Liver transplantation for hepatocellular carcinoma beyond the Milan criteria: A review

Liver transplantation(LT) has been accepted as an effective therapy for hepatocellular carcinoma(HCC). The Milan criteria(MC) are widely used across the world to select LT candidates in HCC patients. However, the MC may be too strict because a substantial subset of patients who have HCC exceed the MC and who would benefit from LT may be unnecessarily excluded from the waiting list. In recent years, many extended criteria beyond the MC were raised, which were proved to be able to yield similar outcomes compared with those patients meeting the MC. Because the simple use of tumor size and number was insufficient to indicate HCC biological features and to predict the risk of tumor recurrence, some biological markers such as Alphafetoprotein, Des-Gamma-carboxy prothrombin and the neutrophil-to-lymphocyte ratio were useful in selecting LT candidates in HCC patients beyond the MC. For patients with advanced HCC, downstaging therapy is an effective way to reduce the tumor stage to fulfill the MC by using liver-directed therapy such as transarterial chemoembolization, radiofrequency ablation and percutaneous ethanol injection. This article reviews the recent advances in LT for HCC beyond the MC.

Milan criteria are useful predictors for favorable outcomes in hepatocellular carcinoma patients undergoing liver transplantation after transarterial chemoembolization

AIM: To evaluate whether the Milan criteria are useful in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE) before liver transplantation (LT). METHODS: Thirty-six HCC patients who fulfilled the Milan criteria after having received TACE and subsequently underwent LT were included (TACE + LT group) in the study. As controls, 21 patients who also met the Milan criteria and underwent LT without prior treatment were selected (LT group). Post-LT clinical outcomes, such as HCC recurrence, survival rate, and histologic features of explanted livers, were compared between the two groups. RESULTS: Baseline characteristics were not different between the two groups. Pre-LT maximal tumor diameter in TACE + LT group was similar to that of LT group (2.0 ± 0.6 cm vs 2.3 ± 0.9 cm; P = 0.10). Post-LT histologic findings also revealed similar maximal tumor diameter in the two groups (2.4 ± 1.4 cm vs 2.3 ± 0.9 cm; P = 0.70). Explanted livers showed similar incidence of unfavorable pathologic features. The morality within 60 d after transplantation was not different between the two groups (8.3% vs 9.5%; P = 0.99). Post-LT 5-year survival rate (57% vs 74%; P = 0.70) and cumulative recurrence rate (8.3% vs 4.8%; P = 0.90) were not significantly different between the two groups. CONCLUSION: The Milan criteria are still a useful selec- tion criteria showing favorable outcomes in HCC patientsreceiving TACE before LT.

Radiofrequency ablation vs surgical resection in elderly patients with hepatocellular carcinoma in Milan criteria

BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patients(>70 years)with HCC in Milan criteria,which underwent liver resection(LR)or RFA.METHODS The study included 594 patients with HCC in Milan criteria(429 in LR group and 165 in RFA group)managed in 10 European centers.Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching(PSM)and Cox regression.RESULTS After PSM,we compared 136 patients in the LR group with 136 patients in the RFA group.Overall survival at 1,3,and 5 years was 91%,80%,and 76%in the LR group and 97%,67%,and 41%in the RFA group respectively(P=0.001).Diseasefree survival at 1,3,and 5 years was 84%,60%and 44%for the LR group,and 63%,36%,and 25%for the RFA group(P=0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group(1%vs 11%,P=0.001)in association with a shorter length of stay(2 d vs 7 d,P=0.001).In multivariate analysis,Model for End-stage Liver Disease(MELD)score(>10)[odds ratio(OR)=1.89],increased value of international normalized ratio(>1.3)(OR=1.60),treatment with radiofrequency(OR=1.46),and multiple nodules(OR=1.19)were independent predictors of a poor overall survival while a high MELD score(>10)(OR=1.51)and radiofrequency(OR=1.37)were independent factors associated with a higher recurrence rate.CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications,surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients(>70 years)with HCC in Milan criteria.

