Predicting utility of a model for end stage liver disease in alcoholic liver disease

瞄准：作为短术语(30 d 和 90 d ) 的预言者为结束阶段肝疾病验证 Maddrey 判别式函数分数和模型的统计实用程序在有含酒精的肝炎并且到的病人的死亡与含酒精的肝炎在临床的特征和病人的实验室变量之中估计预示的因素。方法：有含酒精的肝炎的诊断的 34 个病人承认从 2000 ～ 2005 的雅典的大学医院在当前的回顾的学习被估计，统计分析被进行到 Hippokration。结果：30-d 和 90-d 死亡率在 5.9% 点被报导(2/34 ) 并且 14.7%(5/34 ) 分别地。重要关联为结束阶段肝疾病为模型被表明( P30 = 0.094 ， P90 = 0.046 )并且 Maddrey 判别式功能分数( P30 = 0.033 ， P90 = 0.038 )与 30-d 和 90-d 死亡而一个重要协会也为丙氨酸 aminotransferase 被建立( P = 0.057 )，血纤维蛋白降级产品( P = 0.048 )并且C反应的蛋白质( P = 0.067 )与 90-d 死亡。为 30-d 死亡，在曲线下面的区域是 0.969 (95%CI：0.902-1.036， P = 0.028 ) 为为结束阶段肝疾病 20 和 0.984 的模型(95%CI：0.942-1.027， P = 0.023 ) 为 Maddrey 判别式功能分数与最佳割掉 30.5 的点(敏感 1，特性 0.937 ) 并且 108.68 (敏感 1，特性 0.969 ) 分别地。因此，为 90-d 死亡，在曲线下面的区域是 0.762 (95%CI：0.559-0.965， P = 0.065 ) 为为结束阶段肝疾病 20 和 0.752 的模型(95%CI：0.465-1.038， P = 0.076 ) 为 Maddrey 判别式功能分数与最佳割掉 19 的点(敏感 0.6，特性 0.6 ) 并且 92 (敏感 0.6，特性 0.946 ) 分别地。为不同分数范畴的观察 Kaplan Meier 幸存率与木头等级测试和更高的分数相比价值与更低的幸存被相关。结论：为结束阶段肝疾病和 Maddrey 判别式功能分数的模型的相等被当前的学习暗示，由阴谋的接收装置起作用的曲线和估计的幸存率验证了。90-d 死亡的独立预言者也被验证了的 C 反应的蛋白质，血纤维蛋白降级产品和丙氨酸 aminotransferase 的一个统计上重要的实用程序。

Palliative care for end-stage liver disease and acute on chronic liver failure:A systematic review

BACKGROUND End stage liver disease(ESLD)represents a growing health concern characterized by elevated morbidity and mortality,particularly among individual ineligible for liver transplantation.The demand for palliative care(PC)is pronounced in patients grappling with ESLD and acute on chronic liver failure(ACLF).Unfortunately,the historical underutilization of PC in ESLD patients,despite their substantial needs and those of their family caregivers,underscores the imperative of seamlessly integrating PC principles into routine healthcare practices across the entire disease spectrum.AIM To comprehensively investigate the evidence surrounding the benefits of incorporating PC into the comprehensive care plan for individuals confronting ESLD and/or ACLF.METHODS A systematic search in the Medline(PubMed)database was performed using a predetermined search command,encompassing studies published in English without any restrictions on the publication date.Subsequently,the retrieved studies were manually examined.Simple descriptive analyses were employed to summarize the results.RESULTS The search strategies yielded 721 references.Following the final analysis,32 fulllength references met the inclusion criteria and were consequently incorporated into the study.Meticulous data extraction from these 32 studies was undertaken,leading to the execution of a comprehensive narrative systematic review.The review found that PC provides significant benefits,reducing symptom burden,depressive symptoms,readmission rates,and hospital stays.Yet,barriers like the appeal of transplants and misconceptions about PC hinder optimal utilization.Integrating PC early,upon the diagnosis of ESLD and ACLF,regardless of transplant eligibility and availability,improves the quality of life for these patients.CONCLUSION Despite the substantial suffering and poor prognosis associated with ESLD and ACLF,where liver transplantation stands as the only curative treatment,albeit largely inaccessible,PC services have been overtly provided too late in the course of the illness.A comprehensive understanding of PC's pivotal role in treating ESLD and ACLF is crucial for overcoming these barriers,involving healthcare providers,patients,and caregivers.

Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease:A meta-analysis

BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated cirrhosis.Nevertheless,some studies have contested the prognostic value of NLR in ESLD.AIM To investigate the ability of NLR to predict ESLD.METHODS Databases,such as Embase,PubMed,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Weipu,and Wanfang,were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD.Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1.RESULTS A total of thirty studies involving patients with end-stage liver disease(ESLD)were included in the evaluation.Among the pooled results of eight studies,it was observed that the Neutrophil-to-Lymphocyte Ratio(NLR)was significantly higher in non-survivors compared to survivors(random-effects model:standardized mean difference=1.02,95%confidence interval=0.67-1.37).Additionally,twenty-seven studies examined the associations between NLR and mortality in ESLD patients,reporting either hazard ratios(HR)or odds ratios(OR).The combined findings indicated a link between NLR and ESLD mortality(randomeffects model;univariate HR=1.07,95%CI=1.05-1.09;multivariate HR=1.07,95%CI=1.07-1.09;univariate OR=1.29,95%CI=1.18-1.39;multivariate OR=1.29,95%CI=1.09-1.49).Furthermore,subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality,with Asian studies demonstrating a more pronounced effect.CONCLUSION Increased NLR in patients with ESLD is associated with a higher risk of mortality,particularly in Asian patients.NLR is a useful prognostic biomarker in patients with ESLD.

Indocyanine green clearance test and model for end-stage liver disease score of patients with liver cirrhosis

BACKGROUND: The indocyanine green (ICG) clearance test (clearance rate (K) and retention rate at 15 minutes (R(15))) is a sensitive indicator to evaluate liver function. The model for end-stage liver disease (MELD) score has emerged as a useful tool for estimating the mortality of patients awaiting liver transplantation and has recently been validated on patients with liver diseases of various etiologies and severity. In this study, we investigated the correlation between the ICG clearance test and MELD score of patients with liver cirrhosis. METHODS: From June 2007 to March 2008, 52 patients with liver cirrhosis admitted to our center were classified into Child-Pugh class A (8 patients), B (14) and C (30). The ICG clearance test (K value and R(15)) was performed by ICG pulse spectrophotometry (DDG-3300K), and the MELD scores of patients were calculated. RESULTS: As the Child-Pugh classification of liver function gradually deteriorated, the K value decreased, while R(15) and MELD score increased. There were significant statistical differences in K value, R(15) and MELD score in patients with different Child-Pugh classifications. Significant correlations were found between the parameters of the ICG clearance test (K value and R(15)) and MELD score. A negative correlation was observed between K value and MELD score (r=-0.892, P < 0.05), while a positive correlation was observed between R(15) and MELD score (r=0.804, P < 0.05). CONCLUSIONS: The ICG clearance test and MELD score are good parameters for evaluating liver function. Moreover, K value and R(15) have significant correlations with MELD score, especially the K value, which may be a convenient and appropriate indicator to evaluate liver function of patients with liver cirrhosis.

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.

