肝移植术后乙型肝炎复发患者的预后分析

目的 分析肝移植术后乙型肝炎复发患者的预后及其相关资料.方法 回顾性分析天津市第一中心医院器官移植中心1998年12月至2009年11月因乙型肝炎相关终末期肝病行肝移植术,且术后接受小剂量乙型肝炎免疫球蛋白联合核苷(酸)类似物预防乙型肝炎复发的1506例患者资料.对其中出现复发病例的资料及其预后进行分析.所有患者术后均行HBV相关血液学检测,检测HBV DNA水平、肝功能,HBV血液学标志物阳性时行肝脏病理学活组织检查,随访至2010年11月.生存分析及复发率采用Kaplan-Meier生存分析,复发率及生存率的比较采用log-rank test检验.结果 共有38例肝移植术后病例确诊为乙型肝炎复发,中位随访时间为45.1个月,非肝癌肝移植患者乙型肝炎中位复发时间为31.8个月(0.3 ～ 72.8个月),肝癌肝移植患者乙型肝炎中位复发时间为13.7个月(0.3 ～ 66.6个月);8例患者检测出HBV耐药基因变异;18例病例接受恩替卡韦或阿德福韦酯挽救治疗,病毒复制转为阴性,肝功能恢复正常;其中22例病例由于肝癌复发、肝功能衰竭及其他原因死亡,16例病例生存.结论 HBV耐药基因变异及肝癌复发是肝移植术后乙型肝炎复发的重要原因,良性肝病肝移植患者乙型肝炎复发后接受阿德福韦酯或恩替卡韦挽救治疗可获得较好预后,而肝癌肝移植术后乙型肝炎复发患者预后较差.     

索拉非尼联合TACE治疗肝癌复发生存期影响因素预测模型建立

<正>原发性肝癌是消化系统常见恶性肿瘤,手术治疗效果欠佳,而肝移植术是目前最有效的治疗方式,但肝移植术后肝癌复发的发生率较高,严重影响患者生存率。射频消融、肝动脉灌注化疗栓塞术(TACE)、索拉非尼等均是肝移植术后肝癌复发的常见干预手段,但干预效果大多不理想^[1,2]。有文献报道索拉非尼联合TACE治疗对于肝移植术后肝癌复发的干预效果优于手术切除、射频消融等,在一定程度上提高生存率,明确影响肝移植术后肝癌复发患者生存期的影响因素,     

肝癌肝移植

随着外科技术的提高和新的免疫抑制剂的使用，使得肝移植的适应证逐渐放宽。对肝癌患者是否适宜作肝移植一直存在争论，一方面，确有部分肝癌患者在接受肝移植术后获得了治愈并长期存活，但另一方面，仍有很多肝癌患者移植术后２年内死于肿瘤复发，中、长期疗效不理想。近年来随着临床资料的积累，人们对肝癌肝移植的认识不断加深，从最初的适应证，后来一度改为禁忌证，然后又变为相对适应证，虽然仍有争议但目前还是认为肝癌是肝移植的适应证之一，只要病例选择适当，加以必要的围手术期辅助治疗以减少术后的复发，肝移植治疗肝癌仍可取得…     

预防肝移植患者慢性乙型肝炎复发抗病毒治疗现状及进展

在中国,因乙型肝炎病毒(HBV)感染相关终末期肝病或者肝癌而行肝移植治疗的病例居于肝移植首位。乙型肝炎免疫球蛋白(HBIG)和口服抗HBV药物的上市及抗病毒治疗的不断发展,显著改善了HBV相关肝移植患者的预后。在肝移植术前进行积极的抗病毒治疗可显著降低术后HBV的复发。所有出现HBV相关终末期肝病或原发性肝癌(HCC)等待肝移植的HBsAg阳性患者,在移植前均应接受强效、有高耐药基因屏障的核苷(酸)类药物(NAs)治疗,在移植前达到尽可能低的血清HBV DNA水平。肝移植术中属于无肝期,加用HBIG可以取得更好的效果。术后需HBIG和NAs联合用药以预防HBV复发。术后抗HBV复发常需终身治疗,长期联合应用强效高耐药基因屏障核苷(酸)类似物和小剂量HBIG后,可逐渐停用HBIG,并最好以强效与高基因耐药屏障药物口服NAs药物单药治疗,已成为目前术后预防HBV复发的重要推荐方案。     

