Nonalcoholic fatty liver disease progression rates to cirrhosis and progression of cirrhosis to decompensation and mortality: a real world analysis of Medicare data.

BACKGROUND: Risk factors and timing associated with disease progression and mortality in nonalcoholic fatty liver disease (NAFLD) are poorly understood. AIMS: To evaluate the impact of disease severity, demographics and comorbidities on risk of mortality and time to progression in a large, real-world cohort of diagnosed NAFLD patients. METHODS: Claims data from a 20% Medicare representative sample between 2007 and 2015 were analysed retrospectively. Adults were categorised into disease severity groups: NAFLD/nonalcoholic steatohepatitis (NASH) alone, compensated cirrhosis, decompensated cirrhosis, liver transplant or hepatocellular carcinoma. Cumulative incidence of mortality and disease progression were calculated for each group and multivariate analyses performed adjusting for demographics, comorbidities and disease severity. RESULTS: A total of 10 826 456, patients were assessed and the prevalence of NAFLD was 5.7% (N = 621 253). Among patients with NAFLD, 71.1% had NAFLD/NASH alone and 28.9% had NAFLD cirrhosis. Overall, 85.5% of patients had hypertension, 84.1% dyslipidemia, 68.7% had cardiovascular disease and 55.5% diabetes. The cumulative risk of progression of NAFLD to cirrhosis, and compensated cirrhosis to decompensated cirrhosis was 39% and 45%, respectively, over 8 years of follow-up. The independent predictors of progression included cardiovascular disease, renal impairment, dyslipidemia and diabetes. The cumulative risk of mortality for NAFLD, NAFLD cirrhosis, decompensated cirrhosis and hepatocellular carcinoma was 12.6%, 31.1%, 51.4% and 76.2%, respectively. CONCLUSIONS: The present report (a) demonstrates that NAFLD is grossly underdiagnosed in real-world clinical settings and (b) provides new evidence on the progression rates of NAFLD and risk factors of mortality across the spectrum of severity of NAFLD and cirrhosis.

Pairwise Multiple Comparison Adjustment Procedure for Survival Functions with Right-Censored Data.

The aim of this study is to propose a new pairwise multiple comparison adjustment procedure based on Genz's numerical computation of probabilities from a multivariate normal distribution. This method is applied to the results of two-sample log-rank and weighted log-rank statistics where the survival data contained right-censored observations. We conducted Monte Carlo simulation studies not only to evaluate the familywise error rate and power of the proposed procedure but also to compare the procedure with conventional methods. The proposed method is also applied to the data set consisting of 815 patients on a liver transplant waiting list from 1990 to 1999. It was found that the proposed method can control the type I error rate, and it yielded similar power as Tukey's and high power with respect to the other adjustment procedures. In addition to having a straightforward formula, it is easy to implement.

Quick chronic liver failure-sequential organ failure assessment: an easy-to-use scoring model for predicting mortality risk in critically ill cirrhosis patients.

BACKGROUND AND AIM: Critically ill cirrhosis patients have an increased risk of morbidity and mortality, even after admission to the ICU. Our objectives were to compare the predictive accuracy of model for end-stage liver disease (MELD), MELD-Na, UK model for end-stage liver disease, and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) by the development and validation of an easy-to-use prognostic model [named quick CLIF-SOFA (qCLIF-SOFA)] for early risk prediction in critically ill patients with cirrhosis. PATIENTS AND METHODS: Overall, 1460 patients were extracted from the MIMIC-III database and enrolled in this study at 30-day and 90-day follow-up. qCLIF-SOFA was developed in the established cohort (n=730) and a performance analysis was completed in the validation cohort (n=730) using area under the receiver operating characteristic curve. Results were compared with CLIF-SOFA. RESULTS: The performance of CLIF-SOFA was significantly better than that of MELD, MELD-Na, and UK model for end-stage liver disease for predicting both 30-day and 90-day mortality (all P<0.05). qCLIF-SOFA consisted of five independent factors (bilirubin, creatinine, international normalized ratio, mean arterial pressure, and vasopressin) associated with mortality. In the established cohort, CLIF-SOFA and qCLIF-SOFA predicted mortality with area under the receiver operating characteristic curve values of 0.768 versus 0.743 at 30-day, 0.747 versus 0.744 at 90-day, and 0.699 versus 0.706 at 1 year, respectively (all P>0.05). A similar result was observed in the validation cohort (0.735 vs. 0.734 at 30 days, 0.723 vs. 0.737 at 90 days, and 0.682 vs. 0.700 at 1 year, respectively, all P>0.05). CONCLUSION: The utility of CLIF-SOFA was further shown to predict mortality for critically ill cirrhosis patients. The novel and simpler qCLIF-SOFA model showed comparable accuracy compared with existing CLIF-SOFA for prognostic prediction.

