供肾零点活检病理结果与移植肾功能延迟恢复的相关研究

目的探讨供肾零点活检病理结果与肾移植术后并发移植肾功能延迟恢复(DGF)的关系。 方法回顾性分析西安交通大学第一附属医院肾移植科2018年5月至2019年4月实施的心脏死亡器官捐献(DCD)肾移植供、受者临床资料。采用零点活检病理结果评估供肾质量,并按照Banff 2013标准、Remuzzi评分及马里兰病理指数(MAPI)对供肾进行病理分级和评分。肾小球数量≥7个,小动脉数量≥2支为合格标本。根据受者肾移植术后是否发生DGF,将其分为DGF组和非DGF组。采用Mann-Whitney U检验比较两组供肾肾小球硬化率、小动脉玻璃样变率、Banff 2013标准评分、Remuzzi评分和MAPI评分。采用卡方检验比较两组供肾肾间质纤维化、肾小管萎缩、小动脉内膜纤维化增厚、小动脉管壁透明样变、肾小管损伤/坏死及肾小球内微血栓发生情况。采用logistic回归分析供肾零点活检病理结果与DCD肾移植术后并发DGF的关系。P<0.05为差异有统计学意义。 结果最终纳入133例受者,其中DGF组26例,DGF发生率为19.5%,非DGF组107例。133例合格肾穿刺标本中,平均获得肾小球数量(13±5)个,中位肾小球硬化率5.8%(0～13.3%),中位小动脉数量5支(3～6支),中位小动脉玻璃样变率0(0～11%),肾间质纤维化占47.4%(63/133),肾小管萎缩占48.1%(64/133),小动脉内膜纤维化增厚占58.6%(78/133),小动脉管壁透明样变占36.8%(49/133),未见肾小球内微血栓,所有供肾均合并不同程度肾小管损伤/坏死。两组受者供肾肾间质纤维化、肾小管萎缩、肾小管损伤/坏死以及Remuzzi评分差异有统计学意义(χ²＝7.65、7.92和16.81,Z＝-2.02,P均<0.05)。多因素分析结果显示肾小管损伤/坏死是肾移植术后并发DGF的独立危险因素。 结论供肾零点活检病理学评估对于预测肾移植短期预后具有一定价值,在供者维护和器官保存过程中应尽可能避免造成肾小管缺血/坏死,以降低DGF发生风险。     

Liver graft failure and hyperbilirubinemia in liver transplantation recipients after Clostridium difficile infection

Introduction

Liver transplant recipients are at high risk for Clostridium difficile infection. We have recently encountered multiple cases of CDI in our liver transplant recipients and for some of them it led to severe hyperbilirubinemia, liver failure, and even death. Our goals are to report our experience and analyze the factors that contributed to unfavorable outcomes.

Material and Methods

All liver transplant recipients diagnosed with CDI between December 1, 2007, and January 30, 2009, were included and retrospectively reviewed.

Results

Twenty-four patients were identified, 14 men and 10 women. Fourteen patients experienced hyperbilirubinemia after the infection and 7 progressed to liver failure. Pre-CDI biopsy-proven liver abnormality, use of extended-criteria donors (ECDs) and a donor risk index (DRI) greater than 1.9 were associated with a higher risk of graft failure (P < .05). Hepatitis C, inpatient versus outpatient diagnosis, and a donor age greater than 50 years were not associated with a higher risk of graft failure. Use of ECDs and timing of the infection at more than 1 month but less than 1.5 years posttransplant were also associated with higher chances of sustained hyperbilirubinemia (P < .05).

Conclusion

CDI in liver transplant patients can be very serious and may lead to sustained hyperbilirubinemia or graft failure. Marginal grafts are more susceptible to decompensate after such an infection than standard criteria grafts; moreover, already abnormal grafts do not tolerate this infection well and decompensate to complete failure in 85% of the cases.     