Selection of HCC patients for liver transplantation: the Milan criteria,Hangzhou criteria and beyond

Deceased or living liver graft should be considered as a valuable community resource. They should be implanted in patients who

Hepatocellular carcinoma beyond Milan criteria: Management and transplant selection criteria

Liver transplantation(LT) for hepatocellular carcinoma(HCC) has been established as a standard treatment in selected patients for the last two and a half decades. After initially dismal outcomes, the Milan criteria(MC)(single HCC ≤ 5 cm or up to 3 HCCs ≤ 3 cm) have been adopted worldwide to select HCC patients for LT, however cumulative experience has shown that MC can be too strict. This has led to the development of numerous expanded criteria worldwide. Morphometric expansions on MC as well as various criteria which incorporate biomarkers as surrogates of tumor biology have been described. HCC that presents beyond MC initially can be downstaged with locoregional therapy(LRT). Post-LRT monitoring aims to identify candidates with favorable tumor behavior. Similarly, tumor marker levels as response to LRT has been utilized as surrogate of tumor biology. Molecular signatures of HCC have also been correlated to outcomes; these have yet to be incorporated into HCC-LT selection criteria formally. The ongoing discrepancy between organ demand and supply makes patient selection the most challenging element of organ allocation. Further validation of extended HCCLT criteria models and pre-LT treatment strategies are required.

Expansion of the hepatocellular carcinoma Milan criteria in liver transplantation: Future directions

Milan criteria are currently the benchmark related to liver transplantation(LT) for hepatocellular carcinoma. However, several groups have proposed different expanded criteria with acceptable results. In this article, we review the current status of LT beyond the Milan criteria in three different scenarios-expanded criteria with cadaveric LT, downstaging to Milan criteria before LT, and expansion in the context of adult living donor LT. The review focuses on three main questions: what would the impact of the expansion beyond Milan criteria be on the patients on the waiting list; whether the dichotomous criteria(yes/no) currently used are appropriate for LT or continuous survival estimations, such as the one of "Metroticket" and whether it should enter into the clinical practice; and, whether the use of living donor LT in the context of expansion beyond Milan criteria is justified.

LIN28 expression and prognostic value in hepatocellular carcinoma patients who meet the Milan criteria and undergo hepatectomy

Stem cell marker LIN28,related closely with SOX2 and OCT4,has been studied as a biomarker for the maintainance of pluripotent cells in several malignancies.Our previous study showed that SOX2 and OCT4 were negative predictors for hepatocellular carcinoma(HCC).However,the predictive value of LIN28 in HCC outcome is still undetermined.We hypothesized that LIN28 may also play a role as a biomarker for HCC.To test this hypothesis,we examined the expression of LIN28 in 129 radically resected HCC tissues using reverse transcription-polymerase chain reaction and analyzed the association of LIN28 expression with clinicopathologic features and prognosis.Our study showed that LIN28 was expressed at a higher frequency in tumor tissues than in non-HCC tissues(45.0% vs.21.7%,P = 0.020).Moreover,LIN28 expression was significantly increased in cases with large tumor size(P = 0.010).Univariate analysis did not reveal a significant correlation between LIN28 expression and overall survival or recurrence-free survival.For HCC patients who met the Milan criteria,stratified analysis revealed shorter overall survival(P = 0.007) and recurrence-free survival(P < 0.001) in those with detectable LIN28 expression compared to those with no detectable LIN28 expression.Furthermore,multivariate analysis revealed that LIN28 was a negative independent predictor for both overall survival(hazard ratio= 7.093,P = 0.017) and recurrence-free survival(hazard ratio=5.518,P = 0.004) in patients who met the Milan criteria.Taken together,our results suggest that LIN28 identifies low-risk and high-risk subsets of HCC patients meeting the Milan criteria who undergo hepatectomy.

符合Milan标准肝细胞癌患者行肝移植和肝切除术预后分析

目的：比较符合Milan标准肝细胞癌患者行肝移植和肝切除术后的生存和复发情况，分析影响患者肿瘤复发转移的相关危险因素。方法回顾性分析南方医院从2006年1月-2011年12月88例符合Milan标准肝细胞癌患者行肝移植或肝切除术的临床资料，比较两种术式的生存率及无瘤生存率；对围手术期的12个变量进行单因素分析，筛选影响术后肿瘤复发和转移的危险因素。结果移植组患者1、3、5年生存率与切除组差别无统计学意义（P＆gt;0.05）；移植组患者1、3、5年无瘤生存率优于切除组（P＆lt;0.05）；肝移植组肿瘤复发率明显低于肝切除组（P＆lt;0.05）；多因素分析提示性别、肿瘤大小、肿瘤病理分化程度、镜下微血管癌栓是影响无瘤生存率的重要预后因素。结论治疗符合Milan标准肝细胞癌，肝移植比肝切除能获得较长的无瘤生存时间；男性、肿瘤直径越大、有镜下血管癌栓、肿瘤病理分化程度低的患者术后更容易发生肿瘤复发和转移。

