慢加急性肝衰竭与慢性肝衰竭临床特征对比性分析

目的了解慢加急性肝衰竭(ACLF)与慢性肝衰竭(CLF)的临床特征及预后差异。方法 103例慢性重型肝炎患者按肝衰竭诊疗指南分为ACLF组(35例)和CLF组(68例),比较两组临床及实验室指标、常见并发症、MELD评分及预后。结果 CLF在慢性重型肝炎中占66.02%(68/103),患者年龄较大、病程较长;两组在血常规参数(WBC、HB、PLT、MPV)和凝血指标(PT、APTT、TT)均有差异(P<0.05,P<0.01);ACLF组肝功能AST、ALT、TBIL、ALB高于CLF组,GLO、TBA低于CLF组(P<0.05,P<0.01);两组腹水和肝性脑病发生率差异有统计学意义(P<0.01);ACLF组MELD分值低于CLF组,其预后优于CLF组(P<0.05,P<0.01)。结论 ACLF和CLF在好发年龄、病程、血常规参数、凝血功能、肝功能指标、并发症腹水和肝性脑病发生率、MELD评分及预后均有差异。肝衰竭指南符合国情,有重要的临床应用价值。     

吲哚菁绿清除试验对急性/慢加急性肝衰竭患者预后的评价

目的通过观察肝衰竭患者吲哚菁绿清除试验15 min滞留率(ICG R15)与其他常用肝脏储备功能指标变化,评判ICGR15对预测肝衰竭患者预后的价值。方法对32例肝衰竭患者采用脉搏光度分析法(即PDD法),检测入院时ICG R15,同时检测常用肝功能指标,包括ALT、AST、TBil、Alb、GGT、胆碱酯酶(CHE)、凝血酶原活动度(PTA)和胆固醇(CHO)。计算MELD评分。同时选取15例慢性肝炎患者、94例肝硬化患者作为对照,检测ICG R15及同期Alb、CHE、PTA和CHO。对肝衰竭组患者进行了3个月随访,确定存活及死亡情况,并对ICG R15、MELD评分进行受试者工作特征曲线(ROC曲线)分析,探讨其对预后的判断意义。结果(1)在慢性肝炎、肝硬化和肝衰竭组ICG R15、Alb、PTA、CHE、CHO在3组间差异均有统计学意义(P<0.05),其中ICG R15,Alb,CHE,PTA在慢性肝炎和肝硬化组差异有统计学意义(P<0.05);ICG R15、PTA、CHO在肝硬化和肝衰竭组差异有统计学意义(P<0.05)。(2)3个月时肝衰竭存活组与死亡组ICG R15分别为(50.05±9.04)%、(56.27±5.65)%,差异有统计学意义(P<0.05)。(3)对肝衰竭组ICG R15和MELD评分进行ROC曲线分析,二者曲线下面积分别为75.9%和60.4%,ICG R15对预后的判断优于MELD评分;当ICG R15为52.5%时对预后判断的敏感性为80%,特异性为70.6%。(4)肝衰竭组入院时ICG R15≤50%10例,3个月时死亡2例,病死率20%;>50%22例,3个月时死亡14例,病死率63.6%。结论 (1)在慢性肝炎、肝硬化和肝衰竭组,随着病情加重PTA逐渐下降,ICG R15逐渐升高,两者反映病情的严重程度优于其他指标。(2)比较ICG R15和MELD评分对肝衰竭患者的预后判别作用,ICG R15对3个月预后的判断优于MELD评分。(3)肝衰竭患者ICG R15>50%时预后较差。     

Association between model for end-stage liver disease and spontaneous bacterial peritonitis

