终末期肝病模型动态评分评估HBV相关肝衰竭预后的价值

目的评估终末期肝病模型（MELD）评分及其变化率（△MELD）在预测HBV相关肝衰竭患者预后的价值。方法采用前瞻性研究,选取HBV相关肝衰竭患者98例,随访24周,收集相关临床资料,计算MELD、△MELD分值。比较不同时间点存活与死亡患者MELD及△MELD分值,应用ROC曲线下面积比较MELD及△MELD预测预后的准确性,以最佳临界值分组,比较不同组别不同时间点的病死率;绘制Kaplan-Meier生存曲线,运用生存分析方法比较各组生存率变化。结果98例患者24周内死亡52例,存活46例,死亡组与存活组间MELD、△MELD分值的差异有统计学意义（P〈0．01）;MELDI〉23组8、12、24周病死率均明显高于MELD〈23组,△MELD〉4．5组病死率也高于△MELD〈4．5组,差异有统计学意义（P〈0．001）;判断患者12、24周预后△MELD的AUC（0．823、0．815）明显大于MELD的AUC（0．680、0．684）（P〈0．05）;生存分析显示以最佳临界值分组,各组间累积存活率的差异有统计学意义（P=0．000）。结论终末期肝病模型评分系统适用于我国HBV相关肝衰竭患者预后的预测;△MELD评估预后的准确性要高于初始MELD,有着重要的临床应用价值。     

终末期肝病模型动态评分评估HBV相关肝衰竭预后的价值

目的 评估终末期肝病模型(MELD)评分及其变化率(△MELD)在预测HBV相关肝衰竭患者预后的价值.方法 采用前瞻性研究,选取HBV相关肝衰竭患者98例,随访24周,收集相关临床资料,计算MELD、△MELD分值.比较不同时间点存活与死亡患者MELD及△MELD分值,应用ROC曲线下面积比较MELD及△MELD预测预后的准确性,以最佳临界值分组,比较不同组别不同时间点的病死率;绘制Kaplan-Meier生存曲线,运用生存分析方法比较各组生存率变化.结果 98例患者24周内死亡52例,存活46例,死亡组与存活组间MELD、△MELD分值的差异有统计学意义(P ＜0.01);MELD≥23组8、12、24周病死率均明显高于MELD＜23组,△MELD＞4.5组病死率也高于△MELD＜4.5组,差异有统计学意义(P＜0.001);判断患者12、24周预后△MELD的AUC(0.823、0.815)明显大于MELD的AUC(0.680、0.684) (P ＜0.05);生存分析显示以最佳临界值分组,各组间累积存活率的差异有统计学意义(P =0.000).结论 终末期肝病模型评分系统适用于我国HBV相关肝衰竭患者预后的预测;△MELD评估预后的准确性要高于初始MELD,有着重要的临床应用价值.     

An analysis of tacrolimus-related complications in the first 30 days after liver transplantation

OBJECTIVES:

Orthotopic liver transplantation has improved survival in patients with end-stage liver disease; however, therapeutic strategies that achieve ideal immunosuppression and avoid early complications are lacking. To correlate the dose and level of Tacrolimus with early complications, e.g., rejection, infection and renal impairment, after liver transplantation. From November 2011 to May 2013, 44 adult liver transplant recipients were studied in this retrospective comparative study.

RESULTS:

The most frequent indication for liver transplantation was hepatitis C cirrhosis (47.7%), with a higher prevalence observed in male patients (68.18%). The ages of the subjects ranged from 19-71 and the median age was 55.5 years. The mean length of the hospital stay was 16.1±9.32 days and the mean Model for End-stage Liver Disease score was 26.18±4.28. There were five cases of acute cellular rejection (11.37%) and 16 cases of infection (36.37%). The blood samples that were collected and analyzed over time showed a significant correlation between the Tacrolimus blood level and the deterioration of glomerular filtration rate and serum creatinine (p<0.05). Patients with infections had a higher serum level of Tacrolimus (p = 0.012). The dose and presence of rejection were significantly different (p = 0.048) and the mean glomerular filtration rate was impaired in patients who underwent rejection compared with patients who did not undergo rejection (p = 0.0084).

CONCLUSION:

Blood Tacrolimus levels greater than 10 ng/ml were correlated with impaired renal function. Doses greater than 0.15 mg/kg/day were associated with the prevention of acute cellular rejection but predisposed patients to infectious disease.     