超声弹性成像评估肝移植术后稳定状态受者不同时期肝脏弹性的应用价值

目的  探讨超声弹性成像技术无创性监测肝移植术后稳定状态受者不同时期肝脏弹性的价值。方法  收集73例肝移植术后稳定状态受者的临床资料,根据肝移植术后时间分为早期组（25例）和中长期组（48例）,同时选取38名健康体检者作为对照组。比较各组研究对象的超声指标和肝功能指标;分析各组研究对象的肝脏和脾脏弹性成像指标,并分析其与肝功能指标的相关性。结果  与对照组比较,早期组的各项超声指标和丙氨酸转氨酶（ALT）、γ-谷氨酰转移酶（GGT）、碱性磷酸酶（ALP）升高,差异均有统计学意义（均为P < 0.05）,中长期组的各项超声指标升高,GGT降低,差异均有统计学意义（均为P < 0.05）;与早期组比较,中长期组的肝脏右斜径和ALT、GGT、ALP降低,差异均有统计学意义（均为P < 0.05）。与对照组比较,早期组和中长期组肝脏声触诊弹性成像（STE）值、声触诊弹性测量（STQ）值与脾脏STE值均升高,差异均有统计学意义（均为P < 0.05）;与早期组比较,中长期组的肝脏和脾脏弹性成像指标均降低,差异均有统计学意义（均为P < 0.05）。肝脏弹性成像指标与ALT、天冬氨酸转氨酶（AST）、GGT呈弱相关性,与ALP呈强相关性。脾脏STE值与ALP呈弱相关性。肝脏STE值与肝脏STQ值呈强相关性,肝脏STE值、STQ值与脾脏STE值均呈弱相关性。结论  肝移植术后稳定状态受者不同时期的肝脏弹性特征不同,持续监测肝脏弹性可能为肝移植术后随访提供全新的无创性监测方式。     

Transient elastography for diagnosis of advanced fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation.

Recurrence of hepatitis C after liver transplantation (LT) is the main cause of graft loss and retransplantation. Frequent liver biopsies are essential to follow-up hepatitis C virus (HCV)-induced liver damage. However, liver biopsy is an invasive and expensive procedure. We evaluated prospectively the diagnostic accuracy of noninvasive measurement of liver stiffness (by transient elastography) to assess the severity of hepatitis C recurrence after LT. For this purpose, we included 124 HCV-infected liver transplant recipients who underwent 169 liver biopsies and 129 hepatic hemodynamic studies with determination of hepatic venous pressure gradient (HVPG). Simultaneously, patients underwent measurement of liver stiffness. Liver fibrosis was mild (F0-F1) in 96 cases (57%) and significant (F2-F4) in 73 (43%). HVPG was normal (<6 mm Hg) in 69 cases (54%) and elevated (>or=6 mm Hg) in 60 (46%). Using a liver stiffness cutoff value of 8.5 kilopascals, the sensitivity, specificity, negative predictive value, and positive predictive value for diagnosis of fibrosis >or=F2 were 90%, 81%, 79%, and 92%, respectively. The area under the curve (AUC) for diagnosis of fibrosis >or=F2, >or=F3 and F4 were 0.90, 0.93, and 0.98, respectively. There was a close direct correlation between liver stiffness and HVPG (Pearson coefficient, 0.84; P < 0.001) and the AUC for diagnosis of portal hypertension (HVPG >or=6 mm Hg) was 0.93. Importantly, none of the individuals with liver stiffness below the cutoff value had either bridging fibrosis (F3) or cirrhosis (F4) or significant portal hypertension (HVPG >or=10 mm Hg). In conclusion, determination of liver stiffness is an extremely valuable tool to assess the severity of HCV recurrence after LT and in reducing the need of follow-up liver biopsies.     

