肝癌肝移植术前循环肿瘤细胞检测的预后价值

目的研究分析肝移植术前循环肿瘤细胞(CTC)检测评估预测受者肝癌复发与生存的应用价值。方法收集中山大学附属中山医院于2015年10月至2019年10月期间62例肝癌患者肝移植术前通过Cyttel法检测分析CTC,应用X-tile软件通过Kaplan-Meier法确定术前CTC最佳的截止值,并分析CTC与临床因素的关系;单因素及多因素COX回归分析影响其预后的独立危险因素,采用Kaplan-Meier法描绘肝移植术后无瘤生存期和总生存期的生存曲线。结果确定术前CTC最佳临界值为3个/3.2 ml,将CTC≥3/3.2 mL设置为CTC阳性组,CTC<3个/3.2 ml设置为CTC阴性组;肝移植术前CTC阳性/阴性与术前甲胎蛋白(AFP)水平、最大肿瘤直径、淋巴转移、肝移植标准、分化程度呈显著相关(P<0.05);单因素及多因素COX回归模型法系发现术前CTC个数(HR:1.262,95%CI:1.069~1.489,P=0.006)、微血管侵犯(HR:2.657,95%CI:1.120~6.305,P=0.027)是肝癌肝移植术后无瘤生存期的独立危险因素,而微血管侵犯(HR:3.738,95%CI:1.219-11.459,P=0.027)是影响肝癌肝移植术后总生存期唯一的独立危险因素;术前CTC阳性/阴性与肿瘤复发或转移(未复发、肝内复发与远处转移)差异有统计学意义(χ²=7.790,P=0.020);术前CTC阴性、阳性患者在1年、2年、3年无瘤生存率分别为82.90%、68.70%、58.90%和49.00%、29.40%、22.10%;术前CTC阴性、阳性患者在1年、2年、3年总生存率为85.50%、77.10%、69.79%和64.90%、47.20%、40.50%。术前CTC阴性的无瘤生存率曲线高于CTC阳性,差异有统计学意义(P=0.001);术前CTC阴性的总生存率曲线高于CTC阳性,差异有统计学意义(P=0.005)。结论术前CTC检测对评估肝癌肝移植术后预后具有重要的临床意义及应用前景。     

肝细胞肝癌肝移植受者术后生存及肿瘤复发临床分析

目的比较符合米兰标准和杭州标准的肝细胞肝癌(HCC)肝移植受者术后生存及肿瘤复发情况,分析移植术后生存和肿瘤复发影响因素。 方法回顾性分析青岛大学附属医院器官移植中心2014年2月1日至2018年12月31日符合米兰标准和杭州标准的119例HCC肝移植受者临床资料。符合米兰标准受者79例(米兰标准组),超出米兰标准但符合杭州标准者受者40例(杭州标准组)。所有受者肝移植术后均规律随访,收集受者性别、年龄和手术时间等临床资料。无瘤生存时间以受者移植术后发现肿瘤复发转移为观察终点,累积生存时间以受者移植术后死亡为观察终点。采用Kaplan-Meier法绘制生存曲线,采用log-rank检验比较组间累积生存率和无瘤生存率。采用Cox比例风险模型进行影响累积生存时间和无瘤生存时间的单因素和多因素分析。P<0.05为差异有统计学意义。 结果截至2019年7月31日,119例受者术后中位随访时间为27个月(15～43个月),其中术后因肿瘤复发死亡11例复发转移27例。米兰标准组受者1、3和5年累积生存率分别为98.7%、90.2%和90.2%,杭州标准组分别为97.2%、73.9%和73.9%,差异均无统计学意义(χ²＝0.219、1.598和1.598,P均>0.05)。米兰标准组受者1、3和5年累积无瘤生存率分别为90.3%、82.1%和68.6%,杭州标准组分别为81.6%、56.0%和56.0%,两组受者术后1年和5年累积无瘤生存率差异均无统计学意义(χ²＝1.587和3.707,P均>0.05),3年累积无瘤生存率差异有统计学意义(χ²＝5.543,P<0.05)。多因素分析结果证实术前有无脉管癌栓是影响其累积生存率的独立危险因素,差异有统计学意义(HR＝0.159,P<0.05);术前有无脉管癌栓和病理分化类型是影响无瘤生存的独立危险因素,差异均有统计学意义(HR＝0.338和0.395,P均<0.05)。 结论符合杭州标准的HCC肝移植受者移植术后可获得较好的累积生存率及无瘤生存率,受者术前是否存在脉管癌栓及病理分化程度可以指导移植术后肿瘤复发的预防。     