OBJECTIVE: To determine whether a greater Model for End-Stage Liver Disease (MELD) score is associated with a greater risk of spontaneous bacterial peritonitis (SBP). METHODS: Our retrospective case-control study enrolled 271 consecutive patients with cirrhosis and ascites who underwent diagnostic paracentesis upon hospital admission (2002-2005). After excluding immunosuppressed patients, those recently exposed to antibiotics, those with a potential confounding etiology for ascites, and those with a prior history of SBP, 111 were included in the study. SBP was defined as a paracentesis yielding>or=250 neutrophils/mL ascites fluid. Multivariable logistic regression was performed to determine the odds ratio for the development of SBP associated with MELD score and grouped MELD score (or=25). Potential confounders assessed included age, diabetes mellitus, gender, race, alcohol use, serum sodium, and etiology of liver disease. RESULTS: Twenty-nine of 111 hospitalized patients with cirrhosis were found to have SBP. Patient characteristics were similar between groups with and without SBP. The mean MELD score for patients with SBP was 24 and for those without 18 (P=0.0003). The odds ratio for developing SBP by each MELD point was 1.11 (1.05-1.19, P=0.001). Patients with MELD>or=25 had an odds ratio of 9.67 (2.35-39.82, P=0.002) for SBP, compared to subjects with MELD相似文献   

Model for end-stage liver disease: end of the first decade

The Model for End-stage Liver Disease (MELD) score is the basis for allocation of liver allografts for transplantation in the United States. The MELD score, as an objective scale of disease severity, is also used in the management of patients with chronic liver disease in the nontransplant setting. Several models have been proposed to improve the MELD score. The authors believe that the MELD score is, by design, continually evolving and lends itself to continued refinement and improvement to serve as a metric to optimize organ allocation in the future.     

Current status and future of liver transplantation

Liver transplantation has rapidly advanced from an experimental therapy to a mainstream treatment option for a wide range of acute and chronic liver diseases. Indications for liver transplant have evolved to include previously contraindicated conditions such as hepatocellular carcinoma and alcohol-related liver disease. Cirrhosis from chronic hepatitis C infection remains the most common indication today. Multidisciplinary evaluation for liver transplantation is intended to confirm the patient's suitability and identify the appropriate timing of transplant, although the latter is problematic as a result of the ongoing donor organ shortage. Deceased liver donors have been increasing in number, but increasing donor age has been associated with less satisfactory posttransplant results. Living donor liver transplant is a dramatic but very infrequent procedure; risk to the living donor is of paramount concern. The main focus of deceased donor allocation has transitioned from waiting time to estimation of the likelihood of death without transplant (medical urgency), and now relies upon a laboratory-based Model for End-Stage Liver Disease (MELD) score for candidates with chronic liver disease. Those with acute liver failure are prioritized ahead of those with chronic conditions. Although not used as a direct criterion for allocation, development of the concept of transplant survival benefit, i.e., the extra years of life attributable to transplant, has facilitated better ordering of those candidates likely to have the most benefit, while restricting access to those whose lives will be extended minimally or not at all. Overall posttransplant outcomes have steadily improved, with unadjusted 5-year patient survival rates of 77% among patients transplanted with MELD score between 15 and 20, and 72% for those with MELD scores between 21 and 30.     

Prochlorperazine-induced cholestasis in a patient with alpha-1 antitrypsin deficiency

A case of a 58-year-old woman with history of bilateral lung transplant secondary to alpha-1 antitrypsin deficiency (PIZZ), who presented with a severe drug-induced cholestasis secondary to prochlorperazine is reported. After 27 months of prochlorperazine use, she developed liver failure consisting of jaundice with ascites. Computed tomography of the abdomen, abdominal ultrasonography as well as an endoscopic retrograde cholangiopancreatography showed no evidence for biliary obstruction. Liver biopsy demonstrated diffuse ongoing advanced chronic cholestasis, moderate portal and periportal inflammation as well as bridging fibrosis. During her hospitalization, her total bilirubin increased to 38.6 mg/dL; alkaline phosphatase to 362 IU/L, alanine aminotransferase to 71 IU/L and aspartate aminotransferase to 88 IU/L. After several weeks of ursodiol therapy without clinical improvement the prochlorperazine was discontinued and was followed by a rapid improvement in her measures of liver injury. An immediate decline of her serum total bilirubin and alkaline phosphatase to 21.4 mg/dL and 258 IU/L, respectively, occurred strongly suggesting the idea of a prochlorperazine-induced injury.     