Assessment of graft fibrosis by transient elastography in patients with recurrent hepatitis C after living donor liver transplantation

BACKGROUND: Transient elastography (FibroScan) is a simple and noninvasive method to assess liver fibrosis by measuring liver stiffness and therefore can be a promising tool to evaluate liver fibrosis and avoid liver biopsy. We prospectively assessed the performance of transient elastography in patients with recurrent hepatitis C virus after living donor liver transplantation, in comparison with the surrogate serum markers. METHODS: Fifty-six patients with recurrent hepatitis C virus after living donor liver transplantation, who underwent both liver biopsy and transient elastography were included in this study. The grade of liver fibrosis (the Scheuer classification) obtained by biopsy was compared to liver stiffness measured by the transient elastography. RESULTS: The fibrosis grades were as follows: F0, n=22; F1, n=13; F2, n=9; F3, n=7; and F4, n=5. Liver stiffness values ranged from 2.9 to 72.0 kPa. The optimal cutoff values were 8.8 kPa for F>or=1, 9.9 kPa for F>or=2, 15.4 kPa for F>or=3, and 26.5 kPa for F>or=4. The area under the receiver operator characteristic curve for the diagnosis of fibrosis (F>or=2) by transient elastography was 0.92, while that by hyaluronic acid, type 4 collagen, alanine aminotransferase, and the aspartate transaminase to platelets ratio index were 0.52, 0.62, 0.64, and 0.70, respectively. CONCLUSIONS: These data suggest that transient elastography is a simple, noninvasive and reliable tool to assess liver fibrosis in patients with recurrent hepatitis C virus after living donor liver transplantation.     

Bone loss after kidney transplantation: a longitudinal study in 115 graft recipients

BACKGROUND.: Bone loss is an important problem in renal transplant recipientsimmediately after surgery. No data are available about the boneloss beyond the first post-transplantation year. METHODS.: In a longitudinal, uncontrolled observational study bone mineraldensity (BMD) was measured by dual X-ray absorptiometry in 115renal graft recipients starting at different times after transplantation(0–20 years after transplantation) with a follow-up timeof 12 months. RESULTS.: A total of 56 patients showed a reduction of BMD during theobservation period. Bone loss depended on the time after transplantation.Mean reduction of BMD at lumbar spine was 7±10%, 1±9%during the first and second postoperative year. Beyond the thirdyear bone mineral density did not change or even increased slightly(0±4% during 3–5th year, 1±6% during 6–10thyear and 2±4% during 11–20th year after transplantation).Decrease of BMD correlated with a higher mean daily prednisonedosage (P<0.001), a higher cumulative prednisone dose (P<0.01),a more frequent and more steroid-resistant rejection (P<0.001)and a higher initial parathyroid hormone level (P<0.001).Patients with 25-OH-cholecalciferol therapy (P<0.05) or morephysical activity (P<0.05) had a smaller bone loss. CONCLUSIONS.: Reduction of BMD after transplantation is highest within thefirst post-transplant year. The effects of acute graft rejection,prednisone dosage and initial parathyroid hormone level arepredominant among the multiple factors associated with pronouncedbone loss.     

肝移植后移植物抗宿主病的诊断和治疗

目的 探讨肝移植后发生移植物抗宿主病(GVHD)的诊断和治疗方法.方法 回顾性分析2002年4月至2006年3月间8例肝移植后发生GVHD受者的临床资料,通过观察这8例受者的临床症状与体征,以及分析肝功能、血常规、骨髓细胞学、细菌培养、病毒检测和皮肤病理学等检查结果,总结诊断与治疗经验.结果 肝移植受者发生GVHD的临床表现为:术后1～4周出现发热、全身皮疹、全血细胞减少、腹泻和腹痛等,但肝功能正常.皮肤组织病理学表现为:表皮角化不良、松解,棘层细胞水肿,基底层液化变性,真皮浅层淋巴细胞浸润.8例受者经减少免疫抑制剂的用量、有效控制非特异性炎症反应、改善造血功能、防治感染和加强营养支持等治疗后,其中7例康复出院,并长期健康存活;仅1例治疗无效死亡.结论 肝移植后GVHD的诊断主要依据典型的临床表现和特异性的皮肤组织病理学改变.诊断明确后应最大程度的减少免疫抑制剂的用量,有效控制GVHD引起的急性炎症反应,促进造血功能恢复.     

