Predictors of Outcomes of Patients Referred to a Transplant Center for Urgent Liver Transplantation Evaluation.
ABSTRACT: Liver transplantation (LT) is definitive treatment for end-stage liver disease. This study evaluated factors predicting successful evaluation in patients transferred for urgent inpatient LT evaluation. Eighty-two patients with cirrhosis were transferred for urgent LT evaluation from January 2016 to December 2018. Alcohol-associated liver disease was the common etiology of liver disease (42/82). Of these 82 patients, 35 (43%) were declined for LT, 27 (33%) were wait-listed for LT, 5 (6%) improved, and 15 (18%) died. Psychosocial factors were the most common reasons for being declined for LT (49%). Predictors for listing and receiving LT on multivariate analysis included Hispanic race (odds ratio [OR], 1.89; P = 0.003), Asian race (OR, 1.52; P = 0.02), non-Hispanic ethnicity (OR, 1.49; P = 0.04), hyponatremia (OR, 1.38; P = 0.04), serum albumin (OR, 1.13; P = 0.01), and Model for End-Stage Liver Disease (MELD)-Na (OR, 1.02; P = 0.003). Public insurance (i.e., Medicaid) was a predictor of not being listed for LT on multivariate analysis (OR, 0.77; P = 0.02). Excluding patients declined for psychosocial reasons, predictors of being declined for LT on multivariate analysis included Chronic Liver Failure Consortium (CLIF-C) score >51.5 (OR, 1.26; P = 0.03), acute-on-chronic liver failure (ACLF) grade 3 (OR, 1.41; P = 0.01), hepatorenal syndrome (HRS) (OR, 1.38; P = 0.01), and respiratory failure (OR, 1.51; P = 0.01). Predictors of 3-month mortality included CLIF-C score >51.5 (hazard ratio [HR], 2.52; P = 0.04) and intensive care unit (HR, 8.25; P < 0.001). Conclusion: MELD-Na, albumin, hyponatremia, ACLF grade 3, HRS, respiratory failure, public insurance, Hispanic race, Asian race, and non-Hispanic ethnicity predicted liver transplant outcome. Lack of psychosocial support was a major reason for being declined for LT. The CLIF-C score predicted being declined for LT and mortality.
Project description:BACKGROUND:Patients with acute-on-chronic liver failure (ACLF) precipitated by hepatic injury and extrahepatic insults had distinct clinical phenotypes, and prognosis. This study aimed to validate prognostic models for ACLF and to explore their discriminative abilities in ACLF population categorized by the etiologies of precipitating events. METHODS:This study collected data from 343 consecutive cirrhotic patients hospitalized with the diagnosis of ACLF according to the EASL-CLIF-Consortium definition. The discrimination abilities of prognostic models at the onset of ACLF were tested with the concordance index and area under the receiver operating characteristic curve. RESULTS:Among the entire cohort, 103 patients survived with medical management, nine patients were transplanted, and 231 patients died without liver transplantation. The predictive accuracy of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) for 28-day mortality was similar to the CLIF Consortium Organ Failure (CLIF-C OF) but significantly higher than the CLIF Consortium ACLF, the Child-Turcotte-Pugh, the model for end-stage liver disease (MELD), the MELD-sodium, the integrated MELD, and the Acute Physiology and Chronic Health Evaluation II. Of note, 44 patients had acute hepatic insult triggering ACLF (hepatic-ACLF), 244 were exclusively precipitated by bacterial infection or gastrointestinal bleeding (extrahepatic-ACLF), and 55 cases had no any identifiable potential precipitating events. Patients with hepatic-ACLF had significantly higher 28-day mortality than extrahepatic-ACLF patients. The CLIF-SOFA and CLIF-C OF displayed the highest accuracy significantly outperforming other scoring systems in predicting mortality among patients with hepatic-ACLF and those with extrahepatic-ACLF. CONCLUSION:The CLIF-SOFA and simpler CLIF-C OF are reliable measures of mortality risk in ACLF patients precipitated by either hepatic or extrahepatic insults. Both validated models could be used to stratify the risk of death and improve management of ACLF.