A patient with hepatitis C-related liver cirrhosis and hepatocellular carcinoma who was cured with an orthotopic liver transplantation and interferon therapy

A patient with hepatitis C virus (HCV)-related liver cirrhosis and hepatocellular carcinoma (HCC) was treated successfully with an orthotopic liver transplantation (OLT) followed by interferon therapy. The 36-year-old Japanese man was diagnosed as having liver cirrhosis in 1983. HCC was detected in 1991, and by 1994, jaundice and ascites had developed. The patient underwent OLT in June 1995, after which hepatitis C recurred, with elevated aminotransferases. His liver biopsy specimen showed chronic active hepatitis. He was given interferon-alpha three times weekly for 24 weeks in 1999. Six months after the end of the interferon treatment, the patient's serum HCV RNA became negative, with normalization of aminotransferases, and his liver histology exhibited amelioration of fibrosis and inflammation. At the present time, he remains free of HCC (more than 6.5 years after the OLT) and free of HCV RNA (more than 2.5 years since interferon therapy was completed). This is the first Japanese patient whose HCC was cured by OLT and HCV was eradicated by interferon therapy.     

Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure

BackgroundAcute-on-chronic liver failure (ACLF) is characterised by acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by ascites and/or encephalopathy in patients with previously diagnosed or undiagnosed chronic liver disease. We studied the clinical, biochemical and etiological profiles of ACLF patients investigating variables which could predict mortality.MethodsConsecutive ACLF patients were enrolled and given standard intensive care management. They were monitored for predictors of 90-day mortality.Results91 patients were included; besides jaundice (median bilirubin 23.1 mg/dL) and coagulopathy, acute onset ascites with or without encephalopathy was the presenting symptom in 92%. In all patients a first diagnosis of chronic liver disease was made, mainly due to hepatitis B (37%) or alcohol (34%). Reactivation of chronic hepatitis B and alcoholic hepatitis were the common acute insults. The 90-day mortality was 63%. On multivariate analysis, hepatic encephalopathy, low serum sodium, and high INR were found to be independent baseline predictors of mortality. Amongst all severity scores studied, MELD, SOFA and APACHE-II scores had AUROCs of >0.8 which was significantly higher than that of Child–Turcotte–Pugh.ConclusionsACLF has very high mortality. Hepatic encephalopathy, low serum sodium and high INR predict poor outcome. Mortality can also be predicted by baseline MELD, SOFA or APACHE-II scores.     

不同肝病基础的慢加急性肝衰竭患者临床特征和预后评分模型预测效能比较

目的 探讨不同肝病基础的慢加急性肝衰竭(ACLF)患者临床特征及其各预后评分模型对病情判断的价值。方法 采用回顾性队列研究分析2017年1月～2018年12月我院收治的262例ACLF患者的临床资料,排除70例,在纳入的192例患者中,其肝病基础分别为非肝硬化慢性肝病(A组,n=54)、代偿期肝硬化(B组,n=87)和失代偿期肝硬化(C组,n=51)。分别采用Child-Pugh评分、MELD评分、欧洲肝病学会慢性肝衰竭研究组CLIF-C ACLF评分模型和中国重型乙型肝炎研究组(COSSH)模型预测28 d和90 d生存情况。结果 三组性别、年龄和病因构成比相比,均无显著性差异(P>0.05);三组血清TBIL和INR均无显著性差异(P >0.05);C组腹水和细菌感染发生率分别为70.6%和47.1%,显著高于B组的62.1%和33.3%或A组的40.7%和22.2%(P <0.05);A组28 d和90 d生存率分别为63.0%和59.3%,与B组的69.0% 和57.5%或C组的56.9%和47.1%比,均无显著性差异(P >0.05);血清TBIL、Cr、INR和肝性脑病是ACLF患者90 d死亡的影响因素;MELD、CLIF-C ACLFs和COSSH-ACLFs模型预测生存的效能显著优于Child-Pugh评分,而以MELD评分的效能最优。结论 不同肝病基础的ACLF患者临床特征和并发症存在差异,预后也存在一定的差异,可能需要更长时间的观察。     

Clinical and histological recovery from “life-threatening” severe acute alcoholic hepatic failure with complete hepatofugal portal blood flow

A 25-year-old man who was a heavy alcohol drinker was admitted to our hospital after presenting with general malaise, dyspnea, abdominal distension, systemic edema and jaundice. His liver function tests showed hyperbilirubinemia and prolonged prothrombin time, and a computed tomography scan and ultrasound showed liver atrophy and massive ascites. Furthermore, Doppler ultrasound revealed complete hepatofugal portal blood flow in the portal trunk and intrahepatic portal branches. Causes other than alcohol were excluded, and he was diagnosed as having severe acute alcoholic hepatic failure (Maddrey’s discriminant function score 43.3, MELD score 21), although not clinically typical. He was treated with anti-coagulation therapy according to the precise evaluation of portal blood flow by Doppler ultrasound, and marked clinical, biochemical and hemodynamic improvements were observed. Liver biopsy performed 2 months after onset showed submassive necrosis with pericellular fibrosis. Liver biopsy performed three years after onset showed mild portal fibrosis with a marked improvement. Doppler ultrasound is an indispensable tool for evaluating patients with severe acute hepatitis.     

Application of the model for end-stage liver disease score for transjugular intrahepatic portosystemic shunt in cirrhotic patients with refractory ascites and renal impairment

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) can manage severe complications of portal hypertension. The Mayo Clinic group proposed a so-called model for end-stage liver disease (MELD) to predict survival in cirrhotic patients. High creatinine levels determine a decrease in calculated survival chances with MELD but functional renal disease can be reversed by TIPS. The aim of this study was to evaluate the efficacy of MELD in predicting survival after TIPS, particularly in patients with refractory ascites associated with functional renal failure. METHODS: This retrospective analysis examines 68 cirrhotic patients who underwent elective TIPS: 48 patients had refractory ascites and 20 patients had recurrent variceal bleeding. Multivariate analysis was used to establish predictive parameters of survival after TIPS. Kaplan-Meier and log-rank tests were used to compare survival rates observed in our patients with those evaluated with the MELD score. RESULTS: The age of patients was the only variable shown to have an independent value in predicting survival after TIPS. In patients undergoing shunting for refractory ascites, the survival rates at 6, 12 and 24 months after the procedure were significantly higher than expected with the MELD score. CONCLUSIONS: The MELD scale may underestimate the efficacy of TIPS in end-stage cirrhotic patients with refractory ascites and functional kidney dysfunction. Further studies are needed to confirm this finding and ultimately to assess a correction factor to better predict survival after TIPS in patients with functional renal impairment.     

Evaluation of the increase in model for end-stage liver disease (DeltaMELD) score over time as a prognostic predictor in patients with advanced cirrhosis: risk factor analysis and comparison with initial MELD and Child-Turcotte-Pugh score

BACKGROUND/AIMS: The model for end-stage liver disease (MELD) has been used to prioritize cirrhotic patients awaiting liver transplantation. The change in MELD score over time (DeltaMELD) may have additional prognostic value. We investigated the ability of DeltaMELD to predict the outcome of advanced cirrhosis and prospectively assessed the factors associated with increasing DeltaMELD. METHODS: Risk factors were determined in 58 prospectively followed-up patients. The predictive power of DeltaMELD, initial MELD and Child-Turcotte-Pugh (CTP) score was compared by using c-statistic in 351 patients. RESULTS: Ascites (P=0.020) and hepatic encephalopathy (P=0.023) were significantly associated with increasing MELD score at 3 months. The area under receiver operating characteristic (ROC) curve for DeltaMELD/month was 0.779 compared with 0.718 for MELD (P=0.130) and 0.528 for CTP score (P<0.001) at 6 months; the area was 0.822, 0.744 and 0.528, respectively (P=0.018 and <0.001, respectively) at 12 months. DeltaMELD/month >2.5 was the only significant prognostic predictor at 6 (odds ratio: 9.8, P<0.001) and 12 months (odds ratio: 16.3, P<0.001) in multivariate logistic analysis. CONCLUSIONS: Increasing MELD score is associated with the onset of ascites and encephalopathy. DeltaMELD is superior to initial MELD and CTP scores to predict intermediate term outcome in patients with advanced cirrhosis.     

Chronic liver failure-consortium acute-on-chronic liver failure and acute decompensation scores predict mortality in Brazilian cirrhotic patients

AIM To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian patients.METHODS This is a prospective cohort study designed to assess the prognostic performance of the chronic liver failure-consortium(CLIF-C) acute decompensation score(CLIF-C AD) and CLIF-C acute-on-chronic liver failure score(CLIF-C ACLF),regarding 28-d and 90-d mortality,as well as to compare them to other prognostic models,such as Model for End-Stage Liver Disease(MELD),MELD Sodium(MELD-Na),ChildPugh(CP) score,and the CLIF-C Organ Failure score(CLIF-C OF). All participants were adults with acute decompensation of cirrhosis admitted to the Emergency Department of a tertiary hospital in southern Brazil. Prognostic performances were evaluated by means of the receiver operating characteristic(ROC) curves,area under the curves(AUC) and 95%CI.RESULTS One hundred and thirteen cirrhotic patients were included. At admission,18 patients had acute-onchronic liver failure(ACLF) and 95 individuals had acute decompensation(AD) without ACLF,of which 24 eventually developed ACLF during the course of hospitalization(AD evolving to ACLF group). The AD group had significantly lower 28-d(9.0%) and 90-d(18.3%) mortality as compared to the AD evolving to ACLF group and to the ACLF group(both P 0.001). On the other hand,28-d and 90-d mortalities were not significantly different between AD evolving to ACLF group and ACLF group(P = 0.542 and P = 0.708,respectively). Among patients with ACLF,at 28 d from the diagnosis,CLIF-C ACLF was the only score able to predict mortality significantly better than the reference line,with an AUC(95%CI) of 0.71(95%CI: 0.54-0.88,P = 0.021). Among patients with AD,all prognostic scores performed significantly better than the reference line regarding 28-d mortality,presenting with similar AUCs: CLIF-C AD score 0.75(95%CI: 0.63-0.88),CP score 0.72(95%CI: 0.59-0.85),MELD score 0.75(95%CI: 0.61-0.90),MELD-Na score 0.76(95%CI: 0.61-0.90),and CLIF-C OF score 0.74(95%CI: 0.60-0.88). The same occurred concerning AUCs for 90-d mortality: CLIF-C AD score 0.70(95%CI: 0.57-0.82),CP score 0.73(95%CI: 0.62-0.84),MELD score 0.71(95%CI: 0.59-0.83),MELD-Na score 0.73(95%CI: 0.62-0.84),and CLIF-C OF score 0.65(95%CI: 0.52-0.78).CONCLUSION This study demonstrated that CLIF-C ACLF is the best available score for the prediction of 28-d mortality among patients with ACLF. CLIF-C AD score is also useful for the prediction of mortality among cirrhotic patients with AD not fulfilling diagnostic criteria for ACLF,but it was not superior to other well-established prognostic scores.     

The MELD score in patients awaiting liver transplant: strengths and weaknesses

Adoption of the Model for End-stage Liver Disease (MELD) to select and prioritize patients for liver transplantation represented a turning point in organ allocation. Prioritization of transplant recipients switched from time accrued on the waiting list to the principle of "sickest first". The MELD score incorporates three simple laboratory parameters (serum creatinine and bilirubin, and INR for prothrombin time) and stratifies patients according to their disease severity in an objective and continuous ranking scale. Concordance statistics have demonstrated its high accuracy in stratifying patients according to their risk of dying in the short-term (three months). Further validations of MELD as a predictor of survival at various temporal end-points have been obtained in independent patient cohorts with a broad spectrum of chronic liver disease. The MELD-based liver graft allocation policy has led to a reduction in waitlist new registrations and mortality, shorter waiting times, and an increase in transplants, without altering overall graft and patient survival rates after transplantation. MELD limitations are related either to the inter-laboratory variability of the parameters included in the score, or to the inability of the formula to predict mortality accurately in specific settings. For some conditions, such as hepatocellular carcinoma, widely accepted MELD corrections have been devised. For others, such as persistent ascites and hyponatremia, attempts to improve MELD's predicting power are currently underway, but await definite validation.     

