Diagnostic criteria for acute liver failure due to Wilson disease

AIM: To describe the diagnostic criteria for acute liver failure due to Wilson disease (WD), which is an uncommon cause of acute liver failure (ALF). METHODS: We compared findings of patients presenting with ALF due to WD to those with ALF of other etiologies. RESULTS: Previously described criteria, such as low alkaline phosphatase activity, ratio of low alkaline phosphatase to total bilirubin or ratio of high aspartate aminotransferase (AST) to alanine aminotransferase (ALT), failed to identify patients with ALF due to WD. There were significant differences in low ALT and AST activities (53 ± 43 vs 1982 ± 938, P < 0.0001 and 87 ± 44 vs 2756 ± 2941, P = 0.037, respectively), low choline esterase activity (1.79 ± 1.2 vs 4.30 ± 1.2, P = 0.009), high urine copper concentrations (93.4 ± 144.0 vs 3.5 ± 1.8, P = 0.001) and low hemoglobin (7.0 ± 2.2 vs 12.6 ± 1.8, P < 0.0001) in patients with ALF caused by WD as compared with other etiologies. Interestingly, 4 of 7 patients with ALF due to WD survived without liver transplantation. CONCLUSION: In ALF, these criteria can help establish a diagnosis of WD. Where applicable, slit- lamp examination for presence of Kayser-Fleischer rings and liver biopsy for determination of hepatic copper concentration still remain important for the diagnosis of ALF due to WD. The need for liver transplantation should be evaluated carefully as the prognosis is not necessarily fatal.     

Etiology and treatment of acquired coagulopathies in the critically ill patient

Summary Excessive bleeding frequently complicates the care of critically-ill patients. Except in the case of trauma or in patients with known coagulopathies (e.g., hemophilia), the bleeding is generally not directly related to the illness that results in admission to the intensive care unit. In general, the causes of the bleeding can be divided into 3 categories: consumptive coagulopathies (e.g., DIC), bleeding related to ``hepatic issues' (i.e., liver dysfunction, vitamin K deficiency), and iatrogenic causes. This review will discuss the more common causes of bleeding in the critically-ill patient and outline diagnostic and treatment approaches for these patients. New experimental data linking activation of the coagulation and inflammatory systems with the development of multisystem organ failure is briefly discussed. Received: 8 November 1996 Accepted: 18 November 1996     

Acute liver injury,acute liver failure and acute on chronic liver failure: A clinical spectrum of poisoning due to Gyromitra esculenta

Gyromitra esculenta, also known as “false morel” is one of the most poisonous mushrooms. This species is found all over the world, growing in coniferous forest in early spring time. Common manifestation of poisoning includes gastrointestinal symptoms which include varied degrees of liver impairment.We describe three cases: acute liver injury, acute liver failure and acute-on-chronic liver failure due to G. esculenta poisoning. At admission patients presented with encephalopathy and features of liver failure. Two of them recovered completely following supportive management while the remaining patient who also had preexisting liver disease developed multiorgan failure and subsequently died.Although a rare occurrence, G. esculenta poisoning should be considered in the differential diagnosis of acute liver failure.     

近20年妊娠急性脂肪肝患者预后变化和死亡原因分析

目的 分析近20年我科诊治的妊娠急性脂肪肝(AFLP)患者的临床特征。方法 2002年1月～2011年12月北京佑安医院收治AFLP患者25例(A组),2012年1月～2022年1月收治28例(B组),对比分析两组临床表现、并发症、病死率变化和死亡原因。结果 A组和B组血清总胆红素水平分别为 (239.8±104.2)μmol/l和【(161.9±107.7)μmol/l, P=0.052】, A组肝功能异常率为12.0%,显著低于B组的42.9%(P=0.006);A组剖宫产率为76.0%,显著低于B组的100.0%(P=0.020);A组与B组DIC(40.0%对3.6%,P=0.001)和失血性休克发生率(24.0%和3.6%,P=0.028)存在显著性差异,而产后出血(48.0%对25.0%,P=0.081)无显著性差异;B组产妇病死率为3.6%而胎儿无死亡,显著低于A组的24.0%和12.1%(P<0.05)。结论 DIC和大出血是10年前AFLP产妇的主要死亡原因,近10年AFLP母婴病死率明显下降,但肝衰竭进展仍较常见,仍需早期识别和处理。     

反应停对急性肝衰竭的的预防作用

目的探讨反应停(Thal)对急性肝衰竭的预防作用.方法用D-半乳糖胺(D-GalN,600mg/kg,ip)和细菌脂多糖(LPS,5μg/只,H)复制大鼠急性肝衰竭模型,观察Thal对急性肝衰竭死亡率、细胞因子、转氨酶、肝组织形态学和单个核细胞TNFαmRNA表达的影响.结果Thal可降低急性肝衰竭的死亡率、TNFα和转氨酶的水平(P＜0.05),减轻肝细胞坏死的程度,抑制单个核细胞TNFαmRNA的表达.结论 Thal对实验性肝衰竭的预防和治疗有重大的意义.     