Comparison of four models for end-stage liver disease in evaluating the prognosis of cirrhosis

AIM: To investigate the prognostic value of the model for end-stage liver disease (MELD) and three new MELD-based models combination with serum sodium in decompensated cirrhosis patients-the MELD with the incorporation of serum sodium (MELD-Na), the integrated MELD (iMELD), and the MELD to sodium (MESO) index. METHODS: A total of 166 patients with decompensated cirrhosis were enrolled into the study. MELD, MELD- Na, iMELD and MESO scores were calculated for each patient following the original formula on the first day of admission. All patients were followed up at least 1 year. The predictive prognosis related with the four models was determined by the area under the receiver operating characteristic curve (AUC) of the four parameters. Kaplan-Meier survival curves were made using the cut-offs identif ied by means of receiver operating characteristic (ROC). RESULTS: Out of 166 patients, 38 patients with signifi cantly higher MELD-Na (28.84 ± 2.43 vs 14.72 ± 0.60), iMELD (49.04 ± 1.72 vs 35.52 ± 0.67), MESO scores (1.59 ± 0.82 vs 0.99 ± 0.42) compared to the survivors died within 3 mo (P < 0.001). Of 166 patients, 75 with markedly higher MELD-Na (23.01 ± 1.51 vs 13.78 ± 0.69), iMELD (44.06 ± 1.19 vs 34.12 ± 0.69), MESO scores (1.37 ± 0.70 vs 0.93 ± 0.40) than the survivors died within 1 year (P < 0.001). At 3 mo of enrollment, the iMELD had the highest AUC (0.841), and was followed by the MELD-Na (0.766), MESO (0.723), all larger than MELD (0.773); At 1year, the iMELD still had the highest AUC (0.783), the difference between the iMELD and MELD was statistically significant (P < 0.05). Survival curves showed that the three new models were all clearly discriminated the patients who survived or died in short-term as well as intermediate-term (P < 0.001). CONCLUSION: Three new models, changed with serum sodium (MELD-Na, iMELD, MESO) can exactly predict the prognosis of patients with decompensated cirrhosis for short and intermediate period, and may enhance the prognostic accuracy of MELD. The iMELD is better prognostic model for outcome prediction in patients with decompensated cirrhosis.

Analysis of prognosis on patients with severe viral hepatitis using the model for end-stage liver disease

AIM: To study the practical use of the model for endstage liver disease (MELD) on clinic and assess its validity by the concordance (C)-statistic in predicting the prognosis of the patient with severe viral hepatitis.METHODS: One hundred and twenty-one patients were divided into plasma exchange group and non-plasma exchange group, and were graded with MELD formula.The death rate was observed within 3 mo.RESULTS: Eighty-one patients died within 3 mo (35 cases in PE group, 46 cases in non-PE group). The mortality of patients in PE group whose MELD score between 20-30and 30-40 were 31.6% and 57.7%, respectively, but in non-PE cases they were 67.6%, 81.3% respectively.There was significant difference between PE group and non-PE group (P＜0.05). However, the mortality of patients whose MELD score higher than 40 were 93.3% in PE group and 100% in non-PE group and there was no significant difference between the two groups (P= 0.65＞0.05). The optimal cut-off values of MELD to predict the prognosis of patients were 30 in PE group whose sensitivity, specificity and C-statistic were 80.0%, 52.0% and 0.777, but in non-PE group they were 25, 82.6%, 86.7% and 0.869, respectively.CONCLUSION: The MELD score can act as a disease severity index for patients with severe viral hepatitis, and the mortality of the patient increases with the increase of the MELD score. The MELD can accurately predict the short-term prognosis of patients with severe viral hepatitis.

Relationship between model for end-stage liver disease score and left ventricular function in patients with end-stage liver disease

