肝脏活检在异基因造血干细胞移植中的应用

目的评价肝脏活检在异基因造血干细胞移植（Allo—HSCT）后肝功能损害患者中的诊断及治疗意义。方法病例选自北京大学人民医院血液病研究所1999年2月至2004年1月所做的10例Allo—HSCT并接受肝脏活检的患者,男5例,女5例。年龄15～56岁（中位34．5岁）。其中白血病8例,骨髓异常增生综合征1例,重症再生障碍性贫血1例。移植方式包括非血缘骨髓移植1例,同胞全相合Allo—HSCT6例,单倍体移植1例,脐带血移植2例。预处理方案,采用全身照射加环磷酰胺2例,非全身照射方案8例。移植物抗宿主病全部采用环胞菌素A加短程甲氨蝶呤加霉酚酸酯方案。移植前供受者常规接受肝功能及乙肝、丙肝病毒检测。10例患者均接受经皮肝穿刺活检,得到肝组织标本分别经苏木素-伊红和Masson染色在光学显微镜下观察及免疫组织化学检测。结果10例患者Allo—HSCT后出现肝功能损害的时间为2～5个月,中位3．8个月。移植前7例患者HBV、HCV检测阳性,移植后仍阳性。移植前后3例患者HBV、HCV检测全部阴性,临床诊断为移植物抗宿主病（GVHD）肝损害。10例患者在出现肝功能损害时,9例伴有不同程度慢性GVHD（cGVHD）其他表现。10例患者均根据临床诊断采用初始治疗后,肝功能改善不好。分别于Allo—HSCT后4～12个月（中位5．5个月）行肝脏活检。病理结果3例肝炎病毒阴性者为cGVHD肝损害,其余7例为肝炎病毒感染合并cGVHD肝损害。3例单纯诊断为cGVHD肝损害患者,经调整抗GVHD药物后,肝功能恢复;其余7例患者采用抗病毒及调整免疫抑制剂等综合治疗,结果2例肝功能恢复并存活。5例死亡,其中2例在治疗中肝功能改善不好,因合并肺部感染死亡,3例因肝功能衰竭,肝昏迷死亡。结论Allo—HSCT后,对于临床诊断肝脏GVHD肝损害而治疗效果不好的患者,肝脏活检可起到鉴别诊断和指导进一步治疗的作用。肝炎病毒感染与GVHD肝损害合并存在者预后差。肝活检对指导治疗具有一定局限性,还需结合临床及病理制订治疗方案。     

Human immunodeficiency virus and hepatitis C virus co-infection

Hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma worldwide, as well as the leading cause of liver transplantations in the United States. As a result of similar modes of transmission, approximately 30% of HIV-infected individuals are co-infected with HCV. Among intravenous drug users, almost 90% of people infected with HIV are also infected with HCV. Because of treatment with highly active anti-retroviral therapy, HIV-infected individuals have improved survival and are no longer suffering from opportunistic infections and malignancy as in years past. As a result, co-infection with HCV has now become a frequent cause of morbidity and mortality in HIV-infected individuals. Furthermore, liver disease secondary to HCV infection is now the leading cause of hospital deaths in HIV-infected people in the US. HIV infection accelerates the course of HCV-related liver disease and viremia. It is less clear whether HCV infection affects the clinical course of HIV; however, HCV-related liver disease can limit many individuals from receiving anti-HIV therapy. HIV/ HCV co-infection is common, and serious. Physicians caring for HIV-infected patients worldwide must now address hepatitis C virus co-infection.     

Clinical Practice Guidelines for Liver Transplantation in Saudi Arabia

The demand for liver transplantation in the Kingdom of Saudi Arabia (KSA) is associated with the country’s high burden of liver disease. Trends in the epidemiology of liver transplantation indications among recipients in KSA have changed over 20 years. Non-alcoholic steatohepatitis has eclipsed the hepatitis C virus in the country due to the effective treatment strategies for HCV. Risk factors for NASH, like type 2 diabetes mellitus, obesity, and hyperlipidemia, are becoming a major concern and a leading indication for liver transplantation in the KSA. There is also a significantly increased prevalence and incidence of genetic adult familial liver diseases in KSA. New immunosuppressive agents and preservation solutions, improved surgical capabilities, and early disease recognition and management have increased the success rate of liver transplant outcome but concerns about the side effects of immunosuppressive therapy can jeopardise long-term survival outcomes. Despite this, indications for liver transplantation continue to increase, resulting in ongoing challenges to maximize the number of potential donors and reduce patient mortality rate while expecting to get transplanted. The Saudi Center of Organ Transplant is the recognized National Organ Donation Agency for transplantation, which renders important support for procurement and allocation of organs. This guidance document aims to help healthcare providers in managing patients in the liver transplant setting.     

