Liver transplantation for acute-on-chronic liver failure

Purpose  

To evaluate the outcome of liver transplantation for acute-on-chronic liver failure.     

Modified model for end-stage liver disease improves shortterm prognosis of hepatitis B virus-related acute-on-chronic liver failure

AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum lactate.METHODS This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and compared.RESULTS Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresponding mortality rates within three months were 75% and 90%, respectively.CONCLUSION The short-term prognosis of HBV-related ACLF was improved by using a modified MELD including serum lactate from the present 6-year clinical study.     

Predictors and outcome of emergent Liver transplantation for patients with acute-on-chronic liver failure

Background and aimsControversy exists over whether emergent liver transplantation (LT) should be performed for patients with acute-on-chronic liver failure (ACLF), especially for patients with multiple organ failure.MethodsA total of 110 ACLF patients, defined by the European Association for the Study of the Liver (EASL) Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) criteria were analyzed. The primary outcome was overall survival after ACLF diagnosis.ResultsDuring follow-up, 76 patients received LT (59 received deceased-donor LT and 17 patients received living-donor LT). The overall survival was better for patients who received LT than patients who did not (82.9% vs. 17.6%, P < 0.001). Among the 76 patients who received LT, the overall survival was not different according to ACLF grade at diagnosis (70.0%, 85.3%, and 84.4% at one-year for ACLF grades 1, 2, and 3, respectively, P = 0.45). The baseline model for end-stage liver disease (MELD) score and progression of the ACLF grade during the pre-transplant period were independent factors for survival after LT. The one-year survival rate was 92.3% for patients with baseline MELD scores of ≤ 32 without ACLF grade progression, whereas it was 33.3% for those with baseline MELD scores of > 32 and ACLF grade progression.ConclusionsEmergent LT provided a significant survival benefit to ACLF patients, regardless of the baseline ACLF grade. Post-LT outcomes were associated with baseline MELD scores and ACLF progression during the pre-transplant period, which might be used in the emergent LT plan for patients presenting with ACLF.     

Palliative care for patients with end-stage liver disease ineligible for liver transplantation

The proportion of patients with ESLD who will be managed without liver transplantation will increase in the near future, largely as a result of the increasing age of the population. Patients with ESLD are subject to many physical and psychosocial symptoms that negatively affect health-related quality of life. Sleep quality should be maximized by controlling pruritus and leg cramps. Many frequently used therapies are not supported by a strong evidence base. Advance directives should be addressed with all patients with ESLD, preferably in the outpatient setting before an acute deterioration. Medicare provides a hospice benefit for patients with ESLD, and referral to a hospice is appropriate for patients with an expected survival of 6 months or less.     

Risk factors for liver transplantation waiting list mortality

BACKGROUND AND AIM: The gap between the demand for liver transplantation and organ donation rates has a major impact on waiting list mortality. Understanding the risk factors that predict liver transplant waiting list death may help optimize organ allocation policy and reduce waiting list deaths. METHODS: We analyzed risk factors associated with waiting list mortality in the Liver Transplant Unit Victoria for the period 1988 through 2004. RESULTS: The mean annual waiting list mortality for the period examined was 10.2% (10.6% for adult and 6.4% for pediatric patients). Factors associated with waiting list death included female sex, fulminant hepatic failure, primary non-function, blood group O, more urgent United Network for Organ Sharing (UNOS)-derived medical status, a Child-Turcotte-Pugh (CTP) score >or=11, a model for end-stage liver disease (MELD) score >or=20, and a pediatric end-stage liver disease score >or=20. UNOS-derived medical status, CTP class, and MELD score were significant at the multivariate level. CONCLUSIONS: Disease severity scores, such as MELD, predict the risk of liver transplantation waiting list mortality. Use of such scores in organ allocation in Australian liver transplant units may result in reduced waiting list mortality.     

