Prognostic factors and treatment effect of standard-volume plasma exchange for acute and acute-on-chronic liver failure: A single-center retrospective study

Patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) have a high risk of mortality. Few studies have reported prognostic factors for patients receiving plasma exchange (PE) for liver support. We conducted a retrospective analysis using data of 55 patients with severe ACLF (n?=?45) and ALF (n?=?10) who received standard-volume PE (1–1.5 plasma volume) in the ICU. Hepatitis B virus infection accounts for the majority of ACLF (87%) and ALF (50%) patients. PE significantly improved the levels of total bilirubin, prothrombin time and liver enzymes (P<0.05). Thirteen ACLF patients (29%) and one ALF patient (10%) underwent liver transplantation. Two ALF patients (20%) recovered spontaneously without transplantation. The overall in-hospital survival rates for ACLF and ALF patients were 24% and 30%, and the transplant-free survival rates were 0% and 20%, respectively. For the 14 transplanted patients, the one-year survival rate was 86%. Multivariate analysis showed that pre-PE hemoglobin (P?=?0.008), post-PE hemoglobin (P?=?0.039), and post-PE CLIF-C ACLF scores (P?=?0.061) were independent predictors of survival in ACLF. The post-PE CLIF-C ACLF scores ≥59 were a discriminator predicting the in-hospital mortality (area under the curve?=?0.719, P?=?0.030). Cumulative survival rates differed significantly between patients with CLIF-C ACLF scores ≤ 58 and those with CLIF-C ACLF scores ≥ 59 after PE (P< 0.05). The findings suggest that PE is mainly a bridge for liver transplantation and spontaneous recovery is exceptional even in patients treated with PE. A higher improvement in the post-PE CLIF-C ACLF score is associated with a superior in-hospital survival rate.     

慢加急性肝衰竭

慢加急性肝衰竭是指在慢性肝病基础上出现的急性肝功能失代偿,主要由出血或感染诱发,引起一系列病理生理过程,包括全身血液动力学改变、免疫麻痹与全身炎症反应综合征、肝肾综合征、肝性脑病等。慢加急性肝衰竭病例有部分与慢性肝衰竭相似,慢性肝衰竭应分为肝实质细胞损害为主型和间质细胞损害为主型两类,慢加急性肝衰竭类似于慢性肝衰竭间质细胞损害为主型。     

Clinical characteristics and 28-d outcomes of bacterial infections in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Acute-on-chronic liver failure(ACLF),which includes hepatic and multiple extrahepatic organ failure,is a severe emergency condition that has high mortality.ACLF can rapidly progress and requires an urgent assessment of condition and referral for liver transplantation.Bacterial infections(BIs)trigger ACLF and play pivotal roles in the deterioration of clinical course.AIM To investigate the clinical characteristics and 28-d outcomes of first BIs either at admission or during hospitalization in patients with hepatitis B virus(HBV)-ACLF as defined by the Chinese Group on the Study of Severe Hepatitis B(COSSH).METHODS A total of 159 patients with HBV-ACLF and 40 patients with acute decompensation of HBV-related chronic liver disease combined with first BIs were selected for a retrospective analysis between October 2014 and March 2016.The characteristics of BIs,the 28-d transplant-free survival rates,and the independent predictors of the 28-d outcomes were evaluated.RESULTS A total of 194 episodes of BIs occurred in 159 patients with HBV-ACLF.Among the episodes,13.4%were community-acquired,46.4%were healthcare-associated,and 40.2%belonged to nosocomial BIs.Pneumonia(40.7%),spontaneous bacterial peritonitis(SBP)(34.5%),and bloodstream infection(BSI)(13.4%)were the most prevalent.As the ACLF grade increased,the incidence of SBP showed a downward trend(P=0.021).Sixty-one strains of bacteria,including 83.6%Gramnegative bacteria and 29.5%multidrug-resistant organisms,were cultivated from 50 patients with ACLF.Escherichia coli(44.3%)and Klebsiella pneumoniae(23.0%)were the most common bacteria.As the ACLF grade increased,the 28-d transplant-free survival rates showed a downward trend(ACLF-1,55.7%;ACLF-2,29.3%;ACLF-3,5.4%;P<0.001).The independent predictors of the 28-d outcomes of patients with HBV-ACLF were COSSH-ACLF score(hazard ratio[HR]=1.371),acute kidney injury(HR=2.187),BSI(HR=2.339),prothrombin activity(HR=0.967),and invasive catheterization(HR=2.173).CONCLUSION For patients with HBV-ACLF combined with first BIs,pneumonia is the most common form,and the incidence of SBP decreases with increasing ACLF grade.COSSH-ACLF score,acute kidney injury,BSI,prothrombin activity,and invasive catheterization are the independent predictors of 28-d outcomes.     

肝功能衰竭肝性脑病大鼠5-羟色胺和去甲肾上腺素的变化

目的研究5-羟色胺(5-HT)及去甲肾上腺素(NA)在大鼠急性肝功能衰竭(ALF)和慢性肝功能衰竭(CLF)肝性脑病时的变化。方法将110只SD大鼠随机分为正常对照组(20只)、ALF组(45只)及CLF组(45只)。ALF模型按500mg/kg硫代乙酰胺(TAA)间隔24h两次灌胃;CLF模型按质量分数为0.03%的TAA作为饮用水灌饲10周,并根据每周体重的变化增减50%的TAA含量。造模成功后从眼底静脉丛取血,检测5-HT、NA、血氨和肝功能指标;处死动物,取肝、脑组织,光镜下观察组织病理学变化。结果ALF组和CLF组均出现不同程度的肝功能损害表现,血中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、白蛋白(ALB)、白蛋白/球蛋白(A/G)、血氨均有明显变化(P<0.05或P<0.01);肝脏及脑组织病理学符合ALF和CLF肝性脑病表现。ALF组和CLF组5-HT(16.06±1.08)μmol/L和(15.32±1.48)μmol/L均较正常对照组(2.75±0.26)μmol/L显著升高(P均<0.01),CLF组NA值下降(94.0±2.13)pmol/L比(121.2±14.8)pmol/L,P<0.05。结论5-HT在大鼠ALF和CLF所致肝性脑病时明显升高;NA在大鼠CLF所致肝性脑病时明显下降。     

红细胞分布宽度在慢加急性肝衰竭患者预后预测中的应用

目的 旨在探讨红细胞分布宽度（RDW）在慢加急性肝衰竭（ACLF）患者预测预后中的应用。方法 选取乙型肝炎病毒（HBV）相关性ACLF患者78例,根据预后分为生存及死亡组,检测患者外周血RDW水平及其他相关临床指标。结果 ACLF死亡患者外周血RDW水平高于生存患者（t=-3.568,P=0.004）。RDW与白细胞计数（WBC）、中性粒细胞绝对值/淋巴细胞绝对值（NLR）、总胆红素（TBIL）、终末期肝脏病评分（MELD）存在相关性（P值均<0.05）。受试者工作特征曲线（ROC）分析显示：RDW预测ACLF死亡率的ROC曲线下面积（AUC）为0.64,Cut off值为17.15%,灵敏度和特异度分别为54.2%和67.9%。多因素回归分析显示：RDW、NLR、国际标准化比值（INR）是ACLF患者短期死亡率的独立危险因素（OR值=1.444、1.305、1.891,P值均<0.05）,生存分析显示：RDW≥17.15%患者生存率低于RDW＜17.15%患者（P<0.05）。结论 外周血RDW是临床预测ACLF患者短期预后的简单、有效的指标。     

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     

Dengue and its effects on liver

Dengue has emerged as an important arboviral disease with significant impact on the disease burden in population residing in tropical countries. Dengue is spread by the bite of Aedes mosquito. The virus seems to have some hepatotoxic effects. Affliction of liver in form of derangements in the liver function tests is common and may include mild elevations in serum bilirubin, elevated transaminases and derangements in serum albumin. Although asymptomatic in most cases, clinical manifestations like jaundice, and acute liver failure (ALF) may occasionally complicate the clinical picture. Indeed, dengue has been implicated as an important cause of ALF in endemic countries. The present review focuses on the hepatic manifestations and the pathogenesis of the liver injury in dengue.     

Acute liver failure caused by herpes simplex virus in a pregnant patient: Is there a potential role for therapeutic plasma exchange?

A young woman presented with a febrile illness in the third trimester of pregnancy. Laboratory investigation revealed severe acute hepatitis with thrombocytopenia and coagulopathy. Liver injury progressed despite emergent caesarian section and delivery of a healthy infant. Therefore, therapeutic plasma exchange (TPE) was performed on three consecutive days post‐partum for a presumed diagnosis of acute liver failure (ALF) associated with pregnancy due to hemolysis, elevated liver enzymes, and low platelets (HELLP) or acute fatty liver of pregnancy (AFLP). Treatment with TPE was followed by biochemical and clinical improvement but during her recovery herpes simplex virus type 2 (HSV‐2) infection was diagnosed serologically and confirmed histologically. Changes in the immune system during pregnancy make pregnant patients more susceptible to acute HSV hepatitis, HSV‐related ALF, and death. The disease is characterized by massive hepatic inflammation with hepatocyte necrosis, mediated by both direct viral cytotoxicity and the innate humoral immune response. TPE may have a therapeutic role in acute inflammatory disorders such as HSV hepatitis by reducing viral load and attenuating systemic inflammation and liver cell injury. Further investigation is needed to clarify this potential effect. The roles of vigilance, clinical suspicion, and currently accepted therapies are emphasized. J. Clin. Apheresis, 28:426–429, 2013. © 2013 Wiley Periodicals, Inc.     

