Acute-on-chronic Liver Failure Grade Research Articles

Early Versus Standard Initiation of Terlipressin for Acute Kidney Injury in ACLF: A Randomized Controlled Trial (eTerli Study).

Terlipressin infusion is effective in hepatorenal syndrome (HRS-AKI). However, its efficacy for HRS-AKI resolution in acute-on-chronic liver failure (ACLF) patients has been suboptimal. Progression of AKI is rapid in ACLF. We investigated whether early initiation of terlipressin(eTerli) can improve response rates. Consecutive ACLF patients with stage II/III AKI despite albumin resuscitation (40g) were randomized to receive terlipressin at 2mg/24h plus albumin at 12h (ET, n = 35) or at 48h as standard therapy (ST, n = 35). (June 22, 2020 to June 10, 2022). The primary end-point was AKI reversal by day7. Baseline parameters including AKI stage and ACLF-AARC scores in two arms were comparable. Full AKI response at day 7 was higher in ET [24/35 (68.6%)] than ST arm [11/35 (31.4%; P 0.03]. Day3 AKI response was also higher in ET arm [11/35 (31.4%) vs. 4/35 (11.4%), P 0.04]. Using ST compared to ET [HR 4.3; P 0.026] and day 3 serum creatinine > 1.6mg/dl [HR 9.1; AUROC-0.866; P < 0.001] predicted HRS-AKI non-response at day 7. ET patients showed greater improvement in ACLF grade, mean arterial pressure, and urine output at day 3, and required lower albumin within 7days than ET arm (149.1 ± 41.8g vs. 177.5 ± 40.3g, P 0.006) and had lower 28-day mortality: 40% vs. 65.7%, P 0.031]. Early use of terlipressin than ST [HR 2.079; P 0.038], baseline HE [HR 2.929; P 0.018], and AKI persistence at day 3 [HR 1.369; P 0.011] predicted 28-day mortality. Fifteen (21.4%) patients had treatment related adverse effects, none was life threatening. In ACLF patients, early initiation of terlipressin for AKI persisting after 12h of volume expansion with albumin helps in reduced short-term mortality and early AKI reversal with regression of ACLF stage. These results indicate need for change in current practice for terlipressin usage in HRS-AKI.

Thromboelastography characteristics in critically ill patients with liver disease.

The purpose of this study was to determine how thromboelastography (TEG) parameters differ by various clinical conditions that commonly occur in patients with cirrhosis, including sepsis, acute on chronic liver failure (ACLF), alcohol-associated hepatitis (AAH) and portal vein thrombosis (PVT). TEG, a whole blood assay, is used to assess several parameters of coagulation and is becoming increasingly used in clinical practice. This study was a retrospective chart review of 155 patients admitted to the ICU with decompensated cirrhosis from 2017 to 2019. The R time was significantly shorter in patients when they were septic compared to when they were not and longer in patients with vs. without ACLF grade 3. Alpha angle and maximum amplitude was decreased in patients with severe AAH compared to those without severe AAH; and maximum amplitude was increased in patients with acute PVT compared to those with chronic PVT. R time was positively correlated with Chronic Liver Failure Consortium Organ Failure and Chronic Liver Failure Consortium ACLF scores (rho = 0.22, P = 0.020), while alpha angle and maximum amplitude were negatively correlated with MELD-NA. Findings suggest TEG parameters vary in several clinical conditions in patients with decompensated cirrhosis who are admitted to the ICU. Prospective research is needed to confirm our findings and to determine how this knowledge can be used to guide clinical practice, as well as blood product transfusions in the setting of bleeding or prior to invasive procedures.

Efficiency and safety of total plasma exchange in critically ill cirrhotic patients with acute on chronic liver failure: a pilot study.