利用基因表达谱预测肝癌术后复发：机遇与挑战

术后复发是延长肝癌患者术后生存时间最大的障碍，肝癌根治切除术后3a和5a的复发率分别高达50％和70％。因此，预防和治疗肝癌术后复发是改善肝癌患者预后的重中之重。目前，虽然行之有效的预防肝癌复发的措施尚未出现，但许多研究已经提示无选择地使用术后化疗等预防措施，可能反而会使部分患者的生存时间缩短。这些现状加剧了对肝癌术后复发预后指标、临床分期体系或者预测模型的需求，以指导患者的术后治疗。     

34例肝移植患者术后生存影响因素分析

目的总结肝移植患者术后生存情况,分析影响肝移植术后长期生存的因素。方法回顾分析2002年9月-2014年8月新疆医科大学第一附属医院完成的34例肝移植病例,统计生存率,分析并发症、死亡原因。生存率估计采用Kaplan-Meier法。结果本组1、3、5年实际生存率达到82.8%、64.4%和50.9%。Child-Pugh A级与B/C级患者1、3和5年生存率比较差异均无统计学意义(P值分别为0.756、0.486、0.261)。尸体肝移植患者与活体肝移植患者术后1、3、5年生存率比较差异均有统计学意义(P值分别为0.01、0.006、0.006)。结论有选择地实施肝移植可以取得良好疗效。肝癌复发、胆道吻合口狭窄、免疫抑制剂副作用是影响本组肝移植患者术后长期生存的因素。     

乙型肝炎相关性肝病肝移植术后乙型肝炎复发的预防

肝移植是目前治疗急慢性终末期肝病最有效的方法.近10年来,肝移植技术和器官保存方法的改进以及手术后免疫抑制治疗的进展,肝移植术后长期生存成为可能.我国是肝炎大国,尤以乙型肝炎居多,与乙型肝炎相关的肝炎后肝硬化以及肝癌患者成为我国肝移植患者的主体.     

HBV DNA载量对乙型肝炎相关肝癌手术治疗效果的影响

HBV感染在我国高度流行,长期HBV DNA高载量患者可进展为肝硬化进而导致肝癌的发生。目前,手术仍是治疗乙型肝炎相关肝癌的主要方法。大量研究表明,HBV DNA载量是影响乙型肝炎相关肝癌患者术后肝功能恢复、术后并发症的发生、肝癌复发及肝移植是否成功的重要因素。其机制可能与高HBV DNA载量和HBV再激活相关。通过抗病毒治疗使HBV DNA载量保持一定的低水平状态可改善乙型肝炎相关肝癌患者的预后。综述了术前、术后不同HBV DNA载量对乙型肝炎相关肝癌手术治疗效果的影响,旨在为研究治疗肝癌患者提供参考。     

肝癌患者对肝动脉化疗栓塞治疗的反应与肝移植预后的关系

目前,在患者选择合适的前提下,肝移值已成为治疗肝脏恶性肿瘤的重要手段之一[1].但肝癌患者肝移植术后较高的复发率,也严重影响着患者移植术后的长期生存[2].本研究的目的在于探讨不同肝癌患者移植前对肝动脉化疗栓塞(TACE)治疗的反应与肝移植后患者预后的关系.     

经肝动脉化疗栓塞术在原发性肝癌治疗中的应用

原发性肝癌是我国第4位常见恶性肿瘤及第3位肿瘤致死病因,目前仅20%的肝癌患者可以行根治性手术切除。许多临床研究证实经肝动脉化疗栓塞术(TACE)在抑制肿瘤生长、复发,提高患者的生存率,改善预后等方面具有良好的效果。从TACE治疗原发性肝癌的适应证以及TACE在肝癌术前的新辅助治疗、肝癌术后的辅助治疗、肝癌术后复发治疗、肝移植前的桥接治疗中的应用等方面进行了综述。     

Hepatectomy for hepatocellular carcinoma in the era of liver transplantation

The aim of management of hepatocellular carcinoma (HCC) is to improve the prognosis of the patients by radical resection and preserve remnant liver function. Although liver transplantation is associated with a lower tumor recurrence rate, this benefit is counteracted by long-term complications. Therefore, hepatectomy could be the first choice of treatment in selected patients with HCC. However, the higher frequency of tumor recurrence and the lower rate of resectability after hepatectomy for HCC led to an unsatisfactory prognosis. New strategies are required to improve the long-term outcome of HCC after hepatectomy. In this paper, we introduce some strategies to increase the low rate of resectability and reduce the high rate of tumor recurrence. Some aggressive treatments for tumor recurrence to extend long-term survival are also involved. We believe that hepatectomy combined with other therapies, such as portal vein embolization, transarterial chemoembolization, radioembolization, antiviral treatment, radiofrequency ablation and salvage transplantation, is a promising treatment modality for HCC and may improve survival greatly.     

Treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and is the third highest cause of cancer-related mortality. HCC usually develops in patients with chronic liver disease, particularly in those who also have cirrhosis. The possibility of curative treatment depends on both the stage of tumor and liver function. Effective treatments for HCC include percutaneous ablation, surgical resection, and liver transplantation. Both percutaneous ablation and surgical resection provide a high rate of complete responses and are assumed to improve survival that should exceed 50% at 5 years. Liver transplantation results in a better survival rate, and is not contraindicated by advanced liver dysfunction. However, its application is limited by the scarcity of donor organs. Treatments for advanced HCC include transarterial chemoembolization and chemotherapy. Although short-term prognosis of HCC patients has improved recently due to advances in early diagnosis and treatment, long-term prognosis is as yet far from satisfactory due to frequent recurrence. Prevention of recurrence of HCC remains one of the most challenging tasks in current hepatology.     

Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation

Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral Published online: January 27, 2019 recurrence after LT.Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.     

Targeting of circulating hepatocellular carcinoma cells to prevent postoperative recurrence and metastasis

Currently,the main treatment for hepatocellular carcinoma(HCC)involves the surgical removal of tumors or liver transplantation.However,these treatments are often not completely curative,as they are associated with a risk for postoperative recurrence and metastasis.Circulating tumor cells(CTCs)are increasingly recognized as the main source for recurrence and metastasis after radical hepatectomies are performed.Many studies have demonstrated the association between the presence of either pre-or postoperative CTCs and an increased risk for HCC recurrence.To improve the therapeutic outcome of HCC,a personalized,comprehensive and multidisciplinary approach should be considered,involving the application of appropriate diagnostic and therapeutic measures targeting HCC CTCs in different stages throughout the course of treatment.This article proposes some HCC CTC-based strategies for the treatment of HCC,including the monitoring of HCC CTCs before,during and after radical hepatectomy,therapeutic targeting of HCC CTCs,prevention of the generation and colonization of CTCs,as well as the use of CTC indexes for the selection of indications,prediction of prognoses,and planning of individualized therapeutic regimens.Innovation and technological development of therapies targeting CTCs,as well as their translation into clinical practice,will help to effectively reduce postoperative recurrence and metastasis,and significantly prolong the survival of HCC patients.     

Preventive effect of regional radiotherapy with phosphorus-32 glass microspheres in hepatocellular carcinoma recurrence after hepatectomy

AIM： To evaluate the preventive effects of phosph- orus-32 glass microspheres （P32-GMS） in the recurrence of massive hepatocellular carcinomas （HCCs） after tumor resection. METHODS： Twenty-nine patients with massive HCCs received local P^32-GMS implantation after liver tumors were removed, while the other 38 patients with massive HCCs were not treated with P^32-GMS after hepatectomies. The radioactivity of the blood, urine and liver were examined. The complications, HCC recurrence and overall survival rates in the patients were analyzed. RESULTS： P^32-GMS implanted in the liver did not cause systemic absorption of p^32. There were no significant differences of postoperative complications between the patients with and without P^32-GMS treatment. The shortterm （six months and 1 year） and long-term （2, 3 and over 3 years） recurrence rates in patients who received P^32-GMS radiotherapy were significantly decreased, and the overall survival rates in this group were significantly improved. CONCLUSION： P^32-GMS implantation in the liver can significantly decrease the postoperative recurrence and improve the overall survival in HCCs patients after hepatectomy. This therapy may provide an innovative method in prevention of HCC recurrence after operation.     

Clinical analysis of patients with hepatocellular carcinoma recurrence after living-donor liver transplantation

AIM: To evaluated patterns and outcomes of hepatocellular carcinoma(HCC) recurrence after living donor liver transplantation(LDLT).METHODS: From 2001 to 2014, 293 patients underwent LDLT for HCC at our transplant center. We retrospectively reviewed 54(18.4%) patients with HCC recurrence after LDLT. We evaluated patterns and outcomes of HCC recurrence after LDLT, with particular attention to the Milan criteria at transplantation, treatments for HCC-recurrent patients, and factors related to survival after HCC recurrence. Furthermore, we evaluated the efficacy of combination treatment of sorafenib and an mT OR inhibitor.RESULTS: The 1-, 2-, and 3-year overall survival rates after HCC recurrence were 41.1%, 20.5%, and 15.4%, respectively. The median time interval between LDLT and HCC recurrence was 6.5 mo. Although recurrence rates according to the Milan criteria at LDLT were significantly different, HCC recurrence patterns and survival rates after HCC recurrence were not significantly different between the two groups. Time to recurrence 12 mo(P = 0.048), multiple recurrences at HCC recurrence(P = 0.038), and palliative treatment for recurrent tumors(P = 0.003) were significant independent prognostic factors for poor survival after HCC recurrence in a multivariate analysis. The combination treatment of sorafenib and sirolimus showedsurvival benefits in the palliative treatment group(P = 0.005).CONCLUSION: Curative treatment for recurrent HCC after LDLT is the most important factor in survival rates after HCC recurrence and combination treatments of sorafenib and an m TOR inhibitor could have survival benefits in patients with HCC recurrence after LT in the palliative treatment group.     

Surgical treatment of intra hepatic recurrence of hepatocellular carcinoma

Recurrence after hepatocellular carcinoma(HCC) is frequent.Currently,there are no recommendations on therapeutic strategy after recurrence of HCC.Whereas the 5 year-recurrence rate after resection of HCC is 100%,this drops to 15% after primary liver transplantation.Repeat hepatectomy and salvage liver transplantation(SLT) could be performed in selected patients to treat recurrent HCC and enable prolonged overall survival after treatment of recurrence.Other therapies such as local ablation,chemoembolization or sorafenib could be proposed to those patients unable to benefit from resection or SLT.A clear definition of the place of SLT and "prophylactic" liver transplantation is required.Indeed,identifying risks factors for recurrence at time of primary liver resection of HCC may help to avoid recurrence beyond Milan criteria and non-resectable situations.In this review,we summarize the recent data available in the literature on the feasibility and outcomes of repeat hepatectomy and SLT as treatment for recurrent HCC.     

