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.

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.

Comparative study of indocyanine green-R15,Child-Pugh score,and model for end-stage liver disease score for prediction of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt

BACKGROUND Hepatic encephalopathy(HE)remains an enormous challenge in patients who undergo transjugular intrahepatic portosystemic shunt(TIPS)implantation.The preoperative indocyanine green retention rate at 15 min(ICG-R15),as one of the liver function assessment tools,has been developed as a prognostic indicator in patients undergoing surgery,but there are limited data on its role in TIPS.AIM To determine whether the ICG-R15 can be used for prediction of post-TIPS HE in decompensated cirrhosis patients with portal hypertension(PHT)and compare the clinical value of ICG-R15,Child-Pugh score(CPS),and model for end-stage liver disease(MELD)score in predicting post-TIPS HE with PHT.METHODS This retrospective study included 195 patients with PHT who underwent elective TIPS at Beijing Shijitan Hospital from January 2018 to June 2019.All patients underwent the ICG-R15 test,CPS evaluation,and MELD scoring 1 wk before TIPS.According to whether they developed HE or not,the patients were divided into two groups:HE group and non-HE group.The prediction of one-year post-TIPS HE by ICG-R15,CPS and MELD score was evaluated by the areas under the receiver operating characteristic curves(AUCs).RESULTS A total of 195 patients with portal hypertension were included and 23%(45/195)of the patients developed post-TIPS HE.The ICG-R15 was identified as an independent predictor of post-TIPS HE.The AUCs for the ICG-R15,CPS,and MELD score for predicting post-TIPS HE were 0.664(95%confidence interval[CI]:0.557-0.743,P=0.0046),0.596(95%CI:0.508-0.679,P=0.087),and 0.641(95%CI:0.554-0.721,P=0.021),respectively.The non-parametric approach(Delong-Delong&Clarke-Pearson)showed that there was statistical significance in pairwise comparison between AUCs of ICG-R15 and MELD score(P=0.0229).CONCLUSION The ICG-R15 has appreciated clinical value for predicting the occurrence of post-TIPS HE and is a choice for evaluating the prognosis of patients undergoing TIPS.

End-stage liver disease score and future liver remnant volume predict post-hepatectomy liver failure in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is the world’s sixth most common malignant tumor and the third cause of cancer death.Although great progress has been made in hepatectomy,it is still associated with a certain degree of risk of posthepatectomy liver failure(PHLF),which extends the length of hospital stay and remains the leading cause of postoperative death.Studies have shown that assessment of hepatic functional reserve before hepatectomy is beneficial for reducing the incidence of PHLF.AIM To assess the value of model for end-stage liver disease(MELD)score combined with standardized future liver remnant(sFLR)volume in predicting PHLF in patients undergoing hepatectomy for HCC.METHODS This study was attended by 238 patients with HCC who underwent hepatectomy between January 2015 and January 2018.Discrimination of sFLR volume,MELD score,and sFLR/MELD ratio to predict PHLF was evaluated according to the area under the receiver operating characteristic curve.RESULTS The patients were divided into two groups according to whether PHLF occurred after hepatectomy.The incidence of PHLF was 8.4%in our research.The incidence of PHLF increased with the decrease in sFLR volume and the increase in MELD score.Both sFLR volume and MELD score were considered independent predictive factors for PHLF.Moreover,the cut-off value of the sFLR/MELD score to predict PHLF was 0.078(P<0.001).This suggests that an sFLR/MELD≥0.078 indicates a higher incidence of PHLF than an sFLR/MELD<0.078.CONCLUSION MELD combined with sFLR is a reliable and effective PHLF predictor,which is superior to MELD score or sFLR volume alone.

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.

