Superiority of the new sex-adjusted models to remove the female disadvantage restoring equity in liver transplant allocation.

BACKGROUND AND AIMS: Model for End-stage Liver Disease (MELD) and MELDNa are used worldwide to guide graft allocation in liver transplantation (LT). Evidence exists that females are penalized in the present allocation systems. Recently, new sex-adjusted scores have been proposed with improved performance respect to MELD and MELDNa. GEMA-Na, MELD 3.0, and sex-adjusted MELDNa were developed to improve the 90-day dropout prediction from the list. The present study aimed at evaluating the accuracy and calibration of these scores in an Italian setting. METHODS: The primary outcome of the present study was the dropout from the list up to 90 days because of death or clinical deterioration. We retrospectively analysed data from 855 adults enlisted for liver transplantation in the Lazio region (Italy) (2012-2018). Ninety-day prediction of GEMA-Na, MELD 3.0 and sex-adjusted MELDNa with respect to MELD and MELDNa was analysed. Brier score and Brier Skill score were used for accuracy, and the Greenwood-Nam-D'Agostino test was used to evaluate the calibration of the models. RESULTS: GEMA-Na (concordance = .82, 95% CI = .75-.89), MELD 3.0 (concordance = .81, 95% CI = .74-.87) and sex-adjusted MELDNa (concordance = .81, 95% CI = .74-.88) showed the best 90-day dropout prediction. GEMA-Na showed a higher increase in accuracy with respect to MELD (p = .03). No superiority was shown with respect to MELDNa. All the tested scores showed a good calibration of the models. Using GEMA-Na instead of MELD would potentially save one in nine dropouts and could save one dropout per 285 patients listed. CONCLUSIONS: Validation and reclassification of the sex-adjusted score GEMA-Na confirm its superiority in predicting short-term dropout also in an Italian setting when compared with MELD.

Clinical Profile, Short-term Prognostic Accuracies of CLIF-C ACLF Score and Serial CLIF-C OF Scores in Acute-on-chronic Liver Failure Patients: A Prospective Observational Study.

Background: Acute-on-chronic liver failure (ACLF) is a recently defined entity that carries high short-term mortality. The European Association for Study of Liver (EASL) has given a different definition for ACLF and derived two scores called Chronic Liver Failure-Consortium Organ Failure (CLIF-C OF) and CLIF-C ACLF to diagnose and predict the short-term outcome, respectively. Materials and methods: This was the prospective observational study, included 40 ACLF patients diagnosed as per the EASL definition and calculated CLIF-C ACLF as well as other scores (CTP, MELD, MELD-Na, CLIF-C OF) on admission. Serial CLIF-C OF scores were also calculated (Day 3 and Day 7). The 28-day and 90-day mortality was recorded. Results: Alcohol was the predominant etiology of cirrhosis (32 patients-80%). Infection was the chief precipitating factor in 19 patients (47.5%). The 28-day and 90-day mortality was 45% and 52.5%. Mean (SD) of CLIF-C ACLF scores of survivors and non-survivors on Day-90 were 44.11(6.62) and 53.86 (7.83). The prognostic accuracy of the CLIF-C ACLF score (Area Under Receiver Operating Characteristic Curve-AUROC) to predict 28-day and 90-day mortality was 0.86 and 0.84, respectively. MELD-Na and CLIF-C ACLF scores had higher AUROC for predicting 28-day and 90-day mortality, respectively. The AUROC of the CLIF-C OF score on Day 3 was found to be higher than the values of Day 1 and Day 7, but it was not statistically significant. Conclusion: CLIF-C ACLF has good short-term prognostic accuracy and it is as good as other available scores. Serial CLIF-C OF scores were equally good in predicting in short-term mortality. How to cite this article: Hareesh GJ, Ramadoss R. Clinical Profile, Short-term Prognostic Accuracies of CLIF-C ACLF Score and Serial CLIF-C OF Scores in Acute-on-chronic Liver Failure Patients: A Prospective Observational Study. Indian J Crit Care Med 2024;28(2):126-133.

Acute on Chronic Liver Failure: Lessons from a Decade of EASL-CLIF Definition and Scoring Systems.

How to cite this article: Solao V. Acute on Chronic Liver Failure: Lessons from a Decade of EASL-CLIF Definition and Scoring Systems. Indian J Crit Care Med 2024;28(2):100-102.

[Application of different prognostic scores in liver transplantation decision-making for acute-on-chronic liver failure].