A reliable scoring system after major liver resection in mice.

BACKGROUND: Posthepatectomy liver failure and its transplant counterpart, small-for-size syndrome, remain significant limitations for liver resections and segmental liver transplantation. Partial hepatectomy in mice is one of the most commonly used models to study liver regeneration, but blood and tissue sampling necessary to collect data can affect outcomes or even require euthanasia. We therefore developed a quantitative observational system to predict death from hepatectomy during the first 24 postoperative hours. MATERIALS AND METHODS: A total of 100 female, 10 to 12-week-old C57BL/6 mice underwent two-thirds hepatectomy and were monitored for up to 7 d. Our scoring system was based on five categories, each assigned 0-2 points: activity level, body posture, fur condition, respiratory status, and eye appearance. Seventy-five mice were scored 6 h, 12 h, 24 h, 2 d, 3 d, 5 d, and 7 d after surgery. The remaining 25 mice were scored similarly, but underwent, in addition, blood sampling for serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, or euthanasia with liver sampling for conventional hematoxylin-eosin and Ki-67 staining. RESULTS: Retrospective analysis indicated that body condition scores ≤5 on two consecutive time points within the first 24 postoperative hours accurately predicted eventual death. Animals in the low scoring group also had significantly higher serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, more hepatocyte necrosis in hematoxylin-eosin, and fewer Ki-67 positive hepatocytes. CONCLUSIONS: Our scoring system accurately predicts survival, hepatocyte damage, liver regeneration, and systemic inflammation in a mouse hepatectomy model, within the first 24 hours of surgery. This could be useful in evaluating posthepatectomy interventions for their effect on survival and liver regeneration.

Risk Factors for 30-Day Readmissions of Individuals with Decompensated Cirrhosis.

OBJECTIVES: Patients with cirrhosis have a high rate of 30-day hospital readmission that affects their quality of life and contributes to increased healthcare-related costs. The aim of our study was to identify frequency, predictors, and preventable causes of hospital readmissions among patients with decompensated cirrhosis. METHODS: We retrospectively reviewed electronic medical records of all patients with a confirmed diagnosis of decompensated cirrhosis admitted to Dayton VA Medical Center between 2009 and 2013. Demographics, clinical factors, laboratory values, and outcomes were recorded. Univariate analysis was performed using independent samples t tests and Wilcoxon rank sums tests for continuous variables and χ(2) or Fisher exact tests for categorical variables. A multiple logistic regression analysis was performed for variables found to be significant by univariate analysis to predict the risk factors for 30-day readmission. A detailed chart review was conducted for all patients readmitted within 30 days by a single gastroenterologist to identify the reason for readmission and to decide whether any of these readmissions were preventable. RESULTS: The 30-day readmission rate for decompensated cirrhotic patients was 27.03%. The risk factors for 30-day readmission were higher body mass index (BMI), lower body temperature, higher blood urea nitrogen, higher creatinine, more cirrhosis-related complications, and more readmissions per year per univariate analysis. Multivariable analysis revealed only BMI as a significant predictor of 30-day readmission (P = 0.023). A total of 36.7% of 30-day readmissions were possibly preventable. CONCLUSIONS: The independent variable that predicted 30-day readmission in patients with decompensated cirrhosis was higher BMI. Approximately one-third of 30-day readmissions were possibly preventable. These findings support the need to develop specific interventions for disease management to improve patient care and save on extraneous healthcare costs.