Prognostic models for acute liver failure

BACKGROUND: Acute liver failure (ALF) remains a dramatic and unpredictable disease with high morbidity and mortality. Early and accurate prognostic assessment of patients with ALF is critically important for optimum clinical pathway. DATA SOURCES: Five English-language medical databases, MEDLINE, Science Direct, OVID, Springer Link and Wiley Interscience were searched for articles on 'acute liver failure', 'prognosis', and related topics. RESULTS: Multi-variable prognostic models including the King's College Hospital criteria and the model for end-stage liver disease score have been widely used in determination of the prognosis of ALF, but the results are far from satisfactory. Other prognostic indicators including serum Gc-globulin, arterial blood lactate, serum phosphate, arterial blood ammonia, and serum alpha-fetoprotein are promising but await further assessement. CONCLUSIONS: A reliable prognostic model to be developed in the future should not only have predictive value for poor outcome but also help to predict the survival of patients without a liver transplantation. Further studies are necessary to assess the prognostic accuracy of any new models. (Hepatobiliary Pancreat Dis Int 2010; 9: 122-128)

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.

Fecal cytolysin does not predict disease severity in acutely decompensated cirrhosis and acute-on-chronic liver failure

Background:Cirrhosis with acute decompensation(AD)and acute-on-chronic liver failure(ACLF)are characterized by high morbidity and mortality.Cytolysin,a toxin from Enterococcus faecalis(E.faecalis),is associated with mortality in alcohol-associated hepatitis(AH).It is unclear whether cytolysin also contributes to disease severity in AD and ACLF.Methods:We studied the role of fecal cytolysin in 78 cirrhotic patients with AD/ACLF.Bacterial DNA from fecal samples was extracted and real-time quantitative polymerase chain reaction(PCR)was performed.The association between fecal cytolysin and liver disease severity in cirrhosis with AD or ACLF was analyzed.Results:Fecal cytolysin and E.faecalis abundance did not predict chronic liver failure(CLIF-C)AD and ACLF scores.Presence of fecal cytolysin was not associated with other liver disease markers,including Fibrosis-4(FIB-4)index,‘Age,serum Bilirubin,INR,and serum Creatinine(ABIC)’score,Child-Pugh score,model for end-stage liver disease(MELD)nor MELD-Na scores in AD or ACLF patients.Conclusions:Fecal cytolysin does not predict disease severity in AD and ACLF patients.The predictive value of fecal cytolysin positivity for mortality appears to be restricted to AH.

Lymphocyte-to-white blood cell ratio is associated with outcome in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND The lymphocyte-to-white blood cell ratio(LWR)is a blood marker of the systemic inflammatory response.The prognostic value of LWR in patients with hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF)remains unclear.AIM To explore whether LWR could stratify the risk of poor outcomes in HBV-ACLF patients.METHODS This study was conducted by recruiting 330 patients with HBV-ACLF at the Department of Gastroenterology in a large tertiary hospital.Patients were divided into survivor and non-survivor groups according to their 28-d prognosis.The independent risk factors for 28-d mortality were calculated by univariate and multivariate Cox regression analyses.Patients were divided into low-and high-LWR groups according to the cutoff values.Kaplan-Meier analysis was performed according to the level of LWR.RESULTS During the 28-d follow-up time,135 patients died,and the mortality rate was 40.90%.The LWR level in non-surviving patients was significantly decreased compared to that in surviving patients.A lower LWR level was an independent risk factor for poor 28-d outcomes(hazard ratio=0.052,95%confidence interval:0.005-0.535).The LWR level was significantly negatively correlated with the Child-Turcotte-Pugh,model for end-stage liver disease,and Chinese Group on the Study of Severe Hepatitis B-ACLF II scores.In addition,the 28-d mortality was higher for patients with LWR<0.11 than for those with LWR≥0.11.CONCLUSION LWR may serve as a simple and useful tool for stratifying the risk of poor 28-d outcomes in HBVACLF patients.