Selection criteria for liver resection in patients with hepatocellular carcinoma and chronic liver disease

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with an annual occurrence of one million new cases. An etiologic association between HBV infection and the development of HCC has been established with a relative risk 200-fold greater than in non-infected individuals. Hepatitis C virus is also proving an important predisposing factor for this malignancy with an incidence rate of 7% at 5 years and 14% at 10 years. The prognosis depends on tumor stage and degree of liver function, which affect the tolerance to invasive treatments. Although surgical resection is generally accepted as the treatment of choice for HCC, new treatment strategies, such as local ablative therapies, transarterial embolization and liver transplantation, have been developed nowadays. With increasing detection of small HCCs from screening programs for cirrhotic patients, it is foreseen that locoregional therapy will play an important role in the near future.

Liver transplantation for hepatocellular carcinoma:Historical evolution of transplantation criteria

Liver transplantation(LT) for hepatocellular carcinoma is still a hot topic,and the main factor that is associated with the success of treatment is to determine the patients who will benefit from LT.Milan criteria have been defined 25 years ago and still is being used for patient selection for LT.However,in living donor LT,the Milan criteria is being extended.Current criteria for patient selection do not only consider morphologic characteristics such as tumor size and number of tumor nodules but also biologic markers that show tumor aggressiveness is also being considered.In the present review article,we have summarized all the criteria and scoring systems regarding LT for hepatocellular carcinoma.All criteria have 5-year overall survival rates that were comparable to the Milan Criteria and ranged between 60%-85%.On the other hand,it was seen that the recurrence rates had increased as the Milan criteria were exceeded;the 5-year recurrence rates ranged between 4.9% to 39.9%.Treatment of hepatocellular carcinoma needs a multidisciplinary approach.Ideal selection criteria are yet to be discovered.The same is true for treatment modalities.The goal will be achieved by a harmonic interplay between basic science researchers and clinicians.

Prognosis of Liver Transplantation for Hepatocellular Carcinoma in Terms of Different Criteria:A Single Center Experience

Objective Patients undergoing liver transplantation for hepatocellular carcinoma(HCC)within the Milan criteria have an excellent outcome.We developed a program to analyze and prove that the Milan criteria can be expanded safely and effectively.Methods We retrospectively reviewed 117 HCC patients treated with liver transplantation between January 2013 and December 2017.Patients were grouped according to the Milan criteria,the University of California,San Francisco(UCSF)criteria,Up-to-seven criteria and Hangzhou criteria.Tumor-free and overall survival rates were investigated with a Kaplan-Meier analysis.Multivariable regression Cox models produced survival estimates for the patients that exceeded the Milan criteria.Results The 1-year,3-year and 5-year overall survival rates of patients fulfilling the Milan criteria(n=44)were 100%,87.5%and 78.9%,respectively.Compared with the Milan criteria,the UCSF criteria(n=50),Up-to-seven criteria(n=51)and Hangzhou criteria(n=86)provided an expansion of 13.6%,15.9%and 95.9%,respectively.The 1-year,3-year and 5-year overall survival rates of patients fulfilling UCSF criteria,Up-to-seven criteria and Hangzhou criteria were 96.0%,84.9%,76.9%;96.1%,85.2%,77.6%and 97.7%,83.9%,66.7%,respectively(P>0.05).Multifactor Cox regression showed that tumor diameter and microvascular invasion were independent risk factors for survival in patients that exceeded the Milan criteria.Conclusion Compared with the Milan criteria,the Hangzhou criteria can safely expand the scope of liver transplantation for HCC to a certain extent.By contrast,the UCSF criteria and Up-to-seven criteria result in a limited number of patients which need further expansion.Tumor diameter and microvascular invasion were the independent risk factors for survival in patients that exceeded the Milan criteria.

