Acute liver failure secondary to acute antibody mediated rejection after compatible liver transplant: A case report

BACKGROUNDThe liver has traditionally been regarded as resistant to antibody-mediated rejection (AMR). AMR in liver transplants is a field in its infancy compared to kidney and lung transplants. In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure (ALF) with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies (DSA). This case highlights the need for further investigations and heightened awareness for timely diagnosis.CASE SUMMARYA 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor. The recipient MELD at the time of transplant was 28. The flow cytometric crossmatches were noted to be positive for T and B lymphocytes. The patient had an uneventful recovery postoperatively. Starting on postoperative day 5 the patient developed fevers, elevated liver function tests, distributive shock, renal failure, and hepatic encephalopathy. She went into ALF with evidence of antibody mediated rejection with portal inflammation, bile duct injury, endothelitis, and extensive centrizonal necrosis, and C4d staining on allograft biopsy and elevated DSA. Despite various interventions including plasmapheresis and immunomodulating therapy, she continued to deteriorate. She was relisted and successfully underwent liver retransplantation.CONCLUSIONThis very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.     

慢性乙肝患者脯氨酸肽酶与肝纤维化的关系分析

目的了解血清脯氨酸肽酶（prolidase,PLD）与乙型病毒性肝炎肝纤维化程度的关系。方法测定191例乙型肝炎患者血清中PLD水平,利用ROC曲线分析ALT、AST、AST/ALT和PLD的面积,判断PLD的最优截断点并计算不同标准的灵敏度、特异度、阳性预测值（PPV）、阴性预测值（NPV）、Youden指数。结果慢性乙型肝炎患者PLD值随着肝纤维化严重程度升高,S2-4期（明显肝纤维化）明显高于S0-1期（无明显肝纤维化）（P〈0.01）。ALT、AST、AST/ALT和PLD的ROC曲线下面积分别为0.614、0.648、0.655和0.807。PLD的最优截断点约为1 250 U/L,灵敏度和特异度分别为75.6%和75.2%。结论血清PLD测定对于慢性乙型肝炎患者肝纤维化程度判定有一定的临床价值。     

双环醇治疗慢性乙型病毒性肝炎肝纤维化的临床研究

目的研究双环醇对慢性乙型病毒性肝炎(乙肝)肝纤维化的治疗作用。方法以双环醇治疗慢性乙肝患者20例,疗程6个月。分别于治疗前后检测患者血清丙氨酸氨基转移酶(ALT)、γ谷氨酰转肽酶(GGT)及血清纤维化指标层粘连蛋白(LN)、Ⅳ型胶原(CⅣ)、Ⅲ型前胶原肽(PⅢP)和透明质酸(HA)水平。同时经皮肝活检观察治疗前后肝脏组织病理学变化。结果双环醇可以显著降低慢性乙肝患者血清ALT和GGT水平,复常率分别达95%和70%,同时可以明显降低慢性乙肝患者血清LN、CⅣ和PⅢP水平,尤其PⅢP和CⅣ水平与肝组织纤维化程度呈明显正相关(相关系数分别为0.653和0.530,P<0.01)。结论双环醇可以减轻慢性乙肝患者肝脏炎症反应,保护肝细胞和抑制肝纤维化。     

银杏叶提取物EGb761对慢性乙型肝炎患者肝纤维化的影响

目的:探讨银杏叶提取物(EGb761)对慢性乙型肝炎患者肝组织纤维化的影响.方法:将60例慢性乙型肝炎患者分为EGb761治疗组(n=32)及对照组(n=28),治疗前后分别检测肝功能、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CⅣ)、透明质酸(HA)、层黏蛋白(LN)、血小板活化因子(PAF)、内皮素(ET-1)和转化生长因子-β_1(TGF-β_1)水平.两组中分别有26例和21例患者于治疗前后进行肝活检术,肝组织行HE、胶原纤维、网织纤维染色观察组织学变化.结果:治疗后两组的肝功能水平均较治疗前显著好转,但两组比较无差异.EGb761组治疗后ALT (621.8±271.7 nkat/L vs 1258.6±308.4 nkat/L,P<0.05),TBIL(17.1±9.5μmol/L vs 39.3±21.2μmol/L,P<0.01),PT(13.2±2.1 s vs 15.2±3.4 s,P<0.05),PCⅢ(168±48μg/L vs 307±93μg/L,P<0.95),CⅣ(102±35μg/L vs 191±35μg/L,P<0.01),HA(94±39μg/L vs 178±57μg/L,P<0.05),LN(101±31μg/L vs 193±21μg/L,P<0.05),PAF(7.62±6.54μg/L vs 13.23±9.79μg/L,P<0.05),ET-1(47.61±15.34μg/L vs 68.13±21.71μg/L,P<0.01)及TGF-β_1(17.61±5.06μg/L vs 58.43±11.04μg/L,P<0.05)水平与治疗前相比均显著下降,而ALB水平显著升高(38.2±5.9g/L vs 34.9±4.4g/L,P<0.05).与对照组相比,EGb761组治疗后血清TGF-β_1(17.61±5.06μg/L vs 61.17±11.45μg/L,P<0.05),PAF(7.62±6.54μg/L vs 11.65±8.96μg/L,P<0.05),ET-1(47.61±15.34μg/L vs 61.17±16.45μg/L,P<0.01),PCⅢ(168±48μg/L vs 298±86 ug/L,P<0.05),CⅣ(102±35μg/L vs 178±61 ug/L,P<0.05),HA(94±39μg/L vs 179±82μg/L,P<0.05)及LN(101±31μg/L vs 190±39 ug/L,P<0.01)指标改善更为明显.治疗组肝活检证实,治疗后肝脏细胞损伤减轻,纤维化程度减轻,而对照组治疗前后均无明显变化.结论:银杏叶提取物EGb761对慢性乙肝有明显的抗肝纤维化作用.     

Significance of progressive liver fibrosis in pediatric liver transplants: A review of current evidence

This article reviews the current evidence and knowledge of progressive liver fibrosis after pediatric liver transplantation. This often-silent histologic finding is common in long-term survivors and may lead to allograft dysfunction in advanced stages. Surveillance through protocolized liver allograft biopsy remains the gold standard for diagnosis, and recent evidence suggests that chronic inflammation precedes fibrosis.     

Emphysematous pyelonephritis in renal allograft related to antibody‐mediated rejection: A case report and literature review

Emphysematous pyelonephritis (EPN) is a rare condition which can rapidly progress to sepsis and multiple organ failure with high mortality. We experienced a rare case of EPN in a renal allograft related to antibody‐mediated rejection (AMR). The patient received a deceased donor kidney transplant due to end‐stage renal disease secondary to diabetes mellitus. Cross‐match test was negative but she had remote history of anti‐HLA‐A2 antibody corresponding with the donor HLA. Surgery concluded without any major events. Anti‐thymoglobulin was given perioperatively for induction. She was compliant with her immunosuppressive medications making urine of 2 L/d with serum creatinine of 1.9 mg/dL at discharge on post‐operative day (POD) 6. She did well until POD 14 when she presented to the clinic with features of sepsis, pain over the transplanted kidney area and decline in urine volume with elevated serum creatinine. CT revealed extensive gas throughout the transplanted kidney. Renal scan revealed non‐functional transplant kidney with no arterial flow. Based on these findings, a decision to perform transplant nephrectomy was made. At laparotomy, the kidney was completely necrotic. Pathology showed non‐viable kidney parenchyma with the tubules lacking neutrophilic casts suggestive of ischemic necrosis. Donor‐specific antibody (DSA) returned positive with high intensity anti‐HLA‐A2 antibody. This is the first case of early EPN in allograft considered to have occurred as a result of thrombotic ischemia secondary to AMR. This case suggests consideration of perioperative anti‐B‐cell and/or anti‐plasma cell therapies for historical DSA and strict post‐operative follow‐up in immunologically high‐risk recipients to detect early signs of rejection and avoid deleterious outcomes.     