Safety validation of decision trees for hepatocellular carcinoma.

AIM: To evaluate a different decision tree for safe liver resection and verify its efficiency. METHODS: A total of 2457 patients underwent hepatic resection between January 2004 and December 2010 at the Chinese PLA General Hospital, and 634 hepatocellular carcinoma (HCC) patients were eligible for the final analyses. Post-hepatectomy liver failure (PHLF) was identified by the association of prothrombin time < 50% and serum bilirubin > 50 µmol/L (the "50-50" criteria), which were assessed at day 5 postoperatively or later. The Swiss-Clavien decision tree, Tokyo University-Makuuchi decision tree, and Chinese consensus decision tree were adopted to divide patients into two groups based on those decision trees in sequence, and the PHLF rates were recorded. RESULTS: The overall mortality and PHLF rate were 0.16% and 3.0%. A total of 19 patients experienced PHLF. The numbers of patients to whom the Swiss-Clavien, Tokyo University-Makuuchi, and Chinese consensus decision trees were applied were 581, 573, and 622, and the PHLF rates were 2.75%, 2.62%, and 2.73%, respectively. Significantly more cases satisfied the Chinese consensus decision tree than the Swiss-Clavien decision tree and Tokyo University-Makuuchi decision tree (P < 0.01，P < 0.01); nevertheless, the latter two shared no difference (P = 0.147). The PHLF rate exhibited no significant difference with respect to the three decision trees. CONCLUSION: The Chinese consensus decision tree expands the indications for hepatic resection for HCC patients and does not increase the PHLF rate compared to the Swiss-Clavien and Tokyo University-Makuuchi decision trees. It would be a safe and effective algorithm for hepatectomy in patients with hepatocellular carcinoma.

Individual Organ Failure and Concomitant Risk of Mortality Differs According to the Type of Admission to ICU - A Retrospective Study of SOFA Score of 23,795 Patients.

INTRODUCTION: Organ dysfunction or failure after the first days of ICU treatment and subsequent mortality with respect to the type of intensive care unit (ICU) admission is poorly elucidated. Therefore we analyzed the association of ICU mortality and admission for medical (M), scheduled surgery (ScS) or unscheduled surgery (US) patients mirrored by the occurrence of organ dysfunction/failure (OD/OF) after the first 72h of ICU stay. METHODS: For this retrospective cohort study (23,795 patients; DIVI registry; German Interdisciplinary Association for Intensive Care Medicine (DIVI)) organ dysfunction or failure were derived from the Sequential Organ Failure Assessment (SOFA) score (excluding the Glasgow Coma Scale). SOFA scores were collected on admission to ICU and 72h later. For patients with a length of stay of at least five days, a multivariate analysis was performed for individual OD/OF on day three. RESULTS: M patients had the lowest prevalence of cardiovascular failure (M 31%; ScS 35%; US 38%), and the highest prevalence of respiratory (M 24%; ScS 13%; US 17%) and renal failure (M 10%; ScS 6%; US 7%). Risk of death was highest for M- and ScS-patients in those with respiratory failure (OR; M 2.4; ScS 2.4; US 1.4) and for surgical patients with renal failure (OR; M 1.7; ScS 2.7; US 2.4). CONCLUSION: The dynamic evolution of OD/OF within 72h after ICU admission and mortality differed between patients depending on their types of admission. This has to be considered to exclude a systematic bias during multi-center trials.

Damage Control as a Strategy to Manage Postreperfusion Hemodynamic Instability and Coagulopathy in Liver Transplant.

