MELD 3.0 in Advanced Chronic Liver Disease.

The MELD (model for end-stage liver disease) 3.0 score was developed to replace the MELD-Na score that is currently used to prioritize liver allocation for cirrhotic patients awaiting liver transplantation in the United States. The MELD 3.0 calculator includes new inputs from patient sex and serum albumin levels and has new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is expected that use of MELD 3.0 scores will reduce overall waitlist mortality modestly and improve access for female liver transplant candidates. The utility of MELD 3.0 and PELDcre (pediatric end-stage liver disease, creatinine) scores for risk stratification in cirrhotic patients undergoing major abdominal surgery, placement of a transjugular intrahepatic portosystemic shunt, and other interventions requires further study. This article reviews the background of the MELD score and the rationale to create MELD 3.0 as well as potential implications of using this newer risk stratification tool in clinical practice.

A novel scoring system to predict short-term mortality after living donor liver transplantation for acute liver failure.

Liver transplantation is often the only lifesaving option for acute liver failure (ALF); however, the predictors of short-term mortality (death within one year) after living donor liver transplantation (LDLT) for ALF have yet to be defined. We retrospectively collected patients ≥18 years old who underwent LDLT for ALF between 2010 and 2020 at 35 centers in Asia. Univariate and multivariate logistic regression analyses were conducted to identify the clinical variables related to short-term mortality and establish a novel scoring system. The Kaplan-Meier method was performed to explore the association between the score and overall survival. Of the 339 recipients, 46 (13.6%) died within 1 year after LDLT. Multivariate analyses revealed 4 independent risk factors for death: use of vasopressors or mechanical ventilation, the higher model for end-stage liver disease score, and a lower graft-to-recipient weight ratio. The internally validated c-statistic of the short-term mortality after transplant (SMT) score derived from these 4 variables was 0.80 (95% confidence interval: 0.74-0.87). The SMT score successfully stratified recipients into low-, intermediate-, and high-risk groups with 1-year overall survival rates of 96%, 80%, and 50%, respectively. In conclusion, our novel SMT score based on 4 predictors will guide ALF recipient and living donor selection.

IL-1 Signal Inhibition in Alcohol-Related Hepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial of Canakinumab.

BACKGROUND AND AIMS: Short-term mortality in alcohol-related hepatitis (AH) is high, and no current therapy results in durable benefit. A role for interleukin (IL)-1ß has been demonstrated in the pathogenesis of alcohol-induced steatohepatitis. This study explored the safety and efficacy of canakinumab (CAN), a monoclonal antibody targeting IL-1ß, in the treatment of patients with AH. METHODS: Participants with biopsy-confirmed AH and discriminant function ≥32 but Model for End-Stage Liver Disease ≤27 were randomly allocated 1:1 to receive either CAN 3 mg/kg or placebo (PBO). Liver biopsies were taken before and 28 days after treatment. The primary endpoint was the overall histological improvement in inflammation analyzed by the modified intention-to-treat principle. RESULTS: Fifty-seven participants were randomized: 29 to CAN and 28 to PBO. Two participants had histology that did not corroborate the clinical diagnosis. Of the remaining 55 participants, paired histology data were evaluable from 48 participants. In CAN-treated participants, 14 (58%) of 24 demonstrated histological improvement compared with 10 (42%) of 24 in the PBO group (P = .25). There was no improvement in prognostic scores of liver function. Four (7%) of the 55 participants died within 90 days, 2 in each group. The number of serious adverse events was similar between CAN vs PBO. In post hoc exploratory analyses after adjustment for baseline prognostic factors, CAN therapy was associated with overall histological improvement (P = .04). CONCLUSIONS: CAN therapy in severe AH participants with Model for End-Stage Liver Disease ≤27 did not alter biochemical or clinical outcomes compared with PBO. Nonsignificant histological improvements did not translate into clinical benefit. EudraCT, Number: 2017-003724-79; ClinicalTrials.gov, Number: NCT03775109.

Low liver reserve is a risk factor for acute pancreatitis in patients with acute liver failure.

