Downgrading MELD improves the outcomes after liver transplantation in patients with acute-on-chronic hepatitis B liver failure

Background

High score of model for end-stage liver diseases (MELD) before liver transplantation (LT) indicates poor prognosis. Artificial liver support system (ALSS) has been proved to effectively improve liver and kidney functions, and thus reduce the MELD score. We aim to evaluate whether downgrading MELD score could improve patient survival after LT.

Methodology/Principal Findings

One hundred and twenty-six LT candidates with acute-on-chronic hepatitis B liver failure and MELD score ≥30 were included in this prospective study. Of the 126 patients, 42 received emergency LT within 72 h (ELT group) and the other 84 were given ALSS as salvage treatment. Of the 84 patients, 33 were found to have reduced MELD score (<30) on the day of LT (DGM group), 51 underwent LT with persistent high MELD score (N-DGM group). The median waiting time for a donor was 10 for DGM group and 9.5 days for N-DGM group. In N-DGM group there is a significantly higher overall mortality (43.1%) than that in ELT group (16.7%) and DGM group (15.2%). N-DGM (vs. ECT and DGM) was the only independent risk factor of overall mortality (P = 0.003). Age >40 years and the interval from last ALSS to LT >48 h were independent negative influence factors of downgrading MELD.

Conclusions/Significance

Downgrading MELD for liver transplant candidates with MELD score ≥30 was effective in improving patient prognosis. An appropriate ALSS treatment within 48 h prior to LT is potentially beneficial.     

Scoring Systems for Predicting Mortality after Liver Transplantation

Background

Liver transplantation can prolong survival in patients with end-stage liver disease. We have proposed that the Sequential Organ Failure Assessment (SOFA) score calculated on post-transplant day 7 has a great discriminative power for predicting 1-year mortality after liver transplantation. The Chronic Liver Failure - Sequential Organ Failure Assessment (CLIF-SOFA) score, a modified SOFA score, is a newly developed scoring system exclusively for patients with end-stage liver disease. This study was designed to compare the CLIF-SOFA score with other main scoring systems in outcome prediction for liver transplant patients.

Methods

We retrospectively reviewed medical records of 323 patients who had received liver transplants in a tertiary care university hospital from October 2002 to December 2010. Demographic parameters and clinical characteristic variables were recorded on the first day of admission before transplantation and on post-transplantation days 1, 3, 7, and 14.

Results

The overall 1-year survival rate was 78.3% (253/323). Liver diseases were mostly attributed to hepatitis B virus infection (34%). The CLIF-SOFA score had better discriminatory power than the Child-Pugh points, Model for End-Stage Liver Disease (MELD) score, RIFLE (risk of renal dysfunction, injury to the kidney, failure of the kidney, loss of kidney function, and end-stage kidney disease) criteria, and SOFA score. The AUROC curves were highest for CLIF-SOFA score on post-liver transplant day 7 for predicting 1-year mortality. The cumulative survival rates differed significantly for patients with a CLIF-SOFA score ≤8 and those with a CLIF-SOFA score >8 on post-liver transplant day 7.

Conclusion

The CLIF-SOFA score can increase the prediction accuracy of prognosis after transplantation. Moreover, the CLIF-SOFA score on post-transplantation day 7 had the best discriminative power for predicting 1-year mortality after liver transplantation.     

Pretransplant prediction of posttransplant survival for liver recipients with benign end-stage liver diseases: a nonlinear model

Background

The scarcity of grafts available necessitates a system that considers expected posttransplant survival, in addition to pretransplant mortality as estimated by the MELD. So far, however, conventional linear techniques have failed to achieve sufficient accuracy in posttransplant outcome prediction. In this study, we aim to develop a pretransplant predictive model for liver recipients'' survival with benign end-stage liver diseases (BESLD) by a nonlinear method based on pretransplant characteristics, and compare its performance with a BESLD-specific prognostic model (MELD) and a general-illness severity model (the sequential organ failure assessment score, or SOFA score).