IMPORTANCE: Damage control (DC) with intra-abdominal packing and delayed reconstruction is an accepted strategy in trauma and acute care surgery but has not been evaluated in liver transplant. OBJECTIVE: To evaluate the incidence, effect on survival, and predictors of the need for DC using intra-abdominal packing and delayed biliary reconstruction in patients with coagulopathy or hemodynamic instability after liver allograft reperfusion. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective analysis of adults undergoing liver transplant at a large transplant center from February 1, 2002, through July 31, 2012. MAIN OUTCOMES AND MEASURES: Predictors of DC, effects on graft, and patient survival. RESULTS: Of 1813 patients, 150 (8.3%) underwent DC during liver transplant, with 84 (56.0%) requiring a single additional operation for biliary reconstruction and abdominal closure and 57 (38.0%) requiring multiple additional operations. Compared with recipients without DC, patients requiring DC had greater Model for End-stage Liver Disease scores (33 vs 27; P < .001); more frequent pretransplant hospitalization (72.0% vs 47.9%; P < .001), intubation (33.3% vs 19.9%; P < .001), vasopressors (23.2% vs 10.9%; P < .001), renal replacement therapy (49.6% vs 30.3%; P < .001), and prior major abdominal operations (48.3% vs 21.9%; P < .001), including prior liver transplant (29.3% vs 8.9%; P < .001); greater operative transfusion requirements (37 vs 13 units of packed red blood cells; P < .001); worse intraoperative base deficit (10.3 vs 8.4; P = .03); more frequent postreperfusion syndrome (56.2% vs 27.3%; P < .001); and longer cold (430 vs 404 minutes; P = .04) and warm (46 vs 41 minutes; P < .001) ischemia times. Patients who underwent DC followed by a single additional operation for biliary reconstruction and abdominal closure had similar 1-, 3-, and 5-year graft survival (71%, 62%, and 62% vs 81%, 71%, and 67%; P = .26) and patient survival (72%, 64%, and 64% vs 84%, 75%, and 70%; P = .15) compared with recipients not requiring DC. Multivariate predictors of DC included prior liver transplant or major abdominal operation, longer pretransplant recipient and donor length of stay, greater Model for End-stage Liver Disease score, and longer warm and cold ischemia times (C statistic, 0.75). CONCLUSIONS AND RELEVANCE: To our knowledge, this study represents the first large report of DC as a viable strategy for liver transplant recipients with coagulopathy or hemodynamic instability after allograft reperfusion. In DC recipients not requiring additional operations, outcomes are excellent and comparable to 1-stage liver transplant.

New perspectives in the assessment of future remnant liver.

In order to achieve microscopic radical resection margins and thus better survival, surgical treatment of hepatic tumors has become more aggressive in the last decades, resulting in an increased rate of complex and extended liver resections. Postoperative outcomes mainly depend on the size and quality of the future remnant liver (FRL). Liver resection, when performed in the absence of sufficient FRL, inevitably leads to postresection liver failure. The current gold standard in the preoperative assessment of the FRL is computed tomography volumetry. In addition to the volume of the liver remnant after resection, postoperative function of the liver remnant is directly related to the quality of liver parenchyma. The latter is mainly influenced by underlying diseases such as cirrhosis and steatosis, which are often inaccurately defined until microscopic examination after the resection. Postresection liver failure remains a point of major concern that calls for accurate methods of preoperative FRL assessment. A wide spectrum of tests has become available in the past years, attesting to the fact that the ideal methodology has yet to be defined. The aim of this review is to discuss the current modalities available and new perspectives in the assessment of FRL in patients scheduled for major liver resection.

[Actors in liver transplantation advocate greater transparency and systematic evaluations of transplant centres]. / Akteure der Lebertransplantation befürworten größere Transparenz und systematische Evaluationen der Transplantationszentren.

