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Background & Aims: Kidney dysfunction is a major determinant of prognosis in patients with decompensated cirrhosis awaiting transplantation. We hypothesized that for identical model for end-stage liver disease (MELD) scores at listing, outcomes before and after liver transplantation may vary if the predominant driver of the MELD score is serum creatinine (Cr) vs. serum bilirubin (Br) or international normalized ratio (INR)., Methods: We evaluated all adult patients registered for liver transplantation (LT) between 2016-2020 and excluded patients receiving MELD exceptions or undergoing dual organ transplantation. Using K-Means clustering analysis, we classified each patient as MELD-Br, MELD-INR or MELD-Cr depending on the dominant variable for their MELD score. The primary outcome was intent-to-treat (ITT) survival, defined as survival within 1 year from listing with or without LT., Results: MELD scores of LT waitlist registrants were clustered into three subtypes: MELD-Br (n = 13,658), MELD-INR (n = 13,809), and MELD-Cr (n = 12,412). One-year ITT survival rates were 78% (MELD-Br), 75% (MELD-INR), and 65% (MELD-Cr), p <0.01. ITT survival was lower for each MELD subtype for females compared to males (e.g. MELD-Cr: 63% females vs. 67% males, p <0.0001). The MELD-Cr subtype had the highest MELD at listing (MELD-Cr 23.4 vs. MELD-Br 19.2 vs. MELD-INR 21.0) and the largest decline in MELD over 3 months (23% vs. 12% vs. 21%). In adjusted analyses including MELD-Na, MELD-Cr was associated with higher waitlist mortality (hazard ratio 1.339, 95% CI 1.279-1.402) and lower LT rates (hazard ratio 0.688, 95% CI 0.664-0.713) compaed to the other subtypes., Conclusions: For equivalent listing practices, registrants with the MELD-Cr subtype have lower ITT survival. MELD subtype may serve as a more sophisticated variable for dynamic assessment of mortality risk and to guide organ allocation., Impact and Implications: The model for end-stage liver disease (MELD) score is an excellent predictor of waitlist mortality; however, our work highlights that the driver of a patient's MELD score matters and particularly those driven by elevated creatinine are associated with lower 1-year intent-to-treat survival. The 1-year intent-to-treat survival is also lower for women compared to men within the Cr-dominant subtype. These results are important for physicians and patients undergoing LT evaluation as creatinine may serve as a marker of prognosis and even if creatinine levels improve the prognosis remains poor, necessitating discussion about alternative pathways for transplant. Our work also highlights that the type of kidney injury matters, in that those with acute kidney injury were more likely to die or remain on the waitlist than those with chronic kidney disease within the creatinine-dominant subtype., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model., Methods: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses., Results: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD., Conclusions: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed., Lay Summary: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the characteristics and outcomes of drug-induced liver injury (DILI) caused by paracetamol and non-paracetamol medications, particularly herbal and dietary supplements., Design: Retrospective electronic medical record data analysis., Setting, Participants: Adults admitted with DILI to the Gastroenterology and Liver Centre at the Royal Prince Alfred Hospital, Sydney (a quaternary referral liver transplantation centre), 2009-2020., Main Outcome Measures: 90-day transplant-free survival; drugs implicated as causal agents in DILI., Results: A total of 115 patients with paracetamol-related DILI and 69 with non-paracetamol DILI were admitted to our centre. The most frequently implicated non-paracetamol medications were antibiotics (19, 28%), herbal and dietary supplements (15, 22%), anti-tuberculosis medications (six, 9%), and anti-cancer medications (five, 7%). The number of non-paracetamol DILI admissions was similar across the study period, but the proportion linked with herbal and dietary supplements increased from 2 of 13 (15%) during 2009-11 to 9 of 19 (47%) during 2018-20 (linear trend: P = 0.011). Despite higher median baseline model for end-stage liver disease (MELD) scores, 90-day transplant-free survival for patients with paracetamol-related DILI was higher than for patients with non-paracetamol DILI (86%; 95% CI, 79-93% v 71%; 95% CI, 60-82%) and herbal and dietary supplement-related cases (59%; 95% CI, 34-85%). MELD score was an independent predictor of poorer 90-day transplant-free survival in both paracetamol-related (per point increase: adjusted hazard ratio [aHR], 1.19; 95% CI, 1.09-3.74) and non-paracetamol DILI (aHR, 1.24; 95% CI, 1.14-1.36)., Conclusion: In our single centre study, the proportion of cases of people hospitalised with DILI linked with herbal and dietary supplements has increased since 2009. Ninety-day transplant-free survival for patients with non-paracetamol DILI, especially those with supplement-related DILI, is poorer than for those with paracetamol-related DILI., (© 2021 AMPCo Pty Ltd.)

Background: Different nutritional screening instruments can be used to identify the risk of malnutrition in advanced chronic liver disease patients. The present study aimed to evaluate and compare two nutrition screening tools with the Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria for malnutrition in patients with advanced chronic liver disease., Methods: Two nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002) and Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT), were assessed for 166 patients with liver cirrhosis. We compared medium/high nutritional risk screening with the diagnosis of malnutrition, using the GLIM criteria as the reference standard., Results: According to the GLIM criteria, 57.3% of the patients were malnourished. NRS and RFH-NPT identified, respectively, 36.1% and 52.4% of patients with nutritional risk. RFH-NPT presented better agreement with the diagnosis according to GLIM criteria (k = 0.64; 95% confidence interval = 0.52-0.75), higher sensitivity (80%), higher negative predictive value (79%) and larger area under the curve (82.3%) compared to the NRS., Conclusions: RFH-NPT, when compared with the GLIM method, has substantial agreement in identifying nutritional risk, good sensitivity and good value for diagnosing malnutrition in patients with advanced chronic liver disease., (© 2020 The British Dietetic Association Ltd.)

Objective: To identify changes in demographics, outcomes, and risk factors for patient and graft loss in patients with biliary atresia undergoing liver transplantation since Pediatric End-Stage Liver Disease implementation (2002)., Study Design: Demographics and outcomes were compared between patients enrolled in the Society of Pediatric Liver Transplantation registry before (n = 547) and after (n = 1477) 2002. Kruskal-and χ 2 Wallis tests identified significant differences between eras. Risk factors for patient and graft loss after 2002 were determined by Cox regression model analysis of time to event data., Results: Significant patient differences after 2002 support increasing disease severity including more status 1 patients and those with a derived Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease score of greater than 30 awaiting transplant. Both patient and graft survival improved after 2002 from 90% to 97% and 81% to 90%, respectively (primary transplant; P < .0001). Significant differences in complications within 30 days included reduced relisting for transplant, rejection, culture-positive infection, repeat operation, hepatic artery thrombosis, portal vein thrombosis, and death/transplant before discharge. Multivariable analysis identified deceased technical variant vs whole graft and retransplantation predictive for patient death, hazard ratios of 4.041 and 8.308, respectively. Deceased technical variant vs whole graft (hazard ratio, 1.963) and donor age 0-5 months vs 1-17 years (hazard ratio, 5.525) were risk factors for graft loss., Conclusions: The overall outcomes of patients receiving liver transplantation for patients with biliary atresia have improved since 2002 despite evidence of increased disease severity at the time of transplant. Risk factors impacting post-transplant morbidity and mortality in patients with biliary atresia are now mainly surgical including donor variables., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Equitable deceased donor liver allocation and distribution has remained a heated topic in transplant medicine. Despite the establishment of numerous policies, mixed reports regarding organ allocation persist., Methods: Patient data was obtained from the United Network for Organ Sharing liver transplant database between January 2016 and September 2017. A total of 20,190 patients were included in the analysis. Of this number, 8790 transplanted patients had a median Model for End-Stage Liver Disease (MELD) score of 25 (17-33), after a wait time of 129 (32-273) days. Patients were grouped into low MELD and high MELD regions using a score 25 as the cutoff., Results: Significant differences were noted between low and high MELD regions in ethnicity (white 77.4% vs 60.4%, Hispanic 8.1% vs 24.5%; P < .001) and highest level of education (grade school 4.8% vs 8.5%, Associate/Bachelor's degree 19% vs 15.7%, P < .001), respectively. Patients in high MELD regions were more likely to be multiply listed if they had a diagnosis of hepatocellular carcinoma (12.1% vs 15%, P = .046). Wait-list mortality (4.8% vs 6%, P < .001) and wait-list time (110 [27-238] vs 156 [42-309] days, P < .001) were greater in the high MELD regions., Conclusions: These results highlight some of the existing disparities in the recently updated allocation and distribution policy of deceased donor livers. Our findings are consistent with previous work and support the liver distribution policy revision., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Fulfillment of the diagnostic criteria for -hepatorenal syndrome type 1 (HRS-1) requires prior failure of 2 days of intravenous volume expansion and/or diuretic withdrawal. However, no parameter of volume status is used to guide the need for volume expansion in patients with suspected HRS-1. We hypothesized that point-of-care echocardiography (POCE) may better characterize the volume status in patients with acute kidney injury (AKI) and cirrhosis to ascertain or disprove the diagnosis of HRS-1., Methods: A pilot observational study was conducted to determine the clinical utility of POCE-based examination of inferior vena cava diameter (IVCD) and collapsibility index (IVCCI) to assess intravascular volume status in patients with cirrhosis and AKI who had been deemed adequately volume-repleted and thereby assigned a clinical diagnosis of HRS-1. Early improvement in kidney function was defined as ≥20% decrease in serum creatinine (sCr) at 48-72 h., Results: A total of 53 patients were included. The mean sCr at the time of volume assessment was 3.2 ± 1.5 mg/dL, and the mean Model for End-Stage Liver Disease score was 29 ± 8. Fifteen (23%) patients had an IVCD <1.3 cm and IVCCI >40% and were reclassified as fluid-depleted, 11 (21%) had an IVCD >2 cm and IVCCI <40% and were reclassified as fluid-expanded, and 8 (15%) had and IVCD <1.3 cm and IVCCI <40% and were reclassified as having intra-abdominal hypertension (IAH). Twelve (23%) patients exhibited early improvement in kidney function following a POCE-guided therapeutic maneuver, that is, volume expansion, diuresis, or paracentesis for those deemed fluid-depleted, fluid-expanded or having IAH, respectively., Conclusion: POCE-based assessment of volume status in cirrhotic individuals with AKI reveals marked heterogeneity. Unguided volume expansion in these patients may lead to premature or delayed diagnosis of HRS-1., (© 2019 S. Karger AG, Basel.)

Background: The use of continuous-flow left ventricular assist devices (CF-LVADs) to treat advanced heart failure is increasing. Although risk scores, such as Model for End-Stage Liver Disease and the HeartMate II Risk Score, require the use of the international normalized ratio, many patients are on anticoagulation before CF-LVAD implantation. This study evaluated the ability of the Model of End-Stage Liver Disease-eXcluding International Normalized Ratio (MELD-XI) scoring system to predict clinical outcomes in patients with advanced heart failure who undergo CF-LVAD implantation., Methods: A single-center retrospective review was performed of 524 patients who were implanted with the HeartMate II LVAD (Thoratec Corporation, Pleasanton, CA) or the HeartWare HVAD (HeartWare International Inc, Framingham, MA) between 2004 and 2016. Patients were stratified into two cohorts: those with a MELD-XI score of less than 14 (n = 301) and 14 or higher (n = 223)., Results: Patients with the higher-risk MELD-XI score of 14 or higher demonstrated lower survival rates at 1, 3, 6, 12, and 24 months (p < 0.001 for all) and increased risk of early right heart failure and infections compared with patients with MELD-XI score of less than 14. MELD-XI was not significantly inferior at predicting 90-day mortality compared with the HeartMate II Risk Score (p = 0.92). Patients with elevated MELD-XI scores at follow-up demonstrated higher rates of mortality., Conclusions: These findings suggest that a MELD-XI score of 14 or higher was associated with a higher postoperative mortality rate than that seen in patients with a lower MELD-XI score. The MELD-XI scoring system can be used to predict outcomes in patients with advanced heart failure who undergo CF-LVAD implantation., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The Model for End-Stage Liver Disease (MELD) exception policy in liver transplantation is based on symptoms and clinical conditions not included in the calculated MELD score. Therefore, patients with chronic liver disease, like refractory ascites, chronic encephalopathy, recurrent cholangitis, and refractory pruritus, may benefit with extra points. The objective of this study was to establish the profile of the patients submitted to liver transplantation with MELD exceptions based on symptoms in the University Hospital Walter Cantídio, Ceara, Brazil, between the years of 2012 and 2015, analyzing donor and recipient data, with special attention to patients with refractory ascites and recurrent encephalopathy, including survival rates. The results demonstrated acceptable survival rates for MELD exception patients (78.4% in 3 years), showing that maybe this allocation criterion should be maintained, or even expanded., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Amyloidosis prognosis is often related to the onset of heart failure and a worsening that is concomitant with kidney-liver dysfunction; thus the Model for End-stage Liver disease (MELD) may be an ideal instrument to summarize renal-liver function. Our aim has been to test the MELD score as a prognostic tool in amyloidosis. We evaluated 128 patients, 46 with TTR-related amyloidosis and 82 with AL amyloidosis. All patients had a complete clinical and echocardiography evaluation; overall biohumoral assessment included troponin I, NT-proBNP, creatinine, total bilirubin and INR ratio. The study population was dichotomized at the 12 cut-off level of MELD scores; those with MELD score >12 had a lower survival compared to controls in the study cohort (40.7 vs 66.3 %; p = 0.006). Either as a continuous and dichotomized variable, MELD shows its independent prognostic value at multivariable analysis (HR = 1.199, 95 % CI 1.082-1.329; HR = 2.707, 95 % CI 1.075-6.817, respectively). MELD shows a lower prognostic sensitivity/specificity ratio than troponin I and NT-proBNP in the whole study population and AL subgroup, while in TTR patients MELD has a higher sensitivity/specificity ratio compared to troponin and NT-proBNP (ROC analysis-AUC: 0.853 vs 0.726 vs 0.659). MELD is able to predict prognosis in amyloidosis. A MELD score >12 selects a subgroup of patients with a higher risk of death. The predictive accuracy seems to be more evident in TTR patients in whom currently no effective scoring systems have been validated.

This article reviews the historical evolution of the liver transplant organ allocation policy and the indications/contraindications for liver transplant, and provides an overview of the liver transplant evaluation process. The article is intended to help internists determine whether and when referral to a liver transplant center is indicated, and to help internists to counsel patients whose initial evaluation at a transplant center is pending., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Data from the 24-month randomized, multicenter, open-label H2304 study in 719 de novo liver transplant recipients were analyzed to evaluate the influence of variables potentially affecting immunological or renal response: recipient age, gender, end-stage disease, hepatitis C virus (HCV) status, and Model for End-stage Liver Disease score and estimated glomerular filtration rate (eGFR) at randomization (day 30). Treated BPAR was similar between everolimus with reduced tacrolimus (EVR + Reduced TAC) vs. conventional tacrolimus-based therapy (TAC Control) in all subpopulations, with a trend to lower risk under everolimus with reduced tacrolimus (EVR + Reduced TAC) in patients < 60 yrs and HCV-negative recipients. Risk of graft loss or death was similar in both treatment groups for all subpopulations. The change in eGFR to month 24 showed a benefit for EVR + Reduced TAC vs. TAC Control in all subpopulations other than those with the lowest baseline eGFR (30 to < 55 mL/min/1.73 m(2)), with a significant difference in favor of EVR + Reduced TAC for younger recipients (< 60 yr), female patients, HCV-negative patients and those with baseline eGFR of 55 to < 70 mL/min/1.73 m(2). Everolimus with reduced tacrolimus maintains efficacy to at least two yr after liver transplantation even in patients with risk factors for rejection, with particular renal benefits in specific patient subpopulations., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Unlabelled: BackgroundProlonged cold ischemic time (CIT) and increased donor age are well-known factors negatively influencing outcomes after liver transplantation (LT)., Aims: The aim of this study was to evaluate whether the magnitude of their negative effects is related to recipient model for end-stage liver disease (MELD) score., Methods: This retrospective study was based on a cohort of 1402 LTs, divided into those performed in low-MELD (<10), moderate-MELD (10–20), and high-MELD (>20) recipients., Results: While neither donor age (p = 0.775) nor CIT (p = 0.561) was a significant risk factor for worse 5-year graft survival in low-MELD recipients, both were found to yield independent effects (p = 0.003 and p = 0.012, respectively) in moderate-MELD recipients, and only CIT (p = 0.004) in high-MELD recipients. However, increased donor age only triggered the negative effect of CIT in moderate-MELD recipients, which was limited to grafts recovered from donors aged ≥46 years (p = 0.019). Notably, utilization of grafts from donors aged ≥46 years with CIT ≥9 h in moderate-MELD recipients (p = 0.003) and those with CIT ≥9 h irrespective of donor age in high-MELD recipients (p = 0.031) was associated with particularly compromised outcomes., Conclusions: In conclusion, the negative effects of prolonged CIT seem to be limited to patients with moderate MELD receiving organs procured from older donors and to high-MELD recipients, irrespective of donor age. Varying effects of donor age and CIT according to recipient MELD score should be considered during the allocation process in order to avoid high-risk matches.

Background: After 40 years since establishment of Child-Pugh staging, 14 years since establishment of MELD scoring system, and 25 years since establishment of King's College Criteria, there is still a search for more accurate systems for determination of prognosis in patients with acute liver failure--cirrhosis and prioritization for receipt of a liver transplant--prediction of post transplant mortality. Butrylcholinesterase is an enzyme which is synthesized in the liver. The aim of the study was to evaluate the clinical utility of butrylcholinesterase as a discriminatory and prognostic factor in chronic liver disease patients., Methods: Intergroup diversity for butrylcholinesterase activity was investigated in sixty cirrhotic, 20 chronic hepatitis patients, and 20 healthy subjects. Correlations between butrylcholinesterase activity and Child-Pugh classification and MELD scoring systems were examined., Results: In addition to the statistically significant decrease in butrylcholinesterase activity among Child-Pugh A/B/C stages, the decrease in butrylcholinesterase activity was also statistically significant in control vs. Child-Pugh stage A and chronic hepatitis vs. Child Pugh stage A groups. A statistically significant correlation was determined between butrylcholinesterase activity and Child Pugh/MELD scores., Conclusions: Serum butrylcholinesterase activity might be helpful for discrimination of chronic hepatitis from cirrhosis after determination of reliable cut-off levels and dependent on the reductions of serum levels in acute liver failure and cirrhosis. It might be a useful tool for prioritization of liver transplantation.

Introduction: Faced with a shortage of organs for liver transplantation, the use of grafts from older donors is justified. However, there remains little consensus on how this use impacts the graft and patient outcomes after transplantation from these older donors. The aim of the present analysis was to assess the graft and patient outcomes after liver transplantation from deceased donors >60 years of age., Methods: From January 2007 to January 2011, 505 subjects were identified as liver graft donors after brain death, of which 7.35% were ≥60. To determine the effect of donor age on graft and patient outcomes, we analyzed donor age, recipient age, the Model for End-State Liver Disease (MELD) score of recipients at the time of transplantation, early posttransplant complications, and mortality., Results: The posttransplant follow-up was 29 ± 25.5 months, and 3-year patient mortality from donors, grouped according to age, was 7.92% with donors <30; 15.78% with donors 30-50, 10.68% with donors 50-60, and 12.50% with donors >60. After analysis of patient and graft survival based on donor graft age, 3-year patient survival according donor age was 89.29% with donors <30, 83.85% with donors 30-50, 89.89% with donors 50-60, and 87.50% with donors >60. Analysis showed overall patient and graft survival rates from older donors were not worse than those from younger donors (P > .1). Among the cases, 3-year patient survival according to MELD score was 91.19% with a MELD of I, 85.37% with a MELD of II, and 67.67% with a MELD of III; differences in graft and patient survival when comparing low MELD I and high MELD III were significantly different (P < .01)., Conclusions: A more advanced age of a donor should not be a contraindication for liver transplantation. The present analysis shows that liver grafts from donors >60 can be used safely in older recipients who presented with relatively low MELD scores. Analyses also indicate that high MELD obtained before transplantation may be an important prognostic factor for graft and patient survival.

Background: Severity of liver disease evaluated with Model for End-Stage Liver Disease (MELD)/Child-Pugh-Turcotte (CPT) score is of importance in liver transplantation (LTx) assessment. The Medical Outcomes Study Short Form (SF-36) is a widely used generic questionnaire of health-related quality of life (HRQoL). This study was a prospective analysis of the effect of pretransplantation liver status on HRQoL after the procedure., Materials and Methods: One hundred and seven (62 male, 45 female, median age 52 years) consecutive patients were included. MELD/CPT score and diabetes status were evaluated during LTx assessment. Patients were divided into 3 groups depending on the period after LTx: 6 to 12 months (group I), 13 to 36 months (group II), and >37 months (group III). They also were divided into 2 groups depending on the age at LTx: group I (<50 years) and group II (>50 years). SF-36 was used in the assessment of HRQoL., Results: Correlation between pretransplantation MELD/CPT score and HRQoL was only seen in the general health domain of the SF-36 in patients from group I (r = 0.64; P = .004 and r = 0.61; P = .02, respectively). Diabetes exerted a significant effect on the physical component summary (P = .02), again in group I. No significant correlation was observed between MELD/CPT score and the presence of diabetes in groups II and III. Regarding age at LTx, no significant correlation between MELD/CPT score and HRQoL was seen., Conclusions: Liver status assessed with MELD and CPT scores before transplantation has a minor effect on HRQoL after LTx and exerts no significant effect in patients evaluated >12 months after LTx. Patients with diabetes seem to have worse quality of life early after surgery; however, diabetic and nondiabetic patients had comparable HRQoL scores later on after LTx.

Chronic liver disease can often reliably be assessed only by examination of biopsy material. In this article the possible indications for liver biopsy in viral hepatitis B and C, autoimmune liver disease, steatohepatitis and hereditary metabolic diseases are described. A biopsy may be useful in cases with unclear clinical or serological situations or with questionable chronicity and comorbidities. The assessment of biopsy material should be based on guideline-based classification systems. The value of biopsy diagnosis benefits from a close interdisciplinary clinical pathological cooperation.

Objectives: The outcomes of emergency cardiac transplantation remain controversial, but recipient selection is essential for success. With a shortage of organs, it is essential to determine an objective method, such as a risk score, for choosing patients who are at too great a risk to undergo cardiac transplantation. In this study, we analysed the model for end-stage liver disease in terms of predicting operative mortality after emergency cardiac transplantation., Methods: We analysed the Nancy University database of heart transplantation and selected all patients who underwent emergency heart transplantation between January 2005 and January 2012. The calibration and discriminatory power were evaluated to determine the model for end-stage liver disease (MELD) score. Preoperative and peri-operative variables regarding the prediction of operative mortality were analysed by univariate and multivariate logistic regression models., Results: Forty-three patients underwent emergency cardiac transplantation. The operative mortality was 20.9% (n = 9). The Hosmer-Lemeshow test demonstrated a calibrated model for predicting operative mortality (P = 0.15), and the MELD score presented an excellent discrimination between survivors and non-survivors (AUC: 0.89 ± 0.05; 95% CI: 0.79-0.99). In the univariate analysis, an MELD score of ≥ 16 and bilirubin concentration were predictive markers of operative mortality. Multivariate logistic regression tested the contribution of the univariate risk predictors (P < 0.15) and confirmed that an MELD score of ≥ 16 was predictive of operative mortality., Conclusions: The MELD score appears to be adequate for predicting operative mortality among patients who undergo heart transplantation. The MELD score could therefore be used to guide clinical decision-making for emergency transplantation.

Background: An early and proper diagnosis of acute on chronic liver failure (ACLF), together with the identification of indicators associated with disease severity is critical for outcome prediction and therapy., Objective: To systematically identify and summarize prognostic indicators for patients with ACLF and to evaluate the predictive value of these indicators., Methods: Embase and Ovid-Medline were searched for English-language articles. The search criteria focused on identifying clinical trials and observational studies reporting on indicators used for prediction of mortality in patients with ACLF., Results: Of 2382 studies identified, 19 were included for detailed analysis. Thirteen different definitions of ACLF were found. The main differences were related to acute deterioration in liver function, coagulopathy and hyperbilirubinaemia/jaundice. Seventy three prognostic indicators and their association with mortality were extracted and categorized into seven categories: general markers (n = 13), viral markers (n = 6), bio-markers (n = 22), hemodynamics (n = 1), morphology/histology (n = 17), scoring systems (n = 10) and treatments (n = 4)., Conclusions: The ambiguity and variability in the definition of ACLF and in its predictive indicators hampers comparability among studies. There is a need for a single uniform definition of ACLF. Also absence of a gold standard is an obstacle to render one indicator superior to another. The age, hepatic encephalopathy, model for end-stage liver disease score, total bilirubin and International normalized ratio (prothrombin time) appeared to be promising candidates for evaluation in future studies. The result of this review may be useful as a starting point in developing a standard list of indicators for clinical outcome that concur with the clinicians' subjective views on prognosis in ACLF., (© 2012 John Wiley & Sons A/S.)

Background: The model for end-stage liver disease (MELD) and serum sodium (Na) are important markers for liver functional reserve in patients with hepatocellular carcinoma. We aimed to determine the best model to define the severity of liver dysfunction in terms of outcome prediction among the 4 currently used systems (MELD, MELDNa, MELD-Na and ReFit MELDNa)., Methods: A total of 2308 prospectively enrolled patients with hepatocellular carcinoma were analysed. The prognostic ability was compared by the Akaike information criterion., Results: MELDNa had the best prognostic accuracy overall, and for patients receiving curative and non-curative treatments, followed by MELD-Na, MELD and ReFit MELDNa. When patients were categorized into <8, 8-12, 12-16, 16-20 and >20, the adjusted risk ratios for MELDNa were 1.065 (p=0.46), 0.996 (p=0.973), 1.38 (p=0.048) and 1.563 (p=0.003) for the scores of 8-12, 12-16, 16-20 and >20, respectively, compared to the group with scores <8. The adjusted risk ratio for MELDNa was 1.014 (95% confidence interval, 1.001-1.027; p=0.034) per unit score increment in the Cox model., Conclusions: The MELDNa is the best marker to define the severity of liver dysfunction in hepatocellular carcinoma patients independent of treatment strategy. The ReFit MELDNa does not enhance the predictive accuracy of the MELD., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The Model for End-stage Liver Disease (MELD) score is a marker of multisystem organ dysfunction. It has been used to predict outcomes in patients undergoing hepatic and nonhepatic interventions. End-stage heart disease exhibits a varying degree of multiorgan dysfunction, which impacts the adverse events related to ventricular assist device (VAD) therapy. Our aim for the present study was to investigate the value of MELD score in predicting adverse events related with VAD therapy., Methods: Data were collected on demographics, clinical characteristics, MELD score; Interagency Registry for Mechanically Assisted Circulatory Support-defined VAD adverse events within the first 6 months, and survival from VAD recipients (n=286; from 1996 to 2009). Univariable, multivariable, and Cox regression analyses were performed using SAS software (SAS Institute, Cary, NC)., Results: The mean MELD score was 14.4±5.9. Actuarial incidence of infections, bleeding events, and cardiovascular dysfunction at 6 months was 65.4%, 52.1%, and 45.6%, respectively. Multivariable Cox proportional hazards model (controlling for gender, type of device, diagnosis, intention to treat, urgency, and inotropic use) confirmed that MELD score predicted mortality, respiratory, and renal dysfunction at 6 months (p<0.01)., Conclusions: Preoperative MELD score is predictive of mortality, respiratory, and renal dysfunction at 6 months after controlling for gender, type of device, diagnosis, intention to treat, urgency, and inotropic use. The MELD score may be used as a quantitative tool to assess the adverse events associated with VAD therapy., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Although establishing accurate prognosis in acute liver failure (ALF) is of paramount importance, prognostic scoring systems still fail to achieve success. The pediatric end-stage liver disease (PELD) score has been used as a predictor of mortality in children with chronic liver disease listed for liver transplantation (LT); however, experience with the PELD score in ALF is limited. The goal of the present study was to investigate the prognostic accuracy of the PELD score in children with ALF., Patients and Methods: PELD score was calculated based on results of blood tests obtained at hospital admission from June 1999 to January 2009, in 40 consecutive patients younger than 18 years who presented with ALF. Poor outcome was defined as LT or death., Results: Mean (±SD) age of patients was 5.3 ± 4.4 years (range 6 months-17 years); 52.5% were girls (n = 21). Etiologies of ALF were hepatitis A in 42.5% (17), indeterminate in 35% (14), autoimmune hepatitis in 17.5% (type 1 12.5% [n5], type 2 5% [n2]), and toxic in 5% (2). Mean PELD score was 34.92 ± 10.48 (range 6-55). PELD scores obtained on admission were significantly higher among nonsurvivors (39.8 ± 9.5) and recipients of an LT (39 ± 7.1) compared with those who survived without LT (31.3 ± 3) (P < 0.001). A cutoff of 33 in PELD score using receiver operating characteristic curves showed 81% specificity and 86% sensitivity for poor outcome (positive predictive value 92% and negative predictive value 69%; area under curve 0.88 95% confidence interval 0.77-1.0; P < 0.0001)., Conclusions: PELD score obtained upon admission may be of help to establish the optimal timing for LT evaluation and listing. Further validation in larger and more diverse populations is needed.

The proportion of patients undergoing liver transplantation (LT), with concomitant renal dysfunction, markedly increased after allocation by the model for end-stage liver disease (MELD) score was introduced. We examined the incidence of subsequent post-LT end-stage renal disease (ESRD) before and after the policy was implemented. Data on all adult deceased donor LT recipients between April 27, 1995 and December 31, 2008 (n = 59 242), from the Scientific Registry of Transplant Recipients, were linked with Centers for Medicare & Medicaid Services' ESRD data. Cox regression was used to (i) compare pre-MELD and MELD eras with respect to post-LT ESRD incidence, (ii) determine the risk factors for post-LT ESRD and (iii) quantify the association between ESRD incidence and mortality. Crude rates of post-LT ESRD were 12.8 and 14.5 per 1000 patient-years in the pre-MELD and MELD eras, respectively. Covariate-adjusted post-LT ESRD risk was higher in the MELD era (hazard ratio [HR]= 1.15; p = 0.0049). African American race, hepatitis C, pre-LT diabetes, higher creatinine, lower albumin, lower bilirubin and sodium >141 mmol/L at LT were also significant predictors of post-LT ESRD. Post-LT ESRD was associated with higher post-LT mortality (HR = 3.32; p < 0.0001). The risk of post-LT ESRD, a strong predictor of post-LT mortality, is 15% higher in the MELD era. This study identified potentially modifiable risk factors of post-LT ESRD. Early intervention and modification of these risk factors may reduce the burden of post-LT ESRD., (©2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

In recent years, acute-on-chronic liver failure has been recognized as a specific clinical form of liver failure associated with cirrhosis. The syndrome refers to an acute deterioration of liver function and subsequently of other end organs over a period of weeks following a precipitating event in a patient with previously well- or reasonably well-compensated cirrhosis. These precipitating events include either an indirect (e.g., variceal hemorrhage, sepsis) or a direct (e.g., drug-induced) hepatotoxic factor. The short-term mortality for this condition is more than 50%. At present, considerable efforts are ongoing to better characterize the syndrome, to gain further insight into its pathophysiology and to optimize therapy. This article aims to highlight the current concepts of these various aspects.

Priority for liver transplantation is currently based on the Model for End-stage Liver Disease (MELD) score. The aim of our study was to assess in detail the contribution of international normalized ratio (INR) differences for MELD scores because of interlaboratory variability. The samples from 92 cirrhotic patients were measured on different systems combining three coagulometers and three thromboplastin products to determine variations in INR and MELD score. The INR differences among the first four systems varied between 0 and 0.2, resulting in MELD differences of 0 to 2. The MELD scores of 92 patients changed only among 10 possible integers so that normally 2 to 10 patients shared the same MELD value. In some cases, one MELD score difference resulted in a 10 superpositioning on the waiting list. Including one more system (mechanical vs optical) into our investigations achieved a five MELD difference. Supposing an extreme situation where one patient competes with his or her lowest, all the other with their highest possible score (and visa versa), the difference may be even 20 positions, overturning the complete waiting list. In conclusion substantial interlaboratory differences in MELD score have profound clinical consequences., (Copyright 2010 Elsevier Inc. All rights reserved.)