AIM: Acute pancreatitis is a complication of acute liver failure (ALF). This study aimed to investigate the prevalence of and clinical features associated with acute pancreatitis in patients with ALF. METHODS: We retrospectively analyzed a cohort of ALF patients without hepatic encephalopathy diagnosed during a period 2011-2018, and compared clinical features between patients with acute pancreatitis and those without. Acute pancreatitis was diagnosed according to the Acute Pancreatitis Clinical Practice Guidelines 2021. A multivariate analysis was carried out to identify factors associated with acute pancreatitis. RESULTS: There were 83 ALF patients without hepatic encephalopathy (34 men; 11 deaths; 6 liver transplants; median age, 63 years). Acute pancreatitis occurred in nine patients (10.8%). The median time duration from ALF to the onset of acute pancreatitis was 8 days. The survival rate was lower in patients with than those without acute pancreatitis (22% vs. 86%). The model for end-stage liver disease score (hazard ratio 1.10, 95% confidence interval 1.03-1.18) was found to be a significant factor associated with acute pancreatitis, whereas triglyceride, age, and sex were not. CONCLUSIONS: A high model for end-stage liver disease score may be a marker to stratify patients with ALF at a risk of acute pancreatitis.

Direct-Acting Antiviral Therapy for Patients with Chronic Hepatitis C Infection and Decompensated Cirrhosis.

Patients with chronic hepatitis C virus (HCV) infection and decompensated cirrhosis are an important population for antiviral therapy yet under-represented in clinical trials. HCV direct-acting antiviral (DAA) therapies, unlike interferon-containing regimens, can be safely utilized in decompensated patients. Per guidelines from the American Association for the Study of Liver Diseases (AASLD), therapy of choice in HCV and decompensated cirrhosis is sofosbuvir, an HCV polymerase inhibitor, combined with a replication complex inhibitor (NS5A inhibitor) with or without ribavirin. Combination therapy with a HCV protease inhibitor and an NS5A inhibitor is effective in this population but is specifically not recommended in AASLD guidelines due to safety concerns. Important risk factors for further decompensation during DAA therapy are serum albumin < 3.5 g/dL, MELD (Model for End-Stage Liver Disease) score > 14, or HCV genotype 3 infection. Although sustained virologic response (SVR) is achieved less often in patients with decompensated vs compensated cirrhosis, in clinical studies response rates are > 80%. Both Child-Turcotte-Pugh Class at baseline and viral genotype can affect these response rates. Achieving SVR lowers risk of mortality, but to a lesser extent than in individuals with compensated cirrhosis. Likewise, treating patients for HCV infection along with successful treatment for hepatocellular carcinoma improves risks of both liver-related and overall mortality. In fewer than one third of cases, treating transplant-eligible, HCV-infected patients pre-transplant enables their delisting from transplant wait lists.

Inconsistent values and algorithmic fairness: a review of organ allocation priority systems in the United States.

BACKGROUND: The Organ Procurement and Transplant Network (OPTN) Final Rule guides national organ transplantation policies, mandating equitable organ allocation and organ-specific priority stratification systems. Current allocation scores rely on mortality predictions. METHODS: We examined the alignment between the ethical priorities across organ prioritization systems and the statistical design of the risk models in question. We searched PubMed for literature on organ allocation history, policy, and ethics in the United States. RESULTS: We identified 127 relevant articles, covering kidney (19), liver (60), lung (24), and heart transplants (23), and transplant accessibility (1). Current risk scores emphasize model performance and overlook ethical concerns in variable selection. The inclusion of race, sex, and geographical limits as categorical variables lacks biological basis; therefore, blurring the line between evidence-based models and discrimination. Comprehensive ethical and equity evaluation of risk scores is lacking, with only limited discussion of the algorithmic fairness of the Model for End-Stage Liver Disease (MELD) and the Kidney Donor Risk Index (KDRI) in some literature. We uncovered the inconsistent ethical standards underlying organ allocation scores in the United States. Specifically, we highlighted the exception points in MELD, the inclusion of race in KDRI, the geographical limit in the Lung Allocation Score, and the inadequacy of risk stratification in the Heart Tier system, creating obstacles for medically underserved populations. CONCLUSIONS: We encourage efforts to address statistical and ethical concerns in organ allocation models and urge standardization and transparency in policy development to ensure fairness, equitability, and evidence-based risk predictions.

Successful pathways to liver transplant for undocumented immigrants.

Liver transplant (LT) for undocumented immigrants presents numerous challenges. Although the United Network for Organ Sharing has implemented multiple policy changes to lessen the disparities in LT throughout the years, undocumented immigrants remain especially marginalized and disadvantaged when compared with other populations. Since 2013, the Mount Sinai Hospital's Recanati Miller Transplant Institute has transplanted 16 undocumented immigrants with successful outcomes. Here, we will share our experience of evaluating, caring for, and transplanting these patients and also highlight our team's mission to ensure that this population has equitable access to lifesaving medical treatment.

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

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

Urinary Neutrophil Gelatinase-associated Lipocalin as a Diagnostic and Prognostic Marker for Acute Kidney Injury in Hospitalized Cirrhotic Patients: A Study from North Indian Population.

Background: A serious problem in cirrhosis is acute renal injury. The study aimed to examine the urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a diagnostic and prognostic marker of acute kidney injury (AKI) in cirrhotic patients. Methods: A prospective study was carried out over a period of 1 year. A total of 490 patients suffering from cirrhosis who visited an indoor hospital were screened, and after the exclusion, a total of 90 subjects admitted to the medicine intensive care unit (MICU) fulfilling inclusion criteria were enrolled. Those having a history of renal diseases, on nephrotoxic drugs, in septic shock, peritonitis, UTI, and no urine output were excluded. On admission, for the estimation of uNGAL, urinary levels of sodium, creatinine, fresh urine samples were obtained, and blood samples were taken for serum creatinine estimation. Results: Out of 90 patients, 33.3% did not develop AKI, and 66.7% developed AKI. Urinary neutrophil gelatinase-associated lipocalin levels were six times higher in patients with acute tubular necrosis (259.08 ± 118.41 ng/mL) and three times higher in Hepatorenal syndrome (HRS)-AKI (124.97 ± 16.38) as compared with patients with normal kidney function (39.76 + 5.7). Those who died had a higher uNGAL (171.6 ng/mL) in comparison to those who survived (133.7 ng/mL). At a cutoff value of ≥114.9 (ng/mL), urinary NGAL represents a sensitivity of 86.92% and specificity of 100% to diagnose AKI and AUC 0.966 (95% CI: 0.919-0.990) in cirrhotic patients. Conclusion: Urinary NGAL is good for diagnosing AKI and is a marker to distinguish the types of AKI in liver cirrhosis. How to cite this article: Patel ML, Shyam R, Chaudhary A, Sachan R, Ali W. Urinary Neutrophil Gelatinase-associated Lipocalin as a Diagnostic and Prognostic Marker for Acute Kidney Injury in Hospitalized Cirrhotic Patients: A Study from North Indian Population. Indian J Crit Care Med 2023;27(8):545-551.

The effects of prognostic factors on transplant and mortality of patients with end-stage liver disease using Markov multistate model.

Background: Decompensated cirrhosis patients have a high risk of death which can be considerably reduced with liver transplantation (LT). This study aimed to simultaneously investigate the effect of some patients' characteristics on mortality among those with/without LT and also LT incident. Materials and Methods: In this historical cohort study, the information from 780 eligible patients aged 18 years or older was analyzed by the Markov multistate model; they had been listed between 2008 and 2014, needed a single organ for initial orthotopic LT, and followed at least for up to 5 years. Results: With a median survival time of 6 (5-8) years, there were 275 (35%) deaths. From 255 (33%) patients who had LT, 55 (21%) subsequently died. Factors associated with a higher risk of mortality and LT occurrence were included: higher model for end-stage liver disease (MELD) score (hazard ratio [HR] = 1.16, confidence interval [CI]: 1.09-1.24 and HR = 1.22, CI: 1.41-1.30) and ascites complication (HR = 2.34, CI: 1.74-3.16 and HR = 11.43, CI: 8.64-15.12). Older age (HR = 1.03, CI: 1.01-1.06), higher creatinine (HR = 6.87, CI: 1.45-32.56), and autoimmune disease versus hepatitis (HR = 2.53, CI: 1.12-5.73) were associated with increased risk of mortality after LT. Conclusion: The MELD and ascites are influential factors on waiting list mortality and occurrence of LT. Total life expectancy is not influenced by higher MELD.