BACKGROUND: Following the introduction of the MELD score, the survival rates have worsened after liver transplantation (LTX) in Germany. Existing organ shortages, shorter survival rates after LTX, and failures in the liver allocation process provide true challenges. Facilitated by a structured questionnaire, the appropriate German liver transplantation actors were approached with regard to these challenges for the first time. The aim was to provide a balanced experts' view in an anonymous fashion thereby identifying areas for potential improvement. METHOD: Data collection was performed by a structured, standardised, anonymous survey of all LTX centres in Germany. RESULTS: We received 75 % replies of the questionnaires, 35 of 36 participants responded to more than 75 % of all questions. The following key points were highlighted. A minimum amount of LTX per centre was deemed important and monetary incentives must not exist. The ultimate goal of LTX is a prolongation of life and social as well as occupational reintegration. Quality management and transparent LTX registers are prerequisites for both adequate organ allocation and distribution of resources in order to achieve the best possible transplant outcomes. CONCLUSION: The German liver transplant experts consider transparency of organ allocation and systematic evaluation of the quality of transplant centres and the transplantation process itself to be mandatory, however, executed in a participatory way. A scoring system to facilitate the decision making process in order to predict the likelihood of satisfactory LTX outcome thereby circumventing some of the ethical and constitutional doubts would be highly appreciated.

Risk assessment of liver-related events using transient elastography in patients with chronic hepatitis B receiving entecavir.

GOALS: We investigated whether liver stiffness (LS) values can predict liver-related events (LREs) development in patients with chronic hepatitis B (CHB). BACKGROUND: LS values using transient elastography provides accurate assessment of liver fibrosis in patients with chronic liver disease. METHODS: Between June 2007 and May 2010, a total of 162 patients with CHB who completed 2-year entecavir (ETV) treatment were evaluated. The primary endpoint was LRE development (hepatic decompensation, hepatocellular carcinoma, or liver-related death) during the 2-year ETV treatment. RESULTS: The median age of the patients (99 men, 63 women) was 51 years, and the median LS value was 14.8 kPa. During the 2-year ETV treatment, 15 (9.3%) patients experienced LREs. On univariate analysis, age, the proportion of patients with liver cirrhosis, platelet counts, and baseline LS values were significantly associated with LRE development (all P<0.05). Together with age, multivariate analysis identified baseline LS values as an independent predictor of LRE development (P=0.046; hazard ratio, 1.040; 95% confidence interval, 1.101-1.084). The cutoff LS value maximizing the sum of sensitivity and specificity was 12.0 kPa (area under the receiver operating characteristics curve, 0.736; P=0.003; sensitivity, 93.3%; specificity, 42.2%). In addition, the changes in LS values between baseline and 1-year ETV treatment showed significant correlations with LRE development (P=0.030). CONCLUSIONS: Our data suggest that LS values are predictive of LRE development during 2-year ETV treatment in patients with CHB. The potential role of LS value as a monitoring tool for predicting dynamic changes in the risk of LRE development during long-term ETV treatment should be investigated further.

Regional variability in liver waiting list removals causes false ascertainment of waiting list deaths.

Inconsistent identification of reasons for removal from the liver transplant waiting list by Organ Procurement and Transplantation Network (OPTN) regions may contribute to regional variability in wait-list death rates. We analyzed OPTN and Social Security Administration (SSA) reported deaths of 103 364 liver transplant candidates listed May 8, 2003-April 17, 2011, and determined regional variability in risk of death attributable to differences in use of OPTN removal codes. Only 26% of candidates removed as "too sick" died within 90 days of delisting; 6335 deaths after delisting were not reported to OPTN. The ratio of number of candidates removed as "too sick" to number who died on the waiting list varied by region from 0.23 to 0.94, indicating substantial variability in use of removal codes. Including SSA-reported deaths within 90 days of delisting reduced regional variability in risk of death by 48% compared with deaths on the list alone, and by 35% compared with deaths plus the "too sick" designation. Codes for delisting liver transplant candidates are inconsistently applied among OPTN regions, spuriously elevating estimated regional variability in risk of wait-list death. This variability is ameliorated by including SSA- reported deaths within 90 days of delisting.