Effect of nonviral factors on hepatitis C recurrence after liver transplantation

OBJECTIVE: Hepatitis C (HCV) is now the most common indication for orthotopic liver transplantation (OLT). While graft reinfection remains universal, progression to graft cirrhosis is highly variable. This study examined donor, recipient, and operative variables to identify factors that affect recurrence of HCV post-OLT to facilitate graft-recipient matching. METHODS: Retrospective review of 307 patients who underwent OLT for HCV over a 10-year period at our center. Recurrence of HCV was identified by the presence of biochemical graft dysfunction and concurrent liver biopsy showing diagnostic pathologic features. Time to recurrence was the endpoint for statistical analysis. Five donor, 6 recipient, and 2 operative variables that may affect recurrence were analyzed by univariate comparison and Cox proportional hazard regression models. RESULTS: Recurrence-free survival in the 307 study patients was 69% and 34% at 1 and 5 years, respectively. Four predictive variables related to either donor or recipient characteristics were identified. Advanced donor age, prolonged donor hospitalization, increasing recipient age, and elevated recipient MELD scores were found to increase the relative risk of HCV recurrence. Examination of HLA disparity between donors and recipients demonstrated no correlation between class I or class II mismatches and recurrence-free survival. CONCLUSIONS: We have identified donor and recipient characteristics that significantly predict hepatitis C recurrence following liver transplantation. These factors are identifiable before transplant and, if considered when matching donors to HCV recipients, may decrease the incidence of HCV recurrence after OLT. A change in the current national liver allocation system would be needed to realize the full value of this benefit.     

Chylous ascites after liver transplantation with mesentero-portal jump graft

Chylous effusions and lymphatic leaks occur after trauma, malignant disease, primary lymphatic disorders, and parasitosis, and rarely after abdominal surgery. Chylous ascites after orthotopic liver transplantation is a rare complication. We report a case of chylous ascites occurring after hepatic transplantation with a mesentero-portal venous jump graft, successfully treated with conservative management. Received: November 13, 2000 / Accepted: September 26, 2001     

Rescue hepatectomy for initial graft non-function after liver transplantation

BACKGROUND: Early retransplantation is the therapy of choice in patients with initial graft nonfunction (INF). In rare cases the patients' conditions deteriorate dramatically with severe cardiovascular and/or pulmonary insufficiency while on the waiting list for retransplantation. In this life-threatening situation removal of the graft and temporary portocaval shunt before allocation of a new liver proved to be effective. Our experience with this two-stage hepatectomy and subsequent liver transplantation in patients with complicated INF is reported. METHODS: Hepatectomy was performed in 20 patients with INF associated with severe cardiovascular and pulmonary insufficiency while on the waiting list for emergency liver retransplantation. The mean age was 41.75+/-16.64 years. The time period between primary transplantation and hepatectomy was 2.80+/-2.84 days with a range from 1 to 9 days. RESULTS: Hepatectomy reduced the need for vasopressive agents and improved pulmonary function in the majority of patients. Four patients died before a liver was available due to brain death in one patient and multiorgan failure in three patients. In the remaining 16 patients liver transplantation could be performed after 19.82+/-15.34 hr (range 6.58 to 72.50 hr). Two of the 16 transplanted patients died on the first postoperative day due to multiorgan failure and pneumonia. The remaining 14 of 16 patients survived retransplantation, but 7 died between days 13 and 105 mostly due to sepsis. Seven patients were discharged from the hospital in good condition and show long-term survival. CONCLUSION: Hepatectomy was able to stabilize the cardiovascular and pulmonary function. This study confirms the beneficial effects of hepatectomy and subsequent liver transplantation as a life-saving procedure in patients with INF complicated by cardiovascular and/or pulmonary instability.     