肾移植患者环孢素A肝毒性作用的回顾性研究

目的：了解环孢素Ａ在肾移植患者肝功能受损中的作用和长期服用对患者的影响。方法：回顾性分析了３组资料：（１）１９７８年７月至１９８４年应用二联免疫抑制治疗（硫唑嘌呤＋泼尼松）的肾移植患者８３例，１９８５～１９９１年应用三联免疫抑制治疗（环孢素Ａ＋硫唑嘌呤＋泼尼松）的肾移植患者５８０例；（２）１９９４年１月至１９９７年８月进行的肾移植患者５１９例；（３）随访服用环孢素Ａ免疫抑制治疗８年以上患者６８例，     

肝移植后丙型肝炎病毒的再感染

几乎所有丙型肝炎后肝移植患者均出现丙型肝炎病毒(HCV)复发,其发病机制因疾病的不同阶段而不同。影响复发的因素包括HCV基因型、准种、病毒载量、供体和受体HLA匹配情况、复发的时间、供体的年龄等,而免疫抑制剂的使用是最重要的影响因素。由于抗病毒药物价格昂贵、疗效有限,且耐受性差,因此开始治疗的时间仍有争议,目前认为最可能的方案是长效干扰素单独治疗。     

肝肾综合征的治疗进展

肝肾综合征是继发于严重肝功能障碍和门静脉高压基础之上的功能性肾衰竭,病死率极高。其发病机制复杂,目前仍没有确切有效的治疗方法,除对基础肝病的积极治疗外,肝移植是治疗肝肾综合征最好的方法。血管扩张药物因为副作用和缺乏临床研究证据,不再推荐使用。特利加压素疗效较肯定,但撤药易复发。分子吸附再循环系统治疗、经颈静脉肝内门体分流术在改善肾功能方面仍有待进一步研究。本文对近期肝肾综合征的治疗进展作一综述。     

Detection of Replicative Form of HCV RNA in Peripheral Blood Leukocytes and Its Clinical Significance

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肝移植术后早期急性肾损伤预测指标的研究进展

肝移植术是治疗终末期肝病最有效的方法,术后急性肾损伤(AKI)与患者的预后及长期生存密切相关,因此肝移植术后AKI的早期识别与预防尤为关键。由于血清肌酐(SCr)水平易受肾功能损伤以外因素的影响,常在测得血清SCr升高前肾功能早已发生了损伤。近年来在肾损伤评估中比SCr更灵敏、更准确的新型生物指标不断被报道,使肝移植后AKI早期有效的干预成为可能。文章就肝移植术后早期AKI的新型预测生物指标进行综述。     

Hepatitis C viral infection in a Chinese hemodialysis unit

Background The prevalence of hepatitis C virus （HCV） infection among maintenance hemodialysis （MHD） patients varies among countries and among dialysis units within a single country. The present study aimed to investigate the prevalence and characteristics of HCV infection in MHD patients in a Chinese hemodialysis unit.Methods One hundred and ninety-two patients on MHD for an average of （86.1±30.0） months （range 6-181 months） were enrolled in this cross-sectional study. HCV antibody and HCV-RNA were measured in these MHD patients before hemodialysis by enzyme-linked immunosorbent assay （ELISA） and polymerase chain reaction （PCR） methods.According to the result, all the patients were then divided into two groups： GroupⅠwas positive for HCV antibody and/or HCV-RNA （n=32）, and Group Ⅱ was negative for HCV antibody and HCV-RNA （n=160）. The following information was obtained for all the patients： socio-demographic data, history of blood transfusions and kidney transplantation, and some laboratory values. The MHD patients who were positive for HCV antibody and/or HCV-RNA were followed for more than three years. The disease activities were graded into ＂asymptomatic＂ if alanine aminotransferase （ALT） was less than 40 U/L,＂low activities＂ if ALT was 40-79 U/L, and ＂high activities＂ if ALT was equal to or above 80 U/L.Results The prevalence of HCV infection in MHD patients in our dialysis unit in May 2009 was 16.7, which was significantly higher than in general population （3.2%）. Among the 32 MHD patients with HCV positive, 20 patients were positive for HCV antibody but negative for HCV-RNA, eight patients were positive both for HCV antibody and HCV-RNA,four patients were negative for HCV antibody but positive for HCV-RNA. Eleven patients had a history of kidney transplantation and 12 had a history of blood transfusion, which were significantly more than among the MHD patients without HCV. Thirty of the 32 MHD patients were asymptomatic. There were no significant differences in age, aspartate aminotransferase （AST）, ALT, or between HCV-RNA positive group and HCV-RNA negative group. But the dialysis duration in the HCV-RNA positive group was significantly longer than that in the HCV-RNA negative group. All the 20HCV-RNA negative patients were asymptomatic. Two of the 12 HCV-RNA positive patients had low activity. None of the 32 cases with HCV positive markers had cirrhosis.Conclusions A high prevalence of HCV infection in MHD patients is related to blood transfusion and kidney transplantation. Occult HCV infection is present in MHD patients. Chronic hepatitis C among MHD patients is mild in disease activity, and is not progressive, perhaps due to immunological abnormalities in these patients.     

慢性HBV和HCV合并感染患者肝损害的血清学改变

目的了解乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)合并感染的患者肝损害的血清学改变特点。方法收集225例慢性肝病(包括慢性乙型肝炎,慢性丙型肝炎,乙、丙肝病毒合并感染引起慢性肝炎或肝硬化,肝炎后肝硬化)患者的肝穿病理标本;所有病例均常规检测肝功能、血清HBVDNA、HBV血清标志物、血清HCVRNA,抗-HCV。所有肝活检标本均用10%中性福尔马林固定,石蜡包埋,做苏木素-伊红染色,进行肝炎分级分期,HBsAg、HBcAg免疫组化,HBVDNA、HCVRNA原位杂交检测。结果①重度慢性肝炎患者:HBV/HCV合并感染的患者(B加C组)谷-丙转氨酶(ALT)、谷-草转氨酶(AST)、总胆红素(TB)、直接胆红素(DB)水平与HCV单独感染(C组)患者相比差异无显著性(P>0.05),而比HBV单独感染的患者(B组)低(P<0.05)。②非重度慢性肝炎患者:三组的血清学改变差异无显著性(P>0.05)。③C组与B加C组患者的发病年龄相似(P>0.05),但明显大于B组患者(P<0.01)。④单独感染组发病的病程长短差异无显著性(P>0.05),但比合并感染组长,与单纯感染组相比,合并感染组发展为重肝的时间要短(P<0.01)。结论在重度慢性肝炎的患者中,肝功能损害的血清学指标(AST、ALT、TB、DB)不能很好地反映肝内损害严重度。与单纯感染组相比,HBV与HCV合并感染组发展为重度肝炎的时间要短。     

原位肝移植术后早期发生急性肺损伤危险因素的多元Logistic回归分析

目的分析原位肝移植术后早期发生急性肺损伤（ALI）的危险因素，为临床治疗提供参考。方法回顾性分析275例原位肝移植患者围手术期的临床资料，并将患者分为ALI组和非ALI组，以单因素分析筛选出有统计学意义的危险因素，多元逐步Logistic回归分析确定ALI的独立危险因素。结果275例肝移植患者ALI的发生率为9．8％（27／275），总死亡率10．2％（28／275），ALI病死率22．2％（6／27）。Logistic回归分析筛选出术中大量输血（OR=12．12，95％CI 0．958～25．364）、无肝期过长（OR=1．23，95％CI 1．034～1．410）和冷缺血时间过长（OR=22．35，95％CI 1．266～43．421）为原位肝移植术后发生ALI的独立危险因素。结论原位肝移植术后早期发生ALI与大量输血、无肝期过长、冷缺血时间过长关系密切。     

