中国肝癌肝移植临床实践指南（2014版）

肝移植是被全世界认可的治疗终末期肝病的有效手段之一.目前,肝移植在全国范围内已得到广泛开展,亟待相关临床实践指南来指导全国肝移植工作更规范、有效、安全地开展.中华医学会器官移植学分会、中华医学会外科学分会移植学组及中国医师协会器官移植医师分会组织专家制订了《中国肝癌肝移植临床实践指南（2014版）》,重点阐述肝移植受者选择标准、术前降期治疗、受者抗病毒治疗、受者免疫抑制剂应用、术后肿瘤复发的防治5部分内容.米兰标准是肝癌肝移植受者选择的参考基准,而杭州标准是对米兰标准局限于肿瘤形态学的巨大突破.肝癌肝移植术前肿瘤降期治疗可使不满足肝癌肝移植受者选择标准的患者能够被纳入移植标准,获得肝移植机会.对于乙型病毒性肝炎肝癌肝移植受者行抗病毒治疗,有助于降低移植术后乙型病毒性肝炎复发率,提高受者长期生存率.目前主张个体化的低剂量免疫抑制方案以达到最大限度保护移植肝脏功能,同时减轻其毒副作用,减少移植后肝癌复发.肝癌肝移植术后复发的防治可采用手术、TACE、局部消融以及放射免疫、靶向治疗、系统性化疗等手段,为受者制订个体化治疗方案.     

西罗莫司在肝癌患者肝移植后的应用

肝移植是治疗肝癌的重要手段之一,而肝移植后的肝癌复发是移植医生面临的严峻挑战。临床上常用的钙调磷酸酶抑制剂(CNI)被认为是诱发肝癌复发的独立危险因素,而西罗莫司除了具有良好的免疫抑制效能外,同时还具有抑制肿瘤细胞增殖的作用,从而可防止肝移植术后的肝癌复发。现就此综述如下。一、背景近年来肝癌的肝移植治疗发展十分迅速,较多肝癌患者因接受了肝移植而受益[1]。我国每年接受肝移植的受者中也有近40％是肝癌患者[2-3]。Mazzaferro等[4]提出米兰标准以来,以肝癌的大小、数量及血管侵犯程度等来严格筛选肝癌患者行肝移植,使得肝癌患者肝移植后的存活率与生存质量已接近良性肝病的肝移植受者[5-6]。与良性肝病不同,肝癌患者接受肝移植后将面临肝癌的复发。米兰标准是一个相对苛刻的受者选择标准,符合米兰标准的肝癌患者肝移植后5年总体肝癌复发率为17 ％[4]。而美国加州大学旧金山分校(UCSF)标准[7]、匹兹堡标准[8]和成都标准[9]等是相对宽泛的标准,符合这些标准的肝癌患者肝移植后5年总体肝癌复发率可高达41％[10]。     

西罗莫司应用于肝癌肝移植受者的疗效分析

目的 评估肝癌肝移植受者应用西罗莫司对肿瘤复发和受者存活的影响.方法 回顾性分析2006年1月至2011年1月行肝癌肝移植的142例受者的资料,根据术后是否应用西罗莫司分为研究组(62例)和对照组(80例).采用生存分析方法比较两组患者的无瘤生存时间、带瘤生存时间及受者对西罗莫司的耐受性.结果 两组受者无瘤生存率的差异无统计学意义(P＞0.05).两组符合米兰标准者、超过米兰标准且符合美国加州大学旧金山分校(UCSF)标准者、超过UCSF标准者分别相比较,受者无瘤生存率的差异无统计学意义(P＞0.05).对照组中有35例肝移植后肿瘤复发,其中21例肿瘤复发后加用西罗莫司,带瘤生存时间中位数为12个月;14例复发后继续使用原有免疫抑制剂,带瘤生存时间中位数为8个月;两者带瘤生存时间的差异有统计学意义(P=0.039).研究组新发糖尿病发生率低于对照组,但是口腔溃疡和高脂血症发生率却高于对照组,差异均有统计学意义(P＜0.05).结论 未发现西罗莫司能明显降低肝癌肝移植后肿瘤复发率,但移植后肿瘤复发者应用西罗莫司可延长其带瘤生存时间;应用西罗莫司者移植后糖尿病的发生率较低.     