肝癌肝移植术后复发的危险因素分析

目的探讨原发性肝癌(HCC)肝移植术后肿瘤复发或转移的危险因素。方法回顾性我院2003年4月至2007年11月期间76例HCC患者行肝移植的临床资料,根据随访期间是否有复发分为复发组(n=23)和未复发组(n=53),总结肿瘤复发的特点。结果 76例患者中23例(30.3%)术后复发。单因素分析显示患者性别(P=0.449)、年龄(P=0.091)、术前是否治疗(P=0.958)、肿瘤数目(P=0.212)和是否伴有HBV/HCV感染(P=0.220)与肿瘤的复发无关,而肿瘤包膜完整性(P=0.009)、肿瘤分期(P=0.002)、肿瘤直径(P<0.001)、血管侵犯(P<0.001)以及术前AFP水平(P=0.044)与肿瘤的复发有关,其中肿瘤直径<5.0 cm(P=0.001)和术后2个月AFP水平恢复正常者(P<0.001)1年复发率更低。多因素分析显示肿瘤直径(P=0.001,OR=6.456,95%CI为2.356～17.680)、血管侵犯(P=0.030,OR=10.653,95%CI为1.248～90.910)以及术前AFP水平(P=0.017,OR=2.601,95%CI为2.196～5.658)是肝移植术后肿瘤复发的独立危险因素。结论对于肿瘤直径>5.0 cm、伴有血管侵犯以及术前AFP水平≥400μg/L尤其术后2个月AFP水平仍高于正常者术后需加强监测,必要时尽早给予抗肿瘤治疗。     

原发性肝癌患者手术切除术后早期复发影响因素分析

目的:探讨原发性肝癌(HCC)患者手术切除后早期复发的影响因素。方法:回顾性分析郑州大学第一附属医院2014年1月—2016年1月期间450例经手术切除的HCC患者的临床与随访资料,通过统计学方法分析HCC术后早期复发的影响因素。结果:450例患者中,2年内复发182例(40.4%)。单因素分析结果显示,HCC术后复发与门脉癌栓、术前血清AFP水平、肿瘤数目、最大直径、肿瘤分化程度有关(均P0.05);Cox比例风险回归分析显示,肿瘤数目(RR=2.148,95%CI=1.175～3.924,P=0.013),肿瘤最大直径(RR=1.591,95%CI=1.006～2.518,P=0.047),门脉有无癌栓(RR=1.835,95%CI=1.242～2.709,P=0.001),血清AFP水平(RR=1.722,95%CI=1.141～2.601,P=0.010),肿瘤分化程度(RR=1.463,95%CI=1.071～1.998,P=0.017)均是HCC术后复发的独立因素。通过以上因素建立函数模型对预测HCC术后早期复发的风险程度有一定价值(似然比检验:χ~2=45.727,P0.001)。结论:HCC患者手术切除术后早期复发的影响因素较多,其中门脉癌栓、肿瘤数目、最大直径、肿瘤分化程度、血清AFP水平可能是造成复发的独立危险因素,术前综合评估这些因素对预防术后复发有一定的指导意义。     

超出米兰标准的原发性肝癌肝移植术后预后因素分析

目的探讨影响超出米兰标准的原发性肝癌肝移植术后的预后的主要因素。方法回顾分析2000年9月至2006年9月施行的43例超出米兰标准的HCC肝移植的临床资料和随访结果。用Kaplan-Meier方法计算全组和各组的累积生存率,用Log-Rank检验比较组间生存率的差异。结果随访时间从14个月至55个月,移植术后1、2、3和5年生存率分别为51％、33％、21％和15％;无瘤生存率：移植术后1、2、3和5年无瘤生存率分别为55．1％、37％、13％和5％。生存或复发都不受患者年龄或Child-Pugh分级或肿瘤相关因素（如肿瘤数量、直径和TNM分期）的影响。结论血管侵犯是影响HCC肝移植预后的丰要因素。     