Liver transplantation for acute liver failure: outcome analysis

Summary. Acute liver failure (ALF) remains a major cause of morbidity and mortality. Before the availability of liver transplantation only 20% of patients with ALF survived. The clinical dilemma relates to the prognostication of these patients, as early liver transplantation has been associated with better outcomes. The eligibility for liver transplantation must therefore be quickly established. The patient's age, aetiology of disease, interval between the onset of jaundice and encephalopathy, blood pH, prothrombin time, serum bilirubin and serum creatinine levels has been identified as useful prognostic markers. The degree of hepatocyte necrosis on liver biopsy and estimated hepatic volume by computed tomography may also be valuable predictors of survival; however, further studies are needed.     

Down-regulated expression of AQP5 on lung in rat DIC model induced by LPS and its effect on the development of pulmonary edema

Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by the widespread activation of coagulation, which leads to failure of multiple organs in the body. DIC of rat with lipopolysaccharide (LPS) is associated with subsequent pulmonary edema. Lung tissue is highly water permeable and expresses several aquaporins (AQPs). We therefore explored whether AQP5 involved in the pathogenesis of LPS-induced lung edema. The rats were intravenously infused with LPS (30 mg/kg) for 4 h, 6 h, 8 h, 10 h, and 12 h to induce DIC. Platelets count (PLT), D-Dimer (DD), fibrinogen (FIB), prothrombin time (PT), and activated partial thromboplastin time (APTT) were determined. Real-time quantitative PCR and Western blot were used to analyze the mRNA and protein expression of AQP5. Lung samples were stained with hematoxylin-eosin and lung wet/dry weight (W/D) ratios were measured. Here, we demonstrated that PLT and FIB values were significant decreased, the values for DD, PT, and APTT were marked increased, microthrombus was observed in lung specimens, and simultaneously with the AQP5 showed down-regulated expression following LPS infused from 4 h to 12 h. However, histopathological changes such as pulmonary edema and the increased lung W/D weight ratio were observed after LPS infused from 6 h to 12 h. These results indicated that the decreased expression of AQP5 maybe induce liquid transport obstacles between alveolar and capillary, and provides the report of AQP5 gene regulation, revealing the pathogenesis of pulmonary edema in DIC model of rat.     

慢加急性肝衰竭患者血小板减少的可能原因

目的探讨引起慢加急性肝衰竭患者发生血小板减少的可能原因。方法选取南方医院肝病中心2011年12月至2014年8月住院的慢性乙型肝炎(CHB)、HBV相关肝硬化(CIR)、HBV相关慢加急性肝功能衰竭(ACLF)患者,收集患者相关临床资料,检测网织血小板比例、促血小板生成素水平、血小板活化比例(PAC-1、CD63、CD62p)、糖蕚素、可溶性CD163、凋亡血小板比例等指标,对以上指标进行相关和多元线性回归分析。结果研究共纳入191例患者,其中慢性乙型肝炎组68例,肝硬化组48例,慢加急性肝功能衰竭组75例。慢加急性肝功能衰竭患者血小板计数98(3~253)G/L较慢性乙型肝炎组172(24~327)G/L低(P0.01),与肝硬化患者88(22~244)G/L相当(P=0.913)。ACLF患者入院1周血小板计数71(4~208)G/L较入院当天97(21~267)G/L明显下降(P0.01)。慢加急性肝功能衰竭组患者脾脏厚度(40.4比35.1 mm,P=0.002)、D-二聚体(443.5比90 ug/L,P=0.002)、PT-INR(2.14比1.26,P0.01)、sCD163(5.33比1.81 ln mg/mL,P0.01)均高于慢性乙型肝炎组。但纤维蛋白原水平(1.24比2.25 g/L,P0.01)和血小板PAC-1(+)阳性率(3.33比10.7,P=0.002)均低于慢性乙型肝炎组。网织血小板比例、TPO、CD62p、CD63、糖蕚素、凋亡血小板比例在慢性乙型肝炎组与慢加急性肝功能衰竭组之间差异无统计学意义。血小板计数与脾脏厚度、PT-INR、总胆红素水平、血小板凋亡水平呈负相关,与纤维蛋白原水平、白蛋白水平、糖萼素水平呈正相关。多元线性回归分析显示,脾脏厚度、糖萼素水平,纤维蛋白原水平是ACLF患者血小板减少的独立危险因素(R2=0.597,P=0.011)。入院日的血小板计数可预测28天死亡(AUROC=0.72,P0.01)。结论慢加急性肝衰竭患者脾脏厚度、纤维蛋白原、糖萼素为血小板减少的独立危险因素。入院日血小板计数可预测患者的短期预后。     