Downstaging disease in patients with hepatocellular carcinoma outside up-to-seven criteria: Strategies using degradable starch microspheres transcatheter arterial chemo-embolization

AIM: To evaluate the downstaging rates in hepatitis C virus-patients with hepatocellular carcinoma(HCC), treated with degradable starch microspheres transcatheter arterial chemoembolization(DSM-TACE), to reach new-Milan-criteria(nM C) for transplantation. METHODS: This study was approved by the Ethics Committee of our institution. From September 2013 to March 2014 eight patients(5 men and 3 women) with liver cirrhosis and multinodular HCC, that did not meet n MC at baseline, were enrolled in this study. Patients who received any other type of treatment such as termal ablation or percutaneous ethanol injection were excluded. DSM-TACE was performed in all patients using Embo Cept? S and doxorubicin. Baseline and follow-up computed tomography or magnetic resonance imaging was assessed measuring the longest enhancing axial dimension of each tumor according to the modified Response Evaluation Criteria In Solid Tumors measure-ments, and medical records were reviewed.RESULTS: DSM-TACE was successfully performed in all patients without major complication. We treated 35 lesions(mean 4.3 per patient). Six of eight patients(75%) had their HCC downstaged to meet nM C. Every patient whose disease was downstaged eventually underwent transplantation. The six patients who received transplant were still living at the time of this writing, without recurrence of HCC. Baseline age(P = 0.25), Model for End-stage Liver Disease score(P = 0. 77), and α-fetoprotein level(P = 1.00) were similar between patients with and without downstaged HCC. CONCLUSION: DSM-TACE represents a safely and effective treatment option with similar safety and efficacy of conventional chemoembolization and could be successfully performed also for downstaging disease in patients without n MC, allowing them to reach liver transplantation.

基于术前血清学指标AFP和GGT的标准在预测肝细胞癌患者肝移植术后长期生存中的作用研究

目的分析术前血清学指标对肝细胞癌(HCC)患者肝移植术后长期生存和肿瘤复发的预测作用,探索其对扩大米兰标准的意义。方法回顾性分析669例HCC肝移植受者的临床资料,采用受试者工作特征(ROC)曲线计算最佳截取值,采用单因素和多因素回归分析影响HCC患者肝移植术后总生存率和无复发生存率的危险因素,分析术前血清肝酶与肿瘤病理学特征的相关性,比较甲胎蛋白(AFP)联合γ-谷氨酰转移酶(GGT)以及不同肝移植标准对HCC患者肝移植术后生存和复发的预测价值。结果超米兰标准、肿瘤直径之和(TTD)>8 cm、AFP>200 ng/mL和GGT>84 U/L是影响HCC患者肝移植术后总生存率和无复发生存率的独立危险因素(均为P<0.05)。相关性分析结果显示,术前血清GGT水平与TTD,肿瘤数量,静脉侵犯,微卫星病变,包膜侵犯,肿瘤、淋巴结、转移(TNM)分期,Child-Pugh评分,超米兰标准均存在相关性(均为P<0.05)。将米兰标准、TTD与血清肝酶指标(AFP和GGT)结合,提出Milan-AFP-GGT-TTD(M-AGT)标准。符合M-AGT标准者(其中111例超米兰标准)术后5年总生存率和无复发生存率均高于符合杭州标准者(均为P<0.05),与符合加州大学旧金山分校(UCSF)标准者的术后5年总生存率和无复发生存率比较差异均无统计学意义(均为P>0.05)。结论术前血清学指标AFP和GGT可有效预测HCC患者肝移植术后长期生存和肿瘤复发,建立基于血清学指标的M-AGT标准有助于补充米兰标准,且简单易行。

肝癌肝移植适应证标准——验证及再思考

目的对不同的原发性肝细胞癌(肝癌)肝移植适应证标准进行评价与验证。方法 2001年至2007年上海七家肝移植中心施行的肝癌肝移植病例共948例,采用Kaplan-Meier法分析符合米兰标准、加利福尼亚标准和上海复旦标准的肝癌肝移植患者的术后4年总体生存率及无复发生存率,并作比较。结果符合米兰标准(369例)、加利福尼亚标准(470例)和上海复旦标准(554例)的患者的术后4年总体生存率及无复发生存率分别为65.8%和74.1%、66.0%和73.6%、63.9%和70.4%。三种标准的总体生存率及无复发生存率比较差异无统计学意义(均为P>0.05)。与符合米兰标准的病例相比,超出米兰标准但符合上海复旦标准的185例,其术后4年生存率及无复发生存率分别为61.5%、65.0%,比较差异亦无统计学意义(均为P>0.05)。结论上海复旦标准适度扩大了肝癌肝移植适应证范围且生存率满意,可能更符合中国国情。