Methodology/Principal Findings

With retrospectively collected data on 360 recipients receiving deceased-donor transplantation for BESLD between February 1999 and August 2009 in the west China hospital of Sichuan university, we developed a multi-layer perceptron (MLP) network to predict one-year and two-year survival probability after transplantation. The performances of the MLP, SOFA, and MELD were assessed by measuring both calibration ability and discriminative power, with Hosmer-Lemeshow test and receiver operating characteristic analysis, respectively. By the forward stepwise selection, donor age and BMI; serum concentration of HB, Crea, ALB, TB, ALT, INR, Na⁺; presence of pretransplant diabetes; dialysis prior to transplantation, and microbiologically proven sepsis were identified to be the optimal input features. The MLP, employing 18 input neurons and 12 hidden neurons, yielded high predictive accuracy, with c-statistic of 0.91 (P<0.001) in one-year and 0.88 (P<0.001) in two-year prediction. The performances of SOFA and MELD were fairly poor in prognostic assessment, with c-statistics of 0.70 and 0.66, respectively, in one-year prediction, and 0.67 and 0.65 in two-year prediction.

Conclusions/Significance

The posttransplant prognosis is a multidimensional nonlinear problem, and the MLP can achieve significantly high accuracy than SOFA and MELD scores in posttransplant survival prediction. The pattern recognition methodologies like MLP hold promise for solving posttransplant outcome prediction.     

Effectiveness of cell- and colony stimulating factor-based therapy for liver cirrhosis: a network meta-analysis of randomized controlled trials

Background aimsCirrhosis is the 11th leading cause of death worldwide. Because of the limitations of liver transplantation, cell- and granulocyte colony-stimulating factor (G-CSF)-based therapies are considered potential treatment methods. This work analyzes the effectiveness of cell- and G-CSF-based therapies by network meta-analysis.MethodsA literature search was performed in four databases from inception to September 10, 2021. Registered randomized controlled trials (RCTs) evaluating cell-based therapies and/or G-CSF-based therapies for cirrhosis patients were included. Traditional and network meta-analyses were analyzed in terms of survival, model for end-stage liver disease (MELD) score, Child–Turcotte–Pugh (CTP) score, alanine aminotransferase levels and aspartate aminotransferase levels.ResultsTwenty-four studies were included in this analysis. The results showed that G-CSF-based therapies (odds ratio [OR], 2.38, 95% confidence interval [CI], 1.49–3.79, P < 0.01) and cell-based therapies (OR, 1.54, 95% CI, 1.00–2.40, P = 0.048) improved the transplantation-free survival rate compared with standard medical treatment. Network analysis results showed that G-CSF combined with erythropoietin (EPO) and growth hormone (GH) had a therapeutic advantage, and cell-based therapy with mononuclear cell (MNC) hepatic artery injection and intravenous mesenchymal stem cells (MSCs) combined with G-CSF also had a relative advantage in terms of survival outcome. For the MELD score, G-CSF plus GH and MSC portal vein injection had relative advantages. G-CSF plus GH and G-CSF plus EPO had advantages in terms of CTP scores. The included strategies demonstrated no obvious improvement in liver injury indicators.ConclusionsCell-based therapy has potential therapeutic effects for liver cirrhosis. Among cell-based therapies, intravenous MSCs and hepatic artery injection of MNCs have advantageous therapeutic effects. The use of G-CSF was also noted in regimens that improved survival outcomes. However, more well-designed, large-scale RCTs are needed to confirm this conclusion.     

Pre-Transplant Depression Is Associated with Length of Hospitalization,Discharge Disposition,and Survival after Liver Transplantation

Depression after liver transplantation has been associated with decreased survival, but the effects of pre-transplant depression on early and late post-transplant outcomes remain incompletely evaluated. We assessed all patients who had undergone single-organ liver transplantation at a single center over the prior 10 years. A diagnosis of pre-transplant depression, covariates, and the outcomes of interest were extracted from the electronic medical record. Potential covariates included demographics, etiology and severity of liver disease, comorbidities, donor age, graft type, immunosuppression, and ischemic times. In multivariable models adjusting for these factors, we evaluated the effect of pre-transplant depression on transplant length of stay (LOS), discharge disposition (home vs. facility) and long-term survival. Among 1115 transplant recipients with a median follow-up time of 5 years, the average age was 56±11 and MELD was 12±9. Nineteen percent of the study population had a history of pre-transplant depression. Pre-transplant depression was associated with longer LOS (median = 19 vs. 14 days, IRR = 1.25, CI = 1.13,1.39), discharge to a facility (36% vs. 25%, OR 1.70,CI = 1.18,2.45), and decreased survival (HR = 1.54,CI = 1.14,2.08) in this cohort, accounting for other potential confounders. In conclusion, pre-transplant depression was significantly associated with longer transplant length of stay, discharge to a facility, and mortality in this cohort.     

Comparison of Different Scoring Systems Based on Both Donor and Recipient Characteristics for Predicting Outcome after Living Donor Liver Transplantation

Background and Objectives

In order to provide a good match between donor and recipient in liver transplantation, four scoring systems [the product of donor age and Model for End-stage Liver Disease score (D-MELD), the score to predict survival outcomes following liver transplantation (SOFT), the balance of risk score (BAR), and the transplant risk index (TRI)] based on both donor and recipient parameters were designed. This study was conducted to evaluate the performance of the four scores in living donor liver transplantation (LDLT) and compare them with the MELD score.

Patients and Methods

The clinical data of 249 adult patients undergoing LDLT in our center were retrospectively evaluated. The area under the receiver operating characteristic curves (AUCs) of each score were calculated and compared at 1-, 3-, 6-month and 1-year after LDLT.

Results

The BAR at 1-, 3-, 6-month and 1-year after LDLT and the D-MELD and TRI at 1-, 3- and 6-month after LDLT showed acceptable performances in the prediction of survival (AUC>0.6), while the SOFT showed poor discrimination at 6-month after LDLT (AUC = 0.569). In addition, the D-MELD and BAR displayed positive correlations with the length of ICU stay (D-MELD, p = 0.025; BAR, p = 0.022). The SOFT was correlated with the time of mechanical ventilation (p = 0.022).

Conclusion

The D-MELD, BAR and TRI provided acceptable performance in predicting survival after LDLT. However, even though these scoring systems were based on both donor and recipient parameters, only the BAR provided better performance than the MELD in predicting 1-year survival after LDLT.     

Pre-operative risk factors predict post-operative respiratory failure after liver transplantation

Objective

Post-operative pulmonary complications significantly affect patient survival rates, but there is still no conclusive evidence regarding the effect of post-operative respiratory failure after liver transplantation on patient prognosis. This study aimed to predict the risk factors for post-operative respiratory failure (PRF) after liver transplantation and the impact on short-term survival rates.

Design

The retrospective observational cohort study was conducted in a twelve-bed adult surgical intensive care unit in northern Taiwan. The medical records of 147 liver transplant patients were reviewed from September 2002 to July 2007. Sixty-two experienced post-operative respiratory failure while the remaining 85 patients did not.

Measurements and Main Results

Gender, age, etiology, disease history, pre-operative ventilator use, molecular adsorbent re-circulating system (MARS) use, source of organ transplantation, model for end-stage liver disease score (MELD) and Child-Turcotte-Pugh score calculated immediately before surgery were assessed for the two groups. The length of the intensive care unit stay, admission duration, and mortality within 30 days, 3 months, and 1 year were also evaluated. Using a logistic regression model, post-operative respiratory failure correlated with diabetes mellitus prior to liver transplantation, pre-operative impaired renal function, pre-operative ventilator use, pre-operative MARS use and deceased donor source of organ transplantation (p<0.05). Once liver transplant patients developed PRF, their length of ICU stay and admission duration were prolonged, significantly increasing their mortality and morbidity (p<0.001).

Conclusions

The predictive pre-operative risk factors significantly influenced the occurrence of post-operative respiratory failure after liver transplantation.     

Copeptin as an Indicator of Hemodynamic Derangement and Prognosis in Liver Cirrhosis

Background

Advanced liver cirrhosis is associated with systemic hemodynamic derangement leading to the development of severe complications associated with increased mortality. Copeptin is a stable cleavage product of the precursor of arginine vasopressin, a key-regulator in hemodynamic homeostasis. Copeptin is currently considered a reliable prognostic marker in a wide variety of diseases other than cirrhosis. The present study aimed to assess copeptin, both experimentally and clinically, as a potential biomarker of hemodynamic derangement and to evaluate its prognostic significance in cirrhosis.

Materials and Methods

Two studies were executed: 1) in 18 thioacetamide-induced cirrhotic rats and 5 control rats, plasma copeptin and hemodynamic measurements were performed, 2) in 61 cirrhotic patients, serum copeptin concentration was measured in samples collected at time of registration at the waiting list for liver transplantation. In 46 patients, also a second copeptin measurement was performed during follow-up while registered at the waiting list for liver transplantation. To determine the association of serum copeptin and clinical data with outcome, Cox proportional hazard regression analysis and Kaplan Meier analysis were performed.

Results

Plasma copeptin concentration was significantly higher in cirrhotic rats than in controls (1.6 ± 0.5 vs. 0.9 ± 0.1 pmol/L, p< 0.01) and was negatively correlated to the mean arterial blood pressure (r = -0.574, p = 0.013). In cirrhotic patients, serum copeptin concentration was high [11.0 (5.2–24.0) pmol/L] and increased significantly during the time of registration at the waiting list for liver transplantation. MELD and MELD-sodium score were significantly correlated to serum copeptin [MELD: (r = 0.33, p = 0.01), MELD-sodium: (r = 0.29, p = 0.02)], also at time of the second copeptin measurement [MELD and MELD-sodium: r = 0.39, p< 0.01]. In cirrhotic humans, serum copeptin concentration was significantly associated with outcome, independently of the MELD and MELD-sodium score. Patients with a low serum copeptin concentration at time of registration at the liver transplant waiting list had significantly better transplant-free survival rates at 3, 6 and 12 months of follow-up as compared to those with a high serum copeptin concentration (Log-rank: p< 0.01, p< 0.01 and p = 0.02 respectively).

Conclusions

Circulating copeptin levels are elevated in rats and humans with cirrhosis. Copeptin is independently associated with outcome in cirrhotic patients awaiting liver transplantation.     

Survival in Liver Transplant Recipients with Hepatitis B- or Hepatitis C-Associated Hepatocellular Carcinoma: The Chinese Experience from 1999 to 2010

Background

Hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and hepatitis C virus (HCV)-HCC are the main indications for liver transplantation. We compared differences in survival outcomes between these two conditions.

Methods and Findings

The China Liver Transplant Registry (CLTR) contains data collated from all transplants performed in 86 liver transplantation centers across China. We analyzed CLTR data from January 1999 to December 2010. In all, 7,658 patients (7,162 with HBV-HCC and 496 with HCV-HCC) were included in this study. Clinical characteristics were compared between the HBV-HCC and HCV-HCC groups; Kaplan–Meier analysis was used to calculate the overall, tumor-free and hepatitis-free survival rates. The 1-year, 3-year and 5-year overall survival was significantly higher in HBV-HCC recipients than in HCV-HCC recipients (76.65%, 56.61% and 49.10% vs. 64.59%, 42.78% and 39.20%, respectively; P<0.001). The corresponding tumor-free survival rates (63.55%, 47.37%, 40.99% vs. 56.84%, 38.04%, 35.66%, respectively) and hepatitis-free survival rates (75.49%, 54.84%, 47.34% vs. 63.87%, 42.15%, 39.33%, respectively) were both superior in HBV-HCC recipients (both P<0.001). Multivariate analyses identified hepatitis, preoperative alpha-fetoprotein (AFP) level, size of largest tumor, number of tumor nodules, TNM stage, vascular invasion and preoperative model for end-stage liver disease (MELD) score as independent predictors of overall, tumor-free and hepatitis-free survival.

Conclusions

Survival outcomes after liver transplantation were significantly better in HBV-HCC patients than in HCV-HCC patients. This finding may be used to guide donor liver allocation in transplantation programs.     

Establishing a metabolomic model for the prognosis of hepatitis B virus-induced acute-on-chronic liver failure treated with different liver support systems

Liver failure induced by hepatitis B virus (HBV) is a severe disease with a high mortality rate. Liver support treatment is a powerful method for treating liver failure and is a bridge to liver transplantation. Patients with similar liver function indices, however, have different outcomes following treatment, and no satisfying prediction parameters exist. In this study, we used ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) to investigate plasma metabolites in groups of acute-on-chronic liver failure patients with different prognosis. An orthogonal partial least squares (OPLS) model, with satisfactory explanatory and predictive ability (R ² Y?=?0.943, Q ²?=?0.913) was established using SIMCA-P?+?12.0. The model was based on samples collected just before the first artificial treatment for comparable model efficacy. The concordance statistics of our model was 0.968 (95% CI [0.951, 0.985]) which is superior to that of the MELD (the Model for End-stage Liver Diseases) score (0.737, 95% CI [0.578, 0.896]). Three groups of markers were identified: lysophosphatidylcholine, primary fatty acid amides and conjugated bile acids. Lysophosphatidylcholine and conjugated bile acids were protection factors for survival and primary fatty acid amides were risk factors. The cut-off point for the predictive value of our model was greater than or equal to 0.196, at which the model showed the best discrimination between the recovery and non-recovery groups, with a sensitivity of 95% and a specificity of 87%. This metabolomic model, based on plasma UPLC-MS profiles, provides not only excellent discrimination and prognostic ability for HBV-induced acute-on-chronic liver failure but also early and precise warning of possible liver transplantation.     

Glycemic Control by A Glucose Management Service and Infection Rates After Liver Transplantation

ObjectiveTo present an analysis of glycemic control before and after introduction of a dedicated glucose management service (GMS) and outcomes within 1 year after liver transplantation (LT).MethodsWe conducted a retrospective review of patients undergoing LT, who were treated with insulin infusions after LT, before and after introduction of a GMS. Outcome measures within 1 year after LT included graft rejection, infection, prolonged ventilation (> 48 hours on a ventilator), and graft survival. A multiple logistic regression was used to examine the relationship between GMS use and outcomes.ResultsThis study consisted of 73 (35 GMS and 38 non-GMS) organ transplant recipients. The mean perioperative blood glucose level in the GMS group was lower than in the non-GMS group: unadjusted, by 31.1 mg/dL (P = .001); adjusted for pre-insulin drip glucose, age, sex, Model for End-Stage Liver Disease (MELD) score, and type of transplant, by 23.4 mg/dL (P = .020). There were 27 rejection episodes, 48 infections, 26 episodes of prolonged ventilation, and 64 patients with graft survival at 1 year. The infection rate was lower in the GMS group than in the non-GMS group: the unadjusted odds ratio was 0.28 (P = .015); when adjustments were made for pre-insulin drip glucose, pretransplant glucose, age, sex, MELD score, type of transplant, and diabetes status before transplantation, the odds ratio was 0.24 (95% confidence interval, 0.06 to 0.97; P = .045). No significant associations were noted between GMS group and rejection rates, prolonged ventilation, or graft survival.ConclusionIn this study of LT patients, a GMS was associated with improved glycemic control and reduced postoperative infections. Further studies investigating effects of strict glycemic control after LT are warranted. (Endocr Pract. 2011;17:546-551)     

Baseline MELD Score Predicts Hepatic Decompensation during Antiviral Therapy in Patients with Chronic Hepatitis C and Advanced Cirrhosis

Background and Aims

In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV) infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined.

Methods

In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18±2.72) were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240weeks, ±SD 136weeks).

Results

Eighteen patients (26.5%) achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p<0.001) and higher mean bilirubin levels (26.74 vs. 14.63 µmol/l, p<0.001), as well as lower serum albumin levels (38.2 vs. 41.1 g/l, p = 0.015), mean platelets (102.64 vs. 138.95/nl, p = 0.014) and mean leukocytes (4.02 vs. 5.68/nl, p = 0.002) at baseline as compared to those without decompensation. In the multivariate analysis the MELD score remained independently associated with hepatic decompensation (OR 1.56, 1.18–2.07; p = 0.002). When the patients were grouped according to their baseline MELD scores, hepatic decompensation occurred in 22%, 59%, and 83% of patients with MELD scores of 6–9, 10–13, and >14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001).

Conclusions

Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis.     

Plasma Fibroblast Growth Factor 23 Concentration Is Increased and Predicts Mortality in Patients on the Liver-Transplant Waiting List

High plasma fibroblast growth factor-23 (FGF23) concentration predicts the risk of death and poor outcomes in patients with chronic kidney disease or chronic heart failure. We checked if FGF23 concentration could be modified in patients with end stage liver disease (ESLD) and predict mortality. We measured plasma FGF23 in 200 patients with ESLD registered on a liver transplant waiting list between January 2005 and October 2008. We found that median plasma FGF23 concentration was above normal values in 63% of the patients. Increased FGF23 concentration was not explained by its classical determinants: hyperphosphataemia, increased calcitriol concentration or decreased renal function. FGF23 concentration correlated with the MELD score, serum sodium concentration, and GFR. Forty-six patients died before being transplanted and 135 underwent liver transplantation. We analyzed the prognostic value of FGF23 levels. Mortality was significantly associated with FGF23 levels, the MELD score, serum sodium concentration and glomerular filtration rate. On multivariate analyses only FGF23 concentration was associated with mortality. FGF23 levels were independent of the cause of the liver disease. To determine if the damaged liver can produce FGF23 we measured plasma FGF23 concentration and liver FGF23 mRNA expression in control and diethyl-nitrosamine (DEN)-treated mice. FGF23 plasma levels increased with the apparition of liver lesions in DEN-treated mice and that FGF23 mRNA expression, which was undetectable in the liver of control mice, markedly increased with the development of liver lesions. The correlation between FGF23 plasma concentration and FGF23 mRNA expression in DEN-treated mice suggests that FGF23 production by the liver accounts for the increased plasma FGF23 concentration. In conclusion chronic liver lesions can induce expression of FGF23 mRNA leading to increased FGF23 concentration, which is associated with a higher mortality in patients on a liver-transplant waiting list. In these patients FGF23 concentration was the best predictor of mortality.     

Outcomes of Technical Variant Liver Transplantation versus Whole Liver Transplantation for Pediatric Patients: A Meta-Analysis

Objective

To overcome the shortage of appropriate-sized whole liver grafts for children, technical variant liver transplantation has been practiced for decades. We perform a meta-analysis to compare the survival rates and incidence of surgical complications between pediatric whole liver transplantation and technical variant liver transplantation.

Methods

To identify relevant studies up to January 2014, we searched PubMed/Medline, Embase, and Cochrane library databases. The primary outcomes measured were patient and graft survival rates, and the secondary outcomes were the incidence of surgical complications. The outcomes were pooled using a fixed-effects model or random-effects model.

Results

The one-year, three-year, five-year patient survival rates and one-year, three-year graft survival rates were significantly higher in whole liver transplantation than technical variant liver transplantation (OR = 1.62, 1.90, 1.65, 1.78, and 1.62, respectively, p<0.05). There was no significant difference in five-year graft survival rate between the two groups (OR = 1.47, p = 0.10). The incidence of portal vein thrombosis and biliary complications were significantly lower in the whole liver transplantation group (OR = 0.45 and 0.42, both p<0.05). The incidence of hepatic artery thrombosis was comparable between the two groups (OR = 1.21, p = 0.61).

Conclusions

Pediatric whole liver transplantation is associated with better outcomes than technical variant liver transplantation. Continuing efforts should be made to minimize surgical complications to improve the outcomes of technical variant liver transplantation.     

Artificial Liver Support System Combined with Liver Transplantation in the Treatment of Patients with Acute-on-Chronic Liver Failure

Background

The search for a strategy to provide temporary liver support and salvage the patients with acute-on-chronic liver failure (ACLF) remains an important issue. This study was designed to evaluate the experience in artificial liver support system (ALSS) combined with liver transplantation (LT) in the treatment of ACLF.

Methodology/Principal Findings

One hundred and seventy one patients with HBV related ACLF undergoing LT between January 2001 and December 2009 were included. Of the 171 patients, 115 received 247 sessions of plasma exchange-centered ALSS treatment prior to LT (ALSS-LT group) and the other 56 received emergency LT (LT group). The MELD score were 31±6 and 30±7 in ALSS-LT group and LT group. ALSS treatment resulted in improvement of liver function and better tolerance to LT. The average level of serum total bilirubin before LT was lower than that before the first time of ALSS treatment. The median waiting time for a donor liver was 12 days (2–226 days) from the first run of ALSS treatment to LT. Compared to LT group, the beneficial influences of ALSS on intraoperative blood loss and endotracheal intubation time were also observed in ALSS-LT group. The 1-year and 5-year survival rates in the ALSS-LT group and LT group were 79.2% and 83%, 69.7% and 78.6%.

Conclusions/Significance

Plasma exchange-centered ALSS is beneficial in salvaging patients with ACLF when a donor liver is not available. The consequential LT is the fundamental treatment modality to rescue these patients and lead to a similar survival rate as those patients receiving emergency transplantation.     

Longitudinal Brain White Matter Alterations in Minimal Hepatic Encephalopathy before and after Liver Transplantation

Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6–12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe.     

In-hospital cardiovascular events after liver transplantation: predictors and long-term outcome

Introduction

Liver transplantation has emerged as a successful therapy for end-stage liver disease. However, cardiovascular mortality is the leading cause of fatality in the postoperative period. The aim of this study was to reveal the prevalence and identify risk factors of early cardiovascular events (CVEs).

Methods

We performed a retrospective study of all consecutive patients who underwent a primary liver transplantation from 1986 to 2017 (n?=?916). We investigated the occurrence of in-hospital CVEs, their predictors, and short- and long-term outcome.

Results

The prevalence of CVEs was 11%. The adjusted analysis showed that higher age (OR 1.06, 95% CI 1.03–1.09), higher MELD score (OR 1.04, 95% CI 1.01–1.07 CI) and sinus tachycardia at time of screening (OR 3.12, 95% CI 1.45–6.72) were positive predictors for a CVE. Preoperative propranolol use showed a trend towards a higher risk of CVE (OR 1.66, 95% CI 1.00–2.77, p?=?0.051). In a sub-analysis of patients where echocardiography data were available (n?=?597), a larger left atrial diameter and a higher E/E′ ratio were related to early CVEs. Ten-year survival in 30-day survivors was favourable (68.6%; 56.0% vs. 69.8% in the CVE+ vs. the CVE-group, respectively, p?=?0.056).

Discussion

In conclusion, besides known risk factors (age and MELD score), sinus tachycardia (related to the presence of acute liver failure and cirrhosis) was an independent predictor for CVE after liver transplantation.

     

Recipient outcomes after ABO-incompatible liver transplantation: a systematic review and meta-analysis

Background

ABO-incompatible live transplantation (ILT) is not occasionally performed due to a relative high risk of graft failure. Knowledge of both graft and patient survival rate after ILT is essential for donor selection and therapeutic strategy. We systematically reviewed studies containing outcomes after ILT compared to that after ABO-compatible liver transplantation (CLT).

Methodology/Principal Findings

We carried out a comprehensive search strategy on MEDLINE (1966–July 2010), EMBASE (1980–July 2010), Biosis Preview (1969–July 2010), Science Citation Index (1981–July 2010), Cochrane Database of Systematic Reviews (Cochrane Library, issue 7, 2010) and the National Institute of Health (July 2010). Two reviewers independently assessed the quality of each study and abstracted outcome data. Fourteen eligible studies were included which came from various medical centers all over the world. Meta-analysis results showed that no significantly statistical difference was found in pediatric graft survival rate, pediatric and adult patient survival rate between ILT and CLT group. In adult subgroup, the graft survival rate after ILT was significantly lower than that after CLT. The value of totally pooled OR was 0.64 (0.55, 0.74), 0.92 (0.62, 1.38) for graft survival rate and patient survival rate respectively. The whole complication incidence (including acute rejection and biliary complication) after ILT was higher than that after CLT, as the value of totally pooled OR was 3.02 (1.33, 6.85). Similarly, in acute rejection subgroup, the value of OR was 2.02 (1.01, 4.02). However, it was 4.08 (0.90, 18.51) in biliary complication subgroup.

Conclusions/Significance

In our view, pediatric ILT has not been a contraindication anymore due to a similar graft and patient survival rate between ILT and CLT group. Though adult graft survival rate is not so satisfactory, ILT is undoubtedly life-saving under exigent condition. Most studies included in our analysis are observational researches. Larger scale of researches and Randomized-Control Studies are still needed.     

High Serum Levels of the Interleukin-33 Receptor Soluble ST2 as a Negative Prognostic Factor in Hepatocellular Carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor, usually arises in the setting of liver cirrhosis (LC), and has a poor prognosis. The recently discovered Th2-cytokine interleukin-33 (IL-33) is a possible mediator in pancreatic and gastric carcinogeneses. IL-33 binds to its receptor and to soluble ST2 (sST2), which thereby acts as a regulator. The role of IL-33 and sST2 in HCC has not been elucidated yet. METHODS: We conducted a case-control study with 130 patients and 50 healthy controls (HCs). Sixty-five patients suffered from HCC and 65 patients had LC without HCC. We assessed serum IL-33 and sST2 levels and their association with established prognostic scores, liver function parameters, and overall survival (OS). RESULTS: No significant difference in IL-33 serum levels was found in HCC compared to LC and HCs. IL-33 levels did not correlate with OS, liver function parameters, the Model for End-Stage Liver Disease (MELD) score, or the Cancer of the Liver Italian Program (CLIP) score. sST2 levels were significantly elevated in LC and HCC patients compared to HCs (P < .0001). Mean sST2 levels in LC were higher than in HCC (P < .0001), but a significant association with OS was only observed in the HCC group (P = .003). sST2 in HCC correlated with the CLIP score, the MELD score, and liver function parameters. CONCLUSION: In the present study, the serum concentration of sST2 was associated with OS of HCC. Therefore, sST2 may be considered as a new prognostic marker in HCC and is worth further evaluation.     

Up-regulation of PRKDC was associated with poor renal dysfunction after renal transplantation: A multi-centre analysis

Renal transplantation is the only efficacious treatment for end-stage kidney disease. However, some people have developed renal insufficiency after transplantation, the mechanisms of which have not been well clarified. Previous studies have focused on patient factors, while the effect of gene expression in the donor kidney on post-transplant renal function has been less studied. Donor kidney clinical data and mRNA expression status were extracted from the GEO database (GSE147451). Weight gene co-expression network analysis (WGCNA) and differential gene enrichment analysis were performed. For external validation, we collected data from 122 patients who accepted renal transplantation at several hospitals and measured the level of target genes by qPCR. This study included 192 patients from the GEO data set, and 13 co-expressed genes were confirmed by WGCNA and differential gene enrichment analysis. Then, the PPI network contained 17 edges as well as 12 nodes, and four central genes (PRKDC, RFC5, RFC3 and RBM14) were identified. We found by collecting data from 122 patients who underwent renal transplantation in several hospitals and by multivariate logistic regression that acute graft-versus-host disease postoperative infection, PRKDC [Hazard Ratio (HR) = 4.44; 95% CI = [1.60, 13.68]; p = 0.006] mRNA level correlated with the renal function after transplantation. The prediction model constructed had good predictive accuracy (C-index = 0.886). Elevated levels of donor kidney PRKDC are associated with renal dysfunction after transplantation. The prediction model of renal function status for post-transplant recipients based on PRKDC has good predictive accuracy and clinical application.