Indocyanine green clearance test combined with MELD score in predicting the short-term prognosis of patients with acute liver failure

BACKGROUND: Acute liver failure(ALF) is an acute severe deterioration of liver function with high mortality. Early and accurate prognostic assessment of patients with ALF is critically important. Although the model for end-stage liver disease(MELD) scores and King’s College Hospital(KCH) criteria are well-accepted as predictive tools, their accuracy is unsatisfactory.The indocyanine green(ICG) clearance test(ICGR15, ICG retention rate at the 15 minutes) is a sensitive indicator of liver function. In this study, we investigated the efficacy of the ICGR15 for the short-term prognosis in patients with ALF. We compared the predictive value of ICGR15 with the MELD scores and KCH criteria.METHODS: Sixty-nine patients who had been diagnosed with ALF were recruited retrospectively. ICGR15 had been performed by ICG pulse spectrophotometry and relevant clinical and laboratory indices were analyzed within 24 hours of diagnosis.In addition, the MELD scores and KCH criteria were calculated.RESULTS: The three-month mortality of all patients was 47.83%.Age, serum total bilirubin and creatinine concentrations,international normalized ratio for prothrombin time, ICGR15,MELD scores and KCH criteria differed significantly between surviving and deceased patients. A positive correlation was observed between ICGR15 and MELD scores(r=0.328, P=0.006).The ICGR15-MELD model, Logit(P)=0.096×ICGR15+0.174 ×MELD score–9.346, was constructed by logistic regression analysis. The area under the receiver operating characteristic curve was 0.855. When set the cut-off point to-0.4684, the sensitivity was 87.90% and specificity, 72.20%. The area under the receiver operating characteristic curve of the ICGR15-MELD model(0.855) was significantly higher than that of the ICGR15(0.793), MELD scores(0.776) and KCH criteria(0.659).Based on this cut-off value, the patients were divided into two groups. The mortality was 74.36% in the first group(ICGR15-MELD≥-0.4686) and 13.33% in the second group(ICGR15-MELD<-0.4686), with a significant difference between the two groups(χ2=25.307, P=0.000).CONCLUSION: The ICGR15-MELD model is superior to the ICGR15, MELD scores, and KCH criteria in predicting the shortterm prognosis of patients with ALF.

Increased CD163 expression is associated with acute-on-chronic hepatitis B liver failure

AIM: To assess CD163 expression in plasma and peripheral blood and analyze its association with disease in acute-on-chronic hepatitis B liver failure (ACHBLF) patients. METHODS: A retrospective study was conducted from January 1, 2011 to January 1, 2012. Forty patients with ACHBLF (mean age 44.48 ± 12.28 years, range 18-69 years), 40 patients with chronic hepatitis B (CHB) (mean age 39.45 ± 12.22 years, range 21-57 years) and 20 ageand sex-matched healthy controls (mean age 38.35 ± 11.97 years, range 28-60 years) were included in this study. Flow cytometry was used to analyze the frequency of CD163+ peripheral blood mononuclear cells (PBMCs) and surface protein expression of CD163. Real-time transcription-polymerase chain re-action was performed to assess relative CD163 mRNA levels in PBMCs. Plasma soluble CD163 (sCD163) levels were measured by enzyme-linked immunosorbent assay. Clinical variables were also recorded. Comparisons between groups were analyzed by Kruskal-Wallis H test and Mann-Whitney U test. Statistical analyses were performed using SPSS 15.0 software and a P value < 0.05 was considered statistically significant. RESULTS: Flow cytometry showed that the population of CD163+ PBMCs was significantly greater in ACHBLF patients than in CHB patients and healthy controls (47.9645% ± 17.1542%, 32.0975% ± 11.0215% vs 17.9460% ± 6.3618%, P < 0.0001). However, there were no significant differences in mean fluorescence intensity of CD163+ PBMCs within the three groups (27.4975 ± 11.3731, 25.8140 ± 10.0649 vs 20.5050 ± 6.2437, P = 0.0514). CD163 mRNA expression in ACHBLF patients was significantly increased compared with CHB patients and healthy controls (1.41 × 10 -2 ± 2.18 × 10 -2 , 5.10 × 10 -3 ± 3.61 × 10 -3 vs 37.0 × 10 -4 ± 3.55 × 10 -4 , P = 0.02). Plasma sCD163 levels in patients with ACHBLF were significantly increased compared with CHB patients and healthy controls (4706.2175 ± 1681.1096 ng/mL, 1089.7160 ± 736.8395 ng/mL vs 435.9562 ± 440.8329 ng/mL, P < 0.0001). In ACHBLF patients, plasma sCD163 levels were significantly positively associated with model for end-stage liver disease scores (r = 0.5075, P = 0.008), hepatitis B virus-DNA (r = 0.6827, P < 0.0001), and negatively associated with prothrombin activity (r = -0.3348, P = 0.0347), but had no correlation with total bilirubin (r = 0.2551, P = 0.1122). Furthermore, sCD163 was obviously elevated in non-surviving patients compared with surviving patients with ACHBLF (5344.9080 ± 1589.5199 ng/mL vs 3641.7333 ± 1264.5228 ng/mL, P = 0.0321). CONCLUSION: CD163 and sCD163 may be related to disease severity and prognosis in ACHBLF patients.

Autologous mobilized peripheral blood CD34^+ cell infusion in non-viral decompensated liver cirrhosis

AIM: To study the effect of mobilized peripheral blood autologous CD34 positive(CD34+) cell infusion in patients with non-viral decompensated cirrhosis.METHODS: Cirrhotic patients of non-viral etiology were divided into 2 groups based on their willingness to be listed for deceased donor liver transplant(DDLT)(control, n = 23) or to receive autologous CD34+ cell infusion through the hepatic artery(study group, n= 22). Patients in the study group were admitted to hospital and received granulocyte colony stimulating factor injections 520 μg/d for 3 consecutive days to mobilize CD34+ cells from the bone marrow. On day 4,leukapheresis was done and CD34+ cells were isolated using CliniMAC magnetic cell sorter. The isolated CD34+ cells were infused into the hepatic artery under radiological guidance. The patients were discharged within 48 h. The control group received standard of care treatment for liver cirrhosis and were worked up for DDLT as per protocol of the institute. Both groups were followed up every week for 4 wk and then every month for 3 mo.RESULTS: In the control and the study group, the cause of cirrhosis was cryptogenic in 18(78.2%) and16(72.72%) and alcohol related in 5(21.7%) and6(27.27%), respectively. The mean day 3 cell count(cells/μL) was 27.00 ± 20.43 with a viability of 81.84± 11.99%. and purity of 80%-90%. Primary end point analysis revealed that at 4 wk, the mean serum albumin in the study group increased significantly(2.83± 0.36 vs 2.43 ± 0.42, P = 0.001) when compared with controls. This improvement in albumin was,however, not sustained at 3 mo. However, at the end of3 mo there was a statistically significant improvement in serum creatinine in the study group(0.96 ± 0.33 vs 1.42 ± 0.70, P = 0.01) which translated into a significant improvement in the Model for End-Stage Liver Disease score(15.75 ± 5.13 vs 19.94 ± 6.68,P = 0.04). On statistical analysis of secondary end points, the transplant free survival at the end of 1 mo and 3 mo did not show any significant difference(P =0.60) when compared to the control group. There was no improvement in aspartate transaminase, alanine transaminase, and bilirubin at any point in the study population. There was no mortality benefit in the study group. The procedure was safe with no procedural or treatment related complications.CONCLUSION: Autologous CD 34+ cell infusion is safe and effectively improves liver function in the short term and may serve as a bridge to liver transplantation.

Model for end-stage liver disease-sodium predicts prognosis in patients with chronic severe hepatitis B

Background Serum sodium predicts prognosis in chronic severe hepatitis B and may improve the prognostic accuracy of the model for end-stage liver disease （MELD） score, but the available information is limited. The present study was undertaken to study the clinical use of the serum sodium incorporated MELD （MELD-Na） and assess its validity by the concordance （c）-statistics in predicting the prognosis of the patient with chronic severe hepatitis B.Methods A total of 426 adult patients with a diagnosis of chronic severe hepatitis B between January 1, 2007, and December 31, 2007 at a single center were studied. The scores of serum sodium, MELD, MELD-Na, and ΔMELD-Na （ΔMELD-Na=MELD-Na at 14 days after medical treatment -MELD-Na score on admission） of the patients with chronic severe hepatitis B were calculated. The 3-month mortality in the patients was measured, and the validity of the models was determined by means of the concordance （c） statistics.Results The average MELD, MELD-Na scores of survival group were 25.70±5.08 and 26.60±6.90, and those of dead group were 35.60±6.78 and 42.80±9.57 on admission. There was a significant difference in MELD and MELD-Na between the survival and dead groups （P 〈0.01）. The average △MELD-Na score of the survival group was -0.97±3.51, and that of the dead group was 3.45±2.38 at 2 weeks after the treatment. There was a significant difference in △MELD-Na between the survival and dead groups （P 〈0.01）. The areas under the receiver-operating characteristic curves of Na, MELD and MELD-Na for the occurrence of death in 3 months were 0.742, 0.875 and 0.922. The 3-month mortality of the MELD-Na scores group 〈25, 25-30, 31-34, 35-40 and 〉40 were 2.0%, 5.4%, 35.4%, 53.8 % and 86.9%, respectively. There was a significant difference in the 3-month mortality between the five groups （P 〈0.05）. The 3-month mortality of the △MELD-Na〉0 group was 65.9%, and that of the △MELD-Na ≤0 group was 15.8%; there was a significant difference in the 3-month mortality between the two groups （P 〈0.05）.Conclusions MELD-Na score is a valid model to predict the 3-month mortality in patients with chronic severe hepatitis B. △MELD-Na is a clinically useful parameter for predicting the therapeutic effect of chronic severe hepatitis B.

Soluble mannose receptor as a predictor of prognosis of hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a syndrome with a high short-term mortality rate,and it is crucial to identify those patients at a high mortality risk clinically.AIM To investigate the clinical value of soluble mannose receptor(sMR)in predicting the 90-day mortality of HBV-ACLF patients.METHODS A total of 43 patients were diagnosed with HBV-ACLF between October 2017 and October 2018 at the Second Hospital of Anhui Medical University,and all of them were enrolled in this retrospective study.Their serum sMR levels were determined using an enzyme-linked immunosorbent assay.Demographic and clinical data,including gender,age,albumin level,total bilirubin(TBIL)level,international normalized ratio,HBV-DNA level,HBV serological markers,procalcitonin level,interleukin-6 level,and model for end-stage liver disease(MELD)score were accessed at the time of diagnosis of HBV-ACLF.A multivariate logistic regression analysis was used to analyze the independent risk factors for mortality.RESULTS Serum sMR level was significantly increased in HBV-ACLF patients compared with chronic hepatitis B patients and healthy controls(P<0.01).When compared with surviving patients,it was higher in those patients who succumbed to HBVACLF(P<0.05).Serum sMR level was positively correlated with MELD score(rs=0.533,P=0.001),HBV-DNA level(rs=0.497,P=0.022),and TBIL level(rs=0.894,P<0.001).Serum sMR level(odds ratio=1.007,95%confidence interval:1.004–1.012,P=0.001)was an independent risk factor for the 90-day mortality in the HBV-ACLF cases.The patients with HBV-ACLF were stratified into two groups in accordance with their serum sMR levels at the baseline(low risk:<99.84 pg/mL and high risk:≥99.84 pg/mL).The 90-day mortality rates were 27.3%in the low-risk group and 87.5%in the high-risk group.Furthermore,sMR level apparently improved the performance of MELD score for predicting the prognosis of patients with HBV-ACLF.CONCLUSION Serum sMR level may be a predictor of the prognosis of HBV-ACLF patients.