射频消融治疗符合米兰标准的老年肝癌患者疗效分析

目的评估射频消融术(radiofrequency ablation,RFA)治疗符合米兰标准的老年肝癌患者的疗效。方法回顾性分析1999年6月至2011年6月我院行射频消融治疗的90例≥70岁符合米兰标准的原发性肝细胞癌(Hepatocellular carcinoma,HCC)病例,进行随访观察,评价其疗效,统计初次RFA术后1、2、3、4、5年无瘤生存率及总生存率,同时分析影响预后的相关因素。结果共90例病例纳入本研究。术后出现并发症31例(34.44%),无严重并发症病例及死亡病例。RFA术后中位无瘤生存时间21个月,1、2、3、4、5年无瘤生存率分别为65.56%、46.67%、33.33%、24.44%、17.78%。中位总生存时间49个月,1、2、3、4、5年总生存率分别为91.11%、80.00%、67.78%、52.22%、35.56%。在多因素分析中长期饮酒史、肝炎病毒感染、肝硬化、Child-Pugh B级、AFP>20 ng/mL、HBV-DNA>1 000 cps/mL、Cr>88.4μmol/L、合并症是影响生存率的显著危险因素。对于单发病灶,病灶直径大于3 cm者,无瘤生存率及总生存率明显较低。结论 RFA治疗符合米兰标准的老年肝癌患者,安全性高、并发症少、疗效满意;肝癌直径大于3 cm者行RFA治疗预后较差;但RFA仍是老年早期肝癌患者较好的选择。

手术部分肝切除与射频消融治疗多发肝细胞癌预后比较

目的比较部分肝切除术及射频消融术(radiofrequency ablation,RFA)对符合米兰标准的多发肝癌疗效。方法回顾性分析2007年6月-2013年12在我科接受治疗的140例肝功能良好、多发肝癌(符合米兰标准)的患者资料,其中接受部分肝切除术78例,接受RFA治疗62例,分别对术前主要检查结果、围术期并发症发生率、术后第3天肝功能指标及生存结果进行比较。结果手术组术后贫血、腹水及低蛋白血症的发生率总体上高于RFA组,术后第3天谷丙转氨酶及谷草转氨酶水平显著高于RFA组;1、2、3年生存率手术组分别为80.8%、60.3%、48.7%,RFA组分别为83.9%、48.0%、30.6%。手术组生存率优于RFA组(P=0.037)。1、2、3年无瘤生存率手术组分别为74.4%、47.4%、37.2%,RFA组分别为71.0%、38.7%、21.0%。手术组优于RFA组(P=0.007)。结论符合米兰标准、肝功能Child-Pugh A级的多发肝癌患者仍可能从外科切除中获益。

射频消融治疗超过米兰标准肝细胞肝癌的长期疗效研究

目的探讨射频消融治疗超过米兰标准,在新米兰标准下肝细胞肝癌的临床疗效。方法 2007年1月~2009年12月90例符合新米兰标准的肝细胞肝癌接受B超引导下射频（美国Radio-Therapeutics公司RF1500X射频消融仪）消融治疗,消融采用功率模式,输出功率调至200 W,采用多点位分层消融,至超声下肿瘤完全被强回声覆盖。结果 90例218个肿瘤首次完全消融209个,首次完全消融率95.9%（209/218）。严重并发症2例（2.2%）,肝脓肿1例,胆汁瘤1例,经抗感染及引流后均好转,无治疗相关死亡发生。1、3、5年总体生存率分别为92.2%、67.8%、43.9%,1、3、5年无瘤生存率分别为83.3%、48.9%、31.9%。结论射频消融是治疗新米兰标准肝细胞肝癌安全有效的方式。

