Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure

Summary. Background: It has been well established that hemostatic potential in patients with chronic liver disease is in a rebalanced status due to a concomitant decrease in pro‐ and antihemostatic drivers. The hemostatic changes in patients with acute liver injury/failure (ALI/ALF) are similar but not identical to the changes in patients with chronic liver disease and have not been studied in great detail. Objective: To assess thrombin generation and fibrinolytic potential in patients with ALI/ALF. Methods: We performed thrombin generation tests and clot lysis assays in platelet‐poor plasma from 50 patients with ALI/ALF. Results were compared with values obtained in plasma from 40 healthy volunteers. Results and conclusion: The thrombin generation capacity of plasma from patients with ALI/ALF sampled on the day of admission to hospital was indistinguishable from that of healthy controls, provided thrombomodulin was added to the test mixture. Fibrinolytic capacity was profoundly impaired in patients with ALI/ALF on admission (no lysis in 73.5% of patients, compared with 2.5% of the healthy controls), which was associated with decreased levels of the plasminogen and increased levels of plasminogen activator inhibitor type 1. The intact thrombin generating capacity and the hypofibrinolytic status persisted during the first week of admission. Patients with ALI/ALF have a normal thrombin generating capacity and a decreased capacity to remove fibrin clots. These results contrast with routine laboratory tests such as the PT/INR, which are by definition prolonged in patients with ALI/ALF and suggest a bleeding tendency.     

儿童急性肝衰竭的诊疗进展

急性肝衰竭（acute liver failure,ALF）是一种严重的累及多个系统的临床综合征,在短时间内出现严重的肝功能损伤,并有脑水肿、肝性脑病、多器官衰竭等并发症的出现,病死率极高。ALF在儿童中的确切发生率还不清楚,在需要肝移植的儿童患者中,ALF的患者占10％～15％。对儿童ALF的诊断和治疗,缺乏大规模、多中心的临床研究。目前儿童ALF的诊疗方案,主要来源于成人ALF的经验。但是,儿童ALF的病因、临床特点、发病机制等都有别于成人ALF,因此有必要对儿童ALF进行专门的探讨。本文就儿童ALF的诊疗进展作一综述。     

还原型谷胱甘肽治疗中毒性急性肾衰竭临床研究

目的观察还原型谷胱甘肽对中毒性急性肾衰竭的疗效。方法将急性肾衰竭46例随机分为对照组和治疗组。对照组常规综合治疗，治疗组在常规综合治疗的基础上加用还原型谷胱甘肽1．2g静脉滴注，1次／d。共用14-30d。结果治疗组患者少尿期、多尿期的持续时间、血肌酐恢复时间、尿渗透压恢复时间明显缩短（P＜0．05）；内生肌酐清除率明显增加（P＜0．05），尿NAG酶明显降低（P＜0．05），组问对比差异亦有显著性（P＜0．05）。结论在常规综合治疗基础上加用还原型谷胱甘肽治疗中毒性急性肾衰竭疗效更好。     

血液滤过联合灌流治疗肝移植术后急性肝衰竭的临床观察

目的评价血液滤过联合血液灌流对肝移植术后出现急性肝衰竭患者的临床治疗价值。方法采用血液滤过联合血液灌流治疗9例肝移植术后发生急性肝衰竭的患者,检测治疗前后血常规、肝肾功能等指标并进行比较。结果患者进行血液滤过联合血液灌流治疗后,血液生化指标较治疗前明显下降,其中总胆红素(TB)、血氨(NH3)、谷丙转氨酶(ALT)、尿素氮(BUN)、肌酐(Cr)治疗前后对比具有统计学意义,临床症状明显改善。结论对肝移植术后患者,进行血液滤过联合血液灌流治疗,可有效清除及吸附血液中TB、NH3、ALT、BUN、Cr,是肝移植术后恢复的有效措施之一。     

肝植移术后急性肾功能衰竭患者连续性肾脏替代治疗的护理

采用连续性肾脏替代疗法治疗原位肝移植术后急性肾功能衰竭患4例。通过连续监测生命体征，准确记录每小时出入量，严格按配方配制透析液和置换液，预防感染，保持血管通路通畅等护理措施，保证了连续肾脏替代治疗顺利进行。     