肝移植术后肝癌复发对HBV再感染的影响

目的 探讨肝移植术后肝癌复发对HBV再感染的影响.方法 回顾性分析285例原发病为乙肝相关性疾病且术后随访超过半年的原位肝移植患者资料.结果 285例肝移植患者随访时间为6～59个月,术后HBV再感染10例,再感染率为3.5%.其中9例患者合并肝癌复发,HBV再感染发生于肝癌复发后1～7个月.肝癌复发患者与肝癌未复发和良性肝病患者HBV再感染的差异具有统计学意义.13例肝癌复发或转移灶切除标本中有1例免疫组化染色HBsAg阳性、HBcAg弱阳性.结论 乙肝免疫球蛋白联合核苷类似物是预防肝移植术后乙肝复发的有效治疗措施,肝癌复发是肝移植术后HBV再感染的重要原因.     

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P0.05)。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P0.05)。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。     

肝癌行肝移植术后防止肿瘤复发的策略

自1996年肝癌肝移植米兰标准的发布及应用以来,肝移植在治疗肝癌上取得了良好的效果,5年生存率在60～80%。由于术前外周血潜在肿瘤细胞转移,术中肿瘤的种植以及术后免疫抑制药物的应用,肝癌肝移植术后仍然有较高的复发率,严重影响肝癌肝移植预后,即使符合米兰标准得肝癌行肝移植术后肿瘤复发率也达10%～20%。此外,对于肝癌肝移植术后肿瘤复发的患者,目前尚无有效的治疗手段。     

核苷类似物联合HBIG干预下肝移植后HBV再感染的危险因素及预后分析

目的 探讨肝移植术后在核苷类似物联合低剂量乙肝免疫球蛋白(HBIG)的干预下乙型肝炎病毒(HBV)再感染的危险因素及其预后.方法 回顾性分析340例因HBV相关性终末期肝病行肝移植患者的临床资料.所有患者术前即开始给予核苷类似物控制病情,术中和术后均给予核苷类似物联合低剂量HBIG的预防方案.术后对患者进行定期随访,监测患者的HBV再感染发生率、存活率及预后.记录患者性别、年龄、原发病、术前2周HBV DNA水平、HbeAg水平、YMDD变异以及术后免疫抑制剂和核苷类似物使用情况等指标进行单因素分析,将P<0.1的变量纳入COX多因素回归分析,筛选出影响术后HBV再感染的危险因素.结果 340例患者术后发生HBV再感染33例,再感染率为9.7%,再感染时间为术后(8.4±13.2)个月(2～49个月),术后1、3、5年再感染率分别为7.0%、10%、13%.33例患者HBV再感染后均停用HBIG,并调整核苷类似物的用量,除3例HBV DNA定量为3 log10～5 log10拷贝/ml外,其余均控制在3 log10拷贝/ml以下.340例患者术后1、3、5年存活率分别为89%、83%和82%,其中HBV再感染者分别为94%,87%,81%,未再感染者分别为89%,82%,82%,Log-rank检验显示HBV再感染对患者长期存活率无明显影响(P=0.828).经COX多因素回归分析表明,原发病为原发性肝癌(P=0.035)、HBVDNA定量>5 log10拷贝/ml(P<0.001)是发生HBV再感染的危险因素.进一步分层分析显示,原发性肝癌复发后HBV再感染发生率显著高于未复发者,分别为27.9%和8.7%(P=0.001).结论 原发病为原发性肝癌及术前HBV DNA>5 log10拷贝/ml是影响HBV再感染的高危因素.在核苷类似物联合HBIG预防方案的干预下,HBV再感染对预后影响不大.     

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（...     

Association between hepatitis B and hepatocellular carcinoma recurrence in patients undergoing liver transplantation

BACKGROUND/AIMS: Hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) recurrences affect both patient and graft survivals post-orthotopic liver transplantation (OLT) in HBV patients with HCC. We analyzed the relationship between HBV and HCC recurrence in a large cohort of HBV-OLT patients with versus without HCC. METHODS: Two hundred eighty-seven HBV patients with OLT (72 also with HCC) were included in the study. Mean follow-up in the post-OLT period was 31.7 +/- 24.7 (range, 3-119) months. RESULTS: Post-OLT HBV recurrence observed in 10.1% of patients was more prevalent among the HCC group; 23.6% versus 5.5% in patients with and without HCC, respectively. The mean interval for the development of HBV recurrence was 39.5 +/- 28.5 (range, 2-99) months. Among 72 HCC patients, 8 patients (11.1%) had recurrent HCC, and 7 of them also had HBV recurrence. The mean interval for the development of HCC recurrence was 11.2 +/- 7.85 (range, 2-23) months after OLT. OLT patients with HCC with tumors exceeding the Milan criteria had worse 1-, 3-, and 5-year survival rates than patients with HCC meeting the Milan criteria. HBV and HCC recurrence-free survivals were significantly lower in patients with HCC and HBV recurrence, respectively. In the 7 patients with both HCC and HBV recurrence, mean HBV recurrence time was 9.42 +/- 6.75 months and mean HCC recurrence time was 9.57 +/- 6.75 months. There was a strong correlation between HBV and HCC recurrence times. Cox proportional hazards regression analysis showed that only HCC recurrence was a significant independent predictor of HBV recurrence (P < .001; hazard ratio [HR] = 26.94; 95% confidence interval [CI] = 10.81-67.11). On the other hand, HBV recurrence (P = .013; HR = 5.80; 95% CI = 1.45-23.17) and nodule count (P = .014; HR = 13.08; 95% CI = 1.70-100.83) were significant predictors of HCC recurrence. CONCLUSIONS: HBV and HCC recurrences demonstrate a close relationship in patients with OLT.     

Clinical outcomes of liver transplantation for HBV-related hepatocellular carcinoma: data from the NIH HBV OLT study

Han SH, Reddy KR, Keeffe EB, Soldevila‐Pico C, Gish R, Chung RT, Degertekin B, Lok ASF. Clinical outcomes of liver transplantation for HBV‐related hepatocellular carcinoma: data from the NIH HBV‐OLT study.
Clin Transplant 2011: 25: E152–E162. © 2010 John Wiley & Sons A/S. Abstract: Background: Hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is an indication for orthotopic liver transplantation (OLT) in patients with tumor stage within the United Network for Organ Sharing criteria. The number of patients listed for HBV‐related HCC is increasing, while the number of patients listed for HBV‐related cirrhosis is declining presumptively because of the availability of more effective oral nucleos(t)ide analogues. This study presents the final, long‐term outcome of patients transplanted for HBV‐related HCC in the National Institutes of Health (NIH) HBV OLT Study Group. Results: Ninety‐eight patients (52.4%) in the NIH HBV OLT cohort underwent OLT for HBV‐related HCC. With a mean follow‐up of 36.5 months post‐OLT, 12 (12.2%) patients developed recurrence of HCC. Multivariate analysis did not find a statistically significant role of gender, tumor stage at OLT, pre‐OLT HCC treatment, recurrence of HBV, or duration of HCC diagnosis pre‐OLT in predicting HCC recurrence. Serum alpha‐fetoprotein (AFP) level >200 ng/mL at transplant was found to be statistically significant in predicting HCC recurrence (p = 0.003). HCC recurrence was significantly associated with decreased post‐OLT survival. Conclusion: HCC is the most common indication for OLT in patients with chronic hepatitis B in the era of more effective oral antivirals. Serum AFP at the time of OLT is significantly associated with HCC recurrence.     

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.     

Comparison of clinical outcomes in chronic hepatitis B liver transplant candidates with and without hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) receive a higher MELD score and may undergo liver transplantation (OLT) earlier compared to patients with cirrhosis, potentially decreasing waiting list mortality. However, post-OLT survival may be reduced by recurrence of HCC. We compared clinical outcomes between patients with HBV-cirrhosis and no HCC and patients with HBV-HCC. A total of 279 patients (HBV-cirrhosis = 183; HBV-HCC = 96) in the US HBV-OLT study were followed for a median of 30.2 months from listing. Patients with HCC were older, more likely to be Asian, and had less severe liver impairment than patients with HBV-cirrhosis. Despite a higher rate of OLT in patients with HCC (78.1% vs. 51.4%; P < 0.001), intention-to-treat (ITT) survival (73% vs. 78%) and survival without OLT (82% vs. 79%) at 5 years were similar for patients with and without HCC. Cox regression analysis identified higher albumin, lower MELD, no HCC at listing, and being transplanted to be associated with better ITT survival. Ninety-four patients with HCC (including 19 new HCC) and 75 with HBV-cirrhosis underwent OLT. Post-OLT survival (83% vs. 90%) and HBV recurrence (11% vs. 10%) at 3 years were similar, while disease (HBV and/or HCC) recurrence (19% vs. 10%; P = 0.043) was higher in patients with HBV-HCC vs. HBV-cirrhosis. Disease recurrence was the only independent predictor of post-OLT survival. In conclusion, despite more advanced liver disease and a lower rate of transplantation, ITT survival of patients listed for HBV-cirrhosis was comparable to those with HBV-HCC, possibly related to beneficial effects of antiviral therapy.     