成人Still病致肝功能衰竭行肝移植1例报告

<正>1临床资料患者,女,30岁,因间断关节胀痛1 a,尿黄15 d,面黄、目黄4 d,加重伴头晕2 d于2012年2月5日入院。既往:2010年6月于吉林大学第一医院风湿科诊断为"成人Still病",给予激素及免疫抑制剂治疗,于2010年8月因症状好转停药。同年9月份出现一过性皮疹,再次就诊,继续口服激素,2010年11月逐渐减量,至2011年3月停药。因症状缓解不明显,于2011年4月去上海某医院就诊,诊断"类风湿疾病",自行口服"风湿灵关节炎胶囊"直至发病前1周停药,共约4个月。入院前半个月出现尿黄,4 d前出现面黄、目黄,加重2 d。否认     

Neuropathological changes in the brain of pigs with acute liver failure

Abstract

Objective. Cerebral edema is a serious complication of acute liver failure (ALF), which may lead to intracranial hypertension and death. An accepted tenet has been that the blood-brain barrier is intact and that brain edema is primarily caused by a cytotoxic etiology due to hyperammonemia. However, the neuropathological changes in ALF have been poorly studied. Using a well characterized porcine model we aimed to investigate ultrastructural changes in the brain from pigs suffering from ALF. Materials and methods. Sixteen female Norwegian Landrace pigs weighing 27–35 kg were randomised into two groups: ALF (n = 8) and sham operated controls (n = 8). ALF was induced with an end-to-side portacaval shunt followed by ligation of the hepatic arteries. Biopsies were harvested from three different areas of the brain (frontal lobe, cerebellum, and brain stem) following eight hours of ALF and analyzed using electron microscopy. Results. Profound perivascular and interstitial edema were found in all three areas. Disruption of pericytic and astrocytic processes were seen, reflecting breakdown/lesion of the blood-brain barrier in animals suffering from ALF. Furthermore, neurons and axons were edematous and surrounded by vesicles. Severe damage to Purkinje neuron (necrosis) and damaged myelin were seen in the cerebellum and brain stem, respectively. Biopsies from sham operated animals were normal. Conclusions. Our data support the concept that vasogenic brain edema plays an important role in the development of intracranial hypertension in pigs with ALF.     

Arterial steroid injection therapy can inhibit the progression of severe acute hepatic failure toward fulminant liver failure

INTRODUCTION Although it is accepted that severe acute hepatic failure is self-limiting in most patients, it progresses to fulminant liver failure with a high mortality rate in some patients[1]. Liver transplantation (LT) is the only effective treatment f…     

急性肝衰竭病情严重程度评估

<正>急性肝衰竭(acute liver failure,ALF)被定义为以急性起病,无基础肝病史,2周以内出现Ⅱ期或以上肝性脑病等特征的临床症候群[1]。ALF以其发病急骤、进展迅速、预后凶险等特点成为临床诊治的难点。因此,早期对ALF患者进行病情严重程度评估并选择针对性的治疗方案是降低病死率的关键。1 ALF病因目前,东西方对于ALF的定义不完全相同,其     

Anti-inflammatory effect of recombinant thrombomodulin for fulminant hepatic failure

Fulminant hepatic failure(FHF) is a critical illness that can be comorbid to primary liver damage.FHF shows a high mortality rate,and patients with FHF require intensive therapy,including plasma apheresis.However,intensive care at the present is not enough to restore the severe liver damage or promote hepatocellular reproduction,and a standard therapy for the treatment of FHF has not been established.An 86-year-old female with FHF was admitted to our hospital.Her manifestation demonstrated a clinical situation of systemic inflammatory response syndrome(SIRS) and disseminated intravascular coagulation.A diagnosis of fulminant hepatitis was made according to the definition given in the position paper of the American Association for the Study of Liver Diseases.Her serum hepatocyte growth factor(HGF) level had increased to 11.84 ng/m L.The HGF level indicated massive liver damage as seen in FHF.Recombinant thrombomodulin(r TM) was administered daily from the admission day for 1 wk at 380 U/kg.The patient's white blood cells and C-reactive protein responded to the r TM treatment within a few days.The HGF level and PT recovered to the normal range.The levels of proinflammatory cytokines(tumor necrosis factor-α and interleukin-1β) were suppressed by the administration of r TM.The patient's hepatic function(e.g.,PT and albumin) completely recovered without plasma exchange.r TM may modulate the over-response of SIRS with the improvement of proinflammatory cytokines.The underlying mechanism is thought to be the inhibitory effect of r TM on highmobility group box 1(HMBG1).The pathogenesis of HMBG1 protein in fulminant hepatic failure has beenalready known.A novel favorable effect of r TM for SIRS would be promising for FHF,and the wide application of r TM for SIRS should be considered.     

