重型肝炎

前列腺素El脂微球载体制剂治疗慢性重症肝炎疗效观察，MARS人工肝治疗慢性重型肝炎肝肾综合征疗效观察与护理，肝移植术后胆道系统并发症的原因分析及护理，背驮式原位肝移植及其并发症预防，猪原位肝移植术体外静脉．静脉转流方法的探讨，肝脏移植围手术期凝血功能动态变化及治疗处理，SWH液对大鼠肝脏能量代谢的影响，小型猪原位肝移植的外科技巧及术中管理。     

原位肝移植术后早期并发症护理（附1例报道）

原位肝移植术是现阶段治疗终末期肝病最有效的方法。目前，肝移植术后5年生存率为75％～85％。肝移植术后并发症是直接影响疗效的主要原因。因此，对早期并发症的及时发现治疗和护理是确保肝移植手术成功的关键。     

同种异体原位肝移植14例次治疗经验

目的：总结终末期肝病患者同种异体肝移植手术的临床经验,介绍肝移植供体获取和受体手术的方法和术后处理方案。方法：对13例患者行14次手术(再次肝移植1例),其中乙肝肝硬化并肝癌7例,终末期乙肝肝硬化1例,丙肝肝硬化并“意外癌”1例,重症肝炎肝衰4例(1例为肝移植术后10个月,因乙肝复发,重型肝炎行二次肝移植术)。手术行改良背驮式5例,经典非转流术式9例次,其中1例行减体积肝移植(左肝外叶切除)。结果：手术移植物成活率100％,无原发性移植肝无功能和功能延迟恢复发生。手术成功率：良性终末期肝病和肝癌100％(9／9),重症肝炎为60％(3／5),总成功率为85．7％(12／14)。远期存活8例,存活1年以上5例。结论肝移植是治疗由各种急、慢性肝病导致的终末期肝功能衰竭和肝癌的有效方法。良性终末期肝病和早期肝癌的手术效果良好,明显优于重症肝炎和晚期肝癌。选择适当的手术时机,合理的手术方式,良好的供体质量,术中麻醉管理和术后早期ICU的围手术期管理,术后免疫抑制剂的应用,术后并发症处理是保证手术成功的重要条件。乙肝和肝癌等移植后易复发疾病的控制,对于提高肝移植术后患者的长期存活率非常重要。     

供肝处理对肝移植术后早期胆道并发症的影响

胆道并发症是原位肝移植术后常见的并发症，也是目前导致肝移植失败的主要原因之一。目前，术后胆道并发症的发生率仍高达10％-30％，而且常需要二次手术处理。供肝的质量是术后胆道并发症发生与否的关键。本研究回顾性分析临床资料，观察改进供体处理方法后肝移植术后早期胆道并发症的发生情况。[第一段]     

拉米夫定在肝移植中应用现况

乙型肝炎病毒 (HBV)相关肝病肝移植围手术期存活率与其他肝病相差无几 ,但复发或再感染后病情进展迅速 ,病死率高[1 ,3 ] 。近年发现有效的预防及治疗复发或再感染可改善肝移植的预后。其中认为拉米夫定(lamivudine,heptodin ,贺普丁 )防治疗效较好[1～ 1 0 ] 。在HBV相关肝病肝移植中 ,移植肝的复发或再感染是面临的重要问题。第三军医大学西南医院 1 999年 5月～2 0 0 2年 4月实施肝移植 56例 ,其中 50例为HBV相关肝病 ,在围手术期及肝移植后均常规长期用拉米夫定 ,迄今尚未发现HBV肝炎复发或再感染病例。今结合实践和近年文献 ,对H…     

肝移植与移植肝原发性无功能

原位肝移植已经成为治疗各种不可逆转的终末期肝病可靠的方法。移植后肝脏原发性无功能的发生率很高（达２％￣２３％），是移植术后的主要死亡原因，但其确切机制仍未明了。它可能与供肝的质量、保存再灌注损伤、手术技术、围手术期免疫反应及内毒素血症密切相关。     

