HBV相关肝病肝移植及移植后乙型肝炎复发的防治

肝移植作为HBV相关肝病患者的治疗曾被许多学者置疑,原因就是HBV感染复发导致肝脏再次损伤,发生纤维淤胆性肝炎和肝硬化,最终导致肝功能衰竭。近10年,抗病毒药物和免疫疗法的普遍采用,大大提高了受体的远期疗效,使HBV相关的终末期肝病和其他病因的终末期肝病一样成为肝移植最好的适应证之一。研究表明,乙型肝炎肝硬化失代偿患者用非移植方法治疗1年、5年、     

双肝移植的临床应用进展

亚洲是乙型肝炎流行高发区,有众多的终末期肝病患者,而肝移植是目前治疗终末期肝病最为有效的手段。由于受传统文化、伦理道德观等观念的影响,尸体器官捐献率一直比较低,器官供需之间的矛盾使得活体肝移植成为挽救终末期肝病患者的重要治疗手段。 双肝移植即一个受体同时接收两个供体的部分肝脏。目前双肝移植绝大多数为活体肝移植。韩国 Lee 等首先报道了双肝移植技术［1］,从两个活体捐献者获得两个肝左叶移植给一个患者。双肝移植由于减少了供体捐肝体积最大程度上保证了供体的安全。     

加强肝移植后乙型、丙型肝炎病毒再感染预防和治疗的研究

我国是病毒性肝炎大国，由乙型肝炎或丙型肝炎导致的终末期肝病，包括失代偿性肝硬化、肝癌及肝功能衰竭患者，已越来越多地接受原位肝移植（OLT）治疗。HBV或HCV相关的终末期肝病患者行肝移植后，其预后很大程度上取决于预防和治疗移植肝的再感染。过去的十几年里，尽管在移植后乙型肝炎与丙型肝炎的防治方面取得长足进步，但仍未能完全控制移植后乙型肝炎或丙型肝炎的复发或再感染，当前尚有许多问题急待解决。     

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随着移植学突飞猛进的发展,肝移植被广泛应用于治疗终末期肝病,并成为目前治疗终末期肝病的最有效方法。我国是肝病大国,肝病患者超过3000万,90%肝移植患者与乙型肝炎(简称“乙肝”)病毒(HBV)感染有关;尚有部分肝移植患者与丙型肝炎(简称“丙肝”)病毒(HCV)感染相关。本文就国内外防治肝移植术后肝炎复发的进展及存在的问题进行探讨。1预防肝移植后肝炎复发的重要性在我国,与肝炎病毒感染相关的急慢性肝病是肝移植的主要适应证,肝移植后肝炎复发是影响肝移植术后长期存活率的主要因素之一,肝移植受体带毒状况严重影响肝脏移植的肝炎复发…     

肝移植术后乙型肝炎复发的处理——13例分析

目的总结和探讨乙型肝炎相关终末期肝病肝移植术后乙型肝炎复发的处理方法。方法回顾性分析我院13例肝移植术后患者发生乙型肝炎再感染或复发后的处理措施及疗效。结果13例患者分别采取拉米夫定改为阿德福韦、恩替卡韦或加大乙型肝炎免疫球蛋白用量的方法,其中5例HBsAg经治疗后转阴,5例HBsAg明显下降,总有效率76.9%。结论肝移植术后HBIG、恩替卡韦、阿德福韦能不同程度控制肝移植术后乙型肝炎复发。     

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.     

乙型肝炎相关性肝移植后乙型肝炎复发的临床特点分析

目的 总结和探讨乙型肝炎相关性终末期肝病患者在肝移植术后乙型肝炎复发的临床特点.方法 回顾性分析2005年4月至2010年4月期间的253例乙型肝炎相关性肝移植患者的术后随访资料.结果 253例肝移植患者中乙型肝炎复发16例,复发率6.32%(16/253),中位复发时间为术后13个月,术后1、3、5年的累积复发率分别...     

山东省立医院器官移植、肝脏外科中心简介

山东省立医院器官移植、肝脏外科中心是山东省规模最大的肝脏移植、肝脏外科专业化科室。主要业务范围为肝移植治疗各种恶性终末期肝病（包括各种原因肝硬化晚期肝功能衰竭、门静脉高压症、上消化道大出血、肝癌、先天性肝病等）。     

