Definition Of Acute-on-chronic Liver Failure Research Articles

Extracorporeal Support Strategies in Liver Failure - Focus on Albumin Dialysis and Therapeutic Plasma Exchange

Combining albumin dialysis for the removal of hydrophobic substances with classical haemodialysis in the treatment of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) has a strong theoretical rational and clinical data showed a positive effect on laboratory and partly clinical characteristics of ALF and ACLF. However, neither the MARS nor the Prometheus System has so far been able to demonstrate a mortality benefit in ALF or ACLF patients. To date, only the use of therapeutic plasma exchange (TPE) has demonstrated significant removal of pathogen-associated (PAMPs), damage-associated molecular patterns (DAMPs) and pro-inflammatory cytokines. In addition, TPE also acts simultaneously by replacing protective but depleted mediators, thus improving multiple key pathophysiological principles of both ALF and ACLF. In ALF, both high-volume and standard-volume TPE showed a significant improvement in survival. The data on the use of TPE in ACLF is still sparse, with only two Chinese monocentric studies in patients with exclusively hepatitis B-associated ACLF suggesting potentially improved survival with TPE. The currently recruiting APACHE study will include patients with the modern EASL-CLIF definition of ACLF.

Focusing on timing selection and whole-course management of liver transplantation treatment for patients with acute-on-chronic liver failure

Acute-on-chronic liver failure (ACLF) is a clinical syndrome of acute decompensation accompanied by organ failure that occurs on the basis of chronic liver disease and has a high short-term mortality rate. Currently, there are still differences in relation to the definition of ACLF; thus, baseline characteristics and dynamic changes are important bases for clinical decision-making in patients with liver transplantation and others. The basic strategies for treating ACLF currently include internal medicine treatment, artificial liver support systems, and liver transplantation. Multidisciplinary active collaborative management throughout the whole course is of great significance for further improving the survival rate in patients with ACLF.

An Observational Study to Determine the Combination of Precipitating Factors Predicting 30-Day Mortality in Acute-On-Chronic Liver Failure (ACLF), With Respect to Underlying Disease Etiology and definition of ACLF

An Observational Study to Determine the Combination of Precipitating Factors Predicting 30-Day Mortality in Acute-On-Chronic Liver Failure (ACLF), With Respect to Underlying Disease Etiology and definition of ACLF

Improvement in organ failure in acute on chronic liver failure (ACLF) upon liver transplantation

Background &Aim: The prognostic factors determining the outcome of patients with cirrhosis and multi-organ failure are currently under evaluation. Reversal of organ failure pattern in response to Liver Transplant has not been studied much. It is an understood phenomenon that different organs that failed as consequence of ACLF will ultimately recover from injury upon liver transplantation. The aim of the study was to determine the mean number of days a failing organ in a pre-transplanted patient will take to recover after liver transplantation. Methods: Data was collected from April 2013 till February 2020 in the department of Liver Transplantation, Hepatobiliary and Pancreatic Services, Shifa International Hospital, Islamabad. In this cross-sectional retrospective study, 82 ACLF patients of both genders of age >15 years who fulfilled EASL-AASLD definition and underwent liver transplantation were included in the study. And patients who fulfilled APASL criteria but did not fulfilled EASL-AASLD criteria of definition of ACLF or those who required ventilator support or triple inotropic support before surgery were excluded. Patients with serum creatinine level >1.5mg/dl were labeled as having renal failure. Those with total bilirubin level of >12 mg/dl were labeled as hepatic failure and those with INR >2.5 were having coagulation failure.

Identifying the patient with acute-on-chronic liver failure: navigating through multiple definitions.

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Acute-on-chronic liver failure: Where do we stand?