终末期肾病患者丙肝病毒感染与防治进展

终末期肾病由于反复住院、损伤性操作、输血以及需要采用肾替代治疗等原因,HCV感染率远高于普通人群,早期发现、早期隔离及严格的消毒措施可降低HCV感染率。感染者一般症状较轻,仅有少数人出现ALT升高,定期监测抗-HCV及HCVRNA具有重要意义。合并HCV感染者肾移植术后的存活率及移植肾存活率尚存在争议,多数学者均认为存活率及移植肾存活率均明显下降。终末期肾病患者可以应用干扰素治疗,其疗效与普通人群相似或稍优于普通人群,但副作用大,耐受性差,在严格监测利巴韦林血药浓度及不良反应的基础上,可联合应用干扰素和利巴韦林以提高疗效。     

Paediatric liver transplantation: the surgical view

Liver transplantation is the accepted treatment for a wide variety of liver diseases in children. Over the past 10 years a number of innovative surgical techniques have been developed to overcome the shortage of size matched donors particularly in children less than 5 years of age. Graft and patient survival at one year after liver transplantation has continued to improve, and is now over 85% and higher for good risk cases. Complications are relatively common, but provided graft function is satisfactory, long term survival for these children is to be expected. The need for retransplantation has fallen significantly. Causes of early mortality include graft dysfunction and sepsis. Late mortality is due to sepsis, post-transplant lymphoproliferative disease, and non-compliance. Long term survival with good graft function and excellent quality of life is possible for the majority of children undergoing liver transplantation.     

INFLUENCE OF HEPATITIS B AND HEPATITIS C VIRUS INFECTION ON THE OUTCOME OF KIDNEY TRANSPLANTATION

GREAT improvement inkidneytransplantatioovnerthepasttwo decadesisdue tobetterorganprese-rvatio,nimmunosuppression,and patientselectio.1nA major problem influencinrgenalallografotutcome ispre-sence of chronicliverdisease. In thesecases, hepatitiBsvirus(HBV ) and hepatitiCs virus(HCV ) infectionasrethemain causesofhepaticinjur.yReplicatioonfHBV isenhancedunderimmunosuppressionafterrenaltransplantati,oannd li-verinjuryprogressionseems to be greaterforpatientswithchronicHBV infectionthan th…     

Pediatric liver transplantation in 31 consecutive children

Background Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements.
Methods Thirty-one children （≤18 years old） underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old （ranged from 5 months to 18 years） with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson＇s disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard （without venovenous bypass）, 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug （FK506, steroid, and mycophenolate mofetil） immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months.
Results Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus （HBV） or hepatitis C virus （HCV） infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively.
Conclusions The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients＇ age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher surgical skills. The     

同种异体原位肝脏移植13例次临床经验

目的 总结原位肝脏移植经验。方法 对12例患者实施13例次原位肝脏移植(包括1例再次肝移植)．其中5例终末期肝硬化、4例原发性肝癌、1例肝癌术后肝功能衰竭、1例肝豆状核变性、1例慢性肾功能衰竭合并肝炎后肝硬化。手术方式：经典原位肝移植10例，改良背驮式肝移植2例．再次肝移植1例。结果 全组成功9例．最长存活超过2年；围手术期死亡4例，直接死亡原因脑出血1例、急性呼吸窘迫综合征1例、急性肾功能衰竭1例、肝动脉血栓1例。结论 肝脏移植是治疗各种终末期肝病的有效手段，但应严格掌握适应证，减少术后并发症的发生是提高肝移植成功率及长期存活率的关键。     

同种异体原位肝脏移植术的临床应用研究(附9例报告)

目的总结原位全肝移植术的经验教训，以进一步提高肝移植治疗终末期肝病的效果。方法2001年3月～2006年8月，为9例终末期肝病患者实施了原位全肝移植术，其中6例为良性终末期肝病，3例为肝癌患者。前5例实施背驮式肝移植，后4例实施经典式非转流肝移植。结果1例病人存活3年以上，2例病人存活2年以上，1例病人存活1年以上，2例术后3个月，均恢复正常的工作和生活。手术后死亡病例中，1例术后1年9个月死于应用大剂量激素抗排斥反应所致的应激性溃疡大出血。2例巨大肝癌病人分别于术后27d死于肾功能衰竭、高血钾和术后56d死于脑出血。1例小肝癌病人术后出现神经并发症，术后4个月死于脑出血。结论肝移植是治疗终末期肝病的唯一有效方法。     