Assessment of hemostatic profile in patients with mild to advanced liver cirrhosis

BACKGROUND Hemostasis of patients suffering from liver cirrhosis is challenging due to both,pro-and anticoagulatory disorders leading to hemostatic alterations with distinct abnormalities of coagulation.Pathological changes in conventional coagulation analysis and platelet count are common manifestations of decreased liver synthesis of coagulation factors and reduced platelet count in these patients.However,conventional coagulation analysis and platelet count do not reflect invivo coagulation status or platelet function.The purpose of this present observational study was therefore to assess the haemostatic profile including plasmatic coagulation using thrombelastometry and impedance aggregometry for platelet function in patients suffering from liver cirrhosis.AIM To assess the hemostatic profile of cirrhotic patients according to model for endstage liver disease(MELD)score.METHODS Our study included both in-and outpatients suffering from liver cirrhosis attending the out-and inpatient care of the department of hepatology.Demographic and biochemical data as well as medical history including cause of liver cirrhosis,end stage kidney failure and medication with anticoagulants were recorded.To assess the hemostatic profile,platelet function was analyzed by multiple electrode aggregometry(MEA)using Multiplate^■(ADP-,ASPI-and TRAP-test)and thrombelastometry using ROTEM^■(EXTEM,INTEM,FIBTEM).Data were compared using Mann-Whitney U-or χ^2-test.Spearman correlation was performed to analyze the association between MELD Score and results of thrombelastometry and MEA.RESULTS A total of 68 patients attending the out-and inpatient care suffering from liver cirrhosis were screened.Of these,50 patients were included and assigned to groups according to MELD score 6 to 11(n=25)or≥17(n=25).Baseline patient characteristics revealed significant differences for MELD score(8 vs 22,P<0.0001)and underlying laboratory parameters(international normalized ratio,bilirubine,creatinine)as well as fibrinogen level(275 mg/dL vs 209 mg/dL,P=0.006)and aPTT(30 s vs 35 s,P=0.047).MEA showed a moderately impaired platelet function(medians:AUCADP=43U,AUCASPI=71U,AUCTRAP=92U)but no significant differences between both groups.Thrombelastometry using ROTEM?(EXTEM,INTEM,FIBTEM)revealed values within normal range in both groups.No significant correlation was observed between MELD score and results of MEA/thrombelastometry.CONCLUSION Our data demonstrate a partially impaired hemostatic profile in liver cirrhosis patients unrelated to MELD score.An individual assessment of a potential coagulopathy should therefore be considered.

Prognostic Value of Model for End-Stage Liver Disease Incorporating with Serum Sodium Score for Development of Acute Kidney Injury after Liver Transplantation

Background： Contribution of model for end-stage liver disease incorporating with serum sodium （MELD-Na） score in predicting acute kidney injury （AKI） after orthotopic liver transplantation （OLT） is yet to be identified. This study assessed the prognostic value ot MELD-Na score for the development of AKl following OLT. Methods： Preoperative and surgery-related variables of 321 adult end-stage liver disease patients who underwent OLT in Fuzhou General Hospital were collected. PostoperativeAKI was defined and staged in accordance with the clinical practice guidelines developed by Kidney Disease： Improving Global Outcomes. Univariate and multivariate analysis was performed to determine the risk factors fnr AKI following OLT. The discriminating power of MELD/MELD-Na score on AKI outcome was evaluated by receiver operating characteristic （ROC） curve. Spearman＇s correlation analysis was used for identifying the correlated relationship between MELD/MELD-Na score and the severity levels of AKI. Results： The prevalence of AKI following OLT was in 206 out of 321 patients （64.2%）. Three risk lhctors for AKI post-OLT were presented, preoperative calculated MELD score （odds ratio [OR] = 1.048, P = 0.021）, intraoperative volume of red cell suspension transfusion （OR = 1.001, P 0.002）, and preoperative liver cirrhosis （OR = 2.015, P = 0.012）. Two areas under ROC curve （AUCs） of MELD/MELD-Na score predicting AKI were 0.688 and 0.672, respectively; the difference between two AUCs was not significant （Z= 1.952, P = 0.051）. The Spearman＇s correlation coefficients between MELD/MELD-Na score and the severity levels of AKI were 0.406 and 0.385 （P 0.001, 0.001）, respectively. Conclusions： We demonstrated that preoperative MELD score, intraoperative volume of red cell suspension transfusion and preoperative liver cirrhosis were risk factors for AKI following OLT. Furthermore, we preliminarily validated that MELD score seemed to have a stronger power discriminating AKI post-OLT than that of novel MELD-Na score.

