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Auxiliary partial orthotopic liver transplantation (APOLT) for Crigler-Najjar syndrome: A retrospective analysis 辅助原位部分肝移植治疗Crigler-Najjar综合征的回顾性分析
Pub Date : 2023-08-28 DOI: 10.1016/j.liver.2023.100178
Zubair Saeed , Bilal Ahmed Khan , Abdullah Khalid , Sohail Rashid , Muhammad Yasir Khan , Ihsan-ul Haq , Faisal Saud Dar

Background

Crigler-Najjar syndrome is an ultra-rare hereditary disorder characterized by severe jaundice and risk of neurological complications. Current treatments, such as phototherapy, have limitations, and liver transplantation is often necessary. Auxiliary partial orthotopic liver transplantation (APOLT) is a potential treatment option. Still, its safety and efficacy in Pakistani patients with Crigler-Najjar syndrome Type I (CNS-I) have not been well established.

Methods

This retrospective study reviewed the outcomes of five pediatric patients with CNS-I who underwent APOLT at a tertiary care center in Pakistan. Patient demographics, surgical details, postoperative course, complications, and follow-up data were analyzed. The primary endpoint was the feasibility and safety of APOLT, while secondary endpoints included improvement in serum bilirubin levels, neurological symptoms, and survival rates.

Results

Among five patients diagnosed with CNS-I, APOLT was performed without intraoperative complications. During the median follow-up period of 6 months, there were no cases of relaparotomy, graft rejection, biliary complications, or portal venous thrombosis. One patient developed a portal venous stricture, but his symptoms were controlled with conservative measures. Postoperative liver function tests showed a significant improvement, with an average reduction of 90% in serum bilirubin levels. There was some improvement in neurological symptoms, and the overall patient and graft survival rate was 100%.

Conclusion

This study suggests that APOLT is a feasible and safe treatment option in patients with CNS-I. It improves liver function, bilirubin levels, and neurological symptoms. Further research with larger sample sizes is warranted to confirm these findings and evaluate the long-term outcomes of APOLT in this patient population.

背景Crigler-Najjar综合征是一种极为罕见的遗传性疾病,以严重黄疸和神经系统并发症为特征。目前的治疗方法,如光疗,有局限性,肝移植往往是必要的。辅助原位部分肝移植(APOLT)是一种潜在的治疗选择。尽管如此,它在巴基斯坦I型Crigler-Najjar综合征(CNS-I)患者中的安全性和有效性尚未得到很好的证实。方法本回顾性研究回顾了在巴基斯坦一家三级护理中心接受APOLT的5名CNS-I儿童患者的结果。分析患者人口统计学、手术细节、术后病程、并发症和随访数据。主要终点是APOLT的可行性和安全性,而次要终点包括血清胆红素水平、神经症状和生存率的改善。结果在5例CNS-I患者中,APOLT术中无并发症。在6个月的中位随访期内,没有再造口、移植物排斥反应、胆道并发症或门静脉血栓形成的病例。一名患者出现门静脉狭窄,但他的症状通过保守措施得到了控制。术后肝功能检查显示有显著改善,血清胆红素水平平均降低90%。神经系统症状有所改善,患者和移植物的总生存率为100%。结论APOLT是CNS-I患者可行且安全的治疗方案。它可以改善肝功能、胆红素水平和神经系统症状。需要对更大样本量的进一步研究来证实这些发现,并评估APOLT在该患者群体中的长期结果。
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引用次数: 0
Effectiveness of machine perfusion in liver transplantation: A meta-analysis of randomized controlled trials 机器灌注在肝移植中的有效性:随机对照试验的荟萃分析
Pub Date : 2023-08-18 DOI: 10.1016/j.liver.2023.100176
Xiangfeng Yang, Yunlong Li, Qing Guo, Yuanzhe Li, Xiangyu Zhong

Background

In contemporary transplantation research, the utilization of machine perfusion to facilitate the perfusion, preservation, evaluation, and repair of donor livers has garnered considerable attention.In an effort to comprehensively assess the clinical outcomes of liver transplantation procedures incorporating machine perfusion, a meta-analysis of published randomized controlled trials (RCTs) was undertaken.

Methods

The relevant literature was obtained from PubMed, EMBASE, Web of Science, and other databases up until December 2022. Subsequently, the authors extracted the requisite data, conducted a meta-analysis, and arrived at a conclusion based on the findings derived from the analysis.