70例原位肝脏移植

目的总结肝脏移植治疗不同终末期肝病的经验,探讨肝移植在治疗肝细胞癌(HCC)和重症乙型肝炎(乙肝)的疗效,以及评价拉米夫定对预防乙肝复发的价值.方法回顾性分析了自1993年4月～2000年12月实施的70例肝移植患者的临床资料.肝移植的主要指征是原发性肝癌(26例)、肝硬化(21例)、重症乙型肝炎(12例)、硬化性胆管炎(4例)以及其它终末期肝病(7例).对12例重症乙型肝炎患者应用拉米夫定治疗.采用多元回归分析确定影响肝移植预后的危险因素.结果54例患者存活1个月以上,16例患者在移植术后30d内死亡,院内存活率为77.1%,肝功能属ChildA级和B级的患者院内存活率明显高于ChildC级患者(P＜0.05),小肝癌患者的疗效优于大肝癌患者.移植前APACEⅢ评分,腹水量以及血肌酐水平与肝移植预后有密切关系.在重症乙肝患者中,9例仍存活、存活时间为2～24个月,拉米夫定可有效地预防肝移植术后乙肝复发,且无明显的副作用.结论本研究结果表明原位肝移植可使部分HCC患者获得治愈,部分病例可获得良好的姑息疗效,病例选择对肝癌肝移植的预后极其重要;结果还提示肝移植是治疗各种终末期肝病的有效手段.同时认为拉米夫定是一种疗效肯定,副作用小的预防肝移植术后乙肝病毒复发的药物.     

肝移植治疗乙肝相关疾病

目的 总结原位肝移植（OLT）治疗乙肝相关疾病的疗效,并评价了拉米夫定对肝移植术后乙肝复发的防治作用。方法 自1993年4月-2000年12月,中山医科大学器官移植中心为54例乙肝相关疾病患者实施了肝移植,其中乙肝坏死后肝硬化17例,为第1组,25例同时合并肝癌者为第2组、其余12例暴发性肝功能衰竭患者为3组。回顾性地分析了3组患者术后存活率、早期死亡原因以及拉米夫定对术后乙肝复发的防治情况。结果 乙肝相关疾病患者肝移植术后早期存活率为75.9%,暴发性肝衰组患者术后早期并发症发生率明显高于其它2组;OLT对小肝癌患者的疗效明显优于大肝癌患者;拉米夫定防治乙肝复发辣效好且未发现副作用。结论 结合拉米夫定,OLT是治疗暴发性乙肝、乙肝肝硬化及小肝癌甚或某些选择性大肝癌患者的有效手段。     

Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria: a meta-analysis of 18,421 patients

BackgroundOutcomes after liver resection (LR) and liver transplantation (LT) for hepatocellular carcinoma (HCC) are heterogenous and may vary by region, over time periods and disease burden. We aimed to compare overall survival (OS) and disease-free survival (DFS) between LT versus LR for HCC within the Milan criteria.MethodsTwo authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria. Meta-analyses and metaregression were conducted using random-effects models.ResultsWe screened 2,278 studies and included 35 studies with 18,421 patients. LR was associated with poorer OS [hazard ratio (HR) =1.44; 95% confidence interval (CI): 1.14–1.81; P<0.01] and DFS (HR =2.71; 95% CI: 2.23–3.28; P<0.01) compared to LT, with similar findings among intention-to-treat (ITT) studies. In uninodular disease, OS in LR was comparable to LT (P=0.13) but DFS remained poorer (HR =2.95; 95% CI: 2.30–3.79; P<0.01). By region, LR had poorer OS versus LT in North America and Europe (P≤0.01), but not Asia (P=0.25). LR had inferior survival versus LT in studies completed before 2010 (P=0.01), but not after 2010 (P=0.12). Cohorts that underwent enhanced surveillance had comparable OS after LT and LR (P=0.33), but cohorts undergoing usual surveillance had worse OS after LR (HR =1.95; 95% CI: 1.24–3.07; P<0.01).ConclusionsMortality after LR for HCC is nearly 50% higher compared to LT. Survival between LR and LT were similar in uninodular disease. The risk of recurrence after LR is threefold that of LT.     