Assessment of health-related quality of life in patients receiving stem cell therapy for end-stage liver disease: an Egyptian study.

INTRODUCTION: This prospective cohort study aimed to assess the influence of stem cell therapy (SCT) on health-related quality of life (HRQOL) by using the SF-36 v2 and to elucidate the influence of objective clinical variables on subjective HRQOL. METHODS: The study included 100 chronic liver disease patients (50 received SCT, and 50 received supportive medical treatment (SMT)). Both groups completed a modified SF-36 v2 form before therapy and at 1-, 3-, 6-, and 12-month intervals. Fifty healthy Egyptian volunteers were enrolled in the study and completed the SF-36 v2 form once. RESULTS: Both SCT and SMT groups showed significantly lower pretherapy SF 36 v2 scores compared with healthy volunteers. In SCT-treated patients, limited complications were encountered (SF-36 v2 scores showed significant improvement in all domains throughout the follow-up period) compared with the deterioration shown by SMT patients after therapy. A significant association was detected between SF-36 v2 scores and laboratory data in SCT patients during the first month after therapy. The grade of ascites improved during the follow-up in SCT compared with SMT patients. The mean survival time was 277.56 days (95% CI, 246.217 to 308.903) for SMT and 359.300 days (95% CI, 353.022 to 365.578) for SCT patients (log rank, 0.00). Stem cell-treated patients showed no malignancies. CONCLUSIONS: SCT positively affects health-related quality of life in cirrhosis patients. The survival rate was significantly improved after SCT.

Right hepatectomy with extra-hepatic vascular division prior to transection: intention-to-treat analysis of a standardized policy.

BACKGROUND: Right hepatectomy (RH) is the most common type of major hepatectomy and can be achieved without portal triad clamping (PTC) in non-cirrhotic liver. The present study reviews our standardized policy of performing RH without systematic PTC. METHODS: One hundred and eighty-one consecutive RH were performed in non-cirrhotic patients, with division of the right afferent and efferent blood vessels prior to transection, without systematically using PTC. Prospectively collected data were analysed, focusing on the following endpoints: need for salvage PTC, ischaemic time, blood loss and post-operative outcome. RESULTS: Extra-hepatic division of the right hepatic vessels was feasible in all patients, but was ineffective in 48 patients (26.5%) who required salvage PTC during transection. In those patients, the median ischaemic time was 20 min. The median blood loss was 500 ml (50-3000). Six patients (3.3%) experienced post-operative liver failure. Overall morbidity, severe morbidity and mortality were 42%, 12.1% and 1.6%, respectively, with peri-operative transfusion rate (16.6%) being the only factor associated with morbidity. DISCUSSION: By performing RH with extra-hepatic vascular division prior to transection, PTC can be safely avoided in the majority of patients.

Risk factors for liver transplant waitlist dropout in patients with hepatocellular carcinoma.

Loco-regional therapy has been developed to reduce waitlist dropout in patients with hepatocellular carcinoma (HCC) awaiting liver transplantation. We evaluated the probability of transplantation and waitlist dropout, and analyzed risk factors for waitlist dropout, in 76 patients with HCC from September 2004 to August 2006. Seventy-three (96.1%) patients received one or more preoperative loco-regional treatments and 55 (72.3%) received an orthotopic liver transplantation with a median wait time of seven months (range, 2-26 months). There were 11 dropouts (14.5%) associated with tumor progression or hepatic decompensation (median waiting time; 5.4 months and range, 0.4-13 months). Cumulative probabilities of transplantation at three, six, nine, 12, 15, and 18 months were 5.4%, 35.4%, 67.5%, 78.8%, 80.7%, and 80.7%, respectively and those of waitlist dropout at three, six, nine, 12, 15, and 18 months were 3.9%, 8.7%, 12.8%, 22.9%, 29.3%, and 29.3%, respectively. A laboratory model for end-stage liver disease (MELD) score >15 or multiple tumors at the time of UNOS listing were significant risk factors for waitlist dropout (p = 0.006 and 0.026, respectively). Patients with HCC being managed with loco-regional therapy who have a laboratory MELD score >15 or multiple tumors should be considered for earlier access to liver transplantation to prevent waitlist dropout.

Cost of a quality-adjusted life year in liver transplantation: the influence of the indication and the model for end-stage liver disease score.

Cost issues in liver transplantation (LT) have received increasing attention, but the cost-utility is rarely calculated. We compared costs per quality-adjusted life year (QALY) from the time of placement on the LT waiting list to 1 year after transplantation for 252 LT patients and to 5 years after transplantation for 81 patients. We performed separate calculations for chronic liver disease (CLD), acute liver failure (ALF), and different Model for End-Stage Liver Disease (MELD) scores. For the estimation of QALYs, the health-related quality of life was measured with the 15D instrument. The median costs and QALYs after LT were €141,768 and 0.895 for 1 year and €177,618 and 3.960 for 5 years, respectively. The costs of the first year were 80% of the 5-year costs. The main cost during years 2 to 5 was immunosuppression drugs (59% of the annual costs). The cost/QALY ratio improved from €158,400/QALY at 1 year to €44,854/QALY at 5 years, and the ratio was more beneficial for CLD patients (€42,500/QALY) versus ALF patients (€63,957/QALY) and for patients with low MELD scores versus patients with high MELD scores. Although patients with CLD and MELD scores > 25 demonstrated markedly higher 5-year costs (€228,434) than patients with MELD scores < 15 (€169,541), the cost/QALY difference was less pronounced (€59,894/QALY and €41,769/QALY, respectively). The cost/QALY ratio for LT appears favorable, but it is dependent on the assessed time period and the severity of the liver disease.

Simultaneous liver kidney transplantation: a medical decision analysis.

BACKGROUND: The use of simultaneous liver kidney transplantation has increased dramatically. When the liver and kidney are available from the same deceased donor, what is the best decision? There are two allocation options. In the combined allocation, both organs are allocated to a liver failure (end-stage liver disease [ESLD]) patient on dialysis leaving an end-stage renal disease (ESRD) patient on dialysis. In split allocation, the liver is allocated to the liver failure patient on dialysis and the kidney to the patient with ESRD. METHODS: A computerized medical decision analysis was performed using published US survival data. The two options were compared by examining differences in projected quality-adjusted life years (QALYs). RESULTS: Combined allocation was the best strategy (+0.806 QALYs) if liver transplant recipients on dialysis have proportionately worse survival compared with kidney failure alone patients on dialysis. However, because some patients with hepatorenal syndrome recover kidney function post-liver transplant alone (LTA), a second analysis incorporated the possibilities of being dialysis free. If the chance of recovery of renal function is 50% rather than 0%, the decision reversed. Here, the split allocation provided 1.02 more total QALYs than the combined allocation. CONCLUSIONS: This study demonstrates that simultaneous liver kidney transplantation is an excellent strategy in most patients with both ESLD and ESRD. However, allocating a kidney to a patient with ESLD, who has the potential to be dialysis free without a kidney transplant, does not maximize overall outcomes when all patients are considered.

Increased model for end-stage liver disease score at the time of liver transplant results in prolonged hospitalization and overall intensive care unit costs.

Organ allocation based on Model for End-Stage Liver Disease (MELD) resulted in decreased waiting list mortality in the United States. However, reports suggest an increase in resource utilization as a consequence of this. The aim of this study is to assess the correlation of MELD at transplant with post-liver transplant (LT) intensive care unit (ICU) costs. We assessed clinical and demographic variables of 402 adult patients who underwent LT at King's College Hospital, London, UK, between January 2000 and December 2003. ICU cost calculations were based on the therapeutic intervention scoring system (TISS). Graft quality was assessed using the donor risk index (DRI). Patients with a MELD score > 24 had significantly longer post-LT ICU stay (P < 0.0001) and total post-LT hospital stay (P = 0.008). In addition, they had significantly increased TISS scores, ICU cost, and need for renal replacement therapy (RRT) (P < 0.001). MELD score (by point) and MELD > 24 was associated with prolonged ICU stay (P = 0.004 and P = 0.005, respectively). On univariate analysis, etiology of alcohol-related liver disease (ALD), repeat LT, Budd-Chiari syndrome, and refractory ascites were associated with prolonged ICU stay. Using multivariate analysis, MELD > 24, refractory ascites, ALD and Budd-Chiari syndrome were associated with prolonged ICU stay. There was no association between using grafts with higher DRI and longer ICU stay, need for RRT, increased cost, or hospital survival on univariate analyses (P = not significant). Use of MELD as a method of organ allocation results in significant increase in ICU cost after LT. Using TISS as surrogate marker for ICU costs reveals that the cost implications are related to the need for RRT and prolonged ICU stay.

[Evaluation of extracorporeal liver support systems in the treatment of liver failure. A systematic review]. / Evaluación de los sistemas de soporte hepático extracorpóreo en el tratamiento de la insuficiencia hepática. Revisión sistemática.

OBJECTIVE: To evaluate the safety and efficacy of the MARS and Prometheus extracorporeal liver support systems in the treatment of liver failure. DESIGN: We performed a systematic review of the literature from January 1999 to June 2009 in the Medline, Embase, HTA, DARE, NHSEED, Cochrane Library Plus, Clinical Trials Registry and HSRPROJ databases. Study selection was based on a series of previously established inclusion criteria related to the study design, population, type of intervention, language, and outcome measures. PATIENTS AND INTERVENTIONS: Patients with acute liver failure or acute exacerbations of chronic liver failure treated with the MARS or Prometheus systems. OUTCOME MEASURES: Data on safety, long-term survival, clinical effects and biochemical and hemodynamic variables. RESULTS: We selected 22 studies evaluating the safety and efficacy of the MARS and Prometheus systems. Adequate evaluation of these techniques was hampered by the heterogeneity of the studies and their methodological limitations. CONCLUSIONS: Extracorporeal liver support systems are able to purify both hydrosoluble and protein-bound substances. However, current data show that only the MARS system reduces mortality in acute liver failure and in acute exacerbations of chronic liver failure, although this reduction is non-significant. These techniques can be considered safe, with adverse effects similar to those of the control group. Their main indication is severe liver failure, for short periods while the liver recovers or a liver transplant becomes available.

Survival on waiting list for liver transplantation before and after introduction of the model for end-stage liver disease score.

BACKGROUND: Since July 2006, the Model for End-stage Liver Disease (MELD) score has served as the national basis for allocation of donor livers for transplantation in Brazil. Patients with higher MELD scores receive greater priority for allocation regardless of the time on the waiting list. PURPOSE: To investigate the impact of MELD score implementation on the survival of waiting list patients. METHODS: A retrospective study of patients registered at the national Organ Procurement Organization (OPO) for the liver transplantation waiting list between January 2004 and June 2006 (pre-MELD) and between July 2006 and December 2008 (post-MELD). RESULTS: We included listed patients awaiting liver transplantation in the pre-MELD era (n = 250, 48.4%) and in the post-MELD era (n = 266, 51.6%). The times awaiting transplant prior to and after the MELD system were 487.2 +/- 384.8 days and 183.9 +/- 157.2 days, respectively. Prior to the MELD score, waiting list survivals were greater when compared to rates in the current system. Early posttransplant patient survival rates were significantly reduced in the post-MELD era (83.4%) compared to the period before MELD implementation (93.2%). CONCLUSIONS: MELD score provides a transparent, objective system to drive allocation policy; however, it presents several important limitations. Constant need of changes and reevaluation are needed as an evolutionary process. Future changes in the present system may be addressed by adjusting the MELD system.