Acute liver failure due to enalapril

This report presents a 46-year-old man who was treated for hypertension with the angiotensin-converting-enzyme (ACE) inhibitor enalapril. After 3 years of continuous treatment he presented with jaundice and progressive liver failure that continued despite withdrawal of the medication. The patient was taking no other medication. All known causes of acute liver failure could be excluded indicating a drug-induced liver damage after long-term treatment with enalapril. Analysis of liver biopsies revealed a pathomorphological pattern comparable to than observed in severe halothane hepatitis. Serological studies including T-cell stimulation with enalapril and a broad spectrum of tests for autoimmunity including autoantibodies against calreticulin, the major Ca2+ and Zn2+ binding protein of the endoplasmic reticulum and suggested to be involved in the pathogenesis of halothane hepatitis were negative. Thus, the mechanism of enalapril-induced liver injury remains obscure. Liver failure progressed and finally led to orthotopic liver transplantation. To our knowledge, this is the longest duration of chronic treatment with an ACE inhibitor before liver failure occurred. In addition, liver failure progressed despite withdrawal of the medication. It is concluded that even after long-term treatment with an ACE inhibitor liver failure may be induced. Therefore, regular monitoring of liver enzymes should be considered.     

An exploratory analysis of patient factors influencing acceptance of extended criteria liver grafts

Introduction and ObjectivesThere is a shortage of ideal donor organs with consequential increasing waitlist times, drop-off, and mortality. Teams have thus extended the donor criteria. Little is known about patients’ actual choices and what factors may influence their decisions regarding different extended criteria liver grafts.Patients and MethodsThe documented acceptance or refusal of seven extended criteria liver graft types of patients consented for transplant in a single institution over a 2-year period was reviewed. Patient factors including sex, age, indication, aetiology, and model for end-stage liver disease (MELD) score were analysed using logistic regression.ResultsMost patients were willing to accept most graft types. MELD score did not impact the acceptance or refusal of any graft type. Older patients and those with hepatocellular carcinoma (HCC) or ascites had significantly higher rates of acceptance. Hepatitis B or C disease aetiology was predictive of willingness to accept a similarly infected graft, respectively. HCC was predictive of acceptance of grafts from donors with a cancer history.ConclusionsIn general, patients embrace the available extended criteria donors. Our analysis suggests that consent should be revisited as patients deteriorate or ameliorate on the waitlist, especially if in the form of ascites or HCC but not necessarily MELD score.     

Giant cell hepatitis: an unusual cause of fulminant liver failure

Giant cell hepatitis is a very rare disease of unknown origin. It has been hypothesized that drugs, viral infections, or autoimmune reactions may play a pathogenetic role. Here, we describe a 33 year old patient with bacterial bronchitis who was treated with doxycycline (100 mg/d) for one week. Furthermore the patient complained of malaise and a distinct jaundice. Liver parameters increased dramatically (AST 4670 U/l, ALT 5350 U/l, bilirubin 226 μmol/l) and liver function was impaired (INR = 1,45). The ultrasound scan showed a hepatomegaly with no signs of cirrhosis, normal spleen size and normal bile ducts; liver perfusion was normal. No evidence of Wilson's disease, hemochromatosis, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, hepatitis A, B, C and E, HIV, CMV, VZV, adenoviral infections, or paracetamol intoxication was found. Subsequently, the patient developed acute liver failure (AST 2134 U/l, ALT 2820 U/l, bilirubin 380 μmol/l, INR 3.0) and a beginning renal failure. Therefore, he was transferred to our transplant center. Due to increasing confusion and somnolence due to cerebral edema mechanical ventilation was needed. Because of an acute renal failure and severe hepatic encephalopathia MARS-hemodialysis was performed. Three weeks after the appearance of the jaundice he underwent liver transplantation (MELD 40). Surprisingly, in the explanted liver the diagnosis of giant cell hepatitis was made. Today--2 years after successful liver transplantation--the patient is in very good condition with normal liver function. In conclusion, giant cell hepatitis is a rare cause of acute liver failure that is often recognized only histologically.     

Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis

Background and Objectives: Acute hepatitis A and E are recognized triggers of hepatic decompensation in patients with cirrhosis, particularly from the Indian subcontinent. However, the resulting acute‐on‐chronic liver failure (ACLF) has not been well characterized and no large studies are available. Our study aimed to evaluate the clinical profile and predictors of 3‐month mortality in patients with this distinctive form of liver failure. Methods: ACLF was diagnosed in patients with acute hepatitis A or E [abrupt rise in serum bilirubin and/or alanine aminotransferase with positive immunoglobulin M anti‐hepatitis A virus (HAV)/anti‐hepatitis E virus (HEV)] presenting with clinical evidence of liver failure (significant ascites and/or hepatic encephalopathy) and clinical, biochemical, endoscopic (oesophageal varices at least grade II in size), ultrasonographical (presence of nodular irregular liver with porto‐systemic collaterals) or histological evidence of cirrhosis. Clinical and laboratory profile were evaluated, predictors of 3‐month mortality were determined using univariate and multivariate logistic regression and a prognostic model was constructed. Receiver‐operating curves were plotted to measure performance of the present prognostic model, model for end‐stage liver disease (MELD) score and Child–Turcotte–Pugh (CTP) score. Results: ACLF occurred in 121 (3.75%) of 3220 patients (mean age 36.3±18.0 years; M:F 85:36) with liver cirrhosis admitted from January 2000 to June 2006. It was due to HEV in 80 (61.1%), HAV in 33 (27.2%) and both in 8 (6.1%). The underlying liver cirrhosis was due to HBV (37), alcohol (17), Wilson's disease (8), HCV (5), autoimmune (6), Budd‐Chiari syndrome (2), haemochromatosis (2) and was cryptogenic in the rest (42). Common presentations were jaundice (100%), ascites (78%) and hepatic encephalopathy (55%). Mean (SD) CTP score was 11.4±1.6 and mean MELD score was 28.6±9.06. Three‐month mortality was 54 (44.6%). Complications seen were sepsis in 42 (31.8%), renal failure in 45 (34%), spontaneous bacterial peritonitis in 27 (20.5%), UGI bleeding in 15(11%) and hyponatraemia in 50 (41.3%). On univariate analysis, ascites, hepatic encephalopathy, renal failure, GI bleeding, total bilirubin, hyponatraemia and coagulopathy were significant predictors of mortality. Multivariate analysis revealed grades 3 and 4 HE [odds ratio (OR 32.1)], hyponatraemia (OR 9.2) and renal failure (OR 16.8) as significant predictors of 3‐month mortality and a prognostic model using these predictors was constructed. Areas under the curve for the present predicted prognostic model, MELD, and CTP were 0.952, 0.941 and 0.636 respectively. Conclusions: ACLF due to hepatitis A or E super infection results in significant short‐term mortality. The predictors of ominous outcome include grades 3 and 4 encephalopathy, hyponatraemia and renal failure. Present prognostic model and MELD scoring system were better predictors of 3‐month outcome than CTP score in these patients. Early recognition of those with dismal prognosis may permit timely use of liver replacement/supportive therapies.     

Evolution of liver transplant organ allocation policy: Current limitations and future directions

Since the adoption of the model for end-stage liver disease(MELD) score for organ allocation in 2002, numerous changes to the system of liver allocation and distribution have been made with the goal of decreasing waitlist mortality and minimizing geographic variability in median MELD score at time of transplant without worsening post-transplant outcomes. These changes include the creation and adoption of the MELD-Na score for allocation, Regional Share 15, Regional Share for Status 1, Regional Share 35/National Share 15, and, most recently, the Acuity Circles Distribution Model. However, geographic differences in median MELD at time of transplant remain as well as limits to the MELD score for allocation, as etiology of liver disease and need for transplant changes. Acute-onchronic liver failure(ACLF) is a subset of liver failure where prevalence is rising and has been shown to have an increased mortality rate and need for transplantation that is under-demonstrated by the MELD score. This underscores the limitations of the MELD score and raises the question of whether MELD is the most accurate, objective allocation system. Alternatives to the MELD score have been proposed and studied, however MELD score remains as the current system used for allocation. This review highlights policy changes since the adoption of the MELD score, addresses limitations of the MELD score, reviews proposed alternatives to MELD, and examines the specific implications of these changes and alternatives for ACLF.