Objective: To compare the impact of different prognostic scores in patients with acute-on-chronic liver failure (ACLF) in order to provide treatment guidance for liver transplantation. Methods: The information on inpatients with ACLF admitted at Beijing You'an Hospital Affiliated to Capital Medical University and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2022 was collected retrospectively. ACLF patients were divided into liver transplantation and non-liver transplantation groups, and the two groups prognostic conditions were followed-up. Propensity score matching was carried out between the two groups on the basis of liver disease (non-cirrhosis, compensated cirrhosis, and decompensated cirrhosis), the model for end-stage liver disease incorporating serum sodium (MELD-Na), and ACLF classification as matching factors. The prognostic condition of the two groups after matching was compared. The difference in 1-year survival rate between the two groups was analyzed under different ACLF grades and MELD-Na scores. The independent sample t-test or rank sum test was used for inter-group comparison, and the χ (2) test was used for the comparison of count data between groups. Results: In total, 865 ACLF inpatients were collected over the study period. Of these, 291 had liver transplantation and 574 did not. The overall survival rates at 28, 90, and 360 days were 78%, 66%, and 62%, respectively. There were 270 cases of matched ACLF post-liver transplantation and 270 cases without ACLF, in accordance with a ratio of 1:1. At 28, 90, and 360 days, patients with non-liver transplantation had significantly lower survival rates (68%, 53%, and 49%) than patients with liver transplantation (87%, 87%, and 78%, respectively; P < 0.001). Patients were classified into four groups according to the ACLF classification criteria. Kaplan-Meier survival analysis showed that the survival rates of liver transplantation and non-liver transplantation patients in ACLF grade 0 were 77.2% and 69.4%, respectively, with no statistically significant difference (P = 0.168). The survival rate with an ACLF 1-3 grade was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.05). Patients with ACLF grades 1, 2, and 3 had higher 1-year survival rates compared to non-liver transplant patients by 50.6%, 43.6%, and 61.7%, respectively. Patients were divided into four groups according to the MELD-Na score. Among the patients with a MELD-Na score of < 25, the 1-year survival rates for liver transplantation and non-liver transplantation were 78.2% and 74.0%, respectively, and the difference was not statistically significant (P = 0.149). However, among patients with MELD-Na scores of 25-30, 30-35, and≥35, the survival rate was significantly higher in liver transplantation than that of non-liver transplantation, and the 1-year survival rate increased by 36.4%, 54.9%, and 62.5%, respectively (P < 0.001). Further analysis of the prognosis of patients with different ACLF grades and MELD-Na scores showed that ACLF grades 0 or 1 and MELD-Na score of < 30 had no statistically significant difference in the 1-year survival rate between liver transplantation and non-liver transplantation (P > 0.05), but in patients with MELD-Na score≥30, the 1-year survival rate of liver transplantation was higher than that of non-liver transplantation patients (P < 0.05). In the ACLF grade 0 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 77.8% and 25.0% respectively (P < 0.05); while in the ACLF grade 1 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 100% and 20.0%, respectively (P < 0.01). Among patients with ACLF grade 2, the 1-year survival rate with MELD-Na score of < 25 in patients with liver transplantation was 73.9% and 61.6%, respectively, and the difference was not statistically significant (P > 0.05); while in the liver transplantation patients group with MELD-Na score of ≥25, the 1-year survival rate was 79.5%, 80.8%, and 75%, respectively, which was significantly higher than that of non-liver transplantation patients (36.6%, 27.6%, 15.0%) (P < 0.001). Among patients with ACLF grade 3, regardless of the MELD-Na score, the 1-year survival rate was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.01). Additionally, among patients with non-liver transplantation with an ACLF grade 0~1 and a MELD-Na score of < 30 at admission, 99.4% survived 1 year and still had an ACLF grade 0-1 at discharge, while 70% of deaths progressed to ACLF grade 2-3. Conclusion: Both the MELD-Na score and the EASL-CLIF C ACLF classification are capable of guiding liver transplantation; however, no single model possesses a consistent and precise prediction ability. Therefore, the combined application of the two models is necessary for comprehensive and dynamic evaluation, but the clinical application is relatively complex. A simplified prognostic model and a risk assessment model will be required in the future to improve patient prognosis as well as the effectiveness and efficiency of liver transplantation.

Galectin-3 is overexpressed in advanced cirrhosis and predicts post-liver transplant infectious complications.

BACKGROUND & AIMS: Patients with advanced cirrhosis often have immune dysfunction and are more susceptible to infections. Galectin-3 is a ß-galactoside-binding lectin implicated in inflammation, immune regulation and liver fibrosis. We aim to investigate galectin-3 expression in advanced cirrhosis and its ability to predict post-transplant infectious complications. METHODS: We collected sera and liver samples from 129 cirrhotic patients at the time of liver transplantation and from an external cohort of 37 patients with alcoholic liver disease including alcoholic hepatitis (AH) at the time of diagnosis. Galectin-3 was assessed by ELISA, real-time PCR, immunohistochemistry and RNA-seq. Receiver operating characteristic curves and Cox proportional-hazards regression analysis were performed to assess the predictive power of galectin-3 for disease severity and post-transplant infections. RESULTS: Increased galectin-3 levels were found in advanced cirrhosis. Galectin-3 significantly correlated with disease severity parameters and inflammatory markers. Galectin-3 had significant discriminating power for compensated and advanced cirrhosis (AUC = 0.78/0.84, circulating/liver galectin-3; p < .01), and was even higher to discriminate severe AH (AUC = 0.95, p < .0001). Cox Proportional-hazard model showed that galectin-3, MELD-Na and the presence of SIRS predict the development of post-transplant infectious complications. Patients with circulating galectin-3 (>16.58 ng/ml) were at 2.19-fold 95% CI (1.12-4.29) increased risk, but when combined with MELD-Na > 20.0 and SIRS, the risk to develop post-transplant infectious complications, increased to 4.60, 95% CI (2.38-8.90). CONCLUSION: Galectin-3 is a novel biological marker of active inflammation and disease severity that could be clinically useful alone or in combination with other scores to discriminate advanced cirrhosis and predict post-transplant infectious complications.