Risk factors for in-hospital mortality of patients with high model for end-stage liver disease scores following living donor liver transplantation

Background. Living donor liver transplantation (LDLT) for patients with high model for end-stage liver disease (MELD) scores is controversial due to its poor outcome. However, there is little information regarding which factor would negatively impact the outcome of patients with high MELD scores. The aim of this study was to identify factors associated with the in-hospital mortality of patients with high MELD scores after LDLT.Material and methods. All patients with an MELD scores ≥ 20 who received LDLT from 2005 to 2011 were recruited for the present study. Pre-and intra-operative variables were retrospectively and statistically analyzed. Results. A total of 61 patients were included in the current study. The overall 3-month survival rate was 82% for patients with high MELD scores. Preoperative renal dysfunction, hyponatremia, starting albumin level < 2.8 g/dL, preoperative renal replacement for severe renal failure, anhepatic period > 100 minutes and intraoperative red blood cell (RBC) transfusion ≥ 10 units were identified as potential risk factors by univariate analysis. However, only hyponatremia, preoperative dialysis and massive RBC transfusion were independent risk factors in a multivariate analysis. The 3-month survival rates of patients with two or more independent risk factors and patients with none or one risk factor were 91 and 25%, respectively. A significant difference was observed (P < 0.001).Conclusion. Hyponatremia, preoperative dialysis and massive RBC transfusion were related to poor outcome for sicker patients. Patients with two or more of the above-mentioned risk factors and high MELD scores may exhibit extremely poor short-term survival.     

Elevated neopterin levels are associated with acute-on-chronic liver failure and mortality in patients with liver cirrhosis

BackgroundMacrophage activation plays a central role in hepatic and systemic inflammation and is involved in the pathogenesis of acute-on-chronic liver failure (ACLF).AimsThis study aimed to investigate neopterin levels in patients admitted for acute decompensation (AD) of cirrhosis, evaluating its relationship with ACLF and prognosis.MethodsThis prospective cohort study included 205 adult subjects hospitalized for AD of cirrhosis. Twenty-one healthy subjects and 89 patients with stable cirrhosis were evaluated as controls.ResultsCirculating neopterin was higher in AD as compared to stable cirrhosis and healthy controls (p<0.001). ACLF was independently associated with higher neopterin levels (OR 1.015, 95% CI 1.002–1.028, p = 0.025). In the multivariate Cox regression analysis, neopterin levels (HR = 1.002, IC 95% 1.000–1.004, p = 0.041), Child–Pugh class C, and ACLF were predictors of 30-day survival. Among patients with ACLF, the Kaplan–Meier survival probability was 71.4% in those with neopterin levels < 25 nmol/L and 31.0% if neopterin ≥ 25 nmol/L (p<0.001).ConclusionsHigher circulating neopterin was associated with ACLF in patients hospitalized for AD of cirrhosis. Neopterin levels were also independently predictors of high short-term mortality, especially among patients with ACLF, and could represent a useful biomarker of macrophage activation in clinical practice.     

终末期肝病模型评分与肝移植

随着肝移植技术的逐渐成熟和新型免疫抑制剂的不断问世，肝移植已成为终末期肝病患者的最佳治疗方案。在美国，每年等待肝移植的患者超过18000人，但由于肝源所限，能进行肝移植的却只有5000人。CTP(Child Turcotte Pugh)分级因其本身固有的缺陷已不适于作为肝移植的标准，因此需要制定一个公平、合理的新标准来代替CTP分级。终末期肝病模型(model for end-stage liver disease，MELD)分级是2002年2月由美国器官分配联合网络(United Network for Organ Sharing，UNOS)颁布实施的成人肝移植的新标准。本文就肝移植标准的历史变化和MELD分级的产生、特点、在肝移植方面的应用与发展及目前存在的问题作一叙述。     

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.     

Outcomes of liver transplantation for end-stage biliary disease: A comparative study with end-stage liver disease

AIM: To evaluate the outcomes of patients with endstage biliary disease(ESBD) who underwent liver transplantation, to define the concept of ESBD, the criteria for patient selection and the optimal operation for decision-making.METHODS: Between June 2002 and June 2014, 43 patients with ESBD from two Chinese organ transplantation centres were evaluated for liver transplantation. The causes of liver disease were primary biliary cirrhosis(n = 8), cholelithiasis(n = 8), congenital biliary atresia(n = 2), graft-related cholangiopathy(n = 18), Caroli's disease(n = 2), iatrogenic bile duct injury(n = 2), primary sclerosing cholangitis(n = 1), intrahepatic bile duct paucity(n = 1) and Alagille's syndrome(n = 1). The patients with ESBD were compared with an end-stage liver disease(ESLD) case control group during the same period, and the potential prognostic values of multiple demographic and clinical variables were assessed. The examined variables included recipient age, sex, pre-transplant clinical status, pre-transplant laboratory values, operation condition and postoperative complications, as well as patient and allograft survival rates. Survival analysis was performed using Kaplan-Meier curves, and the rates were compared using log-rank tests. All variables identified by univariate analysis with P values 0.100 were subjected to multivariate analysis. A Cox proportional hazard regression model was used to determine the effect of the study variables on outcomes in the study group.RESULTS: Patients in the ESBD group had lower model for end-stage liver disease(MELD)/paediatric end-stage liver disease(PELD) scores and a higher frequency of previous abdominal surgery compared to patients in the ESLD group(19.2 ± 6.6 vs 22.0 ± 6.5, P = 0.023 and 1.8 ± 1.3 vs 0.1 ± 0.2, P = 0.000). Moreover, theoperation time and the time spent in intensive care were significantly higher in the ESBD group than in the ESLD group(527.4 ± 98.8 vs 443.0 ± 101.0, P = 0.000, and 12.74 ± 6.6 vs 10.0 ± 7.5, P = 0.000). The patient survival rate in the ESBD group was not significantly different from that of the ESBD group at 1, 3 and 5 years(ESBD: 90.7%, 88.4%, 79.4% vs ESLD: 84.9%, 80.92%, 79.0%, χ2 = 0.194, P = 0.660). The graftsurvival rates were also similar between the two groups at 1, 3 and 5 years(ESBD: 90.7%, 85.2%, 72.7% vs ESLD: 84.9%, 81.0%, 77.5%, χ2 = 0.003, P = 0.958). Univariate analysis identified MELD/PELD score(HR = 1.213, 95%CI: 1.081-1.362, P = 0.001) and bleeding volume(HR = 0.103, 95%CI: 0.020-0.538, P = 0.007) as significant factors affecting the outcomes of patients in the ESBD group. However, multivariate analysis revealed that MELD/PELD score(HR = 1.132, 95%CI: 1.005-1.275, P = 0.041) was the only negative factor that was associated with short survival time.CONCLUSION: MELD/PELD criteria do not adequately measure the clinical characteristics and staging of ESBD. The allocation system based on MELD/PELD criteria should be re-evaluated for patients with ESBD.     

乙型肝炎病毒感染所致慢加急性肝衰竭的临床预后分析

目的 对影响乙型慢加急性肝衰竭预后的单因素进行分析,探讨影响慢加急性肝衰竭患者预后的危险因素.方法 将我院2006年1月-2008年6月收治的480例乙型慢加急性肝衰竭患者作为研究对象,分为好转治愈组和无效死亡组,将两组患者的临床资料进行组间比较,将有意义的单因素进一步行Logistic回归分析.结果 133例治愈好转组及347例无效死亡组患者,年龄、基础疾病、肝衰竭分期、持续低钠血症、甲胎蛋白、凝血酶原活动度、总胆红素、肌酐、白蛋白、肝性脑病、腹水、消化道出血等的差异有统计学意义(P值均<0.05);性别、家族史、是否首次发病、有无休克血压等的差异无统计学意义(P值均>0.05).Logistic回归分析结果表明,凝血酶原活动度、低钠血症,肝性脑病、基础疾病和消化道出血是乙型慢加急性肝衰竭的独立危险因素(x2值分别为10.570,15.181,37.041,11.886,4.853,P值均<0.05).结论 凝血酶原活动度、低钠血症、肝性脑病、基础疾病和消化道出血5个因素对慢加急性肝衰竭的预后有重要意义.     

Stratified alpha-fetoprotein pattern accurately predicts mortality in patients with acute-on-chronic hepatitis B liver failure

Background: Alpha-fetoprotein (AFP) has been shown to predict the prognosis of liver disease in several studies. This study aimed to evaluate the prognostic value of stratified AFP in patients with acute-on-chronic hepatitis B liver failure (ACHBLF).

Methods: A total of 192 patients were included and AFP were categorized into quartiles. The prognostic value was determined for overall survival (OS) and assessed by Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazard regression analyses studied the association of all independent parameters with disease prognosis.