肝癌肝移植的标准及其与预后的关系

目的 评价肝移植治疗肝细胞癌的价值以及受者选择对病人术后存活的影响.方法 对我院2000年6月至2007年2月实施的63例原发性肝细胞癌肝移植临床资料进行回顾性分析.采用kaplan-meier法进行生存率统计分析.结果 63例原发性肝细胞癌病人肝移植术后1、3、5年累积生存率分别为77.4%、59.3%、48.9%.符合Milan标准、符合UCSF标准和不符合UCSF标准受者,肝移植术后1、3、5年累积生存率分别为93.8%、92.1%、29.2%;80.8%、79.2%、8.3%;80.8%、79.2%、0.符合Milan标准、符合UCSF标准和不符合UCSF标准受者,术后1、2、3年肿瘤累积复发率分别为6.2%、15.5%、19.2%;7.9%、15.9%、20.8%;70.8%、87.5%、91.7%(P＜0.01).但是,符合UCSF标准与符合Milan标准受者移植术后累积生存率和肝癌累积复发率相似(P＞0.05).结论 以UCSF标准筛选肝癌病人进行肝移植不仅扩大了肝癌肝移植的适应证,还可以取得与Milan标准同样的效果.     

不同肝癌肝移植标准受者预后分析

目的分析不同肝癌肝移植标准受者预后情况,评价不同标准之间的差异。 方法回顾性分析2013年1月至2017年12月首都医科大学附属北京朝阳医院原发性肝癌肝移植受者的临床资料,比较不同肝癌肝移植标准受者的预后情况。采用单因素方差分析比较不同肝癌肝移植标准受者年龄、手术时间、无肝期时间和肿瘤最大直径,采用秩和检验比较AFP、终末期肝病模型评分和出血量。采用Kaplan-Meier法绘制生存曲线,采用Log-Rank检验比较生存率。采用卡方检验比较Child分级、肿瘤分化程度等指标。P<0.05为差异有统计学意义。 结果根据肝移植术后病理结果,115例肝癌肝移植受者中符合米兰标准43例;符合美国加州大学旧金山分校(UCSF)标准49例,较米兰标准扩大14.0%;符合杭州标准91例,较米兰标准扩大111.6%,较UCSF标准扩大85.7%。截至2017年12月,115例受者平均随访(19±17)个月,中位生存时间41.5个月(1.0～57.0个月)。除肿瘤最大直径和肿瘤数目外,3组不同肝癌肝移植标准受者均具有可比性(P均>0.05)。不同肝癌肝移植受者术后1～4年总体和和无瘤生存曲线差异均无统计学意义(P均>0.05)。 结论相较于米兰标准和UCSF标准而言,杭州标准安全地扩大了肝癌肝移植适用范围,使更多的原发性肝癌患者受益。     

不同移植标准下挽救性肝移植的疗效对比分析

目的分析比较符合米兰标准、UCSF标准、杭州标准的肝细胞肝癌(hepatocellular carcinoma, HCC)切除术后肿瘤复发患者肝移植术后的预后情况。方法回顾性分析2015年1月至2019年10月在复旦大学附属华山医院行公民逝世后器官捐献(donation after citizen death, DCD)肝移植的256例HCC患者的临床资料。其中, 行初期肝移植175例(PLT组), 挽救性肝移植81例(SLT组)。采用t检验、秩和检验或χ2检验比较两组受者的一般资料、肿瘤病理特征、术后并发症等, 用Kaplan-Meier法和Log-rank检验比较两组受者的术后总生存率(overall survival rate, OS)和无复发生存率(recurrence-free survival rate, RFS)。SLT组符合米兰标准者31例(米兰标准组)、符合加州大学旧金山分校(UCSF)标准者45例(UCSF标准组)、符合杭州标准者69例(杭州标准组), 比较三组受者的OS和RFS。按肝移植术前是否接受降期/桥接治疗, 将SLT组受者再分为降期治疗组(32例)和未降期...     

肝癌的肝移植治疗现状

肝移植是目前治疗肝癌最有效的方法。肝癌虽然可以作为肝移植的适应证之一,但是肝癌肝移植的选择标准并不统一,目前国际上参照比较多的有Milan标准、匹兹堡标准、加州大学旧金山分校（UCSF）标准,国内有根据我国国情提出的杭州标准、复旦标准。活体肝移植的开展拓宽了肝癌肝移植受体选择的范围,为更多的肝癌患者提供了肝移植治疗的可能。由于肝移植受者的增加和供肝紧缺的日益加重,肝移植受者术前等待时间越来越长,补救性肝移植及等待期间的各种过渡治疗受到重视,这些治疗可有效控制肿瘤生长,延长术前等待期,减少术后肝癌复发,提高肝移植患者长期存活率。     

肝癌肝移植受者的选择标准

肝细胞肝癌(简称肝癌)是肝移植的主要适应证之一,但肝移植术后肝癌的复发和转移严重制约了肝移植治疗的效果.如何降低移植术后肝癌的复发率和提高长期生存率成为各个移植中心非常关心的问题.对于肝癌肝移植受者的选择,世界上各个肝移植中心纷纷提出了各自的标准.     