External Validation of the FIPS Score for Post-TIPS Mortality in a National Veterans Affairs Cohort.

BACKGROUND: The Freiburg index of post-TIPS survival (FIPS) score was recently demonstrated to improve prediction of post-TIPS mortality relative to existing standards. As this score was derived from a German cohort over an extended time period, it is unclear if performance will translate well to other settings. This study aimed to externally validate the FIPS score in a large Veterans Affairs (VA) cohort over two separate eras of TIPS-related care. METHODS: This was a retrospective cohort study of patients with cirrhosis who underwent TIPS placement in the VA from 2008 to 2020. Cox regression models for post-TIPS survival were constructed using FIPS, MELD, MELD-Na, or CTP scores as predictors. Discrimination (Harrell's C) and calibration (joint tests of calibration curve slope and intercept) were evaluated for each score. A stratified analysis was performed for time periods between 2008-2013 and 2014-2020. RESULTS: The cohort of 1,274 patients was 97.3% male with mean age 60.9 years and mean MELD-Na 14. The FIPS score demonstrated the highest overall discrimination versus MELD, MELD-Na, and CTP (0.634 vs. 0.585, 0.626, 0.612, respectively). However, in the modern treatment era (2014-2020), the FIPS score performed similarly to MELD-Na. Additionally, the FIPS score demonstrated poor calibration at one-month and six-month post-TIPS timepoints (joint p = 0.04 and 0.004, respectively). MELD, MELD-Na, and CTP were well-calibrated at each timepoint (each joint p > 0.05). CONCLUSION: The FIPS score performed similarly to MELD-Na in the modern TIPS treatment era and demonstrated regions of poor calibration. Future models derived with contemporary data may improve prediction of post-TIPS mortality.

Refractory Hepatic Hydrothorax Is an Independent Predictor of Mortality When Compared to Refractory Ascites.

BACKGROUND: Hepatic hydrothorax (HHT) is an uncommon but significant complication of cirrhosis and portal hypertension, associated with a worse prognosis and mortality. Nearly 25% of patients with HHT will have refractory pleural effusion. It is unclear if refractory HHT has a different prognosis compared to refractory ascites. AIMS: We aim to evaluate the prognostic significance of refractory HHT when compared to refractory ascites. METHODS: Forty-seven patients who had refractory HHT in a tertiary care center were identified, and matched, retrospectively, one-to-one by age, gender and MELD-Na with 47 patients with refractory ascites. One-year mortality rate was compared between both groups. Cox proportional hazard regression was used to identify the association between different covariates and primary endpoint. RESULTS: The 1-year mortality was 51.06% in the HHT group compared to 19.15% in the refractory ascites group. The median survival for patients with refractory hepatic hydrothorax was 4.87 months while the median survival for patients with refractory ascites exceeded 1 year. The presence of HHT was statistically significant in predicting the development of 1-year mortality [Hazard Ratio (HR) 4.45, 95% Confidence Interval (CI) 2.25-8.82; P value < 0.001]. Furthermore, refractory HHT remained associated with one-year mortality after adjusting for all other covariates. In a subgroup of patients with MELD-Na ≤ 20, HHT continued to be a significant predictor of one-year mortality (HR 3.30, 95% CI 1.47-7.40; P value 0.004). CONCLUSIONS: Refractory HHT is a significant independent predictor of mortality and offers additional prognostic value.

Acute kidney injury defined by cystatin C may be superior for predicting the outcomes of liver cirrhosis with acute gastrointestinal bleeding.