Results

A total of seven high-quality prospective RCTs, comprising 917 patients, were included in the analysis. Machine perfusion demonstrated significant superiority over cold storage in reducing the incidence of major postoperative complications (RR 0.55, 95% CI 0.42 to 0.73; p < 0.0001) and early allograft dysfunction (RR 0.52, 95% CI 0.41 to 0.67; p < 0.00001). Notably, postoperative aspartate aminotransferase peak, bilirubin levels, and post-reperfusion lactate were also found to decrease. However, no statistically significant differences were observed for other outcomes. Hypothermic oxygenation machine perfusion demonstrated a lower frequency of re-transplantation (RR 0.29, 95% CI 0.10 to 0.86; p = 0.03), rejection (RR 0.55, 95% CI 0.32 to 0.95; p = 0.03), and resulted in shorter hospital stays (Std, MD -0.30, 95% CI -0.52 to -0.07; p = 0.009).

Conclusions

The application of machine perfusion can yield significant improvements in the outcomes of liver transplantation.

背景在当代移植研究中,利用机器灌注促进供体肝脏的灌注、保存、评估和修复已经引起了人们的广泛关注。为了全面评估结合机器灌注的肝移植程序的临床结果,对已发表的随机对照试验(RCT)进行了荟萃分析。方法相关文献来源于PubMed、EMBASE、Web of Science等数据库,截至2022年12月。随后,作者提取了必要的数据,进行了荟萃分析,并根据分析结果得出结论。结果共纳入了7项高质量的前瞻性随机对照试验,包括917名患者。机器灌注在降低术后主要并发症(RR 0.55,95%CI 0.42至0.73;p<;0.0001)和早期同种异体移植物功能障碍(RR 0.52,95%CI 0.41至0.67;p&llt;0.00001)的发生率方面表现出明显优于冷藏。值得注意的是,术后天冬氨酸氨基转移酶峰值、胆红素水平和再灌注后乳酸水平也有所下降。然而,在其他结果方面没有观察到统计学上的显著差异。低温氧合机灌注显示出较低的再移植频率(RR 0.29,95%CI 0.10至0.86;p=0.03)、排斥反应(RR 0.55,95%CI 0.32至0.95;p=0.03,并且缩短了住院时间(Std,MD-0.30,95%CI-0.52至-0.07;p=0.009)。结论应用机器灌注可以显著改善肝移植的结果。
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引用次数: 0
24-hour normothermic machine perfusion of discarded human liver grafts: Case series single-center study 废弃人肝移植物的24小时常温机器灌注:病例系列单中心研究
Pub Date : 2023-08-18 DOI: 10.1016/j.liver.2023.100177
Adhnan Mohamed , Tayseer Shamaa , Iman Francis , Catherine Crombez , Jennifer Cui , Brian K. Theisen , Ileana Lopez-Plaza , Shunji Nagai , Kelly Collins , Atsushi Yoshida , Marwan Abouljoud , Michael D. Rizzari

Background

The persistent shortage of liver allografts contributes to significant waitlist mortality. Normothermic machine perfusion (NMP) has the potential to extend viability and allow liver function evaluation in discarded organs. The main aim of the study was to evaluate the possibility for extended preservation and the potential recovery of non-usable human livers utilizing NMP.

Methods

6 high-risk human liver grafts that were discarded after national allocation underwent normothermic liver preservation for an extended period of 24 h. Transmedics Organ Care System™ liver perfusion device was used to preserve a donor liver in a functioning, near physiologic state. Parameters of biochemical and synthetic liver function were collected periodically and subsequently analyzed. Liver parenchyma and bile duct biopsies were obtained pre- and 24 h post-NMP.

Results

4/6 (67%) grafts were DCDs with a median age of 54 (IQR: 42–61) years and median CIT of 262 (IQR: 209–1024) minutes. 5/6 (83%) livers produced a median of 75 ml of bile (Range 55–100) after 24 h of NMP. Lactate dropped to normal levels (<2 mmol/L) for all livers after around 4 h on NMP. The overall cellular architecture, lobular steatosis and necrosis grades were preserved after extended NMP. Biopsies showed improvement of liver parenchyma architecture with reduced inflammation for 2/6 (33%) at the end of the perfusion.