Acute-on-chronic liver failure (ACLF) is defined by the rapid development of organ(s) failure(s) associated with high rates of early (28-day) mortality in patients with cirrhosis. ACLF has been categorized into three grades of increasing severity according to the nature and number of organ failures. In patients with grade 3 ACLF, 28-day mortality is >70%. While the definition of ACLF has been endorsed by European scientific societies, North American and Asian Pacific associations have proposed alternative definitions. A prognostic score called the CLIF-C ACLF score provides a more precise assessment of the prognosis of patients with ACLF. Although bacterial infections and variceal bleeding are common precipitating factors, no precipitating factor can be identified in almost 60% of patients with ACLF. There is increasing evidence that cirrhosis is a condition characterized by a systemic inflammatory state and occult infections or translocation of bacteria or bacterial products from the lumen of the GUT to the systemic circulation which could play a role in the development of ACLF. Simple and readily available variables to predict the occurrence of ACLF in patients with cirrhosis have been identified and high-risk patients need careful management. Whether prolonged administration of statins, rifaximin or albumin can prevent ACLF requires further study. Patients with organ(s) failure(s) may needed to be admitted to the ICU and there should be no hesitation in admitting patients with cirrhosis to the ICU. No benefit to survival was observed with albumin dialysis and rescue transplantation is the best option in the most severe patients. One-year post-transplant survival rates exceeding 70%-75% have been reported, including in patients with grade 3 ACLF but these patients were highly selected. Criteria have been proposed to define futile transplantation (too ill to be transplanted), but these criteria need to be refined to include age, comorbidities and frailty in addition to markers of disease severity.

A study on outcome of patients with acute-on-chronic liver failure at a tertiary care hospital

Acute-on-chronic liver failure (ACLF) is relatively recent entity and is not well described in the literature. The term acute-on-chronic liver failure was first used in 1995 to describe a condition in which two insults to the liver are operating simultaneously, one of them being ongoing and chronic and the other one acute. However, a clear definition of ACLF is still lacking, and this term is being used to mean different entities by different clinicians. Any patient who had underlying chronic liver disease with superimposed acute insult is being labeled as having ACLF. Whatsoever may be the case the most important is the denominator, the presence or absence of underlying liver disease. Prospectively collected data of all patients included demographics, clinical presentation, course in hospital and outcome. All patients had routine hematological biochemical and liver function tests. The etiology of superimposed acute event and chronic liver disease was investigated in detail and prognostic scores were calculated within 24hrs of admission. 60 patients included in our study were followed up for next three months, of which 30 patients died and 30 patients survived. All patients were classified in Child- Pugh class based on CTP score. There were only three patients Child-Pugh class A and none of them died. Child- Pugh class B had 10 patients, out of these 2 patients died & 8 patients survived. Total 47 patients were classified in Child-Pugh class C and 28 (59.57%) & this difference was statistically significant (p=0.013). According EASL-CLIF consortium grading, 23 out of 30 patients of Grade 3 ACLF, 5 out of 16 Grade 2 ACLF, 2 out of 11 Grade 1 ACLF & none of the Grade 0 ACLF patients died. These findings are statistically very much significant (P=0.0001). Even MELD score was significantly high among Non survivors when compared to the Survivors. (30.04 ± 2.37 Vs 25.53 ± 1.81) (p=0.0001).

Acute-on-chronic liver failure: Definitions, pathophysiology and principles of treatment.

SummaryThe term acute-on-chronic liver failure (ACLF) defines an abrupt and life-threatening worsening of clinical conditions in patients with cirrhosis or chronic liver disease. In recent years, different definitions and diagnostic criteria for the syndrome have been proposed by the major international scientific societies. The main controversies relate to the type of acute insult (specifically hepatic or also extrahepatic), the stage of underlying liver disease (cirrhosis or chronic hepatitis) and the concomitant extrahepatic organ failure(s) that should be considered in the definition of ACLF. Therefore, different severity criteria and prognostic scores have been proposed and validated. Current evidence shows that the pathophysiology of ACLF is closely associated with an intense systemic inflammation sustained by circulating pathogen-associated molecular patterns and damage-associated molecular patterns. The development of organ failures may be a result of a combination of tissue hypoperfusion, direct immune-mediated damage and mitochondrial dysfunction. Management of ACLF is currently based on the supportive treatment of organ failures, mainly in an intensive care setting. For selected patients, liver transplantation is an effective treatment that offers a good long-term prognosis. Future studies on potential mechanistic treatments that improve patient survival are eagerly awaited.