Patients with early recurrence of hepatocellular carcinoma have poor prognosis

BACKGROUND： Early recurrence （ER） after hepatic resection （HR） is a poor prognostic factor for patients with hepatocellular carcinoma （HCC）. This study aimed to identify the clinico- pathological features, outcomes, and risk factors for ER after HR for small HCC in order to clarify the reasons why ER is a worse recurrence pattern. METHODS： We retrospectively examined 130 patients who underwent HR for small HCC （___30 mm）. Recurrence was clas- sifted into ER （〈2 years） and late recurrence （LR） （_〉2 years）. The clinicopathological features, outcomes, and risk factors for ER were analyzed by multivariate analysis. RESULTS： ER was observed in 39 patients （30.0%）. The sur- vival rate of the ER group was significantly lower than that of the LR group （P〈0.005）, and ER was an independent prognos- tic factor for poor survival （P=0.0001）. The ER group had a significantly higher frequency （P=0.0039） and shorter interval （P=0.027） of development to carcinoma beyond the Milan criteria （DBMC） compared with the LR group, and ER was an independent risk factor for DBMC （P〈0.0001）. Multi-nodularity, non-simple nodular type, and microvascular invasion were independent predictors for ER （P=0.012, 0.010, and 0.019, respectively）.CONCLUSIONS： ER was a highly malignant recurrence pattern associated with DBMC and subsequent poor survival after HR for small HCC. Multi-nodularity, non-simple nodular type, and microvascular invasion predict ER, and taking these factors into consideration may be useful for the decision of the treatment strategy for small HCC after HR.

雷帕霉素对符合米兰标准的肝细胞癌肝移植患者生存的影响

目的探讨雷帕霉素对符合米兰标准的肝细胞癌(HCC)肝移植患者生存的影响。方法回顾性分析2004年11月至2012年1月北京佑安医院移植中心收治的90例符合米兰标准的HCC肝移植患者的临床资料。按患者是否加用雷帕霉素分为两组。对照组45例,初始免疫抑制方案为:他克莫司(FK506)+吗替麦考酚酯(MMF)+甲泼尼龙(Pred);维持期免疫抑制方案为:FK506+/-MMF。雷帕霉素组45例,初始免疫抑制方案同对照组;维持期免疫抑制方案为:FK506+雷帕霉素。比较两组患者术后生存时间、生存率、无瘤生存率和肿瘤复发率。结果至随访结束时,对照组45例,死亡11例,其中因肿瘤复发死亡9例;雷帕霉素组45例,死亡4例,其中因肿瘤复发死亡2例。对照组术后平均生存时间(72.6±5.8)月,明显低于雷帕霉素组[(84.0±4.0)月,差异有统计学意义(P<0.05)。对照组和雷帕霉素组术后1、2、3、5年的生存率分别为86.5%和97.8%(P=0.11),76.5%和97.8%(P<0.05),73.6%和91.2%(P=0.06),73.6%和87.0%(P=0.20);术后1、2、3、5年的无瘤生存率分别为81.6%和97.7%(P<0.05),73.7%和97.7%(P<0.05),73.7%和88.1%(P=0.15),73.7%和88.1%(P=0.15);术后1、2、3、5年的肿瘤复发率分别为13.3%和2.2%(P=0.11),18.6%和2.2%(P<0.05),21.6%和2.2%(P<0.05),21.6%和6.8%(P=0.06)。结论雷帕霉素能够显著提高符合米兰标准的HCC患者肝转移术后生存时间,降低肿瘤复发率并提高其术后生存率。

联合米兰标准及微血管侵犯预测肝移植术后肝癌复发

目的探讨临床因素及肝细胞生长因子基因多态性与肝移植术后肝癌复发的关系。方法收集95例肝癌肝移植患者的临床资料,基因分型肝细胞生长因子标签单核苷酸多态性。比较肝癌复发患者与未复发患者的临床资料及肝细胞生长因子基因型分布差异。Cox回归分析探讨无瘤生存率及总体生存率的独立影响因素。结果移植前甲胎蛋白、单个结节、最大结节直径、大血管侵犯、微血管侵犯和米兰标准与肝移植术后肝癌复发相关。微血管侵犯、米兰标准是肝移植术后肝癌患者无瘤生存率和总体生存率的独立影响因素。结论联合米兰标准以及微血管侵犯可以有效预测肝移植术后肝癌复发。