急性肝功能衰竭急诊肝移植围术期治疗的单中心经验探讨

背景：急性肝衰竭行急诊肝移植患者围手术期治疗的病情复杂,风险大,并发症多,死亡率高,与普通肝脏移植有着明显不同。目的：总结急诊肝移植治疗急性肝功能衰竭的围手术期治疗经验,以提高急性肝功能衰竭的治疗成功率。方法：回顾性分析38例因急性肝功能衰竭行急诊肝移植患者的临床资料,男21例,女17例,年龄15-69岁。其中乙型肝炎病毒性肝炎23例（其中乙型合并丁型肝炎2例）,Wilsons病7例,3例为毒蕈中毒,2例不明原因药物肝脏损害,1例雷公藤多甙中毒,1例为外伤行肝脏部分切除后失代偿,1例尸体肝移植后患者。结果与结论：38例患者生存时间为13-1740d,中位生存时间为634d。患者的围手术期存活率为76%,1年存活率为63%,2年存活率为58%。9例围手术期死亡原因包括脑水肿及颅内高压、肾功能衰竭、严重肺部感染、多脏器功能衰竭、凝血功能障碍（颅内出血、上消化道出血等）、急性成人呼吸窘迫综合征、移植物原发性无功能。目前急诊肝移植仍是治疗急性肝功能衰竭最有效的方法,出血、感染、排异反应是死亡的主要原因,肝移植围手术期间每一环节的处理,对于肝移植的成功和患者长期存活具有重要意义。     

尿肝型脂肪酸结合蛋白对急性失代偿性心力衰竭患者发生急性肾损伤的预测

目的 探讨尿液中肝型脂肪酸结合蛋白(uL FABP)在急性失代偿性心力衰竭（ADHF）患者发生急性肾损伤（AKI）早期预测中的价值。方法 入选ADHF患者57例,根据是否发生AKI分为两组。分别在入院时、入院12、24、48小时测血清肌酐(SCr)、uL FABP。根据受试者工作特征(ROC)曲线得到12、24、48小时uL FABP诊断AKI的诊断截断值、灵敏度、特异度及ROC曲线下面积(AUC)。结果 AKI组uL FABP水平明显高于非AKI组（P<0.01）,并且早于SCr的升高。ROC曲线分析表明,uL FABP入院12小时截断点为63.28 μg/g·Cr时AUC为0.785,敏感度和特异度分别83%和84%,并且随着时间的延长逐渐升高;24小时截断点为86.12 μg/g·Cr时AUC为0.876,敏感度85%,特异度88%;48小时截断点为105.30 μg/g·Cr时AUC为0.911,敏感度94%,特异度89%。结论 uL FABP可作为早期预测ADHF患者AKI的发病有效标志物,较传统指标SCr能更早预测AKI的发生。     

Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure

Defects in superoxide and hydrogen peroxide production may be implicated in the high incidence of bacterial infections in patients with acute liver failure (ALF). In the present study, oxygen radical production in patients with ALF due to paracetamol overdose was compared with that of healthy volunteers. Neutrophils from 14 ALF patients were stimulated via the complement receptors using zymosan opsonized with ALF or control serum. Superoxide and hydrogen peroxide production by ALF neutrophils stimulated with zymosan opsonized with ALF serum was significantly reduced compared with the control subjects ( P  < 0.01). This defect persisted when zymosan opsonized by control serum was used ( P  < 0.05). Superoxide and hydrogen peroxide production in neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP) from a further 18 ALF patients was unaffected compared with control neutrophils. Serum C3 complement levels were significantly reduced in ALF patients compared with control subjects ( P  < 0.0005). These results demonstrate a neutrophil defect in ALF due to paracetamol overdose, that is complement dependent but independent of serum complement, possibly connected to the complement receptor.     

