152例肝移植术后肝功能异常的肝活检

目的评价肝活检在明确肝移植术后肝损害病因中的作用，分析组织学诊断存在误差的常见原因，进一步提高肝活检的准确性，以利临床治疗。方法260例肝活检来自于152例肝移植受者，术后出现临床无法解释的肝功能异常，肝功能检测结果高于正常值的2倍以上。回顾组织学改变及最终的临床诊断，评价相符程度。结果大部分的组织学诊断与最终的临床诊断相符，有7例组织学改变为胆管炎后经进一步临床检查证实4例为血管并发症、2例为败血症、1例为保存性损伤。2例组织学诊断为保存性损伤的病例后证实为药物性肝损害。结论移植后肝活检可明确许多肝功能异常的原因；评判病变的严重程度，指导临床治疗；对一些复杂病例应将以往的活检和整个临床病程、其他实验室检查及影像学检查进行综合考虑，可提高诊断的准确性。     

药物性肝炎34例临床特点及相关因素分析

目的 通过分析34例药物性肝炎的临床特点和相关因素为临床安全用药、规避药物造成肝损害的不良反应提供依据.方法 对2004～2007 年收治的已经确诊为药物性肝炎的34例患者的临床和组织学资料进行回顾性总结分析.结果 34例患者均有肝功能损害,多数有不同程度的乏力、纳差、恶心、黄疸,部分病例有嗜酸细胞增高、单核细胞数增多;中药致肝损伤占47.1%;女性、年龄大者、药物过敏者发病率较高;皮肤病用药、保健药、中药造成的肝损害有上升趋势.结论 药物性肝炎与病毒性肝炎临床表现相似,淤胆型多见,重型肝炎发病率较低.性别、年龄、特异性体质等与药物性肝炎发生有关,中药所致肝损伤应引起重视.     

肝移植术供体肝脏及其肝穿活检临床病理观察分析

目的 探讨肝移植术时供体肝脏的病理组织学变化与其移植术后肝脏病理改变的关系以及对预后的影响.方法 该研究对87例肝移植术供肝零时活检和术后肝脏活检标本进行病理组织观察分析.结果 (1)87例供肝零时活检肝细胞变性100%;(2)肝窦内皮细胞损伤41.3%;(3)肝细胞脂肪变性18.3%;(4)肝细胞坏死10.3%.结论 供肝肝细胞变性最常见,大多可逐渐恢复.肝窦内皮细胞损伤是观察缺血再灌注损伤的重要指标.中到重度小泡性肝细胞脂肪变是可用的.肝移植术后肝细胞坏死有逐渐加重、范围逐渐增大的趋势时,可使移植肝功能丧失的危险性增加.肝移植术零时供肝活检及术后肝活检的对比观察具有十分重要的诊断价值.     

肾移植术后乙型肝炎病毒相关性纤维化淤胆性肝炎

目的 探讨肾移植术后乙型肝炎病毒相关性纤维化淤胆性肝炎的临床及组织学特征。方法 回顾观察了3例肾移植术后乙型肝炎病毒相关性纤维化淤胆性肝炎患者的临床特点，并对其肝穿刺组织进行HE、浸银染色及乙型肝炎病毒核心抗原（HBcAg)免疫组织化学染色观察。结果 3例患者均表现为进行性肝功能衰竭，血清转氨酶仅轻度上升；汇管区广泛纤维化，毛细胆管及肝细胞内胆汁淤积明显，炎性细胞浸润轻，肝细胞乙型肝炎病毒核心抗原（HBcAg)强表达。结论 肾移植术后的乙型肝炎病毒相关性纤维化淤胆性肝炎是一种特殊的、致死性病毒性肝炎；乙型肝炎病毒无症状携带者肾移植术后应密切监测肝功能的变化。     