肝移植治疗原发性肝癌103例疗效观察

目的 比较不同受体选择标准肝癌肝移植的远期疗效,分析肝痛肝移植术后肿瘤复发相关因素.方法 总结北京佑安医院2004年4月至2008年3月间的103例肝癌肝移植的临床资料,按照肿瘤的特征将其分为3组:符合米兰标准组(A组)、超出米兰标准但满足UCSF标准组(B组)和超出UCSF标准组(C组),比较3组的总体生存率及无瘤生存率,并分析影响远期预后的相关因素.结果 103例肝癌肝移植总体1、2、3年存活率分别为84.0%、70.5%和60.2%.其中A组50例,1、2、3年生存率和无瘤生存率分别为93.4%、83.8%、73.2%和97.3%、93.9%、88.7%;B组17例,1、2、3年生存率和无瘤生存率分别为93.3%、79.4%、66.2%和86.7%、79.4%、66.2%;C组36例,1、2、3年生存率和无瘤牛存率分别为67.0%、45.5%、34.1%和65.8%、50.0%、41.7%.远期生存率A组与B组比较无差异(P=0.631),A组、B组与C组比较具有统计学差异(P值分别为0.001,0.045).结论 米兰标准是肝癌肝移植最佳适应证,超出米兰标准但满足UCSF标准也可获得满意的远期疗效;肿瘤的分期和微血管侵犯是影响远期预后的风险因素.     

肝癌切除术后复发的补救性肝移植

目的 评估肝癌患者肝癌切除术后肝癌复发行补救性肝移植术的临床治疗效果及预后影响因素.方法 回顾性分析本治疗组自2000年4月至2008年6月间实施的88例肝癌切除术后复发行补救性肝移植术病例,分析该组病例手术特征、生存状况、病理因素对预后影响.结果 肝癌切除术后复发行补救性肝移植病例平均年龄为52.4±9.2岁(26....     

Relationship Between Provider Volume and Outcomes For Orthotopic Liver Transplantation

Introduction  Recent data suggests that the previously demonstrable relationship between hospital volume and outcomes for liver transplant procedures may no longer exist. Furthermore, to our knowledge, no study has been published examining whether individual surgeon volume is associated with outcomes in liver transplantation. Materials and methods  The Nationwide Inpatient Sample database was used to obtain early clinical outcome and resource utilization data for liver transplant procedures performed in the USA from 1988 through 2003. The relationship between surgeon and hospital volume and early clinical outcomes was analyzed with and without adjustment for certain confounding variables such as patient age and presence of co-morbid disease. Results  The in-hospital mortality rate, major postoperative complication rate, and length of hospital stay after liver transplantation did not differ significantly based on hospital procedural volume. These outcome variables did, however, exhibit a statistically significant inverse relationship with individual surgeon volume of liver transplant procedures. A significant relationship between procedure volume and outcomes for liver transplantation cannot be demonstrated at the level of transplant center, but does appear to exist at the level of the individual transplant center. Conclusion  Minimal volume requirements for individual liver transplant surgeons may be justified, pending validation of this volume–outcomes relationship using a clinical data source. Presented on March 12, 2006 at the Annual Meeting of the American Hepato-Pancreatico-Biliary Association in Miami Beach, Miami.     

Long Term Outcomes of Liver Transplantation For Patients With Autoimmune Hepatitis

BackgroundAutoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). Data on the long-term outcomes of living-related LT for AIH are limited and inconsistent. The present study aimed to assess the long-term outcomes of deceased donor LT (DDLT) and living donor LT (LDLT) for AIH.MethodsAll patients who received transplants for AIH-related cirrhosis from 2001 to 2018 were included in this study.ResultsSeventy-four patients (31 male, 43 female) received LT. The average follow-up was 7.9 ± 6.9 years (median = 7.2 years), average age was 34.3 ± 13.8 years, and average Model for End-Stage Liver Disease (MELD) score was 23.6 ± 8.5. Thirty-six (49.3%) patients received a graft from a living donor, and 83% of patients were maintained on steroids. The 1-, 3-, 5-, and 10-year survival rates of patients were 91%, 89%, 87%, and 82% and of grafts were 89%, 88%, 86%, and 76%, respectively. In univariate analysis, MELD score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.17; P = .028), donor age (OR per 5 years, 1.45; 95% CI, 1.07-2.02; P = .021), donor type (OR LDLT vs DDLT, 0.19; 95% CI, 0.04-0.67; P = .017), and renal function (OR glomerular filtration rate <60 vs ≥60 mL/min/m², 7.41; 95% CI, 1.88-31.25; P = .004) were significant predictors of graft survival; however, none of the factors remained significant in multivariate analysis.ConclusionWe have shown the highest reported long-term survival rates in LT for AIH, including a large number of patients who underwent LDLT. Standardized management and immunosuppressive therapy, including the maintenance of a low-dose steroid protocol, may have contributed to this outcome.     