Effect of liver cirrhosis on theophylline trough concentrations: A comparative analysis of organ impairment using Child-Pugh and MELD scores.

AIMS: Theophylline clearance is known to be reduced in patients with chronic liver diseases (CLDs) such as chronic hepatitis (CH) and liver cirrhosis (LC). The Child-Pugh (CP) score is generally used for pharmacokinetic evaluation, whilst a model for end-stage liver disease (MELD) has not yet been fully evaluated. This study aimed to predict theophylline clearance in patients with LC classified based on CP and MELD scores by population pharmacokinetic (PPK) analysis. METHODS: PPK analysis included 433 steady-state trough concentrations from 192 Japanese bronchial asthma patients with and without CLDs and was performed using NONMEM. The severity of LC was assessed by CP and MELD scores. RESULTS: The final CP and MELD models which described apparent theophylline clearance (CL/F) were obtained. The CP model showed that the mean CL/F in patients without CLDs, CH patients and LC patients with CP class A, B and C was 0.0473, 0.0413, 0.0330, 0.0280 and 0.0209 L/h kg-1 , respectively. The MELD model predicted that CL/F in patients without CLDs, CH patients and LC patients with MELD scores of <10, 10-14, 15-19, 20-24 and ≥25 was 0.0472, 0.0413, 0.0324, 0.0268, 0.0230, 0.0197 and 0.0155 L/h kg-1 , respectively. CONCLUSIONS: CL/F in various stages of LC was evaluated, and a change in CL/F was highly dependent on the severity of CLDs in both models. The MELD model provided a more accurate and precise description of theophylline clearance in LC than the CP model, which may be due to the wider dynamic range of the MELD score.

Which recipient pretransplant factors, such as MELD, renal function, sarcopenia, and recent sepsis influence suitability for and outcome after living donor liver transplantation? A systematic review of the literature and expert panel recommendations.

BACKGROUND: Varied access to deceased donors across the globe has resulted in differential living donor liver transplant (LDLT) practices and lack of consensus over the influence of models for end stage liver disease (MELD), renal function, sarcopenia, or recent infection on short-term outcomes. OBJECTIVES: Consider these risk factors in relation to patient selection and provide recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central. METHODS: PRIMSA systematic review and GRADE. PROSPERO ID: RD42021260809 RESULTS: MELD >25-30 alone is not a contraindication to LDLT, and multiple studies found no increase in short term mortality in high MELD patients. Contributing factors such as muscle mass, acute physiologic assessment and chronic health evaluation score, donor age, graft weight/recipient weight ratio, and inclusion of the middle hepatic vein in a right lobe graft influence morbidity and mortality in high MELD patients. Higher mortality is observed with pretransplant renal dysfunction, but short-term mortality is rare. Sarcopenia and recent infection are not contraindications to LDLT. Morbidity and prolonged LOS are common, and more frequent in patients with renal dysfunction, nutritional deficiency or recent infection. CONCLUSIONS: When individual risk factors are studied mortality is low and graft loss is infrequent, but morbidity is common. MELD, especially with concomitant risk factors, had the greatest influence on short term outcome, and recent infection had the least. A multidisciplinary team of experts should carefully assess patients with multiple risk factors, and an optimal graft is recommended.

Changing opportunities for liver transplant for patients with hepatocellular carcinoma.

INTRODUCTION: Aim was to study the early impact of acuity circle-based allocation implementation system on liver transplantation for hepatocellular carcinoma (HCC) patients. METHODS: We assessed characteristics of HCC and non-HCC deceased donor orthotopic liver transplants (OLT) in the year before (2/2019-2/2020) and after (3/2020-2/2021) introduction of the acuity circle policy using the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database. RESULTS: Total OLTs reduced from 6699 in the preacuity circle era to 6660 in the postacuity circle era (-.6%); this decrease is mostly driven by a decrease in HCC transplants (1529 to 1351; -11.6%). Six out of 11 regions had a reduction in the absolute number and percentage of HCC transplants with significant reductions in regions 2 (-37.8%, p < .001) and 4 (-28.3%, p = .001). DISCUSSION: The introduction of median model for end-stage liver disease (MELD) at transplant minus 3 (MMaT-3) exception points, has created differential opportunities for HCC patients, in low-MELD as opposed to high-MELD areas, despite having the same disease. This effect has become more prominent following the implementation of acuity circle-based allocation system. Ongoing investigation of these trends is needed to ensure that HCC patients are not disparately disadvantaged due to their location.

Prognostic value of decline in model for end-stage liver disease score and hepatic encephalopathy in hepatitis B-related acute-on-chronic liver failure patients treated with plasma exchange.

OBJECTIVE: To investigate the prognostic value of Model for End-Stage Liver Disease (MELD) score and Hepatic Encephalopathy (HE) for short-term prognosis of Hepatitis B virus-related Acute-on-Chronic Liver Failure (HBV-ACLF) patients treated with plasma exchange (PE). METHODS: A total of 108 patients with HBV-ACLF treated with PE were retrospectively enrolled between January 2014 to December 2020. Based on survival at 28 days, patients were divided into survival (N = 87) and death groups (N = 21). Clinical data and laboratory indicators were analyzed. RESULTS: Compared with the survival group, the death group was associated with higher ACLF grade and incidence of HE. The levels of total bilirubin, prothrombin time, creatinine, blood urea nitrogen, MELD score, and Chinese Group on the Study of Severe Hepatitis B-ACLF II (COSSH II) score were significantly higher in the death group than in the survival group (p < .05). Grade 1 ACLF and the MELD score after PE treatment at one week were independent risk factors for 28-day liver transplantation-free mortality (OR = 0.062, 95%CI: 0.005-0.768; OR = 1.328, 95%CI: 1.153-1.531). A MELD score at one week of at least 25.5 was associated with a poor short-term prognosis. Of note, HE was a strong independent risk factor for a decline in MELD score at one week. (OR = 11.815, 95%CI: 3.187-43.796, p < 0.001). CONCLUSION: We found patients with HE at admission and MELD score of at least 25.5 at one week after PE treatment had a poor short-term prognosis and should prompt preparation for liver transplantation. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565). Registered 13 May 2020.

Association Between Different Versions of the Model for End-Stage Liver Disease Score and Contrast-Associated Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND: Pre-procedure liver dysfunction was associated with acute kidney injury after percutaneous coronary intervention (PCI). The aim of this study is to assess and compare the predictive value of different liver function scoring systems for contrast-associated acute kidney injury (CA-AKI) in patients undergoing elective PCI.Methods and Results:A total of 5,569 patients were retrospectively enrolled. The model for end-stage liver disease (MELD) including albumin (MELD-Albumin) score (AUC=0.661) had the strongest predictive value in comparison to the MELD score (AUC=0.627), the MELD excluding the international normalized ratio (MELD-XI) score (AUC=0.560), and the MELD including sodium (MELD-Na) score (AUC=0.652). In the fully adjusted logistic regression model, the MELD-Albumin score and the MELD-Na score were independently associated with CA-AKI regardless of whether they were treated as continuous or categorical variables; however, this was not the case for the MELD score and the MELD-XI score. Furthermore, the addition of the MELD-Albumin score significantly improved the reclassification beyond the fully adjusted logistic regression model. The study further explored the association between different versions of the MELD score and CA-AKI using restricted cubic splines and found a linear relationship between the MELD-Albumin score and the risk of CA-AKI. CONCLUSIONS: The MELD-Albumin score had the highest predictive value for CA-AKI in patients undergoing elective PCI. The addition of the MELD-Albumin score to the existing risk prediction model significantly improved the reclassification for CA-AKI.

An exploratory analysis of patient factors influencing acceptance of extended criteria liver grafts.

INTRODUCTION AND OBJECTIVES: There is a shortage of ideal donor organs with consequential increasing waitlist times, drop-off, and mortality. Teams have thus extended the donor criteria. Little is known about patients' actual choices and what factors may influence their decisions regarding different extended criteria liver grafts. PATIENTS AND METHODS: The documented acceptance or refusal of seven extended criteria liver graft types of patients consented for transplant in a single institution over a 2-year period was reviewed. Patient factors including sex, age, indication, aetiology, and model for end-stage liver disease (MELD) score were analysed using logistic regression. RESULTS: Most patients were willing to accept most graft types. MELD score did not impact the acceptance or refusal of any graft type. Older patients and those with hepatocellular carcinoma (HCC) or ascites had significantly higher rates of acceptance. Hepatitis B or C disease aetiology was predictive of willingness to accept a similarly infected graft, respectively. HCC was predictive of acceptance of grafts from donors with a cancer history. CONCLUSIONS: In general, patients embrace the available extended criteria donors. Our analysis suggests that consent should be revisited as patients deteriorate or ameliorate on the waitlist, especially if in the form of ascites or HCC but not necessarily MELD score.

Prognostic value of the modified model for end-stage liver disease (MELD) score including albumin in acute heart failure.

BACKGROUND: Liver and renal function evaluated by the model for end-stage liver disease (MELD) score, the MELD excluding the international normalized ratio (MELD_XI) score and the MELD including sodium (MELD_sodium) score have been considered predictors of adverse events for patients with acute heart failure (AHF). However, the prognostic value of the MELD including albumin (MELD_albumin) score in patients with AHF has not been assessed. METHODS: A total of 466 patients with AHF were prospectively evaluated. We compared the accuracy of the 4 MELD score formulas using the time-dependent receiver operating characteristic (ROC) curve and corresponding areas under the curve (AUC). RESULTS: During a median follow-up period of 34 months, 196 deaths occurred. In the fully adjusted Cox regression model, standardized hazard ratios with 95% confidence interval expressing the risk of all-cause mortality were 1.22 (1.06-1.40), 1.20 (1.04-1.39), 1.23 (1.06-1.42) and 1.21 (1.05-1.41) for MELD, MELD_XI, MELD_sodium and MELD_albumin scores, respectively. The MELD_albumin score showed the best prognostic accuracy (AUC = 0.658) for the prediction of long-term all-cause mortality, followed by the MELD_sodium score (AUC = 0.590), the MELD score (AUC = 0.580), and the MELD_XI score (AUC = 0.544); the MELD_albumin score performs significantly more accurate than MELD and MELD_XI score for predicting the risk of all-cause mortality. Considering reclassification, MELD_albumin score increased the net reclassification improvement over and beyond MELD (13.1%, P = 0.003), MELD_XI (14.8%, P = 0.002), and MELD_sodium (11.9%, P = 0.006) scores for all-cause mortality. CONCLUSIONS: The MELD_albumin score increases risk stratification of all-cause mortality over and beyond the MELD score and the other modified MELD scores in patients with acute heart failure.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels are not associated with severity of liver disease and are inversely related to cholesterol in a cohort of thirty eight patients with liver cirrhosis.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is of particular importance in cholesterol metabolism with high levels contributing to hypercholesterolemia. Cholesterol and sphingolipids are low in patients with liver cirrhosis. Purpose of this study was to find associations of plasma PCSK9 with circulating cholesterol and sphingolipid species and measures of liver disease severity in patients with liver cirrhosis. METHODS: PCSK9 protein levels were determined by ELISA in systemic vein (SVP), hepatic vein (HVP) and portal vein plasma of patients with mostly alcoholic liver cirrhosis. PCSK9 and LDL-receptor protein expression were analysed in cirrhotic and non-cirrhotic liver tissues. RESULTS: Serum PCSK9 was reduced in patients with liver cirrhosis in comparison to non-cirrhotic patients. In liver cirrhosis, plasma PCSK9 was not correlated with Child-Pugh score, Model for End-Stage Liver Disease score, bilirubin or aminotransferases. A negative association of SVP PCSK9 with albumin existed. PCSK9 protein in the liver did not change with fibrosis stage and was even positively correlated with LDL-receptor protein levels. Ascites volume and variceal size were not related to PCSK9 levels. Along the same line, transjugular intrahepatic shunt to lower portal pressure did not affect PCSK9 concentrations in the three blood compartments. Serum cholesterol, sphingomyelin and ceramide levels did not correlate with PCSK9. Stratifying patients by high versus low PCSK9 levels using the median as cut-off, several cholesteryl ester species were even low in the subgroup with high PCSK9 levels. A few sphingomyelin species were also reduced in the patients with PCSK9 levels above the median. PCSK9 is highly expressed in the liver but systemic, portal and hepatic vein levels were similar. PCSK9 was not correlated with the inflammatory proteins C-reactive protein, IL-6, galectin-3, resistin or pentraxin 3. Of note, HVP PCSK9 was positively associated with HVP chemerin and negatively with HVP adiponectin levels. CONCLUSIONS: In the cohort of patients with liver cirrhosis mostly secondary to alcohol consumption high PCSK9 was associated with low levels of certain cholesteryl ester and sphingomyelin species. Positive correlations of PCSK9 and LDL-receptor protein in the liver of patients with chronic liver injury are consistent with these findings.

Model for end-stage liver disease score predicts complications after liver transplantation.

PURPOSE: Increased model for end-stage liver disease (MELD) score measured in the early postoperative course is associated with one-year mortality and graft loss. However, the correlation with postoperative complications has not been investigated. The aim of this study was to investigate the association between postoperative MELD score and subsequent complications. METHODS: Adult liver transplant recipients transplanted from January 2011 until December 2016 were included. MELD score days 1-5 were correlated with complications day 6-30, subdivided into type and severity according to Clavien-Dindo classification. RESULTS: We included 246 adult liver transplant recipients. Between days 6 and 30, 671 complications occurred in 201 of the patients (82%) corresponding to 64% of all postoperative complications in the whole postoperative period (days 0-30). In multivariate analyses adjusted for recipient gender and age, preoperative MELD score, and Eurotransplant Donor Risk Index, postoperative MELD score was significantly associated with having one or more complications, any type of complication except cardiovascular and renal complications, and complication severity. CONCLUSIONS: Postoperative MELD score days 1-5 were associated with complications arising in the subsequent period 6-30 days after transplantation. An increased MELD score should heighten the clinician's awareness of a possible complication.

Hepatorenal dysfunction predicts operative mortality after triple valve surgery: Utility of MELD-Na.

BACKGROUND: Despite significant advancements in operative techniques and myocardial protection, triple valve surgery (TVS) remains a formidable operation with a relatively high in-hospital mortality. We evaluated the prognostic value of Model for End-stage Liver Disease score including sodium (MELD-Na) for mortality after TVS and its predictive value when incorporated in the EuroSCORE risk model. METHODS: We performed a retrospective cohort study of 61 consecutive patients who underwent TVS from November 2005 to June 2016. Demographics, clinical, biochemical, and operative data were collected and analyzed. RESULTS: Median follow-up duration was 8.0 years. The majority (70.5%) of patients suffered from rheumatic heart disease and underwent mechanical double valve replacement with tricuspid valve repair. There were six operative deaths (9.84%), with the most common cause of death being multiorgan failure (83.3%). In 26.2% of the cohort, the MELD-Na score was moderately elevated at 9 to 15. A small fraction (4.9%) had a severely elevated MELD-Na greater than 15. Patients with a MELD-Na greater than 9 had a higher unadjusted rate of operative mortality, prolonged ventilation, need for dialysis and acute liver failure after TVS. Hierarchical logistic regression was performed using logistic EuroSCORE as the base model. After risk adjustment, each point of MELD-Na score increase was associated with 1.405 times increase in odds of operative mortality. The regression analysis was repeated by incorporating individual components of the MELD-Na score, including bilirubin, sodium, and albumin. All three biochemical parameters were significantly associated with operative mortality CONCLUSION: MELD-Na score as a quantifier of hepatorenal dysfunction is sensitive and specific for operative mortality after triple valve surgery.