肝移植与移植肝原发性无功能

原位肝移植已经成为治疗各种不可逆转的终末期肝病可靠的方法。移植后肝脏原发性无功能的发生率很高(达2％～23％),是移植术后的主要死亡原因,但其确切机制仍未明了。它可能与供肝的质量、保存再灌注损伤、手术技术、围手术期免疫反应及内毒素血症密切相关。     

胆道闭锁患儿肝移植术后并发症分析

目的分析肝移植治疗胆道闭锁患儿术后并发症及预后。方法回顾性分析2006年6月-2014年4月于重庆医科大学附属儿童医院完成初次肝移植的41例胆道闭锁患儿临床资料,其中活体肝移植28例,心脏死亡器官捐献(DCD)供肝肝移植13例。活体与DCD肝移植受者术后随访时间分别为67~90个月和15~56个月,总结围手术期及随访期并发症发生情况及预后。计数资料组间比较采用Fisher's精确概率法。结果 41例肝移植受者围手术期并发症包括:血管并发症、腹腔出血、肠穿孔、排斥反应、感染并发症等。DCD肝移植组肝动脉栓塞(HAT)的发生率明显高于活体肝移植组(P=0.02)。围手术期死亡10例,其中活体肝移植组4例,包括HAT 1例;因HAT再次行DCD肝移植1例,后因原发肝无功能死亡;呕吐窒息1例;多器官功能衰竭1例。DCD肝移植死亡6例,包括HAT 1例;肺部肺炎克雷伯杆菌感染1例;肠漏后感染性休克1例;循环衰竭1例;严重毛细血管渗漏综合征1例;原发肝无功能1例。随访期活体肝移植死亡4例,包括肝静脉狭窄2例;胆道感染1例;胆道狭窄1例。DCD肝移植随访期间未发生死亡及其他并发症。结论胆道闭锁肝移植术后并发症多样,是影响肝移植手术成功率及长期生存率的重要因素,早期预防、早期发现、及时治疗,对改善肝移植患儿预后至关重要。     

肝移植术的常见并发症及处理

目前肝移植在手术技术以及围手术期处理上已基本成熟，并已成为终末期肝病及暴发性肝炎的常规治疗手段。尽管如此，肝移植术后形形色色的并发症仍难以避免，严重时可造成移植物丢失和受者死亡。因此移植术后并发症的成功防治成为提高肝移植受者生存率的重要条件。现将肝移植术后常见并发症的临床表现、诊断、处理做一简要的介绍。     

体外静脉－静脉转流在肝移植手术中的应用

使用离心泵行体外静脉－静脉（Ｖ－Ｖ）转流的技术，成功地应用于２例同种异体原位肝移植手术。结果表明：（１）肝移植手术使用Ｖ－Ｖ转流，腹腔内脏及下肢血液循环得到保证，避免了无肝期酸硷平衡失调和开放循环后电解质的紊乱；（２）使用离心泵能较好地控制转流期间体内外血流量的平衡，维持血流动力学的稳定；（３）血液变温器的使用可防止转流中及术后低温；（４）部分肝素化使激活凝血时间（ＡＣＴ）控制在２００秒左右，既可预防转流中循环管道系统凝血，又可避免因全身肝素化使手术出血增加。     

Genetic alterations in the S gene of hepatitis B virus in patients with acute hepatitis B, chronic hepatitis B and hepatitis B liver cirrhosis before and after liver transplantation.

BACKGROUND: Several studies have shown that hepatitis B immunoglobulin (HBIG) imposes a selection pressure on the hepatitis B virus (HBV) S gene, and that the emergence of mutations in this region would make reinfection after orthotopic liver transplantation (OLT) possible. AIMS: This study was undertaken to analyze the presence of HBV S-gene mutations in the different stages of HBV infection and the relationship between HBIG therapy and the emergence of mutations in liver transplant recipients. METHODS: The frequency and location of mutations in the coding region of the HBV S gene were studied by PCR and direct sequencing in 30 patients (7 with acute self-limited hepatitis B, 16 with chronic hepatitis B and 7 recipients of (OLT) for HBV-related end stage liver disease who became reinfected). RESULTS: The average number of amino acid changes was higher in patients with a more advanced stage of disease, 0.57 mutations/100 positions in acute hepatitis B and 1.57 in chronic hepatitis B (1.28 in HBeAg-positive and 1.8 in anti-HBe-positive patients). The average number of substitutions in the transplanted patients was 2.7 before OLT and 3 after OLT. No amino acid substitutions were detected in the "a" determinant of HBsAg in acute hepatitis B, however, 8 substitutions were observed in 6 chronic patients. In 3 OLT patients, 4 substitutions were observed in samples before and after OLT. One of these patients, who had protective levels of anti-HBs, showed 3 additional new amino acid substitutions after OLT, suggesting escape mutant selection by the effect of HBIG therapy. No changes were observed between the consensus sequences obtained several years before and after transplantation, indicating consensus sequence stability. CONCLUSION: These results show that there is an accumulation of HBV S-gene mutations in HBV-related end-stage liver disease. Prophylaxis with HBIG mainly obtained from acute self-limited hepatitis patients who have a highly homogeneous viral population, may be one factor underlying the reinfection after liver transplantation.     

肝移植术后乙型肝炎病毒再感染的病因与预后

目的了解肝移植后乙肝复发的原因及对预后影响。方法对终末期肝病患者肝移植前后的HBVDNA水平、HBV变异情况和HBV变异前后肝功能变化进行随访检测;术后肝功能和HBVDNA水平出现异常变化时,做肝脏组织活检。所有患者常规术后拉米夫定和乙肝免疫球蛋白治疗。结果2004年4月-2005年12月20例终末期肝病患者在我院进行了肝移植治疗,其中12例为乙肝肝硬化,8例为乙肝慢重肝合并急性肝衰,术后3例死于移植肝无功能,3例失访,14例随访了60-84个月不等,术后1年内,有6例患者出现乙肝病毒变异,其中3例病理证实乙肝复发,且均为乙肝慢重肝合并急性肝衰患者,2例术前HBVDNA分别为〉10^2copies／mL、〉10^6 copies／mL,另外3例乙肝肝硬化仅仅表现乙肝病毒变异,无肝炎复发。结论肝移植术后接受拉米夫定和乙肝免疫球蛋白治疗者,病毒变异是乙肝复发的主要原因,慢重肝合并急性肝衰、术前HBVDNA阳性的病人,随访时应该特别注意术后乙肝的复发。     

乙型肝炎表面抗原阳性供肝在肝移植中的应用

目的 探讨HBsAg阳性供肝在成人肝移植中应用的安全性及其对患者预后的影响.方法 回顾性分析本中心2007年1月至2010年2月23例接受HBsAg阳性供肝的成人肝移植患者临床资料,患者全部为男性,中位年龄42.5岁(29 ～ 61岁),原发病均为乙型肝炎相关终末期肝病,其中13例术前HBsAg、HBeAg和抗-HBc为阳性,10例术前HBsAg、抗-HBe和抗-HBc为阳性.供体HBsAg均为阳性,术后口服恩替卡韦0.5mg,1次/d,静脉滴注乙型肝炎免疫球蛋白(HBIG),术后1周每天滴注2000 IU.术中及术后采用无激素的免疫抑制方案,术后第1、7、14、21、30天检测患者血清HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc、HBV DNA水平,并行肝脏彩色多普勒超声检查.1个月后每月检测及检查1次,并记录患者术后肝功能、肾功能、急性排斥反应、感染、血管并发症、胆道并发症、乙型肝炎复发、肿瘤复发及患者生存等数据.结果 围手术期2例患者死于严重肺部感染,其余21例患者随访至2010年12月(10 ～ 38个月),所有患者术后乙型肝炎未转阴,其中1例患者于术后5个月因胆道缺血再次行肝移植,3例肿瘤患者分别于术后9、14、18个月死于肿瘤复发,18例患者生存,肝功能良好,彩色多普勒超声监测显示肝脏形态、质地良好,HBV DNA监测显示其均为阴性.随访期内,23例患者的生存率为78.3％(18/23),移植肝生存率为73.9％(17/23),未出现乙型肝炎复发所致的肝功能异常、移植肝丢失和病死患者.结论 HBsAg阳性供肝可以安全地应用于乙型肝炎相关终末期肝病的患者.     

Incidence and treatment of hepatic artery complications after orthotopic liver transplantation

AIM: To investigate the incidence and treatment of hepatic artery complications after orthotopic liver transplantation. METHODS: From February 1999 to May 2002, orthotopic liver transplantations (OLT) were performed in 72 patients with end-stage liver diseases with an average age of 40.2±13.6 years (ranged from 11 to 68 years), 56 were males and 16 females. The preoperative evaluation for the 72 patients was performed using duplexsonography, abdominal CT scan, and angiography of the hepatic artery. All donor grafts were perfused and preserved in University of Wisconsin solution at 4℃. OLT was performed with standard techniques with or without a veno-venous bypass. Reconstructions of hepatic artery were performed between the branch patches of gastroduodenal/hepatic or splenic/common hepatic artery confluence of the donors and recipients, and an end-to-end anastomosis between other arterial vessels of the donors and recipients was done. Arterial anastomosis was performed with interrupted 7-0/8-0 monofilament polypropylene suture under 3.5 x Ioupe magnification. Diagnosis of the complications of hepatic artery after OLT was based on the clinical presentations, ultrasound findings and arterial angiography. All patients were followed up regularly for duplex ultrasound scan after discharge. RESULTS: The overall incidence of arterial complications in 72 patients after OLTs was 1.4% (1/72). One 3cm pseudoaneurysm at the side of anastomotic site of hepatic artery was found by urgent arteriogram due to hemoperitoneum secondary to bile leakage after OLT. Subsequently the pseudoaneurysm was successfully embolized and the blood flow toward the donor liver in hepatic artery remained. The overall postoperative 30day mortality rate was 8.33%. The one-year survival rate was 83.72% in 50 patients with benign diseases and was 71.43% in 22 patients with malignant diseases following OLT. No death associated with complications of hepatic artery occurred. CONCLUSION: Careful preoperative evaluations and intraoperative microsurgical technique for hepatic artery reconstructions are the keys in prevention of hepatic artery complications after OLT.     

Post-operative imaging in liver transplantation: State-of-the-art and future perspectives

Orthotopic liver transplantation (OLT) represents a major treatment for end-stage chronic liver disease, as well as selected cases of hepatocellular carcinoma and acute liver failure. The ever-increasing development of imaging modalities significantly contributed, over the last decades, to the management of recipients both in the pre-operative and post-operative period, thus impacting on graft and patients survival. When properly used, imaging modalities such as ultrasound, multidetector computed tomography, magnetic resonance imaging (MRI) and procedures of direct cholangiography are capable to provide rapid and reliable recognition and treatment of vascular and biliary complications occurring after OLT. Less defined is the role for imaging in assessing primary graft dysfunction (including rejection) or chronic allograft disease after OLT, e.g., hepatitis C virus (HCV) recurrence. This paper: (1) describes specific characteristic of the above imaging modalities and the rationale for their use in clinical practice; (2) illustrates main imaging findings related to post-OLT complications in adult patients; and (3) reviews future perspectives emerging in the surveillance of recipients with HCV recurrence, with special emphasis on MRI.     