Treatment of patients with acute on chronic liver failure (ACLF) admitted to the ICU is very limited. The aim of this pilot study was to evaluate the efficiency on liver function and safety of therapeutic plasma exchange (TPE) in critically ill cirrhotic patients admitted with ACLF in a liver ICU. This is a prospective cohort of patients with ACLF grade > 2 treated by TPE admitted to the ICU that was matched to a control group. TPE was performed using a plasma filter (TPE2000, BAXTER®) on a CRRT machine (Prismaflex®, Baxter®). Ratio and type of fluid replacement were 50% with 5% albumin solution followed by 50% with fresh frozen plasma. Seven patients with a mean age of 50.6 ± 7.8 years (all males) and 14 controls matched to age, sex, etiology and cause of decompensation were recruited. At ICU admission, mean MELD score was 39.1 ± 2.7, mean SOFA score was 11.6 ± 5.2 and mean CLIF SOFA score was 12.9 ± 2.6. The grade of ACLF was 3 for 3 patients (42.9%) and 2 for 4 patients (57.1%). The TPE group had significantly higher levels of bilirubin (392.3 ± 117.1 vs. 219 ± 185, p = 0.04), and INR values (5.7 ± 3.4 vs. 3.5 ± 0.9, p < 0.005) compared to the control group. Patient survival was respectively 28.6% and 14.3% at 30 and 90 days in the TPE group and 35.7% and 7.14% in the control group respectively (HR: 1 (95% CI 0.19- 5.2; p = 1). One patient in the TPE group had a liver transplantation 13 days after admission to ICU and is still alive and none in the control group. Two (28.6%) patients died from complications related to the double lumen catheter used for TPE. This pilot study of TPE in patients with ACLF grade 2 and 3 showed a marked but transient improvement in liver function tests. TPE worth to be evaluated in large trials in ACLF patients, with a liver transplant project, and less organ failure.

Clinical features and prognosis of acute-on-chronic liver failure in patients with recompensated cirrhosis

BackgroundThere are few studies on acute-on-chronic liver failure (ACLF) in patients with recompensated cirrhosis. This study was aimed to investigate the clinical features of ACLF patients with recompensated cirrhosis.MethodsA total of 461 ACLF patients were enrolled and divided into three groups: compensated, recompensated, and decompensated cirrhosis with ACLF. The baseline clinical data and 1-year survival rates were compared among the three groups.ResultsCompared with the decompensated group, in the recompensated group, the levels of hemoglobin, albumin, and serum sodium were significantly higher and the white blood cell count, international normalized ratio, and incidence of respiratory failure were significantly lower; there were no evident differences in other organ failures. The proportion of patients with ACLF grade 3 and 1-year survival rates significantly differed between the two groups. Conversely, compared with the compensated group, in the recompensated group, the platelet and total bilirubin levels were significantly lower and the proportion of patients with ACLF grade 1 was significantly higher. However, other clinical indicators or 1-year survival rates did not significantly differ between the two groups.ConclusionsCompared with patients who developed ACLF with decompensated cirrhosis, those who developed ACLF with recompensated cirrhosis had a less severe condition, lower incidence of respiratory failure, and better 1-year prognosis. However, the baseline clinical features and prognosis were similar between ACLF patients with recompensated and compensated cirrhosis.Trial registrationChinese clinical trials registry: ChiCTR1900021539.

Mechanisms and treatment approaches for ACLF.

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by decompensation of cirrhosis, severe systemic inflammation and organ failures. ACLF is frequently triggered by intra- and/or extrahepatic insults, such as bacterial infections, alcohol-related hepatitis or flares of hepatic viruses. The imbalance between systemic inflammation and immune tolerance causes organ failures through the following mechanisms: (i) direct damage of immune cells/mediators; (ii) worsening of circulatory dysfunction resulting in organ hypoperfusion and (iii) metabolic alterations with prioritization of energetic substrates for inflammation and peripheral organ 'energetic crisis'. Currently, the management of ACLF includes the support of organ failures, the identification and treatment of precipitating factors and expedited assessment for liver transplantation (LT). Early LT should be considered in patients with ACLF grade 3, who are unlikely to recover with the available treatments and have a mortality rate > 70% at 28 days. However, the selection of transplant candidates and their prioritization on the LT waiting list need standardization. Future challenges in the ACLF field include a better understanding of pathophysiological mechanisms leading to inflammation and organ failures, the development of specific treatments for the disease and personalized treatment approaches. Herein, we reviewed the current knowledge and future perspectives on mechanisms and treatment of ACLF.

Living donor liver transplant in acute on chronic liver failure grade 3: Who not to transplant

Background and AimLiver transplantation(LT)offers definitive treatment for acute on chronic liver failure(ACLF) patients. This study was done to analyze and compare the outcomes of living donor LT(LDLT) in patients with ACLF versus Chronic liver disease(CLD) and within the grades of ACLF. Factors affecting mortality in patients with ACLF and ACLF grade3 (ACLF3) following LDLT were also derived. MethodsRecords of adult LDLT between 1/2/2017 and 30/9/2021 were analyzed. ACLF was classified based on EASL-CLIF definition. Post-transplant outcomes of ACLF were compared with CLD and within ACLF grades. Post LDLT mortality predictors were identified in ACLF and ACLF3 patients. ResultsOut of 853 patients who had LT in that period; 704 patients with CLD and 103 with ACLF [of which 54 (52.42%) had ACLF3] underwent LDLT. The one month and one-year post LDLT mortality was 8.81% and 9.80% in CLD; 19.42% and 31.06% in ACLF; and 25.92% and 38.89% in ACLF3 respectively. On log regression analysis, use of grafts from older donors and pre-operative respiratory failure in recipients was associated with poor survival in ACLF, while respiratory failure was a predictor of poor survival in ACLF3 following LDLT. ConclusionOutcomes following LDLT are poorer in ACLF as compared to after CLD. Higher donor age and preoperative respiratory failure with PF Ratio<200 were associated with poor survival post LDLT in ACLF and ACLF3.