45例老年非病毒性肝炎患者肝功能异常临床分析

目的探讨老年非病毒性肝炎患者肝功能异常病因及临床特点。方法检测甲～戊型肝炎病毒血清学标志物、EB病毒等非嗜肝病毒抗体及自身抗体,并行腹部B超或CT等影像学检查,对病因及临床表现进行分析。结果老年人非病毒性肝炎患者肝功能异常的常见原因有胆源性肝损、非肝炎病毒感染、药物性肝损、心源性肝损等,其中胆原性肝损害和非肝炎病毒感染伴肝损共27例,占60%。老年肝功能异常患者常见症状有乏力、纳差、尿黄。肝功能指标中,白蛋白降低、白球比例倒置、γ球蛋白升高等相对明显。结论老年非病毒性肝炎患者肝功能异常病因以胆原性肝损害和非肝炎病毒感染伴肝损为多,其他原因引起的肝功能异常亦不容忽视。     

肝移植术后急性排斥反应的病理诊断——200例次肝穿刺活检的病理组织学分析

目的观察同种异体肝移值术后急性排斥反应病理组织学表现,探讨相关的病理鉴别诊断.方法对136例(200例次)同种异体肝移植术后肝组织穿刺活检明确诊断为急性排斥反应的病理组织学资料进行回顾性分析.结果同种异体肝移植术后的急性排斥反应病理组织学表现为:汇管区内炎细胞浸润136例(200例次);小叶间静脉和(或)中央静脉内皮炎116例(170例次);小叶间胆管上皮变性和(或)炎细胞浸润136例(200例次);肝细胞和毛细胆管淤胆103例(151例次);肝细胞水肿和气球样变性83例(126例次);肝细胞嗜酸性变和点、灶性坏死76例(161例次).结论同种异体肝移植术后肝组织穿刺活检的病理组织学变化对急性排斥反应的诊断及术后各种并发症的鉴别诊断具有重要价值.     

家兔肝缺血性损伤时的血液粘度变化及蝮蛇抗栓酶的保护作用研究

用毛细管式粘度计检测３５只日本大耳白兔肝血流阻断前后的血液粘度、血浆粘度、红细胞压积及纤维蛋白原含量，同时进行肝组织学及肝功能检查。结果显示：与正常对照组（ｎ＝１０）比较，第一肝门血流阻断３０分钟后单纯缺血组（ｎ＝１３）家兔的血液粘度、血浆粘度及红细胞压积显著升高，肝组织学及肝功能出现明显损伤性改变，而蝮蛇抗栓酶组（ｎ＝１２）家兔的血液粘度无明显升高，肝组织学及肝功能损害轻，恢复快。提示肝急性缺血可引起家兔血液粘度、血浆粘度及红细胞压积显著升高，并伴有肝细胞结构和功能的进行性损害。蝮蛇抗栓酶具有降低血液粘度和改善微循环的作用，可以作为肝脏急性缺血情况下的肝脏保护剂。     

肝移植后无症状性肝动脉血栓形成一例

目的 探讨导致移植肝动脉阻塞后无症状的可能原因。方法 通过肝功能监测、彩色多普勒超声、肝动脉造影、肝组织活检以及胆道造影等手段追踪观察肝动脉血栓形成的临床经过，综合分析导致“无症状”的各种可能因素。结果 肝移植术后第4d肝动脉吻合出现血栓形成，至20d肝动脉接近完全阻塞；肝组织学检查见肝内胆汁淤积、肝细胞水样变性、小胆管上皮细胞萎缩以及汇管区纤维化等病理学改变。肝功能检查提示除γ0谷氨本主酶和碱笥磷酸酶升高之外，肝功能恢复顺利。术后71d血管造影显示肝动脉完全阻塞，但有侧枝循环建立和门静脉代偿性扩张。术后患者始终未出现肝动脉阻塞所特有的临床症状。结论 侧枝循环的建立和门静脉的代偿，使移植肝得以存活；术后2周之内经常进行彩色多普勒超声检查对肝动脉血栓形成的早期诊断有帮助。     

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.……     

药物性肝损害诱发重型肝炎20例报道

药物性肝损害是指药物在治疗过程中,肝脏由于药物的毒性损害或对药物的过敏反应所致的炎症和损伤,也称为药物性肝炎.     

肝移植术后排异反应的诊断和鉴别诊断

目的 探讨肝移植术后排异反应的诊断和鉴别诊断标准。方法 对于5例肝移植术后出现并发症的病人，进行了临床表现、实验室检查以及肝脏活检病理检查的综合分析，寻找其临床规律和组织学特征。结果 （1）急、慢性排异反应在临床表现和病理所见上均有其特征性改变和诊断标准。（2）其他并发症，如纤维化胆汁淤滞性肝炎和肝动脉血栓形成，也有各自的临床病理特点。（3）肝移植术前应做供肝质量评定。结论 了解和掌握排异反应的诊断标准、鉴别诊断要点以及其他并发症的临床病理特征非常必要。     

Significance of C4d deposition in the diagnosis of rejection after liver transplantation

C4d immunohistochemical staining of liver allograft biopsies was performed to assess its relationship to other pathological changes in the liver. C4d deposition was detected in 69.2% of liver graft biopsies from patients under going rejection, 33.3% of liver graft biopsies from patients with hepatitis B relapse after transplantation, and 28.6% of liver biopsies from patients with hepatitis B. When rejection occurred C4d deposition was located in the vascular walls of portal areas and hepatic sinusoidal walls. Examination of biopsies from patients with hepatitis B relapse after transplantation or hepatitis B infection showed C4d deposition only in the vascular walls of the portal area. C4d deposition in both vascular walls of portal area and hepatic sinusoidal walls was detected in only one of 12 ischemia-reperfusion damage cases. Repeated biopsy of the same patient 1 month later revealed acute cellular rejection. No C4d deposition was found in biopsies from a patient with bile duct occlusion after liver transplantation. C4d might serve as a sensitive marker for the diagnosis of liver rejection.     

儿童肝移植术后罕见药物性肝损害1例报道并文献复习

目的探讨儿童肝移植术后药物性肝损害的诊疗经验。方法回顾性分析1例小儿肝移植术后药物性肝损害病例的临床资料并进行文献复习。结果患儿于肝移植术后1年4月余出现肝功能异常,其中血碱性磷酸酶(alkalinephos phatase,ALP)水平明显升高,经除外急性排斥反应、维生素D缺乏性佝偻病、胆汁淤积性疾病、病毒感染、骨代谢异常、甲状旁腺功能亢进症及血液系统疾患等原因后,考虑为他克莫司(FK506)不良反应所致肝损害,停用FK506,改为麦考酚吗乙酯(MMF)+环孢素(CsA)抗排斥治疗后,患儿肝功能逐渐好转。结论儿童患者的生理及药物代谢具有特殊性,小儿肝移植术后FK506所致药物性肝损害较为罕见,临床上应予以重视。     

Bile duct apoptosis and cholestasis resembling acute graft-versus-host disease after autologous hematopoietic cell transplantation

BACKGROUND: Acute graft-versus-host disease (GVHD) of the liver is a frequent complication of allogeneic hematopoietic cell transplantation. This report describes hepatic GVHD following autologous transplantation. METHODS: We reviewed 116 consecutive autologous transplant recipients. A diagnosis of GVHD was based on histology (segmental to subtotal destruction of bile ductal epithelial cells with apoptosis and lymphocytic infiltrates), clinical criteria (elevated serum alkaline phosphatase), a response to immunosuppressive therapy, and finding no other cause for cholestatic liver disease. RESULTS: Two patients developed cholestatic liver disease (alkaline phosphatase levels over five times the normal upper limit) and had liver biopsies showing apoptotic and dysmorphic ductular epithelial cells typical of GVHD. Three additional patients developed cholestasis and intestinal symptoms but had gastric biopsies only, showing apoptotic crypt epithelial cells and crypt cell drop-out typical of GVHD. CONCLUSION: Two recipients of autologous hematopoietic cells developed histologic abnormalities of small bile ducts and cholestatic liver disease resembling GVHD of the liver after allogeneic transplant. The mechanisms of bile duct damage in this setting may involve immune dysregulation related to reconstitution of immunity with peripheral blood stem cells.     