Genetic alterations in the S gene of hepatitis B virus in patients with acute hepatitis B,chronic hepatitis B and hepatitis B liver cirrhosis before and after liver transplantation

Abstract: Background: Several studies have shown that hepatitis B immunoglobulin (HBIG) imposes a selection pressure on the hepatitis B virus (HBV) S gene, and that the emergence of mutations in this region would make reinfection after orthotopic liver transplantation (OLT) possible. Aims: This study was undertaken to analyze the presence of HBV S-gene mutations in the different stages of HBV infection and the relationship between HBIG therapy and the emergence of mutations in liver transplant recipients. Methods: The frequency and location of mutations in the coding region of the HBV S gene were studied by PCR and direct sequencing in 30 patients (7 with acute self-limited hepatitis B, 16 with chronic hepatitis B and 7 recipients of (OLT) for HBV-related end stage liver disease who became reinfected). Results: The average number of ammo acid changes was higher in patients with a more advanced stage of disease, 0.57 mutations/100 positions in acute hepatitis B and 1.57 in chronic hepatitis B (1.28 in HBeAg-positive and 1.8 in anti-HBe-positive patients). The average number of substitutions in the transplanted patients was 2.7 before OLT and 3 after OLT. No amino acid substitutions were detected in the “a” determinant of HBsAg in acute hepatitis B, however, 8 substitutions were observed in 6 chronic patients. In 3 OLT patients, 4 substitutions were observed in samples before and after OLT. One of these patients, who had protective levels of anti-HBs, showed 3 additional new amino acid substitutions after OLT, suggesting escape mutant selection by the effect of HBIG therapy. No changes were observed between the consensus sequences obtained several years before and after transplantation, indicating consensus sequence stability. Conclusion: These results show that there is an accumulation of HBV S-gene mutations in HBV-related end-stage liver disease. Prophylaxis with HBIG mainly obtained from acute self-limited hepatitis patients who have a highly homogeneous viral population, may be one factor underlying the reinfection after liver transplantation.     

Ten years of experience with liver transplantation for familial amyloid polyneuropathy in Japan: outcomes of living donor liver transplantations

OBJECTIVE: We summarize 10 years of experience with liver transplantation for FAP patients in Japan and review the current opinions regarding this treatment for FAP. METHODS AND PATIENTS: All basic report data on patients at the time of transplantation were registered with the Japanese Liver Transplantation Society (JLTS). Based on the JLST report data, more detailed information on FAP patients was requested from each center. RESULTS: Living donor liver transplantation (LDLT) for FAP patients was first performed in Japan in 1993. LDLT has since been performed in 41 FAP patients, including nine cases of temporary auxiliary partial orthotopic liver transplantation (APOLT). Orthotopic liver transplantation (OLT) from cadaveric donors for FAP patients began in 1999, but only one FAP patient has subsequently undergone this procedure. Of these total of 43 FAP patients, 36 are currently alive: the one-year survival rate of patients after transplantation was 93%, and the five-year survival rate of these cases was 77%. Preoperative clinical severity and the nutritional status of patients are correlated with their outcome after liver transplantation. Domino (sequential) liver transplantation has been carried out in 20 domino recipients with end-stage liver diseases. Of the 20 domino recipients, 12 are currently alive. CONCLUSION: For FAP patients, these outcomes after the operation were very similar to those of OLT from cadaveric donors reported in other countries. Therefore, we concluded that for the treatment of FAP, LDLT from a living donor is equally effective as OLT from a cadaveric donor.     

Efficacy of lamivudine in patients with hepatitis B virus precore mutant infection before and after liver transplantation