BACKGROUND & AIMS: Acute kidney injury (AKI) is conventionally evaluated by a dynamic change of serum creatinine (Scr). Cystatin C (CysC) seems to be a more accurate biomarker for assessing kidney function. This retrospective multicenter study aims to evaluate whether AKI re-defined by CysC can predict the in-hospital outcomes of patients with liver cirrhosis and acute gastrointestinal bleeding. METHODS: Overall, 677 cirrhotic patients with acute gastrointestinal bleeding, in whom both Scr and CysC levels were detected at admissions, were screened. eGFRScr, eGFRCysC, and eGFRScr-CysC were calculated. MELD-Na score and AKI were re-evaluated by CysC instead of Scr. Odds ratios (ORs) were calculated in the logistic regression analyses. The receiver operating characteristic (ROC) curve analyses were performed. RESULTS: Univariate logistic regression analyses demonstrated that baseline Scr and CysC levels, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, MELD-Na score re-defined by CysC, and AKI re-defined by CysC, but not conventional AKI defined by Scr, were significantly associated with in-hospital death. ROC analyses showed that baseline CysC level, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, and MELD-Na score re-defined by CysC, but not baseline Scr level, could significantly predict the risk of in-hospital death. CONCLUSIONS: AKI re-defined by CysC may be superior for predicting the in-hospital mortality of cirrhotic patients with acute gastrointestinal bleeding.

Emricasan to prevent new decompensation in patients with NASH-related decompensated cirrhosis.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis is a leading cause of end-stage liver disease. Hepatic steatosis and lipotoxicity cause chronic necroinflammation and direct hepatocellular injury resulting in cirrhosis, end-stage liver disease and hepatocellular carcinoma. Emricasan is a pan-caspase inhibitor that inhibits excessive apoptosis and inflammation; it has also been shown to decrease portal pressure and improve synthetic function in mice with carbon tetrachloride-induced cirrhosis. METHODS: This double-blind, placebo-controlled study randomized 217 individuals with decompensated NASH cirrhosis 1:1:1 to emricasan (5 mg or 25 mg) or placebo. Patients were stratified by decompensation status and baseline model for end-stage liver disease-sodium (MELD-Na) score. The primary endpoint comprised all-cause mortality, a new decompensation event (new or recurrent variceal hemorrhage, new ascites requiring diuretics, new unprecipitated hepatic encephalopathy ≥grade 2, hepatorenal syndrome, spontaneous bacterial peritonitis), or an increase in MELD-Na score ≥4 points. RESULTS: There was no difference in event rates between either of the emricasan treatment groups and placebo, with hazard ratios of 1.02 (95% CI 0.59-1.77; p = 0.94) and 1.28 (95% CI 0.75-2.21; p = 0.37) for 5 mg and 25 mg of emricasan, respectively. MELD-Na score progression was the most common outcome. There was no significant effect of emricasan treatment on MELD-Na score, international normalized ratio, total serum bilirubin, albumin level or Child-Pugh score. Emricasan was generally safe and well-tolerated. CONCLUSIONS: Emricasan was safe but ineffective for the treatment of decompensated NASH cirrhosis. However, this study may guide the design and conduct of future clinical trials in decompensated NASH cirrhosis. LAY SUMMARY: Patients with decompensated cirrhosis related to non-alcoholic steatohepatitis are at high risk of additional decompensation events and death. Post hoc analyses in previous pilot studies suggested that emricasan might improve portal hypertension and liver function. In this larger randomized study, emricasan did not decrease the number of decompensation events or improve liver function in patients with a history of decompensated cirrhosis related to non-alcoholic steatohepatitis. CLINICALTRIALS. GOV IDENTIFIER: NCT03205345.

Extreme hyponatremia as a risk factor for early mortality after liver transplantation in the MELD-sodium era.

The impact of hyponatremia on waitlist and post-transplant outcomes following the implementation of MELD-Na-based liver allocation remains unclear. We investigated waitlist and postliver transplant (LT) outcomes in patients with hyponatremia before and after implementing MELD-Na-based allocation. Adult patients registered for a primary LT between 2009 and 2021 were identified in the OPTN/UNOS database. Two eras were defined; pre-MELD-Na and post-MELD-Na. Extreme hyponatremia was defined as a serum sodium concentration ≤120 mEq/l. Ninety-day waitlist outcomes and post-LT survival were compared using Fine-Gray proportional hazard and mixed-effects Cox proportional hazard models. A total of 118 487 patients were eligible (n = 64 940: pre-MELD-Na; n = 53 547: post-MELD-Na). In the pre-MELD-Na era, extreme hyponatremia at listing was associated with an increased risk of 90-day waitlist mortality ([ref: 135-145] HR: 3.80; 95% CI: 2.97-4.87; P < 0.001) and higher transplant probability (HR: 1.67; 95% CI: 1.38-2.01; P < 0.001). In the post-MELD-Na era, patients with extreme hyponatremia had a proportionally lower relative risk of waitlist mortality (HR: 2.27; 95% CI 1.60-3.23; P < 0.001) and proportionally higher transplant probability (HR: 2.12; 95% CI 1.76-2.55; P < 0.001) as patients with normal serum sodium levels (135-145). Extreme hyponatremia was associated with a higher risk of 90, 180, and 365-day post-LT survival compared to patients with normal serum sodium levels. With the introduction of MELD-Na-based allocation, waitlist outcomes have improved in patients with extreme hyponatremia but they continue to have worse short-term post-LT survival.