同种异体原位肝脏移植13例次临床经验

目的 总结原位肝脏移植经验。方法 对12例患者实施13例次原位肝脏移植(包括1例再次肝移植),其中5例终末期肝硬化、4例原发性肝癌、1例肝癌术后肝功能衰竭、1例肝豆状核变性、1例慢性肾功能衰竭合并肝炎后肝硬化。手术方式:经典原位肝移植10例,改良背驮式肝移植2例,再次肝移植1例。结果 全组成功9例,最长存活超过2年;围手术期死亡4例,直接死亡原因脑出血1例、急性呼吸窘迫综合征1例、急性肾功能衰竭1例、肝动脉血栓1例。结论 肝脏移植是治疗各种终末期肝病的有效手段,但应严格掌握适应证,减少术后并发症的发生是提高肝移植成功率及长期存活率的关键。     

Hepatitis C Virus Infection in Haemodialysis Patients: “Wolf in Sheep's Clothing”

Background

170 million people are infected with the Hepatitis C virus (HCV) around the world. Approximately 50%-70% patients infected with HCV develop chronic liver disease. Haemodialysis patients constitute an especially important group with high HCV prevalence. Outbreaks of HCV infection in dialysis units have been documented. Detection of anti-HCV antibodies is a convenient and conventional mode of documentation. However, in this group, it has it''s own caveats.

Methods

48 patients who had undergone or were on haemodialysis (HD) and had undergone a minimum of 15 dialysis sittings were studied. HCV infection was documented both by anti-HCV antibody detection and HCV RNA testing. A comparative evaluation of results by both tests was done.

Results

Out of a total of 48 patients, HCV RNA was detected in 38 (79.16%) and anti-HCV antibodies in 13(27.07%). Out of 48 patients 10(20.83%) were negative for both parameters. 22.91% (11/48) of patients were positive for both HCV RNA and anti-HCV antibody. 56.25% (27/48) were HCV RNA positive but anti-HCV antibodies were not detectable in their sera. 2 patients (04.16%) had a positive anti-HCV antibody status despite HCV RNA being negative. In 20.83% (10/48) both parameters were undetectable.

Conclusion

Chronic liver disease (CLD), particularly due to HCV infection, is a major complication amongst haemodialysis (HD) patients. Without reliable assays for antigenemia and the inability of antibody tests to define viremia in all cases, the detection of viral nucleic acid is necessary for diagnosis of active HCV infection.Key Words: Hepatitis C virus, Haemodialysis     

Marginal grafts increase early mortality in liver transplantation

CONTEXT AND OBJECTIVE: Expanded donor criteria (marginal) grafts are an important solution for organ shortage. Nevertheless, they raise an ethical dilemma because they may increase the risk of transplant failure. This study compares the outcomes from marginal and non-marginal graft transplantation in 103 cases of liver transplantation due to chronic hepatic failure. DESIGN AND SETTING: One hundred and three consecutive liver transplantations to treat chronic liver disease performed in the Liver Transplantation Service of Hospital das Clínicas da Faculdade de Medicina da Universidade de S?o Paulo between January 2001 and March 2006 were retrospectively analyzed. METHODS: We estimated graft quality according to a validated scoring system. We assessed the pre-transplantation liver disease category using the Model for End-Stage Liver Disease (MELD), as low MELD (< 20) or high MELD (>or= 20). The parameters for marginal and non-marginal graft comparison were the one-week, one-month and one-year recipient survival rates, serum liver enzyme peak, post-transplantation hospital stay and incidence of surgical complications and retransplantation. The significance level was 0.05. RESULTS: There were no differences between the groups regarding post-transplantation hospital stay, serum liver enzyme levels and surgical complications. In contrast, marginal grafts decreased overall recipient survival one month after transplantation. Furthermore, low-MELD recipients of non-marginal grafts showed better one-week and one-month survival than did high-MELD recipients of marginal livers. After the first month, patient survival was comparable in all groups up to one year. CONCLUSION: The use of marginal graft increases early mortality in liver transplantation, particularly among high-MELD recipients.