Improved survival outcomes in patients with non‐alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002–2012 United Network for Organ Sharing data

There is an increasing trend of patients with hepatocellular carcinoma (HCC) and non‐alcoholic fatty liver disease undergoing liver transplantation in the US. Our study utilized data from the 2002 to 2012 United Network for Organ Sharing registry to evaluate model for end‐stage liver disease era trends in US liver transplantations focused on patients with non‐alcoholic steatohepatitis (NASH), hepatitis C (HCV), alcoholic liver disease (ALD), and HCC. Survival outcomes were stratified by liver disease etiology and compared across time periods using Kaplan–Meier and Cox proportional hazards models. Patients with NASH were more likely to be women, had higher body mass index (BMI), and had higher prevalence of diabetes and cardiac disease. However, overall long‐term survival was significantly higher in patients with NASH and ALD (p < 0.001). Compared to HCV, patients with NASH had significantly higher post‐transplantation survival (HR 0.69, 95% CI 0.63–0.77), and lower risk of graft failure (HR 0.76, 95% CI 0.69–0.83). Despite having higher BMI and higher prevalence of diabetes and cardiac disease, patients with NASH had better post‐liver transplantation survival compared to patients with HCV or HCC. Patients with ALD also had superior survival outcomes. However, these survival differences were limited to patients without HCC that underwent liver transplantation.     

High Viremia,Prolonged Lamivudine Therapy and Recurrent Hepatocellular Carcinoma Predict Posttransplant Hepatitis B Recurrence†

Hepatitis B virus (HBV) recurrence following orthotopic liver transplantation (OLT) is generally preventable by prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM). However, HBV recurrence sometimes develops despite prophylaxis. This study assessed posttransplant outcomes and identified predictors of HBV recurrence. We analyzed the outcomes of 209 consecutive patients positive for hepatitis B surface antigen who underwent OLT, who received either combination prophylaxis with HBIG and LAM (89.0%) or HBIG monoprophylaxis (11.0%). The median follow‐up was 36.8 months (range, 1.0–84.4). Posttransplant HBV recurrence occurred in 22 patients (10.5%), including 13 patients with drug‐resistant mutations. HBV recurrence was observed in six patients after hepatocellular carcinoma (HCC) recurrence. Independent predictors of HBV recurrence were recurrent HCC (p < 0.001), LAM therapy >1.5 years (p = 0.001) and high HBV DNA titers (≥10⁵ copies/mL) at OLT (p = 0.036). In conclusion, high viremia at OLT and prolonged exposure to LAM should be further stressed as main predictors of HBV recurrence.     

提高原位肝移植术后长期生存率的临床研究

目的 探讨提高原位肝移植术后长期生存率的临床措施。方法 回顾性分析我科3年多来所施行的72例原位肝移植病人术后生存情况、并发症发生的种类及数量，以及诊治处理方法，以探讨成功及失败原因。结果 72例肝移植病人中，原发病为良性疾病50例(其中终末期乙肝肝硬化34例)；恶性疾病22例(其中HCC19例)。术后发生并发症54例次，含因凝血功能紊乱致术后腹腔内继发性出血4例，术前腹水感染未能控制，致术后腹水严重感染2例，激素用量过大致应激性溃疡出血、穿孔1例，胆瘘6例，肺部感染21例，肠道真菌感染5例。全组无原发性肝无功能及血管并发症，随访2～41个月，无远期胆道并发症及慢排发生。住院期死亡6例，随访期死亡6例，目前生存60例，总生存率为83．33％，存活超过1年者32例，最长已3年5个月。结论 ①术中技术的改进及新技术的应用；②采用个体化的免疫抑制方案；③加强术后感染预防与治疗；④加强乙肝复发的预防和治疗；⑤预防肿瘤复发的系列措施，是提高肝移植术后生存率的关键。