Bacterial infection-triggered acute-on-chronic liver failure is associated with increased mortality.

Defining Acute-on-Chronic Liver Failure: Will East and West Ever Meet?

Sarcopenia should be evaluated in patients with acute-on-chronic liver failure and candidates for liver transplantation

Toward an Improved Definition of Acute-on-Chronic Liver Failure

Factors Associated With Survival of Patients With Severe Acute-On-Chronic Liver Failure Before and After Liver Transplantation: Unanswered Questions

Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS

Acute-on-chronic liver failure (ACLF) is a dreaded complication of chronic liver diseases encompassing an acute deterioration of liver function that is associated with extra-hepatic organ failure.1 Patients with ACLF have a high short-term mortality that parallels the number of extra-hepatic organ failures.2 However, early liver transplantation (LT) in carefully selected patients has shown good results regarding short-term survival, and several studies have demonstrated 1-year survival rates >80% even in patients with grade 3 ACLF.3 While these results are poorer than those of patients transplanted without ACLF or those with grade 1 or 2 ACLF, it must be kept in mind that spontaneous 3-month survival is around 20% in this group of patients. Although short-term individual benefit of LT in these patients is clear, these benefits must be balanced with a lower post-LT survival with respect to other indications of LT.4 In addition, when it comes to long-term outcomes of patients transplanted because of ACLF, it is important to highlight that information in this respect is scarce. In this setting, Goosmann et al5 add to our knowledge on long-term results of LT in patients with ACLF in this issue of Liver International. In a single-centre retrospective study that included 250 LT recipients, 98 of whom had ACLF before LT, the authors confirm the worse survival of patients transplanted with ACLF (particularly those with ACLF grade 3) in the short term,6 which indeed is brought forward to the long term. However, it is important to highlight that differences in survival are mediated solely by the early post-operative months, and ACLF patients surviving the early post-transplant period do exactly as well as those without ACLF at LT. These results complement those reported in a recent study that evaluated the UNOS database.7 In that study, patients with ACLF grade 3 at LT had significantly worse overall survival than those without ACLF or with ACLF grade 1 or 2, although again differences were driven only in the first year after LT, so patients surviving the first year after LT had the same long-term survival independently from the presence or grade of ACLF before LT. As expected, in both cohorts infections were the main cause of death in LT recipients presenting with ACLF. Thus, it seems extremely important to be particularly aggressive in the prevention, diagnosis and treatment of infections in this specific group of patients to improve outcomes. Of note, in their study, Goosmann et al explore an issue that usually receives little attention from transplant hepatologists or surgeons, which is long-term quality of life after LT. While it is clear that the main driver of our work is to improve patients’ survival, functional recovery and health-related quality of life are also essential parts of successful transplantation. From a general point of view, LT is associated with improved functional recovery and health-related quality of life,8, 9 although some studies have demonstrated that the social domain and cognitive function do not reach the level of the general population after surgery.10 Quality of life after solid organ transplantation is determined by comorbidities, pre and peri-operative clinical courses, graft function, side effects of medications, particularly immunosuppressants, and psychological and socioeconomic factors.11 In the paper from Goosmann et al, LT survivors were sent a written survey including several health-related quality of life questionnaires, at a median time of approximately 7 years after LT. Although the analysis is limited by a response rate around 60%, ACLF-LT recipients showed significantly worse scores in scales regarding present health status, self-care, the ability to perform usual activities, anxiety and depression. Interestingly, there were no differences between patients with or without ACLF before LT in terms of immunosuppression, graft function, or long-term comorbidities, so these conditions do not seem to affect long-term quality of life in this cohort. On the other hand, patients who reported worse quality of life were those who presented with higher MELD score at LT and had suffered longer duration of ICU stay after LT, both characteristics being typical of ACLF patients. These findings are comparable to the durable consequences also seen in critically ill patients surviving an ICU episode,12 also described as post-ICU syndrome13 and highlight the unmet needs of this population. These results need to be confirmed in larger, prospective studies, and ideally using specific quality of life questionnaires; in addition, more in-depth analyses of the specific risk factors for an impaired quality of life in the long term in LT recipients are necessary, given that a proportion of ACLF patients who undergo LT still have a good quality of life. Nevertheless, it is clear that clinically important consequences can be derived from this nice piece of work. The most important is probably the need to better tackle this infradiagnosed condition after LT. First, considering the importance of quality of life and the consequences in terms of return to a normal life from a patients’ perspective, efforts in order to at least evaluate quality of life in LT recipients, particularly those at highest risk of poorer outcomes, should be made. In addition, interventions aimed at improving global state of health after LT are necessary. While a detailed psychological assessment and intervention in ACLF LT candidates seem difficult to perform before LT considering the severity of patients and their urgency to be included in the waiting list; transferring psychological care to the post-LT period may help improve quality of life and patients perceived global health status, and thus enhance global success of LT, going further and deeper than patient survival.