Evaluation of the updated definition of early allograft dysfunction in donation after brain death and donation after cardiac death liver allografts

BACKGROUND:An updated definition of early allograft dysfunction(EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients.This analysis did not differentiate between donation after brain death(DBD) and donation after cardiac death(DCD) allograft recipients.METHODS:We reviewed our prospectively entered database for all DBD(n=377) and DCD(n=38) liver transplantations between January 1,2006 and October 30,2011.The incidence of EAD as well as its ability to predict graft failure and survival was compared between DBD and DCD groups.RESULTS:EAD was a valid predictor of both graft and patient survival at six months in DBD allograft recipients,but in DCD allograft recipients there was no significant difference in the rate of graft failure in those with EAD(11.5%) compared with those without EAD(16.7%)(P=0.664) or in the rate of death in recipients with EAD(3.8%) compared with those without EAD(8.3%)(P=0.565).The graft failure rate in the first 6 months in those with international normalized ratio ≥1.6 on day 7 who received a DCD allograft was 37.5% compared with 6.7% for those with international normalized ratio <1.6 on day 7(P=0.022).CONCLUSIONS:The recently validated definition of EAD is a valid predictor of patient and graft survival in recipients of DBD allografts.On initial assessment,it does not appear to be a useful predictor of patient and graft survival in recipients of DCD allografts,however a study with a larger sample size of DCD allografts is needed to confirm these findings.The high ALT/AST levels in most recipients of DCD livers as well as the predisposition to biliary complications and early cholestasis make these parameters as poor predictors of graft failure.An alternative definition of EAD that gives greater weight to the INR on day 7 may be more relevant in this population.

Liver cirrhosis-effect on QT interval and cardiac autonomic nervous system activity

AIM To examine the impact of liver cirrhosis on QT interval and cardiac autonomic neuropathy(CAN). METHODS A total of 51 patients with cirrhosis and 51 controls were examined. Standard 12-lead electrocardiogram recordings were obtained and QT as well as corrected QT interval(QTc) and their dispersions(dQT, dQTc) were measured and calculated using a computer-based program. The diagnosis of CAN was based upon the battery of the tests proposed by Ewing and Clarke and the consensus statements of the American Diabetes Association. CAN was diagnosed when two out of the four classical Ewing tests were abnormal. RESULTS QT, QTc and their dispersions were significantly longer(P < 0.01) in patients with cirrhosis than in controls. No significant differences in QT interval were found among the subgroups according to the etiology of cirrhosis. Multivariate regression analysis after controlling for age, gender and duration of cirrhosis demonstrated significant association between QT and presence of diabetes mellitus [standardized regression coefficient(beta) = 0.45, P = 0.02] and treatment with diuretics(beta = 0.55, P = 0.03), but not with the Child-Pugh score(P = 0.54). Prevalence of CAN was common(54.9%) among patients with cirrhosis and its severity was associated with the Child-Pugh score(r = 0.33, P = 0.02). Moreover, patients with decompensated cirrhosis had more severe CAN that those with compensated cirrhosis(P = 0.03). No significant association was found between severity of CAN and QT interval duration.CONCLUSION Patients with cirrhosis have QT prolongation. Treatment with diuretics is associated with longer QT. CAN is common in patients with cirrhosis and its severity is associated with severity of the disease.