Haemostatic problems in acute promyelocytic leukaemia

Despite the development of highly effective treatment strategies for acute promyelocytic leukaemia around 10% of patients die in the presentation period as a consequence of the associated bleeding diathesis. The cause of the coagulopathy is complex resulting from a combination of tissue factor (TF) and cancer procoagulant (CP) induced disseminated intravascular coagulation, exaggerated fibrinolysis due predominantly to enhanced expression of annexin II on APL blast cell membranes and blast cell production of cytokines. All-trans retinoic acid (ATRA) has revolutionised the treatment of APL. When combined with chemotherapy long term survival rates of up to 80% can be achieved. Commencement of ATRA induces APL blast cell differentiation and is associated with a rapid resolution of the bleeding tendency through a combination of effects which include up regulation of thrombomodulin and down regulation of TF and CP production and cell surface expression of annexin II.     

肝细胞移植治疗急性肝衰竭

“20世纪是药物治疗的年代，21世纪却是细胞治疗的年代”。细胞治疗是指将干细胞或由其分化产生的功能细胞植入病变部位代偿病变细胞丧失的功能，或将细胞经体外遗传操作后用于疾病治疗的方法。急性肝衰竭（acute liver failure，ALF）常规药物治疗疗效差，是一种病死率极高的临床综合征，在我国主要由病毒性肝炎引起。近几年开展的较为有效的治疗方法主要有原位肝移植、人工肝支持系统和肝细胞移植（hepatocyte transplantation，HTx）。肝移植被认为是目前治疗ALF的最有效方法，但供肝短缺、免疫排斥和高额费用限制了受益者范围。     

Wilson disease developing osteoarthritic pain in severe acute liver failure: A case report

BACKGROUND Wilson disease(WD) is a rare copper metabolism disorder with symptoms including hepatic disorders, neuropsychiatric abnormalities, Kayser-Fleischer rings, and hemolysis in association with acute liver failure(ALF). Osteoarthritis is a rare manifestation of WD. We experienced a case of WD with arthritic pain in the knee and liver cirrhosis. Here, we report the clinical course in a WD patient with arthritic pain and liver cirrhosis receiving combination therapy with Zn and a chelator and discuss the cause of arthritic pain.CASE SUMMARY We present an 11-year-old boy who developed osteoarthritis symptoms and ALF,with a New Wilson Index Score(NWIS) of 12. He was diagnosed with WD with decreased serum ceruloplasmin and copper levels, increased urinary copper excretion, and ATP7 B gene mutations detected on gene analysis. There was improvement in the liver cirrhosis, leading to almost normal liver function and liver imaging, one year after receiving combination therapy with Zn and a chelator. Moreover, his arthritic pain transiently deteriorated but eventually improved with a decrease in the blood alkaline phosphatase levels following treatment.CONCLUSION Patients with WD who develop ALF with an NWIS 11 may survive after treatment with Zn and chelators, without liver transplantation, when they present with mild hyperbilirubinemia and stage ≤ II hepatic encephalopathy.Osteoarthritis symptoms may improve with long-term Zn and chelator therapy without correlation of liver function in WD.     

Acute fatty liver of pregnancy associated with severe acute pancreatitis: A case report

Acute fatty liver of pregnancy is a rare disease that affects women in the third trimester of pregnancy. Although infrequent, the disease can cause maternal mortality. The diagnosis is not always clear until the pregnancy is terminated, and significant complications, such as acute pancreatitis, can occur. Pancreatic involvement typically only occurs in severe cases after the development of hepatic and renal impairment. To date, little knowledge is available regarding how the disease causes pancreatitis. Treatment involves supportive measures and pregnancy interruption. In this report, we describe a case of a previously healthy 26-year-old woman at a gestational age of 27 wk and 6 d who was admitted with severe abdominal pain and vomiting. This case illustrates the clinical and laboratory overlap between acute fatty liver of pregnancy and pancreatitis, highlighting the difficulties in differentiating each disease. Furthermore, the hypothesis for this overlapping is presented, and the therapeutic options are discussed.