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.     

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.     

非生物型人工肝治疗儿童急性肝衰竭的疗效分析

目的:探讨非生物型人工肝治疗儿童急性肝衰竭(acute liver failure,ALF)的疗效。方法:回顾分析2008年8月—2013年7月复旦大学附属儿科医院收治的47例儿童ALF患者的临床资料,其中17例患者采用常规内科综合治疗(对照组),30例患者在常规内科综合治疗基础上采用非生物型人工肝治疗(研究组),分析ALF患儿的年龄分布特征及病因情况,比较研究组患儿治疗前后主要生化指标、凝血功能指标的变化以及2组患儿病死率。结果:47例ALF患儿中≤1岁患儿23例、1~3岁10例、≥3岁14例;34.0%患儿病因不明。与治疗前比较,研究组患儿治疗后血清总胆红素(total bilirubin,TBIL)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)均降低(P0.05),国际化标准比值(international normalized ratio,INR)、凝血酶原活度(prothrombin time activity,PTA)、白蛋白(albumin,ALB)均升高(P0.05)。研究组病死率低于对照组,但差异无统计学意义。结论:非生物型人工肝治疗儿童ALF是有效的,可改善患儿的生化指标、凝血功能及预后。     

Successful rescue of acute liver failure and hemophagocytic lymphohistiocytosis following varicella infection: A case report and review of literature

Herein we report a case of acute liver failure (ALF) and hemophagocytic lymphohistiocytosis (HLH) induced by varicella infection, successfully rescued by a combination therapy of acyclovir, supportive care, and immunosuppression with dexamethasone and etoposide. A previously healthy 16-year-old boy presented with generalized rash, fever, severe abdominal pain, and abnormal liver function within 4 d. Chickenpox was suspected, and acyclovir and intravenous immunoglobulin were started on admission. However, the patient’s condition deteriorated overnight with soaring transaminases, severe coagulopathy and encephalopathy. On the fourth day of admission, pancytopenia emerged, accompanied by hypofibrinogenemia and hyperferritinemia. The patient was diagnosed with ALF. He also met the diagnostic criteria of HLH according to the HLH-2004 guideline. Polymerase chain reaction (PCR) amplifications of varicella-zoster virus (VZV) were positive, confirming that VZV was a causative trigger for ALF and HLH. In view of the devastating immune activation in HLH, immunosuppression therapy with dexamethasone and etoposide was administered, in addition to high dose acyclovir. The patient’s symptoms improved dramatically and he finally made a full recovery. To our knowledge, this is only the second report of a successful rescue of ALF associated with HLH, without resorting to liver transplantation. The first case was reported in a neonate infected by herpes simplex virus-1. However, survival data in older children and adults are lacking, most of whom died or underwent liver transplantation. Our report emphasizes the clinical vigilance for the possible presence of HLH, and the necessity of extensive investigation for underlying etiologies in patients presenting with indeterminate ALF. Early initiation of specific therapy targeting the underlying etiology, and watchful immunosuppression such as dexamethasone and etoposide, together with supportive therapy, are of crucial importance in this life-threatening disorder.     

BMSC上清对治疗大鼠急性肝衰竭的临床研究分析

目的：探讨骨髓间充质干细胞（BMSC）上清治疗大鼠急性肝衰竭（ALF）的疗效,为其临床应用提供理论依据。方法采用全骨髓贴壁筛选法培养SD大鼠BMSC并收集其上清。腹腔注射D-氨基半乳糖胺（D-gal）建立大鼠ALF模型;将造模成功的大鼠随机分为治疗组和对照组,分别将等体积的BMSC上清及0.9%氯化钠注射液（NS）腹腔注射治疗3d,比较两组动物的肝功能、肝组织病理改变和7d生存率。结果（1）7d存活率分别为：BMSC上清治疗组70%,对照组20%,有显著差异（P＜0.05）。（2）BMSC上清治疗组的ALT、AST、TBIL明显降低,而对照组肝功能损害无明显改变,二者比较有显著性差异（P〈0.01）。（3）BMSC上清治疗组肝脏病理组织学损害明显改善。结论 BMSC上清腹腔注射治疗可明显改善ALF大鼠的肝功能及肝脏组织学损害,提高ALF大鼠的存活率,为ALF的治疗提供了新的途径。     

Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions

Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to restore impaired liver function with artificial extracorporeal blood purification systems. The first such systems were developed at the end of the 20^th century, providing solutions as bridging therapy, either for liver recovery or LT. They enhance the elimination of metabolites and substances that accumulate due to compromised liver function. In addition, they aid in clearance of molecules released during acute liver decompensation, which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy, multiple-organ failure, and other complications of liver failure. As compared to renal replacement therapies, we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems. Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging. The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins. Furthermore, conventional methods such as plasma exchange are being re-evaluated, and novel adsorption filters are increasingly being used for liver indications. These strategies are very promising for the treatment of liver failure. Nevertheless, the best method, system, or device has not been developed yet, and its probability of getting developed in the near future is also low. Furthermore, little is known about the effects of liver support systems on the overall and transplant-free survival of these patients, and further investigation using randomized controlled trials and meta-analyses is needed. This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy. It focuses on general principles of their function, and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF. In addition, we have outlined the basic advantages and disadvantages of each system.     