拉米夫定联合小剂量乙型肝炎免疫球蛋白预防肝移植术后乙型肝炎复发

目的比较单用拉米夫定和拉米夫定联合个体化小剂量肌肉注射乙型肝炎免疫球蛋白两种方案,预防乙型肝炎相关良性终末期肝病患者肝移植术后乙型肝炎复发的疗效。方法111例因乙型肝炎相关良性终末期肝病患者在肝移植术前根据乙型肝炎免疫球蛋白的可获得性非随机分为单用组和联用组,单用组32例患者在移植术后接受拉米夫定100mg/d单药治疗,联用组79例患者在移植术后接受拉米夫定100mg/d和个体化小剂量肌肉注射乙型肝炎免疫球蛋白(维持血清抗- HBs滴度>100U/L)联合治疗。研究总体中位随访时间为32(1～88)个月,监测患者HBsAg、HBV DNA、抗-HBs和YMDD变异情况,随访患者生存率及乙型肝炎复发率。结果单用组共有5例患者乙型肝炎复发,其中3例发生HBV YMDD变异;肝移植术后1、2、3年累积乙型肝炎复发率分别为7.1%、14.3%、17.9%,患者生存率分别为87.5%、84.4%、74.6%。联合组共有2例患者乙型肝炎复发,且均发生YMDD变异;肝移植术后1、2、3年累积乙型肝炎复发率分别为0、1.8%、5.7%,患者生存率分别为83.5%、80.9%、77.6%。两组患者乙型肝炎复发率之间差异有统计学意义(P<0.05),单用组肝移植术前HBV DNA活跃复制与肝移植术后乙型肝炎复发相关(P<0.05),而联用组两者之间无相关性(P>0.05)。结论个体化小剂量肌肉注射乙型肝炎免疫球蛋白联合拉米夫定与单用拉米夫定相比,能更有效地降低良性终末期乙型肝炎患者肝移植术后乙型肝炎复发的风险。     

山东省立医院器官移植、肝脏外科中心简介

山东省立医院器官移植、肝脏外科中心是山东省规模最大的肝脏移植、肝脏外科专业化科室。主要业务范围为肝移植治疗各种良恶性终末期肝病（包括各种原因肝硬化晚期肝功能衰竭，门静脉高压症，上消化道大出血，肝癌，先天性肝病等）。     

骨髓干细胞治疗肝脏疾病的临床应用进展

近年来随着研究的不断深入,骨髓干细胞移植在治疗急慢性肝功能衰竭、终末期肝病及遗传代谢性肝病等方面有了很大的进展,其在近期疗效、安全性、耐受性等方面获得了肯定,且因其本身的优势(如费用低廉、取材方便、不存在免疫排斥反应等)而越来越受到重视.虽然肝移植是治疗各种终末期肝病的有效方法,但由于供肝来源不足、操作复杂、并发症多、...     

Present status and prospects of living-related liver transplantation

Living-related liver transplantation (LRLT) is a relatively new surgical modality that has developed, in part, to overcome the shortage of available cadaveric livers for transplantation and as a method to provide liver graft implants from living donors for patients end-stage with liver disease in areas where the use of cadaveric livers is not yet practiced or permitted. Since 1988 almost 500 LRLTs have been performed globally. The safety of donors who provide a portion of their liver for grafting is of utmost concern, and only one donor death from this procedure has been reported in the literature. Postoperative survival in recipients depends on their pretransplant physical status, but emergency patients in rapid need of a liver have a poorer survival than elective LRLT patients for whom survival is about 80%. Children and infants are the main recipients of LRLTs, but adult patients particularly in Japan, are increasing in number, and present indications for LRLT surgery include not only cholestatic end-stage liver diseases but also metabolic disorders affecting the liver and emergency LRLTs for fulminant hepatic failure. Many ethical problems relating to the concept of liver transplantation, donor liver source, recipient selection, and reimplantation have yet to be resolved. But we believe that LRLTs and cadaveric liver transplantations are saving lives and that the practice should be continued.     

71例人体原位肝移植对终末期肝病的治疗

目的：探讨我国现阶段人体原位肝移植治疗终末期肝病的经验，并总结围手术期处理体会。方法：回顾性分析自1993年4月至2001年8月我院连续实施的71例人体原位肝移植病人的临床资料。结果：良性终末期肝病患者术后1年生存率达到75％，恶性肿瘤受体的生存时间与生活质量也有了较大改善，围手术期单一应用拉米夫定可以明显减少移植术后HBV再感染，术中不用静脉－静脉转流技术，可以缩短手术时间，减少术中出血和输血量，有利于患者术后恢复，术后胆道并发症的发生率为5．98％，血管并发症的发生率为8．96％。结论：原位肝移植可以成为临床上治疗终末期肝病的一项常规方法。HBV相关性肝病肝移植围手术期应常规应用拉米夫定，不用静脉－静脉转流技术的肝移植在大多数成人肝移植中是安全可行，的尽早诊断胆道和血管并发症，及时采用正确的放射介入技术处理胆道与血管并发症可取得较好疗效。     

Liver transplantation for portal hypertension.

Liver transplantation is among the therapies that may be required for patients with variceal bleeding. The indication for transplantation is end-stage liver disease, not the variceal bleeding per se. Selection of patients is based on full evaluation that includes medical necessity, absence of medical contraindication, and psychosocial suitability. Decision algorithms for variceal bleeding must recognize that transplantation may be the endpoint of treatment, and other treatments should take this into consideration. Specific problems related to prior surgery for variceal bleeding should be defined before transplantation, and management strategies should be determined. The outcome for patients with end-stage cirrhosis and variceal bleeding has been dramatically improved by addition of transplantation to the treatment options.     

Stem cell transplantation for the treatment of end-stage liver disease

The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer,liver diseases, and various types of chronic diseases. Indeed, stem cell-based therapies are effective in many diseases, and provide novel insights into the treatment of end-stage liver disease. Several clinical trials have indicated the efficacy profiles of stem cell transplantation in patients with end-stage liver disease, including liver cirrhosis, liver failure, and liver tumors. Animal models of acute liver failure have also provided important insights into the safety,mechanisms, and efficacy of stem cell therapies. Nevertheless, excitement due to this promising field must be tempered with careful and calculated research. In particular, studies on the quality, safety, and efficacy of stem cell transplantation are needed to ensure that qualified products are tested in well-designed clinical trials and approved by governments. Therefore, further investigations are required to effectively balance the safety with the innovation of stem cell transplantation research toward the effective treatment of end-stage liver disease.     

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??Abstract??HBV-related end-stage liver disease and hepatocellular carcinoma (HCC) are the major indications for liver transplantation in China.With the introduction of hepatitis B immunoglobulin (HBIG) and oral nucleos(t)ide analogues (NAs)??new antiviral therapy has significantly improved the prognosis of liver transplantation.Pre-transplant antiviral therapy will significantly reduce the recurrence rates of HBV infection.All HBsAg-positive patients awaiting liver transplantation for HBV-related end-stage liver disease or HCC should be administered with a potent NA with high barrier to drug resistance to achieve the viral load as low as possible.Additional HBIG administration during the anhepatic phase will achieve a better control of HBV infection.HBIG should be used in combination with NAs post-transplantation to prevent HBV recurrence.As the fact that liver transplant recipients usually need life-long medication to prevent HBV recurrence??it is currently recommended that HBIG can be discontinued in patients under long-term administration of potent NAs with high barrier to drug resistance in combination with HBIG.     

儿童肝移植的现状和未来

儿童肝移植已经成为儿童终末期肝病的标准治疗方法。发展儿童肝移植意义重大。本文从适应证、生存率、手术方式、技术性并发症、免疫抑制治疗、远期生存状况和受体危险度分层等方面对目前儿童肝移植的发展水平进行初步概述,并对未来发展作初步展望。     

Renal diseases and the liver

Many liver diseases coexist with chronic renal disease, because many systemic conditions affect both the liver and the kidneys. Certain liver diseases are also common in patients with chronic renal disease, especially viral hepatitis, either because the renal disease occurs as a complication of viral hepatitis, or the viral hepatitis is acquired as a result of dialysis. Renal tubular dysfunction is also frequently observed with cholestasis. However, liver complications of renal diseases are extremely uncommon, notable examples include nephrogenic ascites and nephrogenic hepatic dysfunction. Nephrogenic ascites can mimic liver cirrhosis with ascites, and it improves with renal transplantation. Nephrogenic hepatic dysfunction is a manifestation of renal cell carcinoma, which settles with the removal of the renal cell carcinoma, but returns with the recurrence of the tumor. In general, the presence of liver disease in patients with chronic renal disease makes management of both conditions more challenging. Viral hepatitis should be treated, if possible, before renal transplant. If cirrhosis is present, renal transplant alone is contraindicated; combined liver and kidney transplantation is indicated in patients with end-stage renal disease and advanced cirrhosis.     

The impact of race on liver transplant outcomes in the MELD era: still more questions than answers

Liver transplantation is a life-saving therapy for patients with end-stage liver disease (ESLD); however, donor livers are scarce. Several studies have demonstrated racial disparities in access to liver transplant as well as patient and graft survival after liver transplantation. These studies used data gathered before the model for end-stage liver disease (MELD) was used to determine priority for liver transplant. In this issue of the journal, Drs. Ananthakrishnan and Saeian examine survival after transplant in the MELD era by race and ethnicity, and show that the racial disparities in posttransplant outcomes persist despite MELD. This study provides further evidence that race, which is likely a proxy for a variety of biological and sociological factors, must be considered in any prognostic model for liver transplantation. The impact of race on liver transplantation outcomes should be evaluated further in a well-designed, multicentered, prospective study.     

Management of primary biliary cirrhosis

Opinion statement Primary biliary cirrhosis is a chronic, progressive disease for which there is no definitive treatment. Ursodeoxycholic acid, however, is of benefit for delaying progression to irreversible end-stage liver disease and prolonging survival free of transplantation. It is, therefore, the standard medical therapy for primary biliary cirrhosis. Orthotopic liver transplantation can be offered for patients with end-stage disease. Other important endpoints of treatment in this condition include management of the long-term complications of cholestasis such as pruritus, osteoporosis, and fat-soluble vitamin deficiencies. Pruritus is best treated with cholestyramine; rifampicin, antihistaminics, opioid-antagonists, and ondansetron can also be tried. Osteoporosis should be treated with calcium and vitamin D supplementation. Bisphosphonates or vitamin K2 may be of additional benefit to decrease the risk of fractures, but this is unproved as of yet. Deficiencies of vitamins A, D, E, and K should be treated with appropriate replacement. Finally, orthotopic liver transplant is indicated for cases of liver failure, intractable pruritus, or severe osteoporosis.