Effect of the clinical course of acute-on-chronic liver failure prior to liver transplantation on post-transplant survival.

BACKGROUND & AIMS: Patients with acute-on-chronic liver failure (ACLF) can be listed for liver transplantation (LT) because LT is the only curative treatment option. We evaluated whether the clinical course of ACLF, particularly ACLF-3, between the time of listing and LT affects 1-year post-transplant survival. METHODS: We identified patients from the United Network for Organ Sharing database who were transplanted within 28 days of listing and categorized them by ACLF grade at waitlist registration and LT, according to the EASL-CLIF definition. RESULTS: A total of 3,636 patients listed with ACLF-3 underwent LT within 28 days. Among those transplanted, 892 (24.5%) recovered to no ACLF or ACLF grade 1 or 2 (ACLF 0-2) and 2,744 (75.5%) had ACLF-3 at transplantation. One-year survival was 82.0% among those transplanted with ACLF-3 vs. 88.2% among those improving to ACLF 0-2 (p <0.001). Conversely, the survival of patients listed with ACLF 0-2 who progressed to ACLF-3 at LT (n = 2,265) was significantly lower than that of recipients who remained at ACLF 0-2 (n = 17,631) at the time of LT (83.8% vs. 90.2%, p <0.001). Cox modeling demonstrated that recovery from ACLF-3 to ACLF 0-2 at LT was associated with reduced 1-year mortality after transplantation (hazard ratio0.65; 95% CI 0.53-0.78). Improvement in circulatory failure, brain failure, and removal from mechanical ventilation were also associated with reduced post-LT mortality. Among patients >60 years of age, 1-year survival was significantly higher among those who improved from ACLF-3 to ACLF 0-2 than among those who did not. CONCLUSIONS: Improvement from ACLF-3 at listing to ACLF 0-2 at transplantation enhances post-LT survival, particularly in those who recovered from circulatory or brain failure, or were removed from the mechanical ventilator. The beneficial effect of improved ACLF on post-LT survival was also observed among patients >60 years of age. LAY SUMMARY: Liver transplantation (LT) for patients with acute-on-chronic liver failure grade 3 (ACLF-3) significantly improves survival, but 1-year survival probability after LT remains lower than the expected outcomes for transplant centers. Our study reveals that among patients transplanted within 28 days of waitlist registration, improvement of ACLF-3 at listing to a lower grade of ACLF at transplantation significantly enhances post-transplant survival, even among patients aged 60 years or older. Subgroup analysis further demonstrates that improvement in circulatory failure, brain failure, or removal from mechanical ventilation have the strongest impact on post-transplant survival.

Model for End-Stage Liver Disease Sodium as a Predictor of Surgical Risk in Cirrhotic Patients With Ascites.

BACKGROUND: The Model for End-Stage Liver Disease Sodium (MELD-Na) incorporates hyponatremia into the MELD score and has been shown to correlate with surgical outcomes. The pathophysiology of hyponatremia parallels that of ascites, which purports greater surgical risk. This study investigates whether MELD-Na accurately predicts morbidity and mortality in patients with ascites undergoing general surgery procedures. MATERIALS AND METHODS: We used the National Surgical Quality Improvement Program database (2005-2014) to examine the adjusted risk of morbidity and mortality of cirrhotic patients with and without ascites undergoing inguinal or ventral hernia repair, cholecystectomy, and lysis of adhesions for bowel obstruction. Patients were stratified by the MELD-Na score and ascites. Outcomes were compared between patients with and without ascites for each stratum using low MELD-Na and no ascites group as a reference. RESULTS: A total of 30,391 patients were analyzed. Within each MELD-Na stratum, patients with ascites had an increased risk of complications compared with the reference group (low MELD-Na and no ascites): low MELD-Na with ascites odds ratio (OR) 4.33 (95% confidence interval [CI] 1.96-9.59), moderate MELD-Na no ascites OR 1.70 (95% CI 1.52-1.9), moderate MELD-Na with ascites OR 3.69 (95% CI 2.49-5.46), high MELD-Na no ascites OR 3.51 (95% CI 3.07-4.01), and high MELD-Na ascites OR 7.18 (95% CI 5.33-9.67). Similarly, mortality risk was increased in patients with ascites compared with the reference: moderate MELD-Na no ascites OR 3.55 (95% CI 2.22-5.67), moderate MELD-Na ascites OR 13.80 (95% CI 5.65-33.71), high MELD-Na no ascites OR 8.34 (95% CI 5.15-13.51), and high MELD-Na ascites OR 43.97 (95% CI 23.76-81.39). CONCLUSIONS: MELD-Na underestimates morbidity and mortality risk for general surgery patients with ascites.

LIRER score - a valuable tool to predict medium-long-term outcomes in hepatic cirrhosis decompensation.

BACKGROUND: The liver-renal-risk (LIRER) score was developed to predict adverse outcomes in cirrhotic patients with Model for End-stage Liver Disease (MELD)<18, helping the allocation to liver transplantation in this population. We aimed to assess its prognostic performance compared to other prognostic scores in first admission for hepatic cirrhosis decompensation. METHODS: Retrospective study that included patients admitted for initial decompensation of cirrhosis between January 2010 and February 2017. The LIRER, Child-Pugh (CP), MELD and MELD-sodium (MELD-Na) scores were calculated at admission. RESULTS: One-hundred and forty-six patients were included, 65.1% with MELD < 18. LIRER was a predictor of in-stay (AUC 0.70; p = .04), first-year (0.70; p < .001), two-years (0.72; p < .001) and overall mortality (0.70; p < .001), being the only score with an acceptable discriminating ability (AUC ≥ 0.70). Stratifying patients in MELD < 18 and ≥18, LIRER was found to be an independent predictor of first-year, two-years and overall-mortality only in MELD < 18 patients (AUC 0.67; 0.70; 0.72), being superior to all other scores predicting first-year mortality and the only with an AUC with a reasonable discriminating ability for predicting two-years and overall-mortality. The LIRER was also a predictor of 30-days hospital readmission (AUC 0.75; p < .001), independently of MELD, with patients with LIRER > 15.9 having a significantly higher probability to be readmitted at 30 days. CONCLUSIONS: The LIRER score is a predictor of first-year, two-years and overall-mortality in decompensated cirrhosis, particularly in patients with MELD < 18. LIRER is therefore an important tool to predict medium-long-term outcomes in this population. Besides, it allows predicting the 30-days readmission probability in overall patients, independently of MELD.

Child-Pugh, MELD, MELD-Na, and ALBI scores: which liver function models best predicts prognosis for HCC patient with ascites?

OBJECTIVE: It remains controversial whether certain treatments should apply to HCC patients with ascites due to concerns about worsening liver function. The objective of the present study is to compare the prognostic performance of 4 liver function models currently in use for HCC patients with ascites. METHODS: A total of 437 treatment-naïve, newly diagnosed HCC patients were analyzed. The predictive performance of Child-Pugh, MELD, MELD-Na, and ALBI scores were examined using ROC curve analysis. RESULTS: MELD-Na score showed good performance in predicting 1-, 2-, and 3-year mortality, particularly 1-year mortality. MELD-Na score significantly increased at 30 days after treatment in cases initially receiving best supportive care (14-17, p < .001), TACE (9-11, p < .001), and other treatment (radiotherapy, sorafenib, or systemic chemotherapy) (9-11, p = .021). For patients with advanced tumor stage and MELD-Na score ≥12, HCC-specific treatment did not offer significantly better prognosis compared with only the best supportive care (median survival: 2.2 vs. 1.8 months for HCC-specific treatment vs. best supportive care, p = .15). CONCLUSION: MELD-Na can effectively identify liver functional reserve and prognosis in HCC patients with ascites. MELD-Na, together with the tumor stage, may help establish a therapeutic strategy for them.

Thromboelastography Parameters Are Associated with Cirrhosis Severity.

BACKGROUND: Coagulopathy in cirrhosis represents complex coagulation derangements, and thromboelastography (TEG) measures these complex derangements. AIM: We sought to evaluate associations between TEG parameters and validated measures of cirrhosis severity, which have not been previously investigated. MATERIALS AND METHODS: Adults with cirrhosis undergoing liver transplant (LT) were identified. Patients had TEG drawn immediately prior to LT. TEG parameters included reaction time (R), kinetic time (K), alpha angle (α), and maximum amplitude (MA). The validated measures of cirrhosis severity were MELD-Na and clinical stage of cirrhosis (classified using history of varices, variceal bleeding, or ascites). Multivariable linear and logistic regression analyses were conducted to evaluate the associations between TEG and stage of cirrhosis and MELD-Na. RESULTS: Among 164 patients with cirrhosis, advancing stage of cirrhosis was associated with more hypocoagulable TEG parameters including longer K-time (p = 0.05) and lower MA (p < 0.001). Similarly, with increasing MELD-Na quartiles, K-time was longer (p < 0.001), and both MA and α-angle decreased (p < 0.001, for both). Variceal bleeding within 6 weeks prior to LT was associated with longer R-times (p = 0.02), longer K-times (p = 0.04), smaller α-angle (p = 0.03), and lower MA (p = 0.01). On multivariable analyses, decreasing MA remained statistically significantly associated with advancing stage of cirrhosis and increasing MELD-Na, after adjusting for multiple covariates including platelet count, (p = 0.02 and p < 0.0001, respectively). CONCLUSIONS: Hypocoagulable TEG measurements are associated with advancing stage of cirrhosis and increasing MELD-Na among patients with cirrhosis. These data indicate that TEG, as an informative measure of complex hemostatic function, may be a useful objective marker of liver disease severity in cirrhosis.