终末期肝病模型评分在原发性肝癌合并肝硬化脾功能亢进外科治疗中的作用

目的 探讨终末期肝病模型(MELD)评分评估肝储备功能在原发性肝癌合并肝硬化脾功能亢进中确定手术适应证的应用价值.方法 对2001年1月至2007年1月间行肝癌切除联合脾切除(联合术)治疗的40例原发性肝癌合并肝硬化脾功能亢进患者的临床资料进行回顾性分析.通过MELD评分与Child-Pugh分级比较,结合临床资料及术后并发症分析,确定这一方法在评估肝储备功能中的作用.结果 同一Child-Pugh分级的患者MELD评分结果并不一致,在各级别间有交错现象.术后发生肝功能衰竭组(6例)的MELD评分均值为(24.6±6.6).未发生肝功能衰竭组(34例)的MELD评分均值为(16.3±8.5),差异有统计学意义(P<0.05).根据MELD评分分为A组16例(MELD评分<10),B组17例(MELD评分10-20),C组7例(MELD评分>20).A组术后肝功能衰竭发生率为0,B组为11.8%(2/17),C组为57.1%(4/7),差异有统计学意义(P<0.05).根据Child-Pugh分级分为Ⅰ级26例,Ⅱ级14例.Ⅰ级术后肝功能衰竭发生率为15.4%(4/26),Ⅱ级为14.3%(2/14),差异无统计学意义(P>0.05).结论 MELD评分能够较为客观地反映肝储备功能,对外科术式的选择、手术时机的确定有一定的参考作用.     

The refit model for end-stage liver disease-Na is not a better predictor of mortality than the refit model for end-stage liver disease in patients with cirrhosis and ascites

Background/Aims

The modification of the Model for End-Stage Liver Disease (MELD) scoring system (Refit MELD) and the modification of MELD-Na (Refit MELDNa), which optimized the MELD coefficients, were published in 2011. We aimed to validate the superiority of the Refit MELDNa over the Refit MELD for the prediction of 3-month mortality in Korean patients with cirrhosis and ascites.

Methods

We reviewed the medical records of patients admitted with hepatic cirrhosis and ascites to the Konkuk University Hospital between January 2006 and December 2011. The Refit MELD and Refit MELDNa were compared using the predictive value of the 3-month mortality, as assessed by the Child-Pugh score.

Results

In total, 530 patients were enrolled, 87 of whom died within 3 months. Alcohol was the most common etiology of their cirrhosis (n=271, 51.1%), and the most common cause of death was variceal bleeding (n=20, 23%). The areas under the receiver operating curve (AUROCs) for the Child-Pugh, Refit MELD, and Refit MELDNa scores were 0.754, 0.791, and 0.764 respectively; the corresponding values when the analysis was performed only in patients with persistent ascites (n=115) were 0.725, 0.804, and 0.796, respectively. The significant difference found among the Child-Pugh, Refit MELD, and Refit MELDNa scores was between the Child-Pugh score and Refit MELD in patients with persistent ascites (P=0.039).

Conclusions

Refit MELD and Refit MELDNa exhibited good predictability for 3-month mortality in patients with cirrhosis and ascites. However, Refit MELDNa was not found to be a better predictor than Refit MELD, despite the known relationship between hyponatremia and mortality in cirrhotic patients with ascites.     

409例肝硬化和重型肝炎病例的MELD评分结果的构成分析

目的应用两种评分方法对409例肝硬化及重型肝炎患者进行评估比较，分析血清肌酐、血清胆红素及凝血酶原时间国际标准化比值（INR）对MELD评分结果的影响程度。方法统计409例肝硬化及重型肝炎患者的相关资料，应用Child和MELD评分法分别计算后应用Chiss软件进行统计学分析。结果随着A、B、C、D各个级别的病情的加重，MELD评分明显升高。各个级别的血清胆红素、INR之间存在明显差异；各个级别的血清肌酐之间无明显差异。结论血清胆红素及凝血酶原时间国际标准化比值（INR）的变化及不同能够明显影响到评分结果，而血清肌酐的结果对评分结果的影响不显著。MELD应与多因素分析及临床经验有机结合，才是符合临床实际的判断严重肝病预后的较科学手段。     

Prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation

OBJECTIVE:

Chronic rejection remains a major cause of graft failure with indication for re-transplantation. The incidence of chronic rejection remains high in the pediatric population. Although several risk factors have been implicated in adults, the prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation are not known. Hence, the current study aimed to determine the factors involved in the progression or reversibility of pediatric chronic rejection by evaluating a series of chronic rejection cases following liver transplantation.

METHODS:

Chronic rejection cases were identified by performing liver biopsies on patients based on clinical suspicion. Treatment included maintaining high levels of tacrolimus and the introduction of mofetil mycophenolate. The children were divided into 2 groups: those with favorable outcomes and those with adverse outcomes. Multivariate analysis was performed to identify potential risk factors in these groups.

RESULTS:

Among 537 children subjected to liver transplantation, chronic rejection occurred in 29 patients (5.4%). In 10 patients (10/29, 34.5%), remission of chronic rejection was achieved with immunosuppression (favorable outcomes group). In the remaining 19 patients (19/29, 65.5%), rejection could not be controlled (adverse outcomes group) and resulted in re-transplantation (7 patients, 24.1%) or death (12 patients, 41.4%). Statistical analysis showed that the presence of ductopenia was associated with worse outcomes (risk ratio=2.08, p=0.01).

CONCLUSION:

The presence of ductopenia is associated with poor prognosis in pediatric patients with chronic graft rejection.     

Safety,efficacy, and response predictors of anticoagulation for the treatment of nonmalignant portal-vein thrombosis in patients with cirrhosis: a propensity score matching analysis

Background/Aims

Portal-vein thrombosis (PVT) develops in 10-25% of cirrhotic patients and may aggravate portal hypertension. There are few data regarding the effects of anticoagulation on nonmalignant PVT in liver cirrhosis. The aim of this study was to elucidate the safety, efficacy, and predictors of response to anticoagulation therapy in cirrhotic patients.

Methods

Patients with liver cirrhosis and nonmalignant PVT were identified by a hospital electronic medical record system (called BESTCARE). Patients with malignant PVT, Budd-Chiari syndrome, underlying primary hematologic disorders, or preexisting extrahepatic thrombosis were excluded from the analysis. Patients were divided into two groups (treatment and nontreatment), and propensity score matching analysis was performed to identify control patients. The sizes of the thrombus and spleen were evaluated using multidetector computed tomography.

Results

Twenty-eight patients were enrolled in this study between 2003 and 2014: 14 patients who received warfarin for nonmalignant PVT and 14 patients who received no anticoagulation. After 112 days of treatment, 11 patients exhibited significantly higher response rates (complete in 6 and partial in 5) compared to the control patients, with decreases in thrombus size of >30%. Compared to nonresponders, the 11 responders were older, and had a thinner spleen and fewer episodes of previous endoscopic variceal ligations, whereas pretreatment liver function and changes in prothrombin time after anticoagulation did not differ significantly between the two groups. Two patients died after warfarin therapy, but the causes of death were not related to anticoagulation.

Conclusions

Warfarin can be safely administered to cirrhotic patients with nonmalignant PVT. The presence of preexisting portal hypertension is a predictor of nonresponse to anticoagulation.     

Model for End-Stage Liver Disease,Model for Liver Transplantation Survival and Donor Risk Index as predictive models of survival after liver transplantation in 1,006 patients

OBJECTIVES:

Liver transplantation has not increased with the number of patients requiring this treatment, increasing deaths among those on the waiting list. Models predicting post-transplantation survival, including the Model for Liver Transplantation Survival and the Donor Risk Index, have been created. Our aim was to compare the performance of the Model for End-Stage Liver Disease, the Model for Liver Transplantation Survival and the Donor Risk Index as prognostic models for survival after liver transplantation.

METHOD:

We retrospectively analyzed the data from 1,270 patients who received a liver transplant from a deceased donor in the state of São Paulo, Brazil, between July 2006 and July 2009. All data obtained from the Health Department of the State of São Paulo at the 15 registered transplant centers were analyzed. Patients younger than 13 years of age or with acute liver failure were excluded.

RESULTS:

The majority of the recipients had Child-Pugh class B or C cirrhosis (63.5%). Among the 1,006 patients included, 274 (27%) died. Univariate survival analysis using a Cox proportional hazards model showed hazard ratios of 1.02 and 1.43 for the Model for End-Stage Liver Disease and the Model for Liver Transplantation Survival, respectively (p<0.001). The areas under the ROC curve for the Donor Risk Index were always less than 0.5, whereas those for the Model for End-Stage Liver Disease and the Model for Liver Transplantation Survival were significantly greater than 0.5 (p<0.001). The cutoff values for the Model for End-Stage Liver Disease (≥29.5; sensitivity: 39.1%; specificity: 75.4%) and the Model for Liver Transplantation Survival (≥1.9; sensitivity 63.9%, specificity 54.5%), which were calculated using data available before liver transplantation, were good predictors of survival after liver transplantation (p<0.001).

CONCLUSIONS:

The Model for Liver Transplantation Survival displayed similar death prediction performance to that of the Model for End-Stage Liver Disease. A simpler model involving fewer variables, such as the Model for End-Stage Liver Disease, is preferred over a complex model involving more variables, such as the Model for Liver Transplantation Survival. The Donor Risk Index had no significance in post-transplantation survival in our patients.     

Serum vascular endothelial growth factor and angiopoietin-2 are associated with the severity of systemic inflammation rather than the presence of hemoptysis in patients with inflammatory lung disease

Purpose

Vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) are major mediators of angiogenesis and are induced by tissue inflammation and hypoxia. The purpose of this study was to investigate whether serum VEGF and Ang-2 are associated with the presence of hemoptysis and the extent of systemic inflammation in patients with inflammatory lung diseases.