Transient elastography identifies liver recipients with nonviral graft disease after transplantation: a guide for liver biopsy

Transient elastography (TE) reliably predicts the severity of recurrent hepatitis C virus after orthotopic liver transplantation (OLT); however, its accuracy in evaluating nonviral liver graft damage is unknown. Between 2006 and 2009, 69 OLT recipients [37 for hepatitis B virus/hepatitis D virus (recurrence-free), 20 for autoimmune/cholestatic liver disease, 6 for alcoholic liver disease, and 6 for mixed etiologies] underwent protocol/on-demand liver biopsy (LB) and concomitant TE. A histological diagnosis of graft disease was made according to criteria defined by the Banff working group. Sixty-five patients (94%) had reliable TE examinations during a median post-OLT follow-up of 18 months (range = 7-251 months). LB samples (median length = 35 mm) showed graft damage in 28 patients (43%): idiopathic chronic hepatitis (11), steatohepatitis (3), rejection (3), cholangitis (2), and autoimmune/cholestatic recurrence (9). Patients with graft damage had significantly higher serum liver enzyme levels and TE results (median = 7.8 kPa, range = 5.4-27.4 kPa) than the 37 patients without graft damage (median = 5.3 kPa, range = 3.1-7.4 kPa, P < 0.001). By a receiver operating characteristic curve analysis, 2 TE cutoffs for the diagnosis of graft damage were identified: 5.3 kPa with 100% sensitivity and 7.4 kPa with 100% specificity. The pretest probability of graft damage was 43%; in patients with TE values ≤5.3 kPa, the posttest probability of graft damage fell to 0%, but in patients with TE results >7.4 kPa, the posttest probability increased to 100%. In conclusion, the dual TE cutoff allows accurate discrimination between the absence and presence of nonviral liver graft damage and improves the clinical management of OLT recipients in terms of the selection of patients most in need of LB.     

Interferon alpha 2B and ribavirin in severe recurrent cholestatic hepatitis C

Severe recurrent cholestatic hepatitis C after liver transplantation has a poor prognosis and no standard therapy is currently available. Four cases of severe recurrent cholestatic hepatitis C treated with a combination of interferon alpha 2b and ribavirin are described. All four patients were transplanted for hepatitis C-related cirrhosis. The mean age at transplantation was 45 years (range 41-51 years). Three of the patients were male and one was female. All four patients had hepatitis C virus viremia before and after liver transplantation. At 2 to 23 months after liver transplantation, all four patients developed jaundice, cholestatic elevation of liver enzymes, and histopathology consistent with severe recurrent cholestatic hepatitis C. Combination of interferon and ribavirin was given with prompt virological suppression. Despite this rapid viral suppression, all four patients developed progressive graft failure with three deaths.     