基于索非布韦的方案联合利巴韦林治疗肝移植后HCV基因1型肝炎受者的Meta分析

目的  通过系统评价和Meta分析评估以索非布韦(SOF)为基础的直接抗病毒药物(DAAs)联合利巴韦林(RBV)(联合RBV)治疗肝移植术后丙型肝炎病毒(HCV)基因1型(GT1)肝炎受者能否获益。方法  系统检索国内外多个数据库,根据标准筛选文献,并进行文献质量评价,提取数据。将文献按肝移植术后HCV-GT1肝炎受者接受联合RBV或只用SOF的DAAs不联合RBV(不联合RBV)治疗分为两组。采用Rev Man 5.3和R3.4.3软件对数据进行Meta分析。对治疗结束后12周持续病毒学应答(SVR12)的发生率进行评估。结果  检索文献2 195篇,按纳入标准筛选共纳入6篇英文文献。Meta分析结果表明联合RBV组和不联合RBV组两组间SVR12的发生率差异无统计学意义(P=0.28),但是联合RBV组贫血的发生率明显增高(P < 0.01)。联合RBV或不联合RBV治疗方案对肝移植术后HCV-GT1a和HCV-GT1b两个亚型同样有效,两基因亚型间疗效差异无统计学意义(P=0.33)。将肝移植术后HCV-GT1肝炎受者的疗程从12周延长至24周的SVR率差异无统计学意义(P=0.95)。结论  采用基于SOF的DAAs方案治疗肝移植术后HCV-GT1肝炎受者时,联合RBV不仅不能提高病毒的清除率,反而增加了受者发生贫血的风险,不能从中获益。     

肝脏穿刺活检在肝移植术后的应用

目的 通过对肝移植术后肝脏穿刺活检资料的分析,探讨移植术后各种并发症的病理组织学表现,指导肝移植术后并发症的诊治.方法 回顾性分析198例肝移植术后患者249例次诊断性肝脏穿刺活检组织病理资料和治疗效果.苏木精-伊红染色法分析其病理学形态改变,排斥反应采用Banff排斥反应病理标准、RAI评分分级.结果 所有病理活检资料中,急性排斥反应发病率为最高,共71例次(28.5％),胆道并发症39例次(15.7％)、肝炎病毒感染及复发28例次(11.2％)、药物性损害34例次(13.7％)、再灌注损伤35例次(14.1％)、巨细胞病毒感染14例次(5.6％)、肿瘤复发7例次(2.8％)、慢性排斥反应16例次(6.4％)、原发性移植物无功能2例次(0.8％)、难以确定3例次(1.2％).结论 移植肝行穿刺活检术能很好的明确肝功能异常的病因,进而指导临床进行精确、有效的治疗,建议各移植中心将肝脏穿刺列为肝移植术后的常规检查,定期活检,更好的保护移植物的生存状态.     

肝移植后受者真菌感染的易感因素分析

肝移植为治疗终末期肝病的有效手段.肝移植受者术后常继发真菌感染,其发生率为4%～48%,而病死率则高达50%～80%[1].探讨其易感因素,对真菌感染的预防及早期诊断,对提高疗效具有重要意义.     

Evans' syndrome complicating chronic graft versus host disease after cadaveric liver transplantation

Acute graft versus host disease (GVHD) occurred in a patient after cadaveric liver transplantation from an HLA disparate donor. Immunosuppression resulted in a remission, but chronic GVHD with a scleroderma-like syndrome ensued. This was further complicated by immune hemolytic anemia and thrombocytopenia (Evan's syndrome). Semi-quantitative microsatellite analysis of circulating lymphoid cells showed that T cells were predominantly of donor origin, thereby explaining the chronic GVHD. The marrow hematopoietic cells remained recipient, so that the immune cytopenias were expected to be alloimmune in nature. However, the red cell antibodies were shown to have anti-C and anti-e specificity, with both the donor (R1R1) and recipient (R1r) possessing the C and e antigens. Therefore, the immune hemolysis might be considered both alloimmune and autoimmune. The patient finally died of sepsis. This case illustrates that chronic GVHD due to stable donor T cell engraftment may rarely occur in liver transplantation despite HLA disparity. Immunosuppression may result in dysregulation of T cell functions, leading to alloimmune and autoimmune problems.