Plasma S100A8 and S100A9 Are Strong Prognostic Factors for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

The rapidly evolving organ failure and high short-run mortality of acute-on-chronic liver failure (ACLF) are inseparable from the role of systemic inflammatory response. S100A8 and S100A9 are associated with the excessive cytokine storm and play a decisive part within the process of inflammation. We aimed to clarify the role of them in predicting prognosis of hepatitis B virus-related ACLF (HBV-ACLF). S100A8 and S100A9 levels were analyzed in plasma of 187 transplant-free HBV-ACLF patients, 28 healthy controls and 40 chronic hepatitis B (CHB) patients. S100A8 and S100A9 mRNAs were checked in liver samples from 32 HBV-ACLF patients with liver transplantation, 19 patients undergoing surgery for hepatic hemangioma and 10 CHB patients with needle biopsy. The plasma levels of the S100A8 and S100A9 were higher in HBV-ACLF patients than in CHB patients (S100A8 : P < 0.001 and S100A9 : P < 0.001) and healthy controls (S100A8 : P < 0.001 and S100A9 : P < 0.001), and similar results were obtained for mRNA expression. Moreover, both proteins were related to ACLF grade, different types of organ failure, and infection, and they correlated with other prognostic scoring systems. S100A8 and S100A9 can dependently predict 28/90-day mortality (28-day: S100A8: hazard ratio (HR): 1.027; 95% confidence interval (CI): 1.007-1.048; P=0.026, S100A9 : HR: 1.009; 95% CI: 1.001-1.017; P=0.007, 90-day: S100A8 : HR: 1.023; 95% CI: 1.011-1.035; P=0.004, S100A9 : HR: 1.008; 95% CI: 1.004-1.012; and P < 0.001). Among all of the scoring systems, the combined scoring model (S100A8 and S100A9 jointly with the Chronic Liver Failure-Consortium Organ Failure score (CLIF-C OFs)) displayed the highest area under the receiver operating curve (0.923 (95% CI, 0.887-0.961)) in the prediction of 90-day mortality. S100A8 and S100A9 are promising biomarkers for the analysis of risk stratification and prognosis in ACLF patients. In addition, combining them with the CLIF-C OFs may better predict the prognosis of ACLF.

Baseline characteristics, grading and mortality in acute on chronic liver failure using CLF-C ACLF CRITERIA.

Objective: To observe baseline characteristics, ACLF (Acute on Chronic Liver Failure) grading and mortality in ACLF patients using EASL CLIF CRITERIA. Study Design: Prospective, Observational study. Setting: Medical unit 111, ward 7, Jinnah Postgraduate Medical Centre, Karachi. Period: January 2022 to June 2022. Material &amp; Methods: We prospectively analysed data of hospitalised liver cirrhosis patients at a tertiary care hospital in Karachi, Pakistan. The data was analysed in SPSS version 25. Results: There were a total of 43 ACLF patients, with the median age of IQR of 56(47-62) years, out of which 20 (46.5%) patients were male and 23 (53.5%) were females. The most common etiology of liver cirrhosis was hepatitis C 26(60.5%) followed by other etiologies nine (20.9%) and hepatitis B eight (18.6%). The most common precipitating factor was infection 19(44.2%) and the most frequent organ failure (OF) was renal failure (60.5%), followed by cerebral failure (46.5%) and other OFs. There were 24 patients in ACLF grade one, 13 in grade two and six in grade three ACLF. All six patients of ACLF grade three belonged to CTP C (Child-turcotte-pugh Cirrhosn) (100%) with 100% mortality. ACLF grade two had nine (69.2%) and ACLF grade one had eight (33.33%) CTP C patients. The in hospital mortality of ACLF was 23%. The median MELD Na of these patients was 28 (23-31), CLIF Consortium Organ Failure score was 9(8-10) and CLIF C ACLF Score was 45 (38-55). Conclusion: Highest mortality was observed in Child Pugh C and ACLF grade three in our patients. Such patients must be closely monitored and referred early for medical management and liver transplantation.

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.