ObjectivePrognostic stratification of patients with cirrhosis is common clinical practice. This study compares the prognostic accuracy (28-day and 90-day transplant-free mortality) of the acute-on-chronic liver failure (ACLF) classification (no ACLF,...

To compare the utility of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) and Asia-Pacific Association for the Study of Liver (APASL) definitions of acute-on-chronic liver failure (ACLF) in predicting short-term prognosis of patients with ACLF. Consecutive patients of cirrhosis with acute decompensation were prospectively included. They were grouped into ACLF and no ACLF groups as per CLIF-SOFA and APASL criteria. Patients were followed up for 3 mo from inclusion or mortality whichever was earlier. Mortality at 28-d and 90-d was compared between no ACLF and ACLF groups as per both criteria. Mortality was also compared between different grades of ACLF as per CLIF-SOFA criteria. Prognostic scores like CLIF-SOFA, Acute Physiology and Chronic Health Evaluation (APACHE)-II, Child-Pugh and Model for End-Stage Liver Disease (MELD) scores were evaluated for their ability to predict 28-d mortality using area under receiver operating curves (AUROC). Of 50 patients, 38 had ACLF as per CLIF-SOFA and 19 as per APASL criteria. Males (86%) were predominant, alcoholic liver disease (68%) was the most common etiology of cirrhosis, sepsis (66%) was the most common cause of acute decompensation while infection (66%) was the most common precipitant of acute decompensation. The 28-d mortality in no ACLF and ACLF groups was 8.3% and 47.4% (P = 0.018) as per CLIF-SOFA and 39% and 37% (P = 0.895) as per APASL criteria. The 28-d mortality in patients with no ACLF (n = 12), ACLF grade 1 (n = 11), ACLF grade 2 (n = 14) and ACLF grade 3 (n = 13) as per CLIF-SOFA criteria was 8.3%, 18.2%, 42.9% and 76.9% (χ(2) for trend, P = 0.002) and 90-d mortality was 16.7%, 27.3%, 78.6% and 100% (χ(2) for trend, P < 0.0001) respectively. Patients with prior decompensation had similar 28-d and 90-d mortality (39.3% and 53.6%) as patients without prior decompensation (36.4% and 63.6%) (P = NS). AUROCs for 28-d mortality were 0.795, 0.787, 0.739 and 0.710 for CLIF-SOFA, APACHE-II, Child-Pugh and MELD scores respectively. On multivariate analysis of these scores, CLIF-SOFA was the only significant independent predictor of mortality with an odds ratio 1.538 (95%CI: 1.078-2.194). CLIF-SOFA criteria is better than APASL criteria to classify patients into ACLF based on their prognosis. CLIF-SOFA score is the best predictor of short-term mortality.

BACKGROUND: Acute on chronic liver failure (ACLF) is a well recognized entity, characterized by an acute liver insult in patients with underlying chronic liver disease leading to sudden deterioration of liver function and a high mortality. We aimed to determine hospital, 28 days and 12 weeks mortality of ACLF, its predictors and precipitating factors METHODS: We conducted a prospective descriptive study at AIMS (Asian institute of medical sciences, Hyderabad, Pak.) from January 2018 to December 2018. We enrolled patients of ACLF as defined by Asian Pacific Association for the Study of Liver (APASL, 2014) and collected data to determine cause, precipitating acute insult, organ failure, ACLF grade MELD, and CTP scores. Patients were followed to determine hospital, 28 days and 12 weeks mortality and its predictors. RESULTS: Total patients were 117 with mean age of 40.9 +- 13.9 years (range 12–85). Majority were males 86 (73.5%) and 31 (26.5%) were females. Majority of patients 55 (47%) were Hepatitis B Virus (HBV) positive, among them 24 (43.6%) were with HDV co-infection. The most common precipitating acute insult was SEPSIS 65 (55.6). Others were drug induce liver injury (DILI) 8 (6.8%), HEV acute hepatitis 7 (5.9), HDV superinfection 5 (4.3%), HBV flair 4 (3.4%), alcohol binge drinking 4 (3.4%), surgery 2 (1.7%), acute PVT 2 (1.7%), Upper GI Bleed 1 (0.9%) and 20 (17.1%) were unknown. Hospital mortality was 49 (41.9%), 28 days 71 (60.7%) and 12 weeks mortality was 103 (88.0%). Organ failure (P = 0.002), ACLF grade (P = 0.002), encephalopathy (P = 0.001), MELD (P = 0.01) and AKI (P = 0.02) were found to be predictors of mortality. CONCLUSIONS: Acute-on-chronic liver failure (ACLF) is an acute deterioration of liver function superimposed on Chronic Liver Disease with a high mortality. In our study HBV infection was the commonest cuase of CLD, and sepsis was the commonest acute insult. We found high hospital, 28 days and 12 weeks mortality. Organ failure, ACLF grade, encephalopathy, MELD score and AKI were found to be predictors of mortality of ACLF.

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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.

Background: Acute on chronic liver failure (ACLF) is typically characterized by a rapid progression of liver failure in patients with liver cirrhosis and it is triggered by a precipitant factor, usually a bacterial infection (BI). Considering the low accuracy of the inflammation biomarkers in liver cirrhosis, presepsin and procalcitonin have demonstrated a good diagnostic performance for BI. Understanding the key prognostic factors that influence patient outcomes can significantly impact clinical decision-making and improve patient care in ACLF which can lead to lower mortality rates. Aim: To evaluate the prognostic factors associated with 30-day mortality in patients with alcohol-related liver cirrhosis and ACLF. Methods: This retrospective study on 227 patients diagnosed with ACLF and alcohol-related liver cirrhosis analyzed the prognostic role of presepsin and procalcitonin serum levels. Results: The survival analysis according to the grade of ACLF showed that more than 80% of patients with ACLF grade 1 survived after 30 days, with a mean estimated time of death of 29 ±0.44 days (95 % CI: 28.17-29.92) compared to ACLF grade 2 (24.9±1.064 days; 95 % CI: 22.82-26.99) and ACLF grade 3 (21.05±1.17 days; 95 % CI: 18.75-23.34), with a mean overall survival on entire cohort of 25.69±0.52 days (95 % CI: 24.65-26.73). Presepsin (OR: 4.008, CI 95:3.130-6.456, p=0.001) and procalcitonin (OR: 3.666, CI 95:2.312-5.813, p=0.001) were the most significant factors associated with 30-day mortality. In ACLF grade 2, presepsin provides a better prediction of mortality at the cutoff value of 1050 pg/mL (Sensitivity 72%, Specificity 69%) than procalcitonin (AUC=0.727 95% CI 0.594-0.860, p<0.002) whereas in ACLF grade 3, a cutoff of 1450 pg/mL (Sensitivity 89%, Specificity 91%) presepsin had a more significant accuracy of mortality prediction (AUC=0.93 95% CI 0.81-0.99, p<0.001) than procalcitonin (AUC=0.731 95% CI 0.655-0.807, p<0.001). Conclusion: ACLF is associated with a high mortality rate and the risk of death increases with the grade of ACLF. Presepsin and procalcitonin serum levels are good prognostic factors for 30-day mortality and should be used in clinical practice to stratify the risk and provide and early and efficient treatment in patients with ACLF.

Acute-on-chronic liver failure (ACLF) is an increasingly recognized entity encompassing an acute deterioration of liver function in patients with cirrhosis, either secondary to superimposed liver injury or due to extrahepatic precipitating factors such as infection culminating in the end-organ dysfunction. Its main features are reversibility and high short-term mortality due to multiorgan failure (MOF). We aimed to analyze the clinical, laboratory, and etiological predictors of mortality and outcome in patients with ACLF. We evaluated 1215 patients with chronic liver disease; 90 patients met the criteria for ACLF. The most common cause of underlying chronic liver disease was alcohol, and the most common acute insult (AI) in those patients was superadded alcoholic hepatitis. In all, 50% of all patients died within 30 days (71.1 % within the first 14 days after admission). MOF was the cause of death in 70 % of cases. On multivariate analysis, high serum potassium, serum creatinine higher than 90µmol/L, and C-reactive protein > 30mg/L were found to be independent baseline predictors of mortality. APACHE II (Acute Physiology and Chronic Health Evaluation II) score was the best predictor of short-term mortality (area under the curve (AUC), 0.878). MOF was a valuable predictor of mortality (AUC, 0.923); 33 of 35 patients who had MOF at admission died. Presence of positive systemic inflammatory response syndrome criteria at admission was also correlated with in-hospital mortality (AUC, 0.742). ACLF is a serious condition with high short-term mortality. Because ACLF is reversible, it is necessary to identify at-risk patients as soon as possible to treat acute events in a timely manner.

The aim - to determine the etiology and clinical features of the acute-on-chronic liver failure (ACLF) in patients with acute decompensation of liver cirrhosis (LC). Materials and methods. A retrospective analysis of the clinical features of ACLF was performed in 71 patients with LC, who died within 28 days of hospital stay. The etiology of the LC was determined, traditional clinical, laboratory and instrumental data were performed, the chronic liver failure organ failure score (CLIF OF S), chronic liver failure-consortium acute-on-chronic liver failure score (CLIF-C ACLF S), model for end stage liver disease score (MELD S) and Child-Pugh score (Ch-P S) were calculated. Results. Alcoholic genesis of LC was detected in 63.4% of patients, alcoholic in combination with metabolic (NAFLD) - in 15.5%, alcoholic in combination with viral - in 4,2%, metabolic - in 1,4%, viral - in 4, 2%, autoimmune - in 1,4%, drug - in 1,4%, unidentifiable - in 8.5%. Triggers for the development of ACLF were active alcoholism in 39.4% of patients, bacterial infection in 19.7%, esophageal bleeding in 15.5%, active HCV infection in 4.2%, autoimmune attack in 1,4%. ACLF grade 1 was revealed in 26.8%, ACLF grade 2 - in 19.7%, ACLF grade 3 - in 53.5% of patients. The frequency of organ failures were: liver - 73.2%, kidney - 54.9%, coagulation - 54.9%, cerebral - 21.6%, circulation - 18.3%, lungs - 11.3%. CLIF OF S, CLIF-C ACLF S significantly increased already at ACLF grade 2, and MELD S and Ch-P S - only at ACLF grade 3. Conclusion. The alcoholic genesis of LC was revealed in the most patients (63.4%) and active alcoholism was the trigger for ACLF development (39.4%). The most frequent clinical manifestations of ACLF were liver failure (73.2%), kidney (54.9%) and coagulation (54.9%). CLIF OF S, CLIF-C-ACLF S had better diagnostic and prognostic significance than MELD S and Ch-P S.

Acute on chronic liver failure (ACLF) is a syndrome occurring in patients with chronic liver disease with or without cirrhosis characterised by acute hepatic decompensation and one or more extra...