急性肝功能衰竭的综合治疗

急性肝功能衰竭(ALF)是一种病因多样、病理生理变化复杂、临床表现凶险的综合征,患者自然死亡率高。ALF的治疗包括祛除病因、维持血流动力学和内环境稳定、保护重要脏器功能、人工肝支持和肝脏移植。及早综合利用各种治疗手段可有效地改善患者预后。     

Ammonia predicts poor outcomes in patients with hepatitis B virus-related acute-on-chronic liver failure

BackgroundHepatic encephalopathy (HE) is a common feature of acute liver failure and has been reported to be associated with poor outcomes. Ammonia is thought to be central to the pathogenesis of HE, but its role in hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF) is unclear. The present study aimed to assess the prognostic role of ammonia level for patients with HBV‐ACLF.MethodsWe retrospectively recruited 127 patients diagnosed with HBV‐ACLF for the present study.ResultsAmmonia levels at the time of admission were higher among non‐surviving participants than in survivors. Increased ammonia level was found to be associated with severe liver disease and was identified as an independent predictor for mortality in patients with HBV‐ACLF.ConclusionsOur results suggest that high ammonia level at admission is an independent factor for predicting short‐term mortality in patients with HBV‐ACLF. Therefore, ammonia levels may represent a therapeutic target for this condition.     

Quality of life following emergency liver transplantation for acute liver failure

INTRODUCTION: Liver transplantation is an accepted and successful therapy for both acute and chronic liver diseases (CLDs), with good survival outcomes. Whilst the study of health-related quality of life (HRQoL) post transplantation for CLDs have been well documented, there is little data measuring HRQoL following liver transplantation for acute liver failure (ALF) patients. PATIENTS AND METHODS: Data were collected using between-method triangulation; however, only the quantitative element of the study is reported here. Measuring eight health domains, we distributed the short form 36 (SF-36) questionnaire by post to 96 acute and chronic transplant recipients. Differences between the groups were measured using both parametric and non-parametric t-tests. RESULTS: Overall, the patients showed a satisfactory HRQoL; there were no differences between either acute or chronic transplant groups in seven of the eight domains of quality of life. Among the patients transplanted for ALF, there were no differences in HRQoL between patients transplanted for paracetamol hepatotoxicity compared with other indications, and no variations in HRQoL related to recipient gender, employment or length of survival post transplantation. When compared with the UK SF-36 normal values to the ALF transplant recipients, there was a significantly lower physical functioning and role emotional scores. CONCLUSION: Regardless of aetiology, most of recipients transplanted for ALF have a HRQoL comparable with chronic transplant recipients.     

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.     

滤泡辅助性T细胞在急性肝衰竭小鼠模型中的变化及意义

目的:探讨滤泡辅助性T(T follicular helper,Tfh)细胞及相关细胞因子白细胞介素(interleukin,IL)-21在急性肝衰竭(acute liver failure,ALF)小鼠模型中的变化及意义。方法:将20只雌性C57BL/6小鼠随机分成2组,分别予脂多糖/D-氨基半乳糖或磷酸盐缓冲液(phosphate buffer solution,PBS)腹腔注射,6 h后采集血液、肝脏和脾脏组织标本。采用苏木精-伊红染色法分析肝脏病变情况;流式细胞术分析小鼠脾脏单个核细胞中Tfh细胞的频数;酶联免疫吸附试验分析血清中IL-21和肿瘤坏死因子α(tumor necrosis factorα,TNF-α)的水平。结果:ALF小鼠肝脏肿大而呈暗红色,肝细胞大量坏死和炎性细胞浸润,其血清中TNF-α及IL-21的水平均较正常对照组显著增高(P<0.01,P<0.05);而单个核细胞中CD4+CXCR5+、CD4+PD-1+、CD4+CXCR5+PD-1+T细胞频数亦较正常对照组显著升高(P<0.01)。结论:ALF小鼠脾脏单个核细胞中Tfh细胞频数显著增加,血清IL-21水平显著升高,推测Tfh细胞在ALF的发病过程中起重要作用,本研究结果可能为ALF的治疗提供新思路。     

Animal models applied to acute-on-chronic liver failure: Are new models required to understand the human condition?

The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.