The Role of the CLIF-C OF and the 2016 MELD in Prognosis of Cirrhosis with and without Acute-on-Chronic Liver Failure.

INTRODUCTION AND AIM: Acute-on-chronic liver failure (ACLF) is defined by the development of acute deterioration of liver function associated with failure of other organs and high short-term mortality in patients with chronic liver disease (CLD). There is no consensus on the diagnostic criteria, and its independence from ordinary decompensation of CLD has frequently been questioned. This study aimed to identify and characterize this condition and to test the CLIF-C OF score comparing it to the 2016-MELD (with sodium) and the Child-Pugh. MATERIAL AND METHODS: 18-month prospective observational study with systematic inclusion of admitted patients with CLD decompensation. RESULTS: 39 patients had ACLF (33.1%). These patients experienced higher 28-day and 90-day mortality, when compared to patients without ACLF (43.6% and 64.1% vs. 2.5% and 7.6% respectively, p < 0.0001). ACLF was linked with a higher acute infection rate (74.4%). For all patients (N = 118), the scores 2016-MELD, CLIF-C OF and Child-Pugh showed an area under the curve (AUC) for 28-day mortality of 0.908, 0.844, 0.753 and for 90-day of 0.902, 0.814, 0.724 respectively, p < 0.0001 for all scores. The 90-day mortality 2016-MELD AUC was greater than the CLIF-C OF AUC, p = 0.021. Within ACLF patients, the 2016-MELD, CLIF-C ACLF and Child-Pugh scores showed an AUC of 0.774, 0.734, 0.584 (28-day) and 0.880, 0.771, 0.603 (90-day); for 2016-MELD p = 0.004 (28-day) and p < 0.0001 (90-day). CONCLUSION: ACLF is a frequent and relevant condition, associated with high mortality. The CLIF-C OF score revealed good accuracy and diagnoses ACLF when it is present. However, the 2016-MELD performed better for 90-day mortality prediction.

MELD-Na Score as a Predictor of Anastomotic Leak in Elective Colorectal Surgery.

BACKGROUND: For cirrhotic patients awaiting liver transplantation, the Model for End-Stage Liver Disease Sodium (MELD-Na) model is extensively studied. Because of the simplicity of the scoring system, there has been interest in applying MELD-Na to predict patient outcomes in the noncirrhotic surgical patient, and MELD-Na has been shown to predict postoperative morbidity and mortality after elective colectomy. Our aim was to identify the utility of MELD-Na to predict anastomotic leak in elective colorectal cases. METHODS: The American College of Surgeons National Surgical Quality Improvement Program targeted colectomy database was queried (2012-2014) for all elective colorectal procedures in patients without ascites. Leak rates were compared by MELD-Na score using chi-square tests and multivariate logistic regression analysis. RESULTS: We identified 44,540 elective colorectal cases (mean age, 60.5 y ± 14.4, mean body mass index 28.8 ± 6.6 kg/m2, 52% female), of which 70% were colon resections and 30% involved partial rectal resections (low anterior resections). Laparoscopic approach accounted for 64.72% while 35.3% were open. The overall complication and mortality rates were 21% and 0.7%, respectively, with a total anastomotic leak rate of 3.4%. Overall, 98% had a preoperative MELD-Na score between 10 and 20. Incremental increases in MELD-Na score (10-14, 15-19, and ≥20) were associated with an increased leak rate, specifically in partial rectal resections (3.9% versus 5.1% versus 10.7% P <0.028). MELD-Na score ≥20 had an increased leak rate when compared with those with MELD-Na 10-14 (odds ratio [OR] 1.627; 95% confidence interval [CI] [1.015, 2.607]). An MELD-Na score increase from 10-14 to 15-19 increases overall mortality (OR 5.22; 95% CI [3.55, 7.671]). In all elective colorectal procedures, for every one-point increase in MELD-Na score, anastomotic leak (OR 1.04 95% CI [1.006, 1.07]), mortality (OR 1.24; 95% CI, [1.20, 1.27]), and overall complications (OR 1.10; 95% CI [1.09, 1.12]) increased. MELD-Na was an independent predictor of anastomotic leak in partial rectal resections, when controlling for gender, steroid use, smoking, approach, operative time, preoperative chemotherapy, and Crohn's disease (OR 1.06, 95% CI [1.002, 1.122]). CONCLUSIONS: MELD-Na is an independent predictor of anastomotic leak in partial rectal resections. Anastomotic leak risk increases with increasing MELD-Na in elective colorectal resections, as does 30-d mortality and overall complication rate. As MELD-Na score increases to more than 20, restorative partial rectal resection has a 10% rate of anastomotic leak.

Effectiveness of the MELD/Na Score and the Child-Pugh Score for the Identification of Palliative Care Needs in Patients with Cirrhosis of the Liver.

OBJECTIVE: Identification of palliative care needs in patients with liver cirrhosis using the MELD/Na score and the Child-Pugh score. MATERIALS AND METHODS: A retrospective study of hospitalized patients with hepatic cirrhosis between January 2015 and December 2016 using the Child-Pugh score and the MELD/Na score in January 2018. RESULTS: Recognizing end-of-life patients (the past 12 months of life) is a challenge for health professionals, especially in diseases with poorly defined criteria, such as cirrhosis of the liver. The verification of rapid functional decline and health indicators can be verified using already defined scales such as the Child-Pugh score and the MELD/Na score. Patients were classified according to the Child-Pugh score in Class A (17%), Class B (48.9%), and Class C (34%). The corresponding survival rate was as follows: class A (87.5%), Class B (30.4%), and Class C (31.25%). The MELD/Na score intervals were >9 (2.15%), score 10-19 (46.8%), score 20-29 (27.7%), score 30-40 (19.1%), and score >40 (4.3%). Nearly 51.1% had a MELD/Na score >20 and 48.9% <20. The study revealed that 59.6% of patients died before 12 months. They were end-of-life patients who needed palliative care to reduce the impact of the disease. CONCLUSIONS: The Child-Pugh score and the MELD/Na score represent a viable and easy-to-use tool to identify patients in need of palliative care, among those with liver cirrhosis. Early identification, timely evaluation, and effective treatment of physical, spiritual, family, and social problems improve the quality of life of people with incurable diseases and their families.

Single center validation of mortality scores in patients with acute decompensation of cirrhosis with and without acute-on-chronic liver failure.

OBJECTIVES: Acute decompensation (AD) of cirrhosis is characterized by high mortality. We aimed to validate the performance in predicting mortality of both the chronic-liver-failure-consortium (CLIF-C) acute-on-chronic liver failure (ACLF) and CLIF-C AD scores in a cohort of patients admitted for AD. METHODS: In this prospective cohort study, patients were followed-up during their hospital stay and for 365 days thereafter. RESULTS: About 182 patients with AD were enrolled including 78 (42.8%) who met the criteria for ACLF (ACLF-group) while the remaining had AD without ACLF (AD-group). 56.4% and 56.7% of the ACLF- and AD-groups, respectively, had alcoholic cirrhosis and 85.9% of the ACLF-group hepatic encephalopathy. Only few patients were hospitalized in the intensive care unit (ICU) or transplanted. The probabilities of death estimated for both scores were similar to the overall mortality rates observed at all time points. The model had a good fit in the AD-group at 90 days (p = .974) but a worse, yet adequate, in the ACLF-group at 28 days (p = .08). The CLIF-C ACLF or AD scores had an adequate, predictive discrimination ability for mortality at all time points, with Harrel's concordance index-C ranging between 0.64 and 0.65 or 0.64 and 0.68, respectively. Both scores showed a similar predictive accuracy for mortality compared to those of MELD, MELD-Na and Child-Pugh. CONCLUSIONS: In this population without access to appropriate ICU treatment, the CLIF-C ACLF and AD performed worse than in studies with patients having ICU access. In addition, the CLIF scores were not superior to classical ones in this setting.

Serum sodium concentration is associated with increased risk of mortality in patients with compensated liver cirrhosis.

AIM: Although hyponatremia is associated with a poor prognosis in liver cirrhosis, little is known about the clinical significance of serum sodium concentration in cirrhosis in Japan. This study investigated associations of mortality in Japanese cirrhosis patients taking conventional diuretics with serum sodium concentration and other clinical characteristics. METHODS: A total of 171 consecutive patients with cirrhosis who were taking diuretic medication were enrolled retrospectively. We determined the prevalence of low serum sodium concentration and searched for associations with age, sex, etiology, complications of cirrhosis, liver function tests and Model for End-Stage Liver Disease (MELD) and MELD-Na scores. The predictive ability of sodium level on mortality was also investigated. RESULTS: Median serum sodium concentration was 139 mEq/L (interquartile range, 137-141). Only eight of 171 (4.7%) patients had low serum sodium (<130 mEq/L). Median MELD-Na score was 10.5 (interquartile range, 8.0-14.3). Cumulative survival rates were significantly lower in patients with Na of less than 139 mEq/L or MELD-Na score of 10.5 or more (log-rank test, P = 0.017 and P = 0.0002, respectively). Several liver function tests, MELD and MELD-Na scores, and the incidence of ascites were all significantly associated with patients having Na of less than 139 mEq/L. CONCLUSION: Serum sodium concentration below 139 mEq/L and MELD-Na score above 10.5 may be predictive markers for mortality in patients with cirrhosis despite being within normal ranges. These markers may help to better assess and manage the prognosis of patients with cirrhosis in Japan.