Project description:To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian patients.This is a prospective cohort study designed to assess the prognostic performance of the chronic liver failure-consortium (CLIF-C) acute decompensation score (CLIF-C AD) and CLIF-C acute-on-chronic liver failure score (CLIF-C ACLF), regarding 28-d and 90-d mortality, as well as to compare them to other prognostic models, such as Model for End-Stage Liver Disease (MELD), MELD Sodium (MELD-Na), Child-Pugh (CP) score, and the CLIF-C Organ Failure score (CLIF-C OF). All participants were adults with acute decompensation of cirrhosis admitted to the Emergency Department of a tertiary hospital in southern Brazil. Prognostic performances were evaluated by means of the receiver operating characteristic (ROC) curves, area under the curves (AUC) and 95%CI.One hundred and thirteen cirrhotic patients were included. At admission, 18 patients had acute-on-chronic liver failure (ACLF) and 95 individuals had acute decompensation (AD) without ACLF, of which 24 eventually developed ACLF during the course of hospitalization (AD evolving to ACLF group). The AD group had significantly lower 28-d (9.0%) and 90-d (18.3%) mortality as compared to the AD evolving to ACLF group and to the ACLF group (both P < 0.001). On the other hand, 28-d and 90-d mortalities were not significantly different between AD evolving to ACLF group and ACLF group (P = 0.542 and P = 0.708, respectively). Among patients with ACLF, at 28 d from the diagnosis, CLIF-C ACLF was the only score able to predict mortality significantly better than the reference line, with an AUC (95%CI) of 0.71 (95%CI: 0.54-0.88, P = 0.021). Among patients with AD, all prognostic scores performed significantly better than the reference line regarding 28-d mortality, presenting with similar AUCs: CLIF-C AD score 0.75 (95%CI: 0.63-0.88), CP score 0.72 (95%CI: 0.59-0.85), MELD score 0.75 (95%CI: 0.61-0.90), MELD-Na score 0.76 (95%CI: 0.61-0.90), and CLIF-C OF score 0.74 (95%CI: 0.60-0.88). The same occurred concerning AUCs for 90-d mortality: CLIF-C AD score 0.70 (95%CI: 0.57-0.82), CP score 0.73 (95%CI: 0.62-0.84), MELD score 0.71 (95%CI: 0.59-0.83), MELD-Na score 0.73 (95%CI: 0.62-0.84), and CLIF-C OF score 0.65 (95%CI: 0.52-0.78).This study demonstrated that CLIF-C ACLF is the best available score for the prediction of 28-d mortality among patients with ACLF. CLIF-C AD score is also useful for the prediction of mortality among cirrhotic patients with AD not fulfilling diagnostic criteria for ACLF, but it was not superior to other well-established prognostic scores.
Project description:BACKGROUND:Acute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis and is defined by organ failure and high rates of short-term mortality. Patients with ACLF are managed with multiorgan support in the intensive care unit (ICU). Currently, it is unclear when this supportive care becomes futile, particularly in patients who are not candidates for liver transplant. The aim of this study was to determine whether the currently available prognostic scores can identify patients with ACLF in whom prolonged ICU care is likely to be futile despite maximal treatment efforts. METHODS:Data of 202 consecutive patients with ACLF admitted to the ICU at the Royal Free Hospital London between 2005 and 2012 were retrospectively analyzed. Prognostic scores for chronic liver diseases, such as Child-Pugh, Model for End-Stage Liver Disease (MELD), European Foundation for the study of chronic liver failure (CLIF-C) organ failure (OF), and CLIF-C ACLF, were calculated 48 hours after ICU admission and correlated with patient outcome after 28 days. RESULTS:The CLIF-C ACLF score, compared with all other scores, most accurately predicted 28-day mortality, with an area under the receiver operator characteristic of 0.8 (CLIF-C OF, 0.75; MELD, 0.68; Child-Pugh, 0.66). A CLIF-C ACLF score cutoff ??70 identified patients with a 100% mortality within 28 days. These patients had elevated inflammatory parameters representing a systemic inflammatory response, most often renal failure, compared with patients below this cutoff. CONCLUSIONS:Patients with ACLF and high CLIF-C ACLF score (??70) after 48 hours of intensive care may reach a threshold of futility for further ongoing intensive support. The best treatment options in this scenario remain to be determined but may include palliative care.