BACKGROUND:Decreased cardiac contractility has been observed in cirrhosis,suggesting a latent cardiomyopathy in these patients.This study was designed to evaluate left ventricular structure and function in patients with end-stage liver disease by the model for end-stage liver disease(MELD) scoring system. METHODS:We recruited 82 patients(72 male,10 female; mean age 50.3±8.9 years)with end-stage liver disease who underwent orthotopic liver transplantation between January 2002 and May 2008.Seventy-eight patients had cirrhosis and 4 had primary liver cancer.Patients were categorized into three groups on the basis of MELD score:≤9(27 patients, 33%);10-19(40,49%);and≥20(15,18%).The relationship between MELD score and cardiac structure and function was determined.Preoperative assessments of blood biochemistry, blood coagulation,serum virology,echocardiography and electrocardiography were performed. RESULTS:MELD score was positively correlated with enlarged left atrial diameter,increased interventricular septum thickness(IVST),increased aortic flow,corrected QT interval (QTc)extension and cardiac output(P=0.033,0.002,0.000, 0.000 and 0.009,respectively).International normalized ratio also had a correlation with the above parameters and enlarged left ventricular end-diastolic diameter(P=0.043,0.010,0.000, 0.001,0.016 and 0.008,respectively).Serum creatinine was positively correlated with IVST(r=0.257,P=0.020),but negatively correlated with early maximal ventricular filling velocity/late diastolic or atrial velocity ratio(r=-0.300, P=0.006).A difference of QTc>440 ms among the three groups was statistically significant(χ2=9.791,P=0.007).CONCLUSIONS:Abnormalities in cardiac structure and function are common in patients with end-stage liver disease. MELD score is a practically useful approach for the assessment of cardiac function in such patients.

Survival outcomes of right-lobe living donor liver transplantation for patients with high Model for End-stage Liver Disease scores

BACKGROUND: Controversy exists over whether living donor liver transplantation (LDLT) should be offered to patients with high Model for End-stage Liver Disease (MELD) scores. This study tried to determine whether a high MELD score would result in inferior outcomes of right-lobe LDLT. METHODS: Among 411 consecutive patients who received right-lobe LDLT at our center, 143 were included in this study. The patients were divided into two groups according to their MELD scores: a high-score group (MELD score ≥25; n=75) and a low-score group (MELD score 【25; n=68). Their demographic data and perioperative conditions were compared. Univariable and multivariable analyses were performed to identify risk factors affecting patient survival. RESULTS: In the high-score group, more patients required preoperative intensive care unit admission (49.3% vs 2.9%; P【0.001), mechanical ventilation (21.3% vs 0%; P【0.001), or hemodialysis (13.3% vs 0%; P=0.005); the waiting time before LDLT was shorter (4 vs 66 days; P【0.001); more blood was transfused during operation (7 vs 2 units; P【0.001); patients stayed longer in the intensive care unit (6 vs 3 days; P【0.001) and hospital (21 vs 15 days; P=0.015) after transplantation;more patients developed early postoperative complications (69.3% vs 50.0%; P=0.018); and values of postoperative peak blood parameters were higher. However, the two groups had comparable hospital mortality. Graft survival and patient overall survival at one year (94.7% vs 95.6%; 95.9% vs 96.9%), three years (91.9% vs 92.6%; 93.2% vs 95.3%), and five years (90.2% vs 90.2%; 93.2% vs 95.3%) were also similar between the groups. CONCLUSIONS: Although the high-score group had signifi-cantly more early postoperative complications, the two groups had comparable hospital mortality and similar satisfactory rates of graft survival and patient overall survival. Therefore, a high MELD score should not be a contraindication to right-lobe LDLT if donor risk and recipient benefit are taken into full account.

Living donor liver transplantation for high model for endstage liver disease score:What have we learned?

AIM: To assess the impact of model for end-stage liver disease(MELD) score on patient survival and morbidity post living donor liver transplantation(LDLT). METHODS: A retrospective study was performed on 80 adult patients who had LDLT from 2011-2013. Nine patients were excluded and 71 patients were divided into two groups; Group 1 included 38 patients with a MELD score < 20, and Group 2 included 33 patients with a MELD score > 20. Comparison between both groups was done regarding operative time, intra-operative blood requirement, intensive care unit(ICU) and hospital stay, infection, and patient survival.RESULTS: Eleven patients died(15.5%); 3/38(7.9%)patients in Group 1 and 8/33(24.2%) in Group 2 with significant difference(P = 0.02). Mean operative time, duration of hospital stay, and ICU stay were similar in both groups. Mean volume of blood transfusion and cell saver re-transfusion were 8 ± 4 units and 1668 ± 202 m L, respectively, in Group 1 in comparison to 10 ± 6 units and 1910 ± 679 m L, respectively, in Group 2 with no significant difference(P = 0.09 and 0.167, respectively). The rates of infection and systemic complications(renal, respiratory, cardiovascular and neurological complications) were similar in both groups. CONCLUSION: A MELD score > 20 may predict mortality after LDLT.