Results: The optimal cut-off points of AFP were: (Q1) 252.3–4800.0 ng/ml, (Q2) 76.0–252.2 ng/ml, (Q3) 18.6–75.9 ng/ml, and (Q4) 0.7–18.5 ng/ml. Based on the Kaplan-Meier analysis of the OS, each AFP quartile revealed a progressively worse OS and apparent separation (log-rank P = 0.006). The second-highest quartiles of AFP (Q2) always demonstrated an extremely favorable short-term survival. Combining the lowest AFP quartiles with a serum sodium < 131mmol/L or an INR ≥ 3.3 showed a poor outcome (90-days survival of 25.0% and 11.9% respectively).

Conclusions: Stratified AFP could strengthen the predictive power for short-term survival of patients with ACHBLF. Combining AFP quartiles with low serum sodium and high INR may better predict poor outcome in ACHBLF patients.     

多种肝功能评分系统预测血浆置换治疗肝衰竭患者预后的价值探讨

目的：探讨终末期肝病模型（MELD）和MELD-Na评分系统及Child-Pugh分级系统对血浆置换治疗的肝衰竭患者预后的价值。方法回顾性分析我院2005年1月至2012年9月收治的238例乙型肝炎肝衰竭患者的临床资料,应用MELD、MELD-Na和Child-Pugh评分系统判断患者在观察3个月期内的预后情况。结果在3个月的观察期内,本组患者生存145例,死亡93例（39.1%）;生存患者入院时凝血酶原时间、INR、血清总胆红素、血清钠和肌酐水平分别为（19.6±3.7）秒、（1.6±2.2）、（199.8±50.6）μmol/L、（137.6±7.7） mmol/L和（127.3±10.8）μmol/L,与死亡患者比[分别为（25.3±5.8）秒、（2.3±1.5）、（332.7±120.9）μmol/L、（127.0±14.6） mmol/L和（210.7±75.3）μmol/L],均有显著性统计学差异（P〈0.01）;生存患者MELD、MELD-Na和Child-Pugh计分分别为（19.3±6.9）、（21.1±4.6）和（11.4±2.3）,均显著低于死亡患者[分别为（29.2±13.4）、（32.4±5.7）和（15.2±6.7）,P〈0.05];MELD-Na和MELD评分系统在预测肝衰竭近期病死率方面优于Child-Pugh分级计分。结论MELD、MELD-Na评分系统和Child-Pugh分级系统对于肝衰竭患者的病情判断均有较好的价值,但MELD和MELD-Na评分系统对肝衰竭预后判断的价值更高。     

Feasibility of ABO-incompatible adult liv-ing donor liver transplantation for acute-on-chronic liver failure

<正>To the Editor:In Korea,the annual number of deceased donors for or gan transplantation per million people is still less than10.Thus,approximately 40%of patients with acute liver failure or acute-on-chronic liver failure undergo living donor liver transplantation(LDLT).~([1])Although the use of ABO-incompatible(ABOi)living donors is an attrac tive option,ABOi LDLT has very restricted applications     

Associations between body mass index and mortality in acute-on-chronic liver failure patients

Introduction and objectivesThe association between the level of body mass index (BMI) and the mortality of patients with critical liver disease remains unclear. This study aimed to examine the association between BMI and hospital mortality of patients with acute-on-chronic liver failure (ACLF).MethodsClinical data from 146 ACLF patients were collected and analyzed. BMI was categorized into three groups: lower BMI (<18.5 kg/m²), normal BMI (18.5–24.9 kg/m²), and overweight (25.0–32.0 kg/m²). BMI and laboratory parameters were measured one day before, or on the day of the start of the treatment. Values of BMI and laboratory parameters were compared between survivors and non-survivors, and then hospital mortality rates were compared among patients with different BMI levels.ResultsThe prognosis of ACLF patients was significantly correlated with international normalized ratio (INR), albumin and BMI. The ACLF patients with low albumin level and high INR values tend to have a high mortality rate. Also, survival time was significantly shorter in the ACLF patients with lower BMI, while patients with normal and overweight values had longer survival time.ConclusionsA graded association between BMI and hospital mortality with a strong significant trend was found in ACLF patients in China.