Impact of antiviral therapy on post-hepatectomy outcome for hepatitis B-related hepatocellular carcinoma

The outcome after curative resection for hepatocellular carcinoma (HCC) remains unsatisfactory due to the high recurrence rate after surgery. In patients with hepatitis B virus (HBV)-related HCC, which is the majority of patients with HCC in Asia, a high viral load is a strong risk factor for HCC recurrence. It is logical to believe that antiviral therapy may improve the post-operative outcome by promoting viral clearance and hepatocyte regeneration, as well as improving residual liver volume in HCC patients with hepatitis B. However, the effect of antiviral therapy on clinical outcomes after liver resection in patients with HBV-related HCC remains to be established. There are two main groups of antiviral treatment for HBV-oral nucleos(t)ide analogues and interferon. Interferon treatment reduces the overall incidence of HBV-related HCC in sustained responders. However, side effects may limit its long-term clinical application. Nucleos(t)ide analogues carry fewer side effects and are potent in terms of viral suppression when compared to interferon and are typically implemented for patients with more advanced liver diseases. They may also improve the outcome after curative resection for HBV-related HCC. There are increasing evidence to suggest that antiviral therapy could suppress HBV, decrease the perioperative reactivation of viral replication, reduce liver injury, preserve the liver function before and after operation, and may lower the risk of HCC recurrence. After all, antiviral therapy may improve the survival after liver resection by reducing recurrence and delaying the liver damage by the virus, resulting in a higher chance of receiving aggressive salvage therapy during HCC recurrence.     

Liver transplantation for solitary hepatocellular carcinoma less than 3 cm in diameter in Child A cirrhosis

Liver transplantation for hepatocellular carcinoma (HCC) is the treatment of choice for patients with unresectable tumors within the Milan criteria associated with Child B or C cirrhosis. Liver transplantation provides the best cure for both the HCC and the underlying cirrhosis. In recent years, some authors have advocated liver transplantation even for resectable early HCC associated with Child A cirrhosis, leading to a controversy of whether resection or transplantation should be the first-line therapy for patients with small HCC in Child A cirrhosis. Recent studies comparing liver resection and transplantation for early HCC demonstrated similar long-term survival of 60-70%, but liver transplantation is associated with a lower tumor recurrence rate. However, the current shortage of deceased donor liver grafts limits the applicability of liver transplantation for HCC. The use of live donor liver transplantation for patients with a small solitary HCC in Child A cirrhosis that is resectable may not be justified ethically because of the potential risk to the donors. Patients put on a transplantation waiting list run a significant risk of tumor progression and dropout, while liver resection is immediately applicable to all. Advocating primary liver transplantation for patients with early HCC associated with compensated cirrhosis will increase the waiting time for transplantation and further increases the chance of dropout. Resection first and salvage transplantation for recurrent tumors or liver failure is an alternative strategy that may reduce the use of liver grafts. However, the long-term survival result of such a strategy compared with primary liver transplantation remains unclear.     

Salvage liver transplantation in the treatment of hepatocellular carcinoma: a meta-analysis

AIM: To evaluate survival and recurrence after salvage liver transplantation (SLT) for the treatment of hepatocellular carcinoma (HCC) compared with primary liver transplantation (PLT) using a meta-analysis.METHODS: Literature on SLT versus PLT for the treatment of HCC published between 1966 and July 2011 was retrieved. A meta-analysis was conducted to estimate pooled survival and disease-free rates. A fixed or random-effect model was established to collect the data.RESULTS: The differences in overall survival and disease-free survival rates at 1-year, 3-year and 5-year survival rates were not statistically significant between SLT group and PLT group (P > 0.05). After stratifying the various studies by donor source and Milan criteria, we found that: (1) Living donor liver transplantation recipients had significantly higher 1-year survival rate, lower 3-year and 5-year survival rates compared with deceased-donor liver transplantation (DDLT) recipients. And in DDLT recipients they had better 1-year and 5-year disease-free survival rate in SLT group; and (2) No difference was seen in 1-year, 3-year and 5-year survival rates between two groups who beyond Milan criteria at the time of liver transplantation.CONCLUSION: SLT can be effectively performed for patients with recurrence or deterioration of liver function after hepatectomy for HCC. It does not increase the perioperative mortality and has a similar long-term survival rates compared to PLT.