Model for end-stage liver disease-Na score or Maddrey discrimination function index, which score is best?

AIM: To compare the ability of model for end-stage liver disease(MELD)-Na and Maddrey discrimination function index(DFI) to predict mortality at 30 and 90 d in patients with alcoholic hepatitis(AH).METHODS: We prospectively assessed 52 patients with AH. Demographic, clinical and laboratory parameters were obtained. MELD-Na and Maddrey DFI were calculated on admission. Short-term mortality was assessed at 30 and 90 d. Receiver operating characteristic curve analysis was performed. RESULTS: Thirty-day and 90-d mortality was 44% and 58%, respectively. In the univariate analysis, sodium levels was associated with mortality at 30 and 90 d(P = 0.001 and P = 0.03). Child stage, encephalopathy, ascites, or types of treatment were not associated with mortality. MELD-Na was the only predictive factor for mortality at 90 d. For 30-d mortality area under the curve(AUC) was 0.763(95%CI: 0.63-0.89) for Maddrey DFI and 0.784 for MELD-Na(95%CI: 0.65-0.91, P = 0.82). For 90-d mortality AUC was 0.685(95%CI: 0.54-0.83) for Maddrey DFI and 0.8710 for MELD-Na(95%CI: 0.76-0.97, P = 0.041). CONCLUSION: AH is associated with high shortterm mortality. Our results show that MELD-Na is a more valuable model than DFI to predict short-term mortality.

Bone marrow derived stem cells for the treatment of end-stage liver disease

End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell(BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups.

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.

Stem cells for end stage liver disease: How far have we got?

End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and in some cases recidivism of the pre-transplant disease. These factors account for the recent growing interest in regenerative medicine. Experiments have sought to identify an optimal source of stem cells, sufficient to generate large amounts of hepatocytes to be used in bioartificial livers or injected in vivo to repair the diseased organ. This update aims to give non-stem cell specialists an overview of the results obtained to date in this fascinating field of biomedical research.

Application of a biochemical and clinical model to predict individual survival in patients with end-stage liver disease

AIM:To investigate the capability of a biochemical and clinical model,BioCliM,in predicting the survival of cirrhotic patients.METHODS:We prospectively evaluated the survival of 172 cirrhotic patients.The model was constructed using clinical(ascites,encephalopathy and variceal bleeding) and biochemical(serum creatinine and serum total bilirubin) variables that were selected from a Cox proportional hazards model.It was applied to estimate 12-,52-and 104-wk survival.The model's calibration using the Hosmer-Lemeshow statistic was computed at 104 wk in a validation dataset.Finally,the model's validity was tested among an independent set of 85 patients who were stratified into 2 risk groups(low risk≤8 and high risk>8).RESULTS:In the validation cohort,all measures of fi t,discrimination and calibration were improved when the biochemical and clinical model was used.The proposed model had better predictive values(c-statistic:0.90,0.91,0.91) than the Model for End-stage Liver Disease(MELD) and Child-Pugh(CP) scores for 12-,52-and 104-wk mortality,respectively.In addition,the Hosmer-Lemeshow(H-L) statistic revealed that the biochemical and clinical model(H-L,4.69) is better calibrated than MELD(H-L,17.06) and CP(H-L,14.23).There were no significant differences between the observed and expected survival curves in the stratified risk groups(low risk,P=0.61;high risk,P=0.77).CONCLUSION:Our data suggest that the proposed model is able to accurately predict survival in cirrhotic patients.

Beyond the Pediatric end-stage liver disease system: Solutions for infants with biliary atresia requiring liver transplant

Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches:(1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and(2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.

Stem cell transplantation for the treatment of end-stage liver disease

The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer,liver diseases, and various types of chronic diseases. Indeed, stem cell-based therapies are effective in many diseases, and provide novel insights into the treatment of end-stage liver disease. Several clinical trials have indicated the efficacy profiles of stem cell transplantation in patients with end-stage liver disease, including liver cirrhosis, liver failure, and liver tumors. Animal models of acute liver failure have also provided important insights into the safety,mechanisms, and efficacy of stem cell therapies. Nevertheless, excitement due to this promising field must be tempered with careful and calculated research. In particular, studies on the quality, safety, and efficacy of stem cell transplantation are needed to ensure that qualified products are tested in well-designed clinical trials and approved by governments. Therefore, further investigations are required to effectively balance the safety with the innovation of stem cell transplantation research toward the effective treatment of end-stage liver disease.

Bioengineered functional humanized livers： An emerging supportive modality to bridge the gap of organ transplantation for management of end-stage liver diseases

End stage liver diseases(ESLD) represent a major, neglected global public health crisis which requires an urgent action towards finding a proper cure. Orthotropic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients limits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolutionized the field of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into preclinical and clinical settings targeting appropriate app-lications in specific disease conditions. Earlier studieshave demonstrated the applicability of this particularapproach to generate functional organ in rodent systemby connecting them with portal and hepatic circulatorynetworks. However, such strategy requires very highlevel of surgical expertise and also poses the technicaland financial questions towards its future applicability.Hence, alternative sites for generating secondary organsare being tested in several types of disease conditions.Among different sites, omentum has been proved tobe more appropriate site for implanting several kindsof functional tissue constructs without eliciting muchimmunological response. Hence, omentum may be considered as better site for transplanting humanized bioengineered ex vivo generated livers, thereby creatinga secondary organ at intra-omental site. However, theexpertise for generating such bioengineered organs arelimited and only very few centres are involved for investigating the potential use of such implants in clinicalpractice due to gap between the clinical transplantsurgeons and basic scientists working on the conceptevolution. Herein we discuss the recent advances andchallenges to create functional secondary organs through intraomental transplantation of ex vivo generated bioengineered humanized livers and their furtherapplication in the management of ESLD as a supportivebridge for organ transplantation.

A retrospective study on use of palliative care for patients with alcohol related end stage liver disease in United States

BACKGROUND Palliative care(PC)has been shown to be beneficial in end stage liver disease(ESLD),yet the hospitalization data for PC utilization is unknown.AIM To identify the trend of PC utilization for the special population of alcoholassociated ESLD patients,factors affecting its use and ascertain its impact on healthcare utilization.METHODS We analyzed around 78 million discharges from the 2007-2014 national inpatient sample and 2010-2014 national readmission database including adult patients admitted for decompensated alcohol-associated cirrhosis.We identified patients with PC consultation as a secondary diagnosis.Odds ratios(OR)and means were adjusted for confounders using multivariate regression analysis models.RESULTS Out of the total 1421849 hospitalizations for decompensated liver cirrhosis,62782(4.4%)hospitalizations had a PC consult,which increased from 0.8%(1258)of all alcohol-associated ESLD hospitalizations in 2007 to 6.6%in 2014(P<0.01).Patient and hospital characteristics associated with increased odds of PC utilization were advanced age,lower income,Medicaid coverage,teaching institution,urban location,length of stay>3 d,prolonged ventilation,and administration of total parenteral nutrition(all P<0.01).Palliative encounters in alcohol-associated ESLD and acute-onchronic liver failure(ACLF)score were associated with increased odds of discharge to a rehabilitation facility,but significantly lower odds of 30-d readmissions(aOR:0.35,95%CI:0.31-0.41),lower total hospitalization charges and lower mean hospitalization days(all P<0.01).CONCLUSION Inpatient PC is sparingly used for patients with decompensated alcohol related liver disease,however it has increased over the past decade.PC consultation is associated with lower 30-d readmission rates on multivariate analysis,and lower hospitalization cost and length of stay in patients with ACLF score≥2.