Materials and Methods

We prospectively enrolled 52 patients with inflammatory lung disease between June 2008 and October 2009.

Results

The median values of VEGF and Ang-2 were 436 pg/mL and 2383 pg/mL, respectively. There was a significant positive correlation between serum Ang-2 and VEGF levels. VEGF levels were not significantly different according to the presence of hemoptysis. C-reactive protein (CRP) and Ang-2 level were significantly higher in patients without hemoptysis (n=26) than in those with hemoptysis (n=26; p<0.001 and p<0.001, respectively). CRP and arterial oxygen tension (PaO₂) were significantly correlated with both serum VEGF (p=0.032 and p=0.016, respectively) and Ang-2 levels (p<0.001 and p=0.041, respectively), after adjusting for other factors. Age and the absence of hemoptysis were factors correlated with serum Ang-2 levels

Conclusion

Our study suggests that serum VEGF and Ang-2 levels are associated with PaO₂ and the severity of inflammation rather than the presence of hemoptysis in patients with inflammatory lung diseases. Thus, hemoptysis may not be mediated by increased serum levels of VEGF and Ang-2 in patients with inflammatory lung diseases, and further studies are required to determine the mechanisms of hemoptysis.     

Accuracy of quick Sequential Organ Failure Assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria for predicting mortality in hospitalized patients with suspected infection: a meta-analysis of observational studies

ObjectiveTo identify sensitivity, specificity and predictive accuracy of quick sequential organ failure assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria to predict in-hospital mortality in hospitalized patients with suspected infection.MethodsThis meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group consensus statement for conducting and reporting the results of systematic review. PubMed and EMBASE were searched for the observational studies which reported predictive utility of qSOFA score for predicting mortality in patients with suspected or proven infection with the following search words: ‘qSOFA’, ‘q-SOFA’, ‘quick-SOFA’, ‘Quick Sequential Organ Failure Assessment’, ‘quick SOFA’. Sensitivity, specificity, area under receiver operating characteristic (ROC) curves with 95% confidence interval (CI) of qSOFA and SIRS criteria for predicting in-hospital mortality was collected for each study and a 2 × 2 table was created for each study.ResultsData of 406 802 patients from 45 observational studies were included in this meta-analysis. Pooled sensitivity (95% CI) and specificity (95% CI) of qSOFA ≥2 for predicting mortality in patients who were not in an intensive care unit (ICU) was 0.48 (0.41–0.55) and 0.83 (0.78–0.87), respectively. Pooled sensitivity (95% CI) of qSOFA ≥2 for predicting mortality in patients (both ICU and non-ICU settings) with suspected infection was 0.56 (0.47–0.65) and pooled specificity (95% CI) was 0.78 (0.71–0.83).ConclusionqSOFA has been found to be a poorly sensitive predictive marker for in-hospital mortality in hospitalized patients with suspected infection. It is reasonable to recommend developing another scoring system with higher sensitivity to identify high-risk patients with infection.     

HLA-inferred extended haplotype disparity level is more relevant than the level of HLA mismatch alone for the patients survival and GvHD in T cell-replate hematopoietic stem cell transplantation from unrelated donor

Serious risks in unrelated hematopoietic stem cell transplantation (HSCT) including graft versus host disease (GvHD) and mortality are associated with HLA disparity between donor and recipient. The increased risks might be dependent on disparity in not-routinely-tested multiple polymorphisms in genetically dense MHC region, being organized in combinations of two extended MHC haplotypes (Ehp). We assessed the clinical role of donor-recipient Ehp disparity levels in N?=?889 patients by the population-based detection of HLA allele phase mismatch. We found increased GvHD incidences and mortality rates with increasing Ehp mismatch level even with the same HLA mismatch level. In multivariate analysis HLA mismatch levels were excluded from models and Ehp disparity level remained independent prognostic factor for high grade acute GvHD (p?=?0.000037, HR?=?10.68, 95%CI 5.50–32.5) and extended chronic GvHD (p?<?0.000001, HR?=?15.51, CI95% 5.36–44.8). In group with single HLA mismatch, patients with double Ehp disparity had worse 5-year overall survival (45% vs. 56%, p?=?0.00065, HR?=?4.05, CI95% 1.69–9.71) and non-relapse mortality (40% vs. 31%, p?=?0.00037, HR?=?5.63, CI95% 2.04–15.5) than patients with single Ehp disparity. We conclude that Ehp-linked factors contribute to the high morbidity and mortality in recipients given HLA-mismatched unrelated transplant and Ehp matching should be considered in clinical HSCT.