Conclusion

Prolonged NMP for discarded liver grafts can be safely maintained on NMP and may identify certain grafts that are suitable for transplantation. Further studies utilizing NMP with subsequent transplantation would validate this strategy, as well as existing viability markers.

背景同种异体肝移植的持续短缺导致了严重的等待名单死亡率。Normothemic机器灌注(NMP)有可能延长生存能力,并允许对废弃器官进行肝功能评估。该研究的主要目的是评估利用NMP延长保存时间的可能性和不可用人类肝脏的潜在回收率。方法对6例在国家分配后丢弃的高危人肝移植物进行常温保存24小时。Transmedics器官护理系统™ 肝脏灌注装置用于将供体肝脏保持在功能正常、接近生理状态。定期收集生化和合成肝功能的参数,随后进行分析。在NMP前和NMP后24小时进行肝实质和胆管活检。结果4/6(67%)移植物为DCD,中位年龄为54岁(IQR:42-6 1),中位CIT为262分钟(IQR:209-1024)。NMP 24小时后,5/6(83%)的肝脏产生的胆汁中位数为75 ml(范围55-100)。NMP作用约4小时后,所有肝脏的乳酸降至正常水平(<2mmol/L)。延长NMP后,整体细胞结构、小叶脂肪变性和坏死分级得以保留。活检显示肝实质结构改善,灌注结束时炎症减少2/6(33%)。结论废弃肝移植物的长期NMP可以安全地维持在NMP上,并可能确定某些适合移植的移植物。利用NMP进行后续移植的进一步研究将验证这一策略以及现有的生存能力标志物。
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引用次数: 0
The author's reply 提交人的答复
Pub Date : 2023-08-12 DOI: 10.1016/j.liver.2023.100175
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引用次数: 0
The German transplantation scandal – The missing references 德国移植丑闻——缺失的参考文献
Pub Date : 2023-08-11 DOI: 10.1016/j.liver.2023.100174
Björn Nashan
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引用次数: 0
Severe thrombocytopenia in cirrhotic patients treated with Piperacillin-Tazobactam 哌拉西林-他唑巴坦治疗肝硬化患者的严重血小板减少症
Pub Date : 2023-08-03 DOI: 10.1016/j.liver.2023.100170
Lívia Guimarães , Juliana Piedade , Tamires Rocha , Caroline Baldin , Lívia Victor , Gustavo Pereira

portal hypertension and bacterial infections are frequent in cirrhosis and their coexistence may render this population susceptible to severe drug-induced thrombocytopenia. We describe frequency, clinical characteristics and prognosis of Piperacillin/Tazobactan associated thrombocytopenia. 84 patients [Child 10±1, MELD 18±8; SIRS and ACLF in 28% and 24%] were included. Thrombocytopenia developed in 12 patients and was associated with a higher frequency of bleeding from multiple sites and platelet transfusion. Severe/persistent thrombocytopenia correlated with in-hospital mortality. In conclusion, development of thrombocytopenia is frequent in cirrhotic patients treated with Piperacillin/Tazobactan and this complication, especially in most severe forms, is associated with high morbidity and mortality.

肝硬化中门静脉高压和细菌感染很常见,它们的共存可能使这一人群容易患上严重的药物诱导的血小板减少症。我们描述哌拉西林/他唑巴坦相关血小板减少症的发生率、临床特征和预后。84例患者[Child 10±1,MELD 18±8;SIRS和ACLF分别占28%和24%]。12名患者出现血小板减少症,且多处出血和血小板输注频率较高。严重/持续性血小板减少症与住院死亡率相关。总之,在接受哌拉西林/他唑巴坦治疗的肝硬化患者中,血小板减少症的发生率很高,这种并发症,尤其是在最严重的情况下,与高发病率和死亡率有关。
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引用次数: 1
Surgical management of a large hepatic artery pseudoaneurysm from a bile leak after liver transplantation 肝移植术后胆漏致大肝动脉假性动脉瘤的外科治疗
Pub Date : 2023-08-01 DOI: 10.1016/j.liver.2023.100161
Joshua A Villarreal, Clifford Akateh, Kazunari Sasaki, Marc L Melcher
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引用次数: 0
Investigating Ineligibility of Potential Living Liver Donors for Transplantation: Experience from a Large Liver Transplant Center in Pakistan 调查潜在的活体肝供者是否适合移植:来自巴基斯坦一个大型肝移植中心的经验
Pub Date : 2023-08-01 DOI: 10.1016/j.liver.2023.100163
Abdullah Khalid , Bilal Ahmed Khan , Imran Ali Syed , Touseef Ahmed , Faisal Saud Dar , Sohail Rashid , Ihsan-ul-Haq , Yasir Khan

Background

Living Donor Liver Transplantation (LDLT) is common in Pakistan, where the deceased organ donation is lacking. However, not all potential living donors are suitable for the procedure due to various medical, technical, psychosocial, and ethical reasons. This study aims to investigate the reasons for the ineligibility of potential living liver donors in Pakistan.