Effects of Hemi-Portocaval Shunts For Inflow Modulation on the Outcome of Small-for-Size Grafts in Living Donor Liver Transplantation

Graft hyperperfusion in small-for-size grafts (SFSG) is considered the main causal factor of small-for-size syndrome (SFSS). We compared SFSG with a graft-to-recipient body ratio < or =0.8, with and without graft inflow modulation (GIM) by means of a hemi-portocaval shunt (HPCS). Thirteen patients underwent adult-to-adult living donor liver transplantation (AALDLT): G1, n = 5 [4 right livers (RL) and 1 left liver (LL)] without GIM, and G2, n = 8 (4 RL and 4 LL) with GIM. In G2 patients, portal vein flow (PVF) was significantly reduced by HPCS: 190 +/- 70 mL/min/100 g liver in G2 vs. 401 +/- 225 ml/min in G1 (p = 0.002). One- and 6-month post-transplantation graft volume/standard liver volume (GV/SLV) ratio was of 72% and 79.5% in G1; 80% and 101% in G2 (p = ns). SFSS was observed in three G1 recipients (who were retransplanted), but in none of the G2 patients. At 1-year, patient and graft survival was respectively of 40% and 20% in G1, 87.5% and 75% in G2 (p = 0.024 and 0.03). It is concluded that drastic reduction of PVF by means of HPCS improves overall patient and graft survival by averting the occurrence of SFSS. Graft inflow modulation through HPCS reduces the risk of complications when transplanting SFSG in adult recipients.     

Liver Transplantation for Hepatocellular Carcinoma Within Milan Criteria in Patients With Model For End-Stage Liver Disease Score Below 15: The Impact of the Etiology of Cirrhosis on Long-Term Survival

Background

Liver transplantation (OLT) is the gold standard therapy for patients with cirrhosis complicated by hepatocellular carcinoma (HCC) within Milan Criteria (MC). We evaluated the impact of the etiology of the underlying liver disease on long-term outcomes of patients undergoing OLT for HCC within MC having a Model for End-stage Liver Disease (MELD) score < 15.

Methods

From November 2002 to December 2009, we performed 203 primary OLTs from brain-dead donors in recipients with HCC and cirrhosis with biochemical MELD scores below 15. We excluded 31 patients outside MC on the explant pathology of the native liver. The remaining 172 were divided into 3 groups according to the etiology of the underlying cirrhosis: hepatitis C virus-positive (HCV+; n = 78; 45%), hepatitis B virus-positive (HBV+; n = 65; 38%) and other indications (n = 29; 17%). The groups were compared for donor and recipient features, donor-recipient match, and transplant variables. The study endpoint was long-term patient survival.

Results

The groups were similar, except for a greater prevalence of hepatitis B core antibody-positive grafts in the HBV+ group and less frequent HCC bridging procedures in the other indications group. After a median follow-up of 72 months, HCC recurrence was observed in 8 (4.7%) patients (6 HCV+, 2 other indications), 5 of whom died. Overall 5-year patient survival of 82%, revealed significant differences among groups: 98.3% in HBV+, 67.1% in HCV+, and 85.8% in other indications (HBV+ vs other indications: P = .01; HBV+ vs HCV+: P = .0001; HCV+ vs other indications: P = NS). In the HCV+ group, recurrent HCV hepatitis was the most frequent cause of death. Upon multivariate analysis, HBV positivity in the recipient was an independent predictor of better patient survival (hazard ratio = 0.10, 95% confidence interval 0.02–0.64, P = .013).

Conclusions

Etiology of the underlying cirrhosis significantly influenced the long-term survival after OLT of patients with HCC within MC and MELD < 15. It should be taken into account in estimation of survival benefit.     

肝脏良性疾病的肝移植

肝脏移植作为终末期肝病的治疗，自上个世纪80年代在欧美国家获得公认以来，已在世界各国得到迅速开展。我国自90年代后期以来，在全国掀起了第二个肝移植的热潮，迄今已完成1000余例肝移植．在围手术期处理、手术技术、介人放射、移植免疫、抗感染治疗等各个方面均获得丰富的经验．我国肝移植的效果及长期生存率亦逐步赶上国际先进水平。