OBJECTIVE: Hepatitis B virus (HBV) precore mutant infection is associated with a more severe liver disease and a poorer response to interferon. We evaluated the efficacy and tolerance of lamivudine to induce complete and sustained suppression of viral replication in seven patients infected with HBV precore mutant (HBeAg-/HBeAb+/HBV DNA+) (in three patients mutation at codon 1896 was detected by direct sequencing). METHODS: Of the seven patients, five had decompensated HBV cirrhosis in a replicative phase and were liver transplant candidates (Group A) and two patients underwent orthotopic liver transplantation (OLT) for HBV liver cirrhosis and developed recurrent HBV infection in the grafted liver (Group B). Lamivudine 100 mg daily was administered orally for a period of 6-75 wk. RESULTS: After 6-8 wk lamivudine therapy was well tolerated and successfully suppressed HBV replication to an undetectable serum level of HBV DNA by polymerase chain reaction in six patients. In Group A, two patients underwent successful OLT with no evidence of HBV reinfection 2-14 months later. Lamivudine was continued after OLT with no episodes of rejection. Three patients died before a suitable liver could be found (one remained serum HBV DNA+ after 6 wk of lamivudine therapy). In Group B, 9-14 months after lamivudine therapy both patients developed lamivudine resistance (increased liver enzymes, reappearance of serum HBsAg and HBV DNA [by hybridization]). In both patients liver histology had progressed and in both, mutation at codon 552 of the HBV polymerase gene was detected. CONCLUSIONS: Lamivudine is well tolerated in patients with decompensated liver cirrhosis due to HBV precore mutant infection who are liver transplant candidates. In four patients (80%) potent suppression of viral replication was detected, allowing OLT to be performed. However, post-OLT, a resistant mutant developed under lamivudine therapy. Combination therapy with other antiviral agents should be evaluated to discourage the emergence of lamivudine-resistant mutants.     

Favorable outcome of orthotopic liver transplantation in a patient with subacute liver failure due to the emergence of a hepatitis B YMDD escape mutant virus.

BACKGROUND/AIMS: Patients with end-stage liver disease due to chronic hepatitis B infection in whom a YMDD escape hepatitis B virus (HBV) mutant has emerged under lamivudine treatment are generally denied liver transplantation (OLT). METHODS: We report the case of a male patient who was started on prophylactic treatment with lamivudine in the context of recurrent episodes of HBV reactivation during high dose immunosuppressive therapy for relapsing severe pulmonary sarcoidosis. RESULTS: Following the emergence of a YMDD escape mutant virus under lamivudine treatment, he developed subacute liver failure requiring liver transplantation. The patient was treated with a combination of intravenous hepatitis B immune globulin (HBIG) which was started perioperatively and also continued lamivudine after OLT. Twelve months after OLT, there was no evidence of HBV reinfection of the liver graft with the use of HBIG and lamivudine. CONCLUSIONS: This observation suggests that emergence of the YMDD mutation is not a contra-indication to OLT, providing adequate immunoprophylaxis using HBIG and lamivudine combination therapy.     

Lamivudine and low-dose hepatitis B immune globulin for prophylaxis of hepatitis B reinfection after liver transplantation – possible role of mutations in the YMDD motif prior totransplantation as a risk factor for reinfection

BACKGROUND/AIMS: Reinfection with hepatitis B virus (HBV) after liver transplantation (OLT) is associated with an unfavourable clinical course. Lamivudine/hepatitis B immune globulin (HBIG) combination treatment reduces reinfection rates. However, it is unclear at what time point lamivudine should be started and which HBIG doses are sufficient. METHODS: Twenty-one patients receiving combination treatment were studied. Lamivudine was started up to 16.5 months before OLT and continued thereafter. HBIG was started intraoperatively and continued according to anti-HBs-titers. Median follow-up after OLT was 20 months. RESULTS: Eleven patients received lamivudine pretreatment for >2 (median 6) months due to initial HBV-DNA-positivity (median 749 pg/ml). After initial lamivudine response HBV-DNA increased in two of them to concentrations above 10 pg/ml prior to OLT. Both had developed mutations in the YMDD motif and suffered from HBV reinfection 13 and 75 days postoperatively. Individual HBIG consumption was highly variable (range 787-4,766 lU/month). Twenty-two percent of anti-HBs titers measured before HBIG administration were below 100 IU/l. CONCLUSIONS: Combined reinfection prophylaxis with lamivudine and HBIG is effective in patients with controlled viral replication at the time of OLT. However, pretransplantation lamivudine resistance is a risk factor for reinfection. Low dose HBIG maintenance therapy individualized according to anti-HBs-titers appears to be tenable.