Candida hepatitis. Histopathologic diagnosis

Candida hepatitis, usually a manifestation of disseminated candidiasis in immunocompromised patients, is difficult to diagnose antemortem. We studied six patients with proven hepatic candidiasis to assess features helpful in deriving a correct diagnosis. Five patients were immunosuppressed as a result for treatment for leukemia; one was immunosuppressed due to renal transplantation. All had sustained fevers greater than 101 degrees F, elevated alkaline phosphatase levels, and multiple hepatic and splenic defects--presumably abscesses--on abdominal CT scan. Twelve liver biopsies (nine needle, three wedge) were examined. Biopsies from four patients contained identifiable Candida organisms within suppurative granulomas; a biopsy from a fifth patient grew Candida albicans in cultures. In the sixth patient, the first biopsy was culture positive for Candida albicans, and the second biopsy, a fine-needle aspirate, contained Candida organisms and purulent material. In all of the nondiagnostic biopsies, as well as in regions of the diagnostic biopsies around the suppurative granulomas, mass-associated obstructive changes were noted. These included pericentral sinusoidal dilatation and cholestatic inflammation characterized by periportal ductular proliferation with surrounding neutrophils and edema. We conclude that in the appropriate clinical setting, these mass-associated histologic findings are suggestive of adjacent Candida abscesses. Definite diagnosis requires either the identification of Candida organisms within inflammatory hepatic lesions or positive culture of Candida from the liver biopsy.     

Effects of cholestatic hepatic disease and chronic renal failure on alfentanil pharmacokinetics in children

The role of the liver and the kidney in alfentanil metabolism has not been defined. The effects of cholestatic hepatic disease and chronic renal failure on the pharmacokinetics of alfentanil were evaluated in 9 children undergoing liver transplantation and 10 children undergoing kidney transplantation. These findings were compared with data from 10 children with normal hepatic and renal function undergoing other surgical procedures. There was no statistical difference among the 3 groups with respect to apparent volume of distribution, half-life, or clearance. In a subgroup of 3 patients undergoing liver transplantation alfentanil kinetics were determined both before and after the allograft was incorporated into the recipient's circulation. Though both volume of distribution and elimination half-life increased in the posttransplantation period, only the decrease in clearance was statistically significant. Thus, it appears that alfentanil may be a useful anesthetic agent in pediatric patients with cholestatic hepatic disease or chronic renal failure. The dose of alfentanil in these patients need not be altered except in the period immediately after liver transplantation.     

肝移植术后纤维化胆汁淤滞性肝炎

目的 探讨肝移植术后乙型肝炎复发的病理学特征和鉴别诊断。方法 对１例乙型肝炎后肝硬化患者在肝移植术后进行定期肝穿刺组织学检查。结果 肝移植术后２５ｄ血中ＨＢｓＡｇ,ＨＢｅＡｇ和ＨＢＶ－ＤＡＮ均转为阴性。然而,术后５８ｄＨＢｓＡｇ再次阳性。同时肝刺组织学检查见肝细胞气球样变并互相融合形成片状坏死,汇管区和门静脉周围出现纤维化,部分肝细胞和肝小管内可见胆汁淤带,肝细胞呈ＨＢｓＡｇ和ＨＢｃＡｇ免疫反应性     

C4d in Acute Rejection After Liver Transplantation—A Valuable Tool in Differential Diagnosis to Hepatitis C Recurrence

Hepatitis C is the most common indication for liver transplantation. Recurrence of HCV is universal leading to graft failure in up to 40% of all patients. The differentiation between acute rejection and recurrent hepatitis C is crucial as rejection treatments are likely to aggravate HCV recurrence. Histological examination of liver biopsy remains the gold standard for diagnosis of acute rejection but has failed in the past to distinguish between acute rejection and recurrent hepatitis C. We have recently reported that C4d as a marker of the activated complement cascade is detectable in hepatic specimen in acute rejection after liver transplantation. In this study, we investigate whether C4d may serve as a specific marker for differential diagnosis in hepatitis C reinfection cases. Immunohistochemical analysis of 97 patients was performed. A total of 67.7% of patients with acute cellular rejection displayed C4d-positive staining in liver biopsy whereas 11.8% of patients with hepatitis C reinfection tested positive for C4d. In the control group, 6.9% showed C4d positivity. For the first time we were able to clearly demonstrate that humoral components, represented by C4d deposition, play a role in acute cellular rejection after LTX. Consequently C4d may be helpful to distinguish between acute rejection and reinfection after LTX for HCV.