Impact of acute-on-chronic liver failure on post-transplant survival and on kidney outcomes

We aimed to evaluate the effect of acute-on-chronic liver failure (ACLF) on patients' 1-year post-liver transplant (LT) survival. In addition, we evaluated the effect of ACLF on the development of post-LT chronic kidney disease (CKD) and early allograft dysfunction (EAD). A retrospective cohort of patients who underwent transplantation from 2010 to 2016 was studied. EASL-CLIF's definition of ACLF was used. The risk of post-LT death, CKD, and EAD was estimated with regression models weighted by inverse probability weighting considering the recipients' characteristics. Donor's BMI and donor risk index were included in the models as well. A total of 185 patients were included: 125 (67.6%) without ACLF and 60 (32.4%) with ACLF. The 1-year post-LT survival rate was 91.2% [95% confidence interval (CI): 84.6-95.1%] in patients without ACLF versus 84.9% (95% CI: 73.1-91.9%) in patients with ACLF. Post-LT CKD occurred in 43 (38.7%) patients without ACLF versus 26 (52.0%) patients with ACLF. EAD occurred in 40 (32.3%) patients without ACLF versus 15 (28.8%) patients with ACLF. No effect of ACLF was found on survival (hazard ratio 1.75; 95% CI: 0.64-4.75, P = 0.272), CKD (odds ratio: 1.31; 95% CI: 0.60-2.86; P = 0.491), or EAD (odds ratio: 0.74; 95% CI: 0.38-1.66, P = 0.473). In this study, which included mainly patients with grade 1 ACLF at the time of LT, its presence had no impact on post-LT survival or on the occurrence of CKD or EAD.

Acute on Chronic Liver Failure—In-Hospital Predictors of Mortality in ICU

We studied in-hospital predictors of mortality of acute on chronic liver failure (ACLF) in Indian patients. Patients admitted to the intensive care unit of our institute fulfilling the definition of ACLF based on the Asia-Pacific Association for Study of Liver Disease (APASL) consensus were included. Complete history and medical evaluation to assess the etiology of underlying liver cirrhosis and to identify the acute precipitating insult of worsening liver function was done. Data was prospectively recorded and various scoring systems and individual clinical and laboratory parameters were assessed to identify predictors of 28 days mortality. 64 out of 240 patients screened for ACLF were analyszed in the study. Median age was 44 years and 53% were males. Alcohol was the primary cause of cirrhosis in 60.93%. Infections and active alcoholism was the main precipitating acute insult in 43% and 37% patients respectively. 28% patients had history of ingestion of hepato-toxic drugs as the acute insult. More than one acute insult was seen in 37.5% patients and type-II hepatic injury was the most common type. 28 days in hospital mortality was 43.75% and was highest in patients with sepsis (67.8%). Presence of hepato-renal syndrome and need for ventilation was associated with poor outcome. Though multiple variables were significant in predicting mortality on univariate analysis, yet on regression model only APACHE II and shock could significantly predict mortality with odds ratio of 3.18 and 9.14 respectively. Highest mortality was seen with cerebral and lung as organ failure and mortality increased as the number of organ failure worsened. CLIF-SOFA and APACHE-II scores having area under curve>0.8 had higher ability to predict mortality. ACLF carries high short-term mortality and early intervention by liver transplantation should be considered in patients who shows high risk of mortality.

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

Acute-on-chronic liver failure (ACLF) is characterized by an acute deterioration of liver function in patients with cirrhosis in combination with recently defined organ failures. Our aim was to independently validate the prognostic value of the recently established EASL-CLIF-Consortium definition of ACLF and to identify new predictors of short-term mortality. Patients with cirrhosis and the International Classification of Diseases, Tenth Revision diagnosis of (sub)acute liver failure were retrospectively categorized according to the EASL-CLIF-Consortium definition. Logistic regression analyses were performed to identify clinical and epidemiological predictors of 30- and 90-day mortality. From 2008 to 2015, 257 patients were included. Overall, 173 (67%) patients met the EASL criteria for ACLF (grade 1: n=43 [25%], grade 2: n=52 [30%], grade 3: n=79 [45%]). Mortality within 30days in patients without ACLF was 3.6%, and 18.6%, 37.3% and 62.0% in patients with ACLF grades 1, 2 and 3 respectively. Outcome of patients with bacterial infection-triggered ACLF was distinct from non-infection-triggered ACLF (71.6% vs 33.8% 30-day survival, P<.001), and infection-triggered ACLF was independently associated with increased mortality (odds ratio [OR]=4.28, P<.001). Pneumonia was a particularly frequent infection and burdened with high mortality. In addition, infections with multidrug-resistant organisms were frequent and independently associated with mortality (P=.030, OR=4.41), as was glycopeptide antