stage liver disease. We transplanted 49 right liver lobes, 16 left lobes, and 36 hepatic segments II and III. Most donors (46%) were parents of the recipients. Seventeen recipients had concomitant hepatocellular carcinoma and cirrhosis. Retransplantation was performed in two recipients. Ten hepatic arterial thromboses, 1 hepatic arterial bleeding, and 12 biliary leaks occurred in the early postoperative period. Most complications were treated with interventional techniques. Three hepatic vein stenoses, three portal vein stenoses, one hepatic arterial stenosis, and six biliary stenoses developed during the late postoperative period. Recipients with those complications were treated with interventional techniques. Mean follow-up was 14.2 +/- 10.9 months. During that time, no tumor recurrence was detected in any recipient with hepatocellular carcinoma. Twenty-two recipients died during the follow-up. At this time, the remaining 77 recipients (77%) are alive, exhibiting good graft function. In general, complication rates are slightly higher after LDLT than after cadaveric liver transplantation. However, most complications can be treated with interventional techniques. LDLT continues to be a life-saving option in countries without satisfactory cadaveric donation rates.     

Living and deceased donor liver transplantation for unresectable hepatoblastoma at a single center

Hepatoblastoma (HB) is the most common malignant liver tumor in children. The application of living donor liver transplantation (LDLT) in the management of unresectable HB may add new therapeutic opportunities. We evaluated the outcomes of patients who underwent liver transplantation for treatment of unresectable HB in the period between August 1985 and June 2003. Ten children had a diagnosis of unresectable HB. Mean age at transplantation was 5.8 yr. Eight patients were transplanted with deceased donor grafts. Two patients underwent LDLT. Pre-transplant chemotherapy was used in 90% of cases. Post-transplant survival ranges from 3.7 to 18.6 yr. Three patients died of recurrent disease at 4, 14 and 38 months. The two LDLT recipients were able to get pre-transplant chemotherapy with a rapid decision towards transplantation; both are alive and well at 5.5 and 11 yr post-transplant. Our experience supports the role of LDLT and deceased donor liver transplantation in the management of unresectable HB when waiting times can be detrimental to the patient's survival.     

Long-term analysis of combined liver and kidney transplantation at a single center

OBJECTIVE: To analyze use of combined liver and kidney transplantation (CLKT) for patients with chronic primary diseases of both organs and for patients with hepatorenal syndrome. DESIGN: Retrospective case series. SETTING: Multiorgan transplantation service in a large university medical center. PATIENTS: A total of 98 patients underwent 99 CLKTs during a 16-year period; 76 had primary renal diseases, and 22 had hepatorenal syndrome. Patients receiving isolated liver and kidney transplants were analyzed for comparison. MAIN OUTCOME MEASURES: Patient and graft survival, rejection rates, and need for hemodialysis before and after transplantation. RESULTS: Overall patient survival was 76%, 72%, and 70% at 1, 3, and 5 years, respectively; liver graft survival was 70%, 65%, and 65%; and kidney graft survival was 76%, 72%, and 70%. No risk factors analyzed for recipients or donors were associated significantly with early posttransplantation mortality or graft loss. In 28 patients who received monoclonal antibody induction therapy with interleukin 2 blockers, there were significantly fewer episodes of acute liver rejection. For patients with hepatorenal syndrome, CLKT did not confer a survival advantage over liver-only transplantation (1-year patient survival was 72% vs 66%; P = .88). The 1-year acute kidney rejection rate in the adult CLKT group was 14% vs 23% in a 5-year cadaveric renal transplantation cohort (P<.01). CONCLUSIONS: First, CLKT is indicated in patients with dual organ disease and achieves excellent results. Second, CLKT for hepatorenal syndrome is indicated in patients receiving hemodialysis for longer than 8 weeks and confers advantages in patient survival and use of hospital resources. Third, the liver is immunoprotective for the kidney.     

单中心肝移植治疗多囊肝病的疗效分析

目的 探讨肝移植治疗多囊肝病的疗效.方法 回顾性分析2003年9月至2009年7月中山大学附属第三医院收治的8例接受肝移植术的多囊肝病患者的临床资料.手术方式均采用附加腔静脉整形的改良背驮式肝移植术,其中1例同时行肝肾联合移植.术后对急性排斥反应、并发症、移植物功能、患者生存时间等进行随访.结果 全组患者手术均获得成功.平均手术时间为(7.5±2.8)h(4～11 h);平均无肝期时间为(42±14)min(25～70 min);术中平均出血量为(2250±1850)ml(2000～6500ml).围手术期患者死亡2例,其中1例于肝移植术后第39天死于肺部感染和MODS,另1例于肝肾联合移植术后第59天死于MODS.1例患者于肝移植术后第45天因肝动脉狭窄行再次肝移植术.6例患者中位随访时间为60个月(37 ～93个月),生存3年以上6例、5年以上4例、7年以上2例.截至随访终点,未发现移植物急性排斥反应.结论 肝移植是治疗多囊肝病患者安全、有效的方法.     

Predicting outcomes after liver transplantation. A connectionist approach.

OBJECTIVE: The authors sought to train an artificial neural network to predict early outcomes after orthotopic liver transplantation. SUMMARY BACKGROUND DATA: Reliable prediction of outcomes early after liver transplantation would help improve organ use and could have an impact on patient survival, but remains an elusive goal. Traditional multivariate models have failed to attain the sensitivity and specificity required for practical clinical use. Alternate approaches that can help us model clinical phenomena must be explored. One such approach is the use of artificial neural networks, or connectionist models. These are computation systems that process information in parallel, using large numbers of simple units, and excel in tasks involving pattern recognition. They are capable of adaptive learning and self-organization, and exhibit a high degree of fault tolerance. METHODS: Ten feed-forward, back-propagation neural networks were trained to predict graft outcomes, using data from 155 adult liver transplants. The data included information that was available by the second postoperative day. Ten separate training and testing data subsets were prepared, using random sampling, and the ability of the different networks to predict outcomes successfully was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Four of the networks showed perfect discrimination, with an area under the ROC curve (Az) of 1.0. Two other networks also had excellent performance, with an Az of 0.95. The sensitivity and specificity of the combined networks was 60% and 100%, respectively, when using an output neuron activation of 0.6 as the cutoff point to decide class membership. Lowering the cutoff point to 0.14 increased the sensitivity to 77%, and lowered the specificity to 96%. CONCLUSIONS: These results are encouraging, especially when compared to the performance of more traditional multivariate models on the same data set. The robustness of neural networks, when confronted with noisy data generated by nonlinear processes, and their freedom from a priori assumptions regarding the data, make them promising tools with which to develop predictive clinical models.     

Simultaneous combined liver and kidney transplantation: a single center experience

Chava SP, Singh B, Stangou A, Battula N, Bowles M, O’Grady J, Rela M, Heaton ND. Simultaneous combined liver and kidney transplantation: a single center experience.
Clin Transplant 2010: 24: E62–E68. © 2010 John Wiley & Sons A/S. Abstract Renal dysfunction is common in patients awaiting liver transplantation (LT) and affects outcome following LT. Combined liver and kidney transplantation (CLKT) has been proposed as effective treatment for patients with chronic diseases of both organs, some with hepatorenal syndrome and for liver‐based metabolic diseases affecting kidney. This study is undertaken to analyze results of CLKT at a single center. Of 2690 LTs performed between 1992 and 2007, there were 39 CLKTs; most common indications were metabolic, cirrhosis and polycystic disease. With follow‐up of up to 170 months, 11 died (overall survival 71.8%); one‐, five‐, and 10‐yr patient and liver graft survival is 77%, 73.7%, and 73.7%, respectively, and kidney graft survival is 77%, 70%, and 70%, respectively. Survival among metabolic group (78.6%) appeared to be better than non‐metabolic group (68%); however, this difference was not significant (p = 0.39). Fifteen surviving patients (53.6%) have mild/moderate renal impairment (creatinine ≥125 μmol/L). None has severe renal failure (serum creatinine ≥250 μmol/L) or end‐stage renal disease requiring hemodialysis. CLKT has good results in selected groups of patients. It provides protection to kidney allograft in liver‐based metabolic diseases affecting kidney. The rate of acute rejection episodes of kidney is low. Significant proportion develops long‐term mild/moderate renal dysfunction. Careful attention to immunosuppression to minimize nephrotoxicity may help.     