TECAI型生物人工肝支持系统治疗急性肝衰竭犬的实验研究

目的评价经改进的TECAI型生物人工肝脏支持系统（bioartificial liver supportsyst em,BALSS）治疗醋氨酚诱发急性肝衰竭(acute liver failure,ALF)犬的有效性和安全性。方法采用多次皮下注射醋氨酚的方法建立ALF模型犬。分离中国实验用小型猪肝细胞并培养于BALSS中,对ALF犬进行6小时的治疗,观察治疗前后犬生理、生化和组织学的变化,与常规药物治疗组和对照组进行比较。结果注射醋氨酚48小时后,可建立ALF犬模型,模型成功率为63.16%。应用我们改进的酶消化法,平均从每只小型猪的肝脏可得到（0.8～3.0）×10     

实时二维剪切波弹性成像评价急性肝衰竭大鼠肝脏硬度

目的 探讨实时二维剪切波弹性成像（2D-SWE）对于检测大鼠急性肝衰竭（ALF）和指导预防性用药治疗的应用价值。方法 将28只雄性SD大鼠分为4组，即对照组（8只）、模型组（8只）、乳果糖组（6只）和美常安组（6只）。实验第1~8天，对美常安组予以美常安稀释后灌胃，乳果糖组予以乳果糖灌胃，对照组和模型组予以等量生理盐水。实验第6、7天，对模型组、乳果糖组和美常安组大鼠均腹腔注射硫代乙酰胺，对照组注射生理盐水。实验第8天，采用2D-SWE技术测量4组大鼠肝脏硬度值（LSM）。构建ROC曲线，根据AUC选出准确率最高的LSM进行组间比较。实验第9天，取大鼠肝组织行病理检查。结果 模型组主要病理表现为炎症、坏死；美常安组及乳果糖组炎症坏死程度较模型组减轻；对照组表现为正常肝组织。根据模型组LSM构建的ROC曲线中，平均值诊断效能最佳；以8.44 kPa为截断值，其AUC、敏感度和特异度分别为0.768、100%和62.50%。模型组LSM较其他3组明显升高（P均<0.05）。结论 ALF大鼠LSM增高。2D-SWE对检测ALF及预防性用药后疗效评估具有一定价值。     

167例急性肾功能衰竭患者预后的临床因素分析

目的：探讨影响急性肾功能衰竭（肾衰）患者预后的重要临床因素。方法：采用多元分析方法；回顾分析１６７例急性肾衰患者的１８个临床指标，从中筛选出对预后有重要影响的临床因素；建立判别函数。结果：急性心肌梗死（心梗）或心力衰竭（心衰）、昏迷、辅助呼吸、严重感染及透析前２４小时输液量与预后密切相关，由急性心梗或心衰、昏迷和透析前２４小时输液量３个变量组成判别函数，其阳性预测值和敏感度分别为８２．１％和８０．９％。结论：预防并及时治疗心、肺、脑器官衰竭和严重感染，严格遵循“量出为入，宁少勿多”的输液原则，是减少急性肾衰患者死亡的重要环节；判断函数有助临床医师估计患者预后并采取相应措施。     

Managing patients with acute liver failure: developing a tool for practitioners

Patients with acute liver failure (ALF) are treated on the general intensive care unit (ICU) within this regional centre for hepatology and liver transplantation. This group of patients are at high risk of developing cerebral oedema, but because of the associated coagulopathy, intracranial pressure is not measured invasively. The safe management of these patients is vital to their outcome, and yet, there is no national or local guidance on the best practice for this group of patients. An absence of guidelines, or evidence base specific to caring for hepatology patients, was highlighted as we reviewed local clinical practices and those at other liver specialty centres, the British Liver Trust and published literature. We identified a need to develop evidence-based guidance for staff caring for patients with ALF within ICUs. A systematic approach enabled us to identify best practice to support the development of a structured evidence-based approach to care.     

Successful treatment of drug‐induced acute liver failure with high‐volume plasma exchange

We report two patients with drug‐induced liver injury (DILI)‐related acute liver failure (ALF) who were successfully treated with high‐volume plasma exchange without liver transplantation. The first patient was a 66‐year‐old man admitted because of a perforated duodenal ulcer complicated with peritonitis and septic shock. After treatment with multiple antibiotics, the patient developed DILI and ALF. Grade 3 hepatic encephalopathy and profound jaundice were present. Symptoms and signs of ALF improved dramatically after initiation of plasma exchange. The patient was discharged uneventfully. The second patient was a 94‐year‐old man admitted for treatment of newly diagnosed pulmonary tuberculosis. DILI and ALF developed 5 days after initiation of anti‐tuberculosis treatment. Grade 4 hepatic encephalopathy was present. After plasma exchange, the patient's level of consciousness improved dramatically, and he recovered from ALF. These 2 cases show the potential of plasma exchange in the treatment of DILI despite occurrence acute liver failure. J. Clin. Apheresis, 28:430–434, 2013. © 2013 Wiley Periodicals, Inc.     