Project description:Background:Acute-on-chronic liver failure (ACLF), which is characterized by rapid deterioration of liver function and multiorgan failure, has high mortality. This study was designed to identify prognostic scores to predict short-term and long-term outcome in patients with ACLF to facilitate early treatment and thereby improve patient survival. Materials and Methods:We retrospectively analyzed 102 ACLF patients who were hospitalized in the gastroenterology department. The EASL-CLIF criteria were used to define the ACLF. The demographic characteristics and biochemical examination results of the patients were acquired, and seven scores (CTP score, MELD score, MELD-Na, CLIF ACLF score, CLIF-C OF score, and CLIF SOFA score) were calculated 24 h after admission. All patients were observed until loss to follow-up, death, or specific follow-up times (28 days, 3 months, and 6 months), which were calculated after the initial hospital admission. The receiver operating characteristic (ROC) curve was employed to estimate the power of six scores to forecast ACLF patients' outcome. Results:All scores were distinctly higher in nonsurviving patients than in surviving patients and had predictive value for outcome in patients with ACLF at all time points (P < 0.050). The areas under the ROC curve (AUROCs) of the CLIF-SOFA score were higher than those of other scores at all time points. The comparison of the AUROC of the CLIF-SOFA score with other scores was statistically significant at 28 days (P < 0.050), which was the only time point at which it was greater than 0.800. Conclusion:Patients with ACLF have high mortality. These six scores are effective tools for assessing the prognosis of ACLF patients. The CLIF-SOFA score is especially effective for evaluating 28-day mortality.
Project description:The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were 'hepatic' and 'coagulation'. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p?<?0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles.
Project description:Limited data is available on long-term outcome predictions for patients with acute-on-chronic liver failure (ACLF) in an intensive care unit (ICU) setting. Assessing the reliability and accuracy of several mortality prediction models for these patients is helpful. Two hundred forty-nine consecutive patients with ACLF and admittance to the liver ICU in a single center in northern Taiwan between December 2012 and March 2015 were enrolled in the study and were tracked until February 2017. Ninety-one patients had chronic hepatitis B-related cirrhosis. Clinical features and laboratory data were collected at or within 24 h of the first ICU admission course. Eight commonly used clinical scores in chronic liver disease were calculated. The primary endpoint was overall survival. Acute physiology and chronic health evaluation (APACHE) III and chronic liver failure consortium (CLIF-C) ACLF scores were significantly superior to other models in predicting overall mortality as determined by time-dependent receiver operating characteristic (ROC) curve analysis (area under the ROC curve (AUROC): 0.817). Subgroup analysis of patients with chronic hepatitis B-related cirrhosis displayed similar results. CLIF-C organ function (OF), CLIF-C ACLF, and APACHE III scores were statistically superior to the mortality probability model III at zero hours (MPM0-III) and the simplified acute physiology (SAP) III scores in predicting 28-day mortality. In conclusion, for 28-day and overall mortality prediction of patients with ACLF admitted to the ICU, APACHE III, CLIF-OF, and CLIF-C ACLF scores might outperform other models. Further prospective study is warranted.
Project description:BACKGROUND/AIMS:This study examined the risk factors associated with mortality in cirrhotic patients hospitalized with variceal bleeding, and evaluated the effects of acute-on-chronic liver failure (ACLF) on the prognosis of these patients. METHODS:This study was retrospectively conducted on patients registered in the Korean acute-on-chronic liver failure study cohort, and on 474 consecutive cirrhotic patients hospitalized with variceal bleeding from January 2013 to December 2013 at 21 university hospitals. ACLF was defined as described by the European Association for the Study of Liver-Chronic Liver Failure Consortium. RESULTS:Among a total of 474 patients, 61 patients were diagnosed with ACLF. The cumulative overall survival (OS) rate was lower in the patients with ACLF than in those without (P<0.001), and patients with higher ACLF grades had a lower OS rate (P<0.001). The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score was identified as a significant prognostic factor in patients hospitalized with variceal bleeding (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.30-1.50; P<0.001), even in ACLF patients with variceal bleeding (HR, 1.32; 95% CI, 1.19-1.46, P<0.001). Concerning the prediction of the mortality risk at 28- and 90-day using CLIF-SOFA scores, c-statistics were 0.895 (95% CI, 0.829-0.962) and 0.897 (95% CI, 0.842-0.951), respectively, and the optimal cut-off values were 6.5 and 6.5, respectively. CONCLUSION:In cirrhotic patients hospitalized with variceal bleeding, the prognosis was poor when accompanied by ACLF, especially depending upon CLIF-SOFA score. CLIF-SOFA model well predicted the 28-day or 90-day mortality for cirrhotic patients who experienced variceal bleeding.
Project description:The mortality of acute-on-chronic liver failure (ACLF) patients complicated with invasive pulmonary aspergillosis (IPA) was extremely high. We aimed to explore prognostic value of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) lung score and to establish an optimal voriconazole regimen for ACLF patients complicated with IPA. We retrospectively screened hospitalized ACLF patients in our hospital from July 2011 to April 2016, from which 20 probable IPA cases were diagnosed. Along with onsets of IPA, deteriorated diseases severity, especially lung conditions were found in those 20 ACLF patients. It was found that IPA patients with CLIF-SOFA lung score <2 had better 28-day survival than those with lung score >1 (11/13 vs 0/7, p?<?0.001). Based on plasma voriconazole concentration measurement, an optimal voriconazole regimen (loading doses: 0.2?g twice daily; maintenance doses, 0.1?g once daily) was established, which resulted in rational trough plasma drug concentrations (1-5??g/mL), good clinical outcomes (90-day survival rate of 6/8) and no observed adverse events. In conclusion, CLIF-SOFA lung score >1 was able to identify ACLF patients complicated with IPA encountering much higher 28-day mortality. An optimal voriconazole regimen was safe and effective in our ACLF patients complicated with IPA.
Project description:Our previous study demonstrated that Th17 cells increased significantly in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). However, their prognostic role in HBV-ACLF patients remains unknown.Sixty-eight consecutive HBV-ACLF patients were enrolled in this cohort study. Th17 cells were examined using flow cytometry. Disease severity scores were assessed. ROC curves were used to evaluate the value in predicting prognosis. Survival was analyzed using Kaplan-Meier curves. Predictors of mortality were determined by regression analysis.Th17 cells were significantly higher in HBV-ACLF patients compared to patients with chronic hepatitis B and normal controls (both P?<?.001). Also, Th17 cells were higher in nonsurviving HBV-ACLF patients than in surviving patients (P?=?.014). Th17 cells were positively correlated with CLIF-Consortium ACLF (CLIF-C ACLF) score (r?=?0.240, P?=?.048). ROC curves showed that the frequency of Th17 cells had accuracy in predicting 90-day prognosis equivalent to MELD, MELD-Na and CLIF-C ACLF scores in HBV-ACLF (P?=?.34, P?=?.26, and P?=?.15, respectively). More importantly, the area under the ROC curve (AUROC) increased when Th17 cells were combined with MELD, MELD-Na or CLIF-C ACLF score than using Th17 cells alone (P?=?.021, P?=?.006, and P?=?.023, respectively). Kaplan-Meier analysis revealed that higher Th17 cells (?5.9%) were closely associated with poor overall survival in HBV-ACLF (P?=?.0086). Additionally, multivariate regression analysis showed that the frequency of Th17 cells over 5.9% was an independent predictor of mortality (OR?=?0.154, P?=?.025).Circulating Th17 cells positively correlated with disease severity in HBV-ACLF. The frequency of Th17 cells over 5.9% could serve as a prognostic biomarker for HBV-ACLF patients.
Project description:Acute deterioration of liver cirrhosis (e.g., infections, acute-on-chronic liver failure [ACLF]) requires an increase in cardiac contractility. The insufficiency to respond to these situations could be deleterious. Left ventricular global longitudinal strain (LV-GLS) has been shown to reflect left cardiac contractility in cirrhosis better than other parameters and might bear prognostic value. Therefore, this retrospective study investigated the role of LV-GLS in the outcome after transjugular intrahepatic portosystemic shunt (TIPS) and the development of ACLF. We included 114 patients (48 female patients) from the Noninvasive Evaluation Program for TIPS and Their Follow-Up Network (NEPTUN) cohort. This number provided sufficient quality and structured follow-up with the possibility of calculating major scores (Child, Model for End-Stage Liver Disease [MELD], Chronic Liver Failure Consortium acute decompensation [CLIF-C AD] scores) and recording of the events (development of decompensation episode and ACLF). We analyzed the association of LV-GLS with overall mortality and development of ACLF in patients with TIPS. LV-GLS was independently associated with overall mortality (hazard ratio [HR], 1.123; 95% confidence interval [CI],1.010-1.250) together with aspartate aminotransferase (HR, 1.009; 95% CI, 1.004-1.014) and CLIF-C AD score (HR, 1.080; 95% CI, 1.018-1.137). Area under the receiver operating characteristic curve (AUROC) analysis for LV-GLS for overall survival showed higher area under the curve (AUC) than MELD and CLIF-C AD scores (AUC, 0.688 versus 0.646 and 0.573, respectively). The best AUROC-determined LV-GLS cutoff was -16.6% to identify patients with a significantly worse outcome after TIPS at 3 months, 6 months, and overall. LV-GLS was independently associated with development of ACLF (HR, 1.613; 95% CI, 1.025-2.540) together with a MELD score above 15 (HR, 2.222; 95% CI, 1.400-3.528). Conclusion: LV-GLS is useful for identifying patients at risk of developing ACLF and a worse outcome after TIPS. Although validation is required, this tool might help to stratify risk in patients receiving TIPS.