血清透明质酸预测肝纤维化的再评价

目的 分析影响慢性肝炎患者血清透明质酸(HA)水平的因素,进一步探讨血清HA预测肝纤维化的价值.方法 慢性肝炎81例,诊断参照2000年全国病毒性肝炎及肝病学术会议修订的标准;血清HA采用放射免疫法检测,肝穿刺活检标本进行分级和分期.统计分析采用SPSS 11.5软件,采用有交互作用的双因素协方差分析,考察影响血清HA水平的主要因素.结果 年龄与病理分级和分期之间无显著相关性(rs=-0.006,P=0.956和rs=0.124,P=0.270),年龄与血清HA水平之间呈显著正相关(r=0.413,P=0.000);病理分级与分期之间呈显著正相关(rs=0.633,P=0.000);病理分级和分期与血清HA水平之间呈显著正相关(rs=0.290,P=0.009和rs=0.543,P=0.000);单因素方差分析结果显示,不同病理分级和分期患者血清HA水平之间均存在显著性差异(F=3.871,P=0.025和F=8.476,P=0.000),双因素协方差分析结果显示,影响血清HA水平的主要因素依次为年龄和病理分期,其偏Eta平方值分别为0.198和0.103.结论 血清HA水平可预测慢性肝炎肝纤维化,但血清HA受年龄因素的影响.     

慢性乙型肝炎肝纤维化患者的血浆CCL24水平及意义

目的 探究慢性乙型肝炎(CHB)肝纤维化患者的血浆C-C基序趋化因子配体24(CCL24)水平及与肝纤维化程度的关系.方法 选择2018年1月至2020年1月在云南省传染病医院确诊的143例CHB患者作为研究对象.采用酶联免疫吸附测定(ELISA)法检测血浆CCL24水平,分析其在显著肝纤维化和肝硬化评估中的价值.结果...     

瞬时弹性扫描检测慢性乙型肝炎患者肝纤维化的临床研究

目的:研究肝脏瞬时弹性检测仪(Fibroscan)在慢性乙型肝炎患者中的应用.方法:收集诊断为慢性乙型肝炎患者310例,其中包括23例慢性重型肝炎及65例肝硬化患者,使用Fibroscan检测肝脏硬度值,同时检测乙肝标志物HBV DNA、丙氨酸氨基转移酶、总胆红素水平.结果:慢性乙肝肝硬化患者的肝脏硬度值显著高于非肝硬化患者.肝脏重度炎症如重型肝炎,也可导致肝脏硬度值增大.年龄和性别因素可能对肝脏硬度值有影响.结论:Fibfroscan是评价慢性乙肝患者肝脏纤维化程度和诊断肝硬化的有效方法.在对个体病例进行分析时,需要考虑年龄和性别、肝脏炎症因素对肝脏硬度值的影响.     

Non-invasive assessment of liver fibrosis in chronic hepatitis C

Quantification of hepatic fibrosis is of critical importance in chronic hepatitis C not only for prognosis, but also for antiviral treatment indication. Two end points are clinically relevant: detection of significant fibrosis (indication for antiviral treatment) and detection of cirrhosis (screening for eosphageal varices and hepatocellular carcinoma). Until recently, liver biopsy was considered the reference method for the evaluation of liver fibrosis. Limitations of liver biopsy (invasiveness, sampling error, and inter-observer variability) have led to the development of non-invasive methods. Currently available methods rely on two different approaches: a “biological” approach based on the dosage of serum fibrosis biomarkers; and a “physical” approach based on the measurement of liver stiffness, using transient elastography (TE). This review is aimed at discussing the advantages and limits of non-invasive methods and liver biopsy and the perspectives for their rational use in clinical practice in the management of patients with chronic hepatitis C.     