Methods

Between June 2022 and March 2023, 530 potential living liver donors were assessed for liver transplant recipients at the Pakistan Kidney and Liver Institute & Research center (PKLI&RC). Potential donors were evaluated in three steps, including laboratory tests imaging, and consultations. Prospectively maintained data on all potential donors were examined and retrospectively assessed to identify the causes of donor rejection.

Results

Of the 530 potential living donors evaluated, 364 of the potential donors were considered ineligible (68.67% of donors were rejected). From these rejected donors, 193 (53%) were males, and 171 (47%) were females. The mean age of the rejected donors was 26 years old. The most common reason for disqualifying potential living liver donors was a withdrawal of consent (65 cases, 17.9%). Other factors contributing to ineligibility included fatty liver infiltration reflected by a liver attenuation index (LAI) < 0, future liver remnant (FLR) < 28%, and a graft-to-recipient weight ratio (GRWR) < 0.6. Medical issues, such as abnormal liver function tests and positive hepatitis serology, also resulted in disqualification.

Conclusion

This study highlights the importance of meticulous assessment of potential living liver donors to ensure their safety and the success of the transplant. The high rate of withdrawal of consent and the prevalence of medical issues indicates the need for addressing ethical concerns and improving public education on the donation process. This study also emphasizes the importance of a deceased organ donation in developing countries like Pakistan to ensure the availability of organs for transplantation.

活体肝脏移植(LDLT)在巴基斯坦很常见,那里缺乏死者的器官捐赠。然而,由于各种医学、技术、社会心理和伦理原因,并不是所有潜在的活体捐赠者都适合这项手术。本研究旨在调查巴基斯坦潜在活体肝脏供体不合格的原因。方法在2022年6月至2023年3月期间,在巴基斯坦肾脏和肝脏研究所评估了530名潜在的活体肝脏供者作为肝移植接受者。研究中心(PKLI&RC)。对潜在捐助者的评估分三个步骤进行,包括实验室检查、成像和咨询。对所有潜在供体的前瞻性数据进行检查和回顾性评估,以确定供体排斥反应的原因。结果在评估的530名潜在活体献血者中,364名潜在献血者被认为不符合条件(68.67%的人被拒绝)。在这些被拒绝的献血者中,193例(53%)为男性,171例(47%)为女性。被拒绝的捐献者的平均年龄为26岁。取消潜在活体肝供体资格的最常见原因是撤回同意(65例,17.9%)。其他导致不合格的因素包括由肝脏衰减指数(LAI)反映的脂肪肝浸润;0、未来肝残体(FLR) <28%,移植物与受体重量比(GRWR) <0.6. 医疗问题,如肝功能检查异常和肝炎血清学阳性,也导致取消资格。结论本研究强调了对潜在活体肝供者进行细致评估的重要性,以确保其移植的安全性和成功。撤回同意的高比率和普遍存在的医疗问题表明,有必要解决道德问题,并改进有关捐赠程序的公众教育。这项研究还强调了在巴基斯坦等发展中国家,捐献死者器官对于确保移植器官的可用性的重要性。
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引用次数: 1
Iatrogenic hypervitaminosis A: An underrecognized complication in the liver transplant recipient 医源性维生素过多症A:肝移植受者的一种未被认识的并发症
Pub Date : 2023-08-01 DOI: 10.1016/j.liver.2023.100162
Raimund H Pichler, Lydia S Sun, Cary H Paine, Renuka Bhattacharya, Lei Yu, Scott W Biggins, Lena Sibulesky
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引用次数: 1
Operative risk assessment in liver transplant candidates: an important step to improve the prognosis 肝移植候选者手术风险评估:改善预后的重要一步
Pub Date : 2023-08-01 DOI: 10.1016/j.liver.2023.100166
Daniel Eyraud
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引用次数: 0
期刊
Journal of Liver Transplantation
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