Hemodynamics and metabolic studies on septic shock in patients with acute liver failure

Backgrounds

Acute liver failure is often accompanied by hyperdynamic circulation, which is also a characteristic of septic shock. Pre-existing acute liver failure may worsen the hemodynamic impairment and prognosis in sepsis.

Aims

To evaluate the hemodynamic and metabolic characteristics and clinical outcomes of septic shock in patients with acute liver failure.

Methods

Twenty patients with acute liver failure and 19 patients without preexisting liver disease were evaluated. Systemic hemodynamics, arterial and mixed vein blood gases, arterial lactate levels, plasma renin activity, and plasma aldosterone levels were checked during the early phase of septic shock.

Results

In acute liver failure group, cardiac index (4.92 ± 1.13 vs 3.69 ± 1.06 L/min per square meter, P < .001) and oxygen delivery (604.7 ± 139.7 vs 485.4 ± 137.3 mL/min per square meter, P = .011) were significantly higher than those without preexisting liver diseases, while systemic vascular resistance index (1041.2 ± 503.3 vs 1409 ± 505.25 dyne·s/cm⁵·m²), oxygen consumption (119.1 ± 29.2 vs 162.4 ± 49.4 mL/min per square meter) and oxygen extraction ratio (20% ± 6% vs. 32% ± 8%) were significantly higher in the latter group. Furthermore, the patients with acute liver failure had higher arterial lactate (P = .026), plasma renin activity (P = .03), plasma aldosterone levels (P < .001), and intensive care unit as well as hospital mortality rates (P = .005, and 0.02 respectively).

Conclusions

In patients with acute liver failure, septic shock was characterized by an accentuated hyperdynamic circulation, hyperlactatemia and an augmented renin-angiotensin-aldosterone system activity. Pre-existing liver failure has a significant impact on the disease severity of septic shock and portends a grave prognosis.     

Recurrent acute liver failure associated with novel SCYL1 mutation:A case report

BACKGROUND Pediatric recurrent acute liver failure(RALF) with recovery between episodes is rare. Causes include autoimmune disease, which may flare and subside;intermittent exposure to toxins, as with ingestions; and metabolic disorders,among them the fever-associated crises ascribed to biallelic mutations in SCYL1,with RALF beginning in infancy. SCYL1 disease manifest with RALF, as known to date, includes central and peripheral neurologic and muscular morbidity(hepatocerebellar neuropathy syndrome). Primary ventilatory and skeletal diseases also have been noted in some reports.CASE SUMMARY We describe a Han Chinese boy in whom fever-associated RALF began at age 14 mo. Bilateral femoral head abnormalities and mild impairment of neurologic function were first noted aged 8 years 6 mo. Liver biopsy after the third RALF episode(7 years) and during resolution of the fourth RALF episode(8 years 6 mo) found abnormal architecture and hepatic fibrosis, respectively. Whole-exome sequencing revealed homozygosity for the novel frameshift mutation c.92_93 insGGGCCCT, p.(H32 Gfs~*20) in SCYL1(parental heterozygosity confirmed).CONCLUSION Our findings expand the mutational and clinical spectrum of SCYL1 disease. In our patient a substantial neurologic component was lacking and skeletal disease was identified relatively late.     

Serial changes of liver stiffness measured by acoustic radiation force impulse imaging in acute liver failure: a case report

Acoustic radiation force impulse (ARFI) imaging is a new technology used to determine liver elasticity. We report the case of a patient that survived hyperacute-type acute liver failure (ALF) and who showed a dramatic change in the value of shear wave velocity (SWV) measured by ARFI, which corresponded with the severity of her liver damage. The value of SWV increased significantly up to 3.6 ± 0.3 m/s during the encephalopathy phase and then decreased along with the recovery of liver function, the blood flow of the right portal vein, and the liver volume. These findings suggest the value of SWV in ALF as a reliable marker of liver tissue damage. Further investigations of the pathophysiological significance of SWV in ALF are warranted.