肝细胞癌肝移植术后复发和转移的研究:单中心经验

目的 研究肝细胞癌肝移植术后复发和转移的临床特点及治疗方法.方法 回顾分析2003年1月至2005年11月收治的95例肝细胞癌肝移植术后肝癌复发转移病例的临床资料.结果 在随访期内,42例(43.2%)患者被诊断为肝癌复发.复发部位最多见于移植肝(32例)、肺(21例)、骨(7例).单因素分析结果显示,肿瘤大小、肿瘤分布、肝硬化背景、术前甲胎蛋白浓度、组织学分期、大血管侵犯6项因素对肝移植术后生存和(或)肝癌复发有明显影响.多因素分析结果显示,肿瘤分布、组织学分期、大血管侵犯是影响术后总体生存率和肝癌复发率的独立危险因素.肝癌复发后的介入治疗及内放疗可延缓肿瘤进展,选择合适病例行复发灶手术切除可最大限度地改善预后.结论 合理选择接受肝移植的肝癌患者可能可以大幅度降低移植术后肝癌的复发率.在现阶段,外科治疗应是目前移植术后复发性肝癌的首选治疗手段.     

Korean red ginseng: a new approach for the treatment of graft-versus-host disease after liver transplantation

Background

Graft-versus-host disease (GVHD) is a rare complication after liver transplantation with an extremely poor prognosis; its occurrence offers great challenges.

Methods

We have reported herein one case of acute GVHD after liver transplantation who was treated with a traditional Chinese medicine named Korean Red Ginseng (KRG).

Results

The acute GVHD was successfully cured by KRG.

Conclusions

The successful salvage of acute GVHD after liver transplantation by KRG may provide a new viable therapeutic option.     

Identifying a targeted population at high risk for infections after liver transplantation in the MELD era

Sun H‐Y, Cacciarelli TV, Singh N. Identifying a targeted population at high risk for infections after liver transplantation in the MELD era.
Clin Transplant 2011: 25: 420–425. © 2010 John Wiley & Sons A/S. Abstract: Impact of model for end‐stage liver disease (MELD) scoring system on post‐transplant infections and associated risk factors are unknown. Infections <90 d post‐transplant were assessed in 277 consecutive liver transplant recipients from 1999 to 2008. “High‐risk” factors for infections were pre‐defined as MELD score >30, ICU stay >48 h prior to transplant, intraoperative transfusion ≥15 units, retransplantation, post‐transplant dialysis, or reoperation. Of the 240 recipients in the MELD era (2002–2008), 48.5% had any high‐risk factor. The OR for infection was 1.69, 2.00, 18.00, and 4.50 in recipients with any 1, 2, 3, and ≥4 high‐risk factors, respectively (χ² for trend, p < 0.001). In logistic regression model, recipient age (OR 1.12, p < 0.05) and any high‐risk factor (OR 2.42, p < 0.05) were associated with infections. Compared with 37 pre‐MELD recipients, the overall infections and mortality at 12 months did not differ in the two eras. In Cox regression model, recipient age (OR 1.09, p < 0.05) and any high‐risk factor (OR 2.42, p < 0.05) remained associated with infections. The overall frequency of infections did not increase in the MELD era. Pre‐defined risk factors accurately predicted the risk of infections in these patients.     

Osteoporosis after renal transplantation: single center experience

BACKGROUND: Osteoporosis is a major source of morbidity after renal transplantation. The aim of this retrospective study was to determine the independent influences of different parameters on bone mineral density (BMD) in various parts of the body after renal transplantation. METHODS: BMD was measured in 130 of 954 renal allograft recipients who underwent surgery between 1985 and 1999. RESULTS: Time since transplantation and cumulative prednisolone doses were significantly higher in patients who had osteoporosis of the lumbar vertebrae (P=0.06 and 0.034, respectively). Logistic regression analysis revealed that cumulative prednisolone dose was the only significant predictor of low vertebral BMD (P=0.02, r=0.33). For the neck of the femur, high blood urea nitrogen and low Mg levels were found to be the predictors of low bone density (P=0.002 and 0.04, respectively). Although parathyroid hormone levels were higher in femoral osteoporosis patients than in those not affected at this site, the difference was not statistically significant (P=0.294). Time since transplantation, cumulative prednisolone dose, and cyclosporine A dose were all found to have a major negative impact on BMD in the radius region (P=0.001, 0.000, 0.001, respectively). Regression analysis showed that cumulative prednisolone dose (P=0.0008, r=0.34), time since transplantation (P=0.005, r=0.27), body mass index (P=0.01, r=-0.21), male gender (P=0.02, r=-0.21), and age (P=0.04, r=0.16) all had major effects on radius BMD. In conclusion, the radius seems to be one of the major parts of the skeleton affected by factors introduced after renal transplantation.