乙肝Ⅲ号内外合用治疗慢性乙型肝炎后肝纤维化63例

目的:观察乙肝Ⅲ号内外合用治疗慢性乙型肝炎后肝纤维化的远期疗效.方法:随机选择乙肝肝纤维化患者240例,分为乙肝Ⅲ号外用膏组(n=58),内服组(n=62),内外合用组(n=63),对照组(n=57).治疗后3 mo,观察各组临床症状、肝功能、肝纤维化指数、PGA参数、血液动力学等.结果:4组皆能改善临床症状,但以内外合用组为著;4组改善肝功能、肝纤三项、PGA参数,治疗后3 mo以内外合用组疗效显著(t=6.1201,P=0.000;t=20.8201,P=0.000;t=20.5154,P=0.000);血液动力学检测显示,各治疗组治疗后门、脾静脉血管直径、血流量皆有下降(t=3.6153,P=0.0004;t=6.8052,P=0.000),内外合用组血流量下降明显(t=6.3969,P=0.000).随访12 mo后仍是内外合用组疗效为优.但各组在抗病毒指标上,无统计学意义.结论:乙肝Ⅲ号内外合用治疗乙肝后肝纤维化有一定远期疗效,且较单一方法疗效明显,疗程以3 mo为优.     

慢性乙型肝炎患者肝组织病理学改变与血小板计数和血清肝纤维化指标的相关性

目的探讨慢性乙型肝炎患者肝组织炎症分级及纤维化分期与患者血小板计数和肝纤维化指标的关系。方法在136例慢性乙型肝炎患者行肝穿刺活检,同时检测患者血小板计数及Ⅲ型前胶原（PC-III）、Ⅳ型胶原（CⅣ）、透明质酸（HA）,层粘连蛋白（LN）。结果肝组织纤维化分期及炎症分级均与血小板计数呈负相关（r分别为-0.370和-0.356,P值分别为0.02和0.0003）;肝组织纤维化分期及炎症分级与PC-Ⅲ、C-Ⅳ、HA和LN均存在明显正相关（r分别为0.414、0.390、0.419、0.393及0.426、0.375、0.548、0.343,P值均小于0.05）。结论血小板计数、Ⅲ型前胶原、Ⅳ型胶原、透明质酸和层粘连蛋白对预测慢性乙型肝炎患者的肝组织损伤程度有一定临床意义。     

慢性乙型肝炎患者肝组织病理学改变与血小板计数和血清肝纤维化指标的相关性研究

目的探讨慢性乙型肝炎患者肝组织炎症分级及纤维化分期与患者血小板计数和肝纤维化四项指标的关系,寻找能较好反映肝脏组织学损伤的无创检查指标。方法对136例慢性乙型肝炎患者行肝穿刺活检,并采集静脉血检测血小板计数及Ⅲ型前胶原(PC-III)、Ⅳ型胶原(CⅣ)、透明质酸(HA)和层粘连蛋白(LN),分别对以上5项指标与肝组织炎症分级及纤维化分期进行相关性检验。结果肝组织纤维化分期及炎症分级均与血小板计数呈负相关(r分别为-0.370和-0.356,P值分别为0.02和0.0003);肝组织纤维化分期及炎症分级与PC-Ⅲ、C-Ⅳ、HA和LN均存在明显正相关(r分别为0.414、0.390、0.419、0.393及0.426、0.375、0.548、0.343,P值均小于0.05)。结论血小板计数、Ⅲ型前胶原、Ⅳ型胶原、透明质酸和层粘连蛋白对预测慢性乙型肝炎患者的肝组织损伤程度有一定临床意义。     

Staging of liver fibrosis in chronic hepatitis B patients with a composite predictive model:A comparative study

AIM:To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B(CHB) patients.METHODS:Seventy-eight CHB patients were consecutively enrolled in this study.Liver biopsy was performed and blood serum was obtained at admission.Histological diagnosis was made according to the METAVIR system.Significant fibrosis was defined as stage score ≥ 2,severe fibrosis as stage score ≥ 3.The diagnostic accuracy of ...     

慢性乙型肝炎患者血清瘦素水平与肝纤维化程度相关

目的研究血清瘦素与慢性乙型肝炎肝脏炎症和肝纤维化程度之间的关系.方法20例慢性乙型肝炎患者在聚乙二醇α-2a干扰素治疗前及治疗48周、随访24周后进行肝穿刺病理学检查,另20例患者进行1次肝穿刺.采用ELISA方法检测40例慢性乙型肝炎患者血清瘦素水平,20名健康人作为对照组,对血清瘦素与肝组织炎症分级、纤维化分期间的关系进行分析.结果慢性乙型肝炎患者血清瘦素水平(12.89±7.47)ng/ml明显高于健康对照组(2.57±1.29)ng/ml,差异有统计学意义(P＜0.05).S0(5例)、S1(14例)、S2(16例)、S3(14例)、S4(11例)期肝纤维化血清瘦素水平分别为(2.62±0.89)ng/ml、(5.26±1.60)ng/ml、(13.15±4.52)ng/ml、(17.08±3.78)ng/ml、(21.56±5.89)ng/ml,随纤维化程度加重,血清瘦素水平增加;血清瘦素水平与肝组织纤维化分期成正相关(r=0.845,P＜0.01).20例患者在聚乙二醇α-2a干扰素治疗前、后肝组织纤维化计分分别为10.91±6.32和7.43±4.15,差异有统计学意义(P＜0.05);治疗前、后血清瘦素水平分别为18.35±4.93和13.57±5.39,差异有统计学意义(P=0.006).G0(4例)、G1(12例)、G2(22例)、G3(16例)、G4(6例)级炎症血清瘦素水平分别为(2.66±1.03)ng/ml、(9.04±4.92)ng/ml、(13.22±7.38)ng/ml、(16.19±7.71)ng/ml、(17.41±4.25)ng/ml,G0与G1级、G1与G2级患者血清瘦素水平差异无统计学意义(P=0.006),G2、G3、G4级患者血清瘦素水平差异无统计学意义(P＞0.05),G3～G4级患者血清瘦素水平与G1级相比,差异有统计学意义(P＜0.05).结论血清瘦素与慢性乙型肝炎肝组织纤维化分期密切相关.     

肝脏硬度值检测诊断慢性乙型肝炎患者肝组织纤维化的效能分析*

目的 探讨采用肝脏硬度测定（LSM）诊断慢性乙型肝炎（CHB）患者肝纤维化分期的效能。方法 2016年1月~2018年7月我院收治的112例CHB患者和选择同期健康志愿者30例,使用肝脏瞬时弹性检测仪（FT）检测LSM,所有患者均接受肝活检,采用Ishak评分系统行肝组织纤维化分期。结果 本组112例CHB患者经Ishak评分诊断为肝组织无肝纤维化（S0期）16例（14.3%）,轻度肝纤维化（S1期）40例（35.7%）,中度肝纤维化（S2~S3期）40例（35.7%）,重度肝纤维化和肝硬化（S4期）16例（14.3%）;肝组织纤维化S0期、S1期、S2~S3期和S4期LSM值分别为（5.4±0.8） kPa、（7.1±2.1） kPa、（9.9±2.5） kPa和（15.8±3.4） kPa,而正常志愿者LSM值为（5.3±0.9）kPa;分别以LSM=5.90、LSM=7.61、LSM=9.25和LSM=14.84为诊断S0期、S1期、S2~S3和S4期的截断点,诊断的曲线下面积分别为0.943、0.800、0.568和1.000,其诊断的灵敏度和特异度分别为100.0%和89.6%、100.0%和69.4%、100.0%和52.1%,和100.0%和100.0%。结论 使用FT检测LSM值对CHB患者肝组织纤维化分期有一定的诊断价值,值得在临床上进一步验证。