The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure

Twenty-eight-day mortality ranges from 30-90% in patients with acute-on-chronic liver failure grades 2/3 (severe ACLF). Though liver transplantation (LT) has demonstrated a survival benefit, the scarcity of donor organs and uncertainty regarding post-LT mortality among patients with severe ACLF may cause hesitancy. We developed and externally validated a model to predict 1-year post-LT mortality in severe ACLF, called the Sundaram ACLF-LT-Mortality (SALT-M) score, and estimated the median length of stay (LoS) after LT (ACLF-LT-LoS). In 15 LT centers in the US, we retrospectively identified a cohort of patients with severe ACLF transplanted between 2014-2019, followed up to Jan'2022. Candidate predictors included demographics, clinical and laboratory values, and organ failures. We selected predictors in the final model using clinical criteria and externally validated them in two French cohorts. We provided measures of overall performance, discrimination, and calibration. We used multivariable median regression to estimate LoS after adjusting for clinically relevant factors. We included 735 patients, of whom 521 (70.8%) had severe ACLF (120 ACLF-3, external cohort). The median age was 55 years, and 104 with severe ACLF (19.9%) died within 1-year post-LT. Our final model included age >50 years, use of 1/≥2 inotropes, presence of respiratory failure, diabetes mellitus, and BMI (continuous). The c-statistic was 0.72 (derivation) and 0.80 (validation), indicating adequate discrimination and calibration based on the observed/expected probability plots. Age, respiratory failure, BMI, and presence of infection independently predicted median LoS. The SALT-M score predicts mortality within 1-year after LT in patients with ACLF. The ACLF-LT-LoS score predicted median post-LT stay. Future studies using these scores could assist in determining transplant benefits. Liver transplantation (LT) may be the only life-saving procedure available to patients with acute-on-chronic liver failure (ACLF), but clinically instability can augment the perceived risk of post-transplant mortality at 1 year. We developed a parsimonious score with clinically and readily available parameters to objectively assess 1-year post-LT survival and predict median length of stay after LT. We developed and externally validated a clinical model called the Sundaram ACLF-LT-Mortality score in 521 US patients with ACLF with 2 or ≥3 organ failure(s) and 120 French patients with ACLF grade 3. The c-statistic was 0.72 in the development cohort and 0.80 in the validation cohort. We also provided an estimation of the median length of stay after LT in these patients. Our models can be used in discussions on the risks/benefits of LT in patients listed with severe ACLF. Nevertheless, the score is far from perfect and other factors, such as patient's preference and center-specific factors, need to be considered when using these tools.

Risk stratification based on acute-on-chronic liver failure in cirrhotic patients hospitalized for acute variceal bleeding

Background and aimsAcute variceal bleeding (AVB) is a life-threatening complication of cirrhosis. Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of cirrhosis, multiple organ failures and high short-term mortality. This study aimed to evaluate the role of ACLF in the risk stratification of cirrhotic patients with AVB.MethodsProspective data of 335 cirrhotic patients hospitalized for AVB were retrospectively extracted from Medical Information Mart for Intensive Care (MIMIC)-IV database. ACLF was defined by European Association for the Study of Liver-Chronic Liver Failure Consortium and diagnosed/graded with chronic liver failure-organ failure (CLIF-OF) score. Cox-proportional hazards regression analysis was performed to identify the risk factors for 6-week morality in AVB patients. Discrimination and calibration of prognostic scores were evaluated by plotting the receiver operating characteristics (ROC) curve and calibration curve, respectively. Overall performance was assessed by calculating the Brier score and R2 value.ResultsA total of 181 (54.0%) patients were diagnosed with ACLF (grade 1: 18.2%, grade 2: 33.7%, grade 3: 48.1%) at admission. The 6-week mortality in patients with ACLF was significantly higher than that in patients without ACLF (43.6% vs. 8.4%, P < 0.001) and increased in line with the severity of ACLF (22.5%, 34.2% and 63.8% for ACLF grade 1, 2 and 3, P < 0.001). In multivariate analysis, presence of ACLF remained as an independent risk factor for 6-week mortality after adjusting for confounding factors (HR = 2.12, P = 0.03). The discrimination, calibration and overall performance of CLIF-C ACLF and CLIF-C AD were superior to the traditional prognostic scores (CTP, MELD and MELD-Na) in the prediction of 6-week mortality of patients with and without ACLF, respectively.ConclusionThe prognosis of cirrhotic patients with AVB is poor when accompanied by ACLF. ACLF at admission is an independent predictor for the 6-week mortality in cirrhotic patients with AVB. CLIF-C ACLF and CLIF-C AD are the best prognostic scores in AVB patients with and without ACLF, respectively, and can be used for the risk stratification of these two distinct entities.

Epidemiology, characteristics, and outcomes of patients with acute-on-chronic liver failure in Australia.

Acute-on-chronic liver failure (ACLF) is distinct from acute decompensation (AD) of cirrhosis in its clinical presentation, pathophysiology, and prognosis. There are limited published Australian ACLF data. We performed a single-center retrospective cohort study of all adults with cirrhosis admitted with a decompensating event to a liver transplantation (LT) centre between 2015 and 2020. ACLF was defined using the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) definition while those who did not meet the definition were classified as AD. The primary outcome of interest was 90-day LT-free survival. A total of 615 patients had 1039 admissions for a decompensating event. On their index admission, 34% (209/615) of patients were classified as ACLF. Median admission model for end-stage liver disease (MELD) and MELD-Na scores were higher in ACLF patients compared with AD (21 vs 17 and 25 vs 20 respectively, both P<0.001). Both the presence and severity of ACLF (grade ≥2) significantly predicted worse LT-free survival compared with patients with AD. The EASL-CLIF ACLF score (CLIF-C ACLF), MELD and MELD-Na scores performed similarly in predicting 90-day mortality. Patients with index ACLF had a higher risk of 28-day mortality (28.1% vs 5.1%, P<0.001) and shorter times to readmission compared with those with AD. ACLF complicates over a third of hospital admissions for cirrhosis with decompensating events and is associated with a high short-term mortality. The presence and grade of ACLF predicts 90-day mortality and should be identified as those at greatest risk of poor outcome without intervention such as LT.

Impact of donor diabetes mellitus status on liver transplant outcomes in patients with acute-on-chronic liver failure

ABSTRACT Background Liver transplantation (LT) is the most effective way to save patients with acute-on-chronic liver failure (ACLF). However, the impact of donor diabetes mellitus (DM) on LT outcomes in patients with ACLF has not been fully investigated. Research design and methods We retrospectively analyzed data from the Scientific Registry of Transplant Recipients (SRTR) between January 1st, 2008 to December 31st, 2017 in this study. All the patients were divided into donors with DM and without DM group (DM: 1,394; non-DM: 11138). We compared the overall survival (OS) and graft survival (GS) across different estimated ACLF (estACLF) grades between two groups. Results There were 25.10% estACLF-3 patients in the entire cohort. And in estACLF-3 patients, 318 patients had DM donors. The estACLF-3 associated 5-year OS rate in the non-DM group was 74.6%, significantly better than that in the DM group, with corresponding survival rate at 64.9% (P < 0.001). Donor DM was an independent predictor for OS in the entire cohort as well as in estACLF-3 patients. Conclusions Donor DM was associated with inferior outcomes of LT in patients with estACLF-3. However, the differences were not obvious in recipients with other estACLF grades.

FATORES PROGNÓSTICOS DE TRANSPLANTE HEPÁTICO EM “ACUTE-ON-CHRONIC LIVER FAILURE”

ABSTRACT BACKGROUND: Liver transplantation (LT) is the only treatment that can provide long-term survival for patients with acute-on-chronic liver failure (ACLF). Although several studies identify prognostic factors for patients in ACLF who do not undergo LT, there is scarce literature about prognostic factors after LT in this population. AIM: Evaluate outcomes of ACLF patients undergoing LT, studying prognostic factors related to 1-year and 90 days post-LT. METHODS: Patients with ACLF undergoing LT between January 2005 and April 2021 were included. Variables such as chronic liver failure consortium (CLIF-C) ACLF values and ACLF grades were compared with the outcomes. RESULTS: The ACLF survival of patients (n=25) post-LT at 90 days, 1, 3, 5 and 7 years, was 80, 76, 59.5, 54.1 and 54.1% versus 86.3, 79.4, 72.6, 66.5 and 61.2% for patients undergoing LT for other indications (n=344), (p=0.525). There was no statistical difference for mortality at 01 year and 90 days among patients with the three ACLF grades (ACLF-1 vs. ACLF-2 vs. ACLF-3) undergoing LT, as well as when compared to non-ACLF patients. CLIF-C ACLF score was not related to death outcomes. None of the other studied variables proved to be independent predictors of mortality at 90 days, 1 year, or overall. CONCLUSIONS: LT conferred long-term survival to most transplant patients. None of the studied variables proved to be a prognostic factor associated with post-LT survival outcomes for patients with ACLF. Additional studies are recommended to clarify the prognostic factors of post-LT survival in patients with ACLF.

Therapeutic plasma-exchange improves short-term, but not long-term, outcomes in patients with acute-on-chronic liver failure: A propensity score-matched analysis.

Acute-on-chronic liver failure (ACLF) is associated with a high short-term mortality rate in the absence of liver transplantation. The role of therapeutic plasma exchange (TPE) in improving the outcomes of ACLF and acute decompensation (AD) is unclear. In this retrospective analysis, we aimed to determine the impact of TPE on mortality in patients with ACLF. ACLF patients receiving TPE with standard medical treatment (SMT) were propensity score matched (PSM) with those receiving SMT alone (1:1) for sex, grades of ACLF, CLIF C ACLF scores, and the presence of hepatic encephalopathy. The primary outcomes assessed were mortality at 30 and 90 days. Survival analysis was performed using Kaplan Meier survival curves. A total of 1151 patients (ACLF n=864 [75%], AD [without organ failure] n=287 [25%]) were included. Of the patients with ACLF (n=864), grade 1, 2, and 3 ACLF was present in 167 (19.3%), 325 (37.6%), and 372 (43.0%) patients, respectively. Thirty-nine patients received TPE and SMT, and 1112 patients received only SMT. On PSM analysis, there were 38 patients in each group (SMT plus TPE vs SMT alone). In the matched cohort, the 30-days mortality was lower in the TPE arm compared to SMT (21% vs 50%, P=.008), however, the 90-day mortality was not significantly different between the two groups (36.8% vs 52.6%, P=.166); HR, 0.82 (0.44-1.52), P=.549. TPE improves short-term survival in patients with ACLF, but has no significant impact on long-term outcomes. Randomized control trials are needed to obtain a robust conclusion in this regard.

Applicability of the Chronic Liver Failure-Consortium score in patients with cirrhosis and bacterial infections: a single-clinic experience

Background. The frequency and characteristics of acute-on-chronic liver failure (ACLF) are reported in numerous articles from different countries. The aim of the study was to assess the cirrhosis decompensation in patients with bacterial infections based on the Chronic Liver Failure-Consortium (CLIF-C) score in one of the city clinics in Belarus. Materials and methods. The patients underwent laboratory and instrumental studies during the hospitalization. The assessment of the syndrome of acute-on-chronic liver failure was performed using the CLIF-C score. Bacterial infections were diagnosed on the basis of standard criteria. Results. The study included 151 cirrhotic patients, 87 males and 64 females. Median age was 55 years (Q1=43; Q3=61). Cirrhosis was predominantly due to alcohol addiction— 83 patients (55%). ACLF was diagnosed in 44 of 151 patients with cirrhosis (29.1%; 95% confidence interval (CI) 22.0–37.1). Bacterial infections were detected in 67 people (44.4%; 95% CI 36.3–52.7). Most often patients had liver failure that was detected by an increase in serum bilirubin level. Among individuals with upper gastrointestinal bleedings, number needed to harm for developing ACLF was 3.3 (95% CI 2.2–4.4). The risk of developing ACLF grade 2 and 3 in cirrhotic patients with infections was 8.2, with 95% CI 1.0–69.6 (number needed to harm was 12.9; 95% CI 10.7–15.0). Bacterial infections increase the risk of acute decompensation in patients with cirrhosis (odds ratio=2.0, p=0.048). Conclusions. The CLIF-C score is quite applicable in our cohort of patients with cirrhosis.

Five-year all-cause mortality in critically ill liver transplant patients with coronary artery disease: analysis of acute-on chronic liver failure

Patients with acute-on-chronic liver failure (ACLF) are critically ill and have high waiting-list mortality. Although studies demonstrated that appropriately treated coronary artery disease (CAD) should not be regarded as a contraindication to liver transplant (LT), data regarding long-term outcomes in critically ill liver LT recipients are lacking. The aim of this study was to compare the rates of all-cause death at 5 years following LT in patients with ACLF with or without CAD. Between 2010 and 2020, we evaluated 921 consecutive LT patients (MELD score, 32 ± 9) and ACLF classified by CLIF-C ACLF score. Up to 5-year all-cause death according to the CAD status was examined. CAD was defined as a preoperative history of coronary artery bypass graft or a percutaneous intervention and old myocardial infarction. Kaplan-Meier survival analysis was used. Up to 5 years, 212 (23.0%) of all ACLF patients (n = 921) in whom 17 (29.3%) of 58 CAD patients died. In patients with CAD (6.3%, 58/921), the Kaplan-Meier cumulative mortality rate at 5 years was numerically higher but was not statistically significant when compared with those without CAD (32.9% vs. 23.5%, log-rank, P = 0.25). In subgr oup analysis, there were comparable risks of cumulative mortalities at 5 years across the stratification of ACLF grade 1, 2, and 3 (log-rank P = 0.062, P = 0.72, and P = 0.999, respectively). All-cause mortality is high in patients with ACLF after LT but is not related to the presence of revascularized or treated CAD, across the stratification of ACLF grades.

Clinical Features of Hepatitis C Virus-related Acute-on-chronic Liver Failure in a Korean Population.

Acute-on-chronic liver failure (ACLF) is a widely recognized concept in which acute decompensation (AD) in patients with cirrhosis results in organ failure and high short-term mortality. On the other hand, few studies reflecting the various etiologies of cirrhosis are available. This study examined the clinical features of patients with hepatitis C virus (HCV)-related ACLF. Between January 2005 and December 2018, 109 HCV-related cirrhosis patients hospitalized for AD (ascites, hepatic encephalopathy, gastrointestinal hemorrhage, and bacterial infection) were enrolled for ACLF defined by the European Association for the Study of the Liver (EASL). ACLF developed in 35 patients (32.1%) on admission. Eight, eight, and 19 patients had ACLF grades 1, 2, and 3, respectively. The 28-day and 90-day mortality rates were very low (2.7% and 5.4%, respectively) in patients without ACLF and very high (60.0% and 74.3%, respectively) in those with ACLF. In patients with HCV-related ACLF, compared to previous studies on hepatitis B virus-related ACLF and alcohol-related ACLF, the prevalence of liver failure was very low (17.1%), whereas that of kidney failure was very high (71.4%). Compared with all other prognostic scores, the Chronic liver failure Consortium Organ Failure score predicted the 90-day mortality most accurately, with an area under the receiver operator characteristic of 0.921. HCV-related ACLF has unique clinical characteristics distinct from hepatitis B virus-related and alcohol-related ACLF. ACLF defined by EASL can be useful for predicting the short-term mortality in HCV-related cirrhosis.

Liver transplantation is beneficial regardless of cirrhosis stage or acute-on-chronic liver failure grade: A single-center experience

Liver transplantation for the most critically ill remains controversial; however, it is currently the only curative treatment option. To assess immediate posttransplant outcomes and compare the short (1 year) and long-term (6 years) posttransplant survival among cirrhotic patients stratified by disease severity. We included cirrhotic patients undergoing liver transplantation between 2015 and 2019 and categorized them into compensated cirrhosis (CC), decompensated cirrhosis (DC), and acute-on-chronic liver failure (ACLF). ACLF was further divided into severity grades. Our primary outcomes of interest were total days of intensive care unit (ICU) and hospital stay, development of complications and posttransplant survival at 1 and 6 years. 235 patients underwent liver transplantation (CC = 11, DC = 129 and ACLF = 95). Patients with ACLF had a significantly longer hospital stay [8.0 (6.0-13.0) vs CC, 6.0 (3.0-7.0), and DC 7.0 (4.5-10.0); P = 0.01] and developed more infection-related complications [47 (49.5%), vs CC, 1 (9.1%) and DC, 38 (29.5%); P < 0.01]. Posttransplant survival at 1- and 6-years was similar among groups (P = 0.60 and P = 0.90, respectively). ACLF patients stratified according to ACLF grade [ACLF-1 n = 40 (42.1%), ACLF-2 n = 33 (34.7%) and ACLF-3 n = 22 (23.2%)], had similar ICU and hospital stay length (P = 0.68, P = 0.54), as well as comparable frequencies of overall and infectious post-transplant complications (P = 0.58, P = 0.80). There was no survival difference between ACLF grades at 1 year and 6 years (P = 0.40 and P = 0.15). Patients may benefit from liver transplantation regardless of the cirrhosis stage. ACLF patients have a longer hospital stay and frequency of infectious complications; however, excellent, and comparable 1 and 6-year survival rates support their enlisting and transplantation including those with ACLF-3.

S1302 Effect of Bed Size of the Hospital on the Risk of Development of Acute on Chronic Liver Failure (ACLF) in Patients With Decompensated Cirrhosis

Introduction: The healthcare cost and utilization project has classified hospitals as small, medium, and large bed size. This division is based on the hospital's region, location, and teaching status. To our knowledge, there have been no studies assessing the impact of bed size on the development of acute on chronic liver failure (ACLF) in patients with decompensated cirrhosis. We hypothesize that large bed size hospitals care for a sicker population and admitted patients have a higher incidence and risk of developing ACLF. Methods: We queried the National Inpatient Sample (NIS) database using ICD-10 codes. ACLF was defined as the presence of renal failure or hepatic encephalopathy and one other organ dysfunction or two non-renal organ failures in patients with cirrhosis and a decompensating event. Decompensating events were defined as presence of ascites, varices, hepatic encephalopathy, or infection. The relationship between hospital bed size and ACLF in patients with decompensated cirrhosis was examined using multivariate analysis. Results: A total of 1.78 million adult patients were admitted with a diagnosis of acute decompensation of cirrhosis. Of these, 945,440 (52.8%) were admitted to large bed size hospitals. Patients admitted to large bed size hospitals had a higher incidence of hepatic encephalopathy, ascites, and variceal bleeding. Patient demographics are presented in Table. Of the total patients admitted with a decompensating event, 830,365 patients (46.4%) met criteria for ACLF. A total of 453,095 patients (54.6%) who developed ACLF were admitted to large bed size hospitals. Our study found that patients admitted to large bed size hospitals have 20% higher odds of developing ACLF (aOR-1.20, 95% CI-1.17-1.23, p< 0.001). Large bed size hospitals were also associated with a higher risk of developing ACLF grades 2 and 3 (aOR-1.27, 95% CI-1.24-1.32, p< 0.001 and aOR-1.73, 95% CI-1.51-1.98, p< 0.001, respectively). Conclusion: Our study identifies hospital bed size as a significant predictor for development of ACLF in patients admitted with decompensated cirrhosis. Targeted education and implementation of best practices focused on large hospitals may help reduce the risk of ACLF. Table 1. - Characteristics of patients with decompensated cirrhosis stratified by bed size of the hospital Small bed size Medium bed size Large bed size Age category < 0.001 18-44 31,090 (9.47) 50,045 (9.73) 101,445 (10.73) 45-64 171,485 (52.23) 272,360 (52.93) 512,485 (54.21) >65 125,725 (38.3) 192,165 (37.34) 331,510 (35.06) Gender < 0.001 Males 189,850 (57.83) 300,920 (58.48) 556,670 (58.88) Females 138,450 (42.17) 213,650 (41.52) 388,770 (41.12) Race < 0.001 White 227,390 (69.26) 340,635 (66.2) 625,285 (66.14) Black 29,690 (9.04) 48,575 (9.44) 92,860 (9.82) Hispanic 50,625 (15.42) 91,275 (17.74) 162,900 (17.23) Asian/Pacific Islander 6,020 (1.83) 9,455 (1.84) 21,015 (2.22) Primary expected payer < 0.001 Medicare 162,880 (49.61) 247,930 (48.18) 441,145 (46.66) Medicaid 77,670 (23.66) 123,200 (23.94) 244,975 (25.91) Private 60,210 (18.34) 96,575 (18.77) 178,480 (18.88) Uninsured 16,945 (5.16) 29,410 (5.72) 50,160 (5.31) Median household income < 0.001 Lowest quartile 95,060 (28.96) 172,670 (33.56) 350,665 (37.09) Second quartile 90,575 (27.59) 135,295 (26.29) 250,605 (26.51) Third quartile 82,330 (25.08) 116,010 (22.55) 207,695 (21.97) Highest quartile 60,335 (18.38) 90,595 (17.61) 136,475 (14.44) Region of hospital < 0.001 Northeast 66,420 (20.23) 94,705 (18.4) 129,295 (13.68) Midwest 67,370 (20.52) 75,890 (14.75) 208,140 (22.02) South 130,055 (39.61) 238,385 (46.33) 365,320 (38.64) West 64,455 (19.63) 105,590 (20.52) 242,685 (25.67) Location < 0.001 Rural 16,570 (5.05) 24,690 (4.8) 86,345 (9.13) Urban 311,730 (94.95) 489,880 (95.2) 859,095 (90.87) Hospital teaching status < 0.001 Non-Teaching 71,525 (21.79) 150,630 (29.27) 292,045 (30.89) Teaching 256,775 (78.21) 363,940 (70.73) 653,395 (69.11) Etiology Alcoholic liver disease 156,510 (47.67) 244,380 (47.49) 446,455 (47.22) 0.3666 Hepatitis C 34,540 (10.52) 56,480 (10.98) 100,680 (10.65) 0.1372 Decompensations Hepatic encephalopathy 115,795 (35.27) 185,220 (36.00) 354,280 (37.47) < 0.001 Ascites 186,590 (56.84) 300,505 (58.4) 582,875 (61.65) < 0.001 Varices 24,005 (7.31) 42,230 (8.21) 75,715 (8.01) < 0.001 Bacterial infections 145,525 (44.33) 221,525 (43.05) 386,985 (40.93) < 0.001 ACLF 142,565 (43.43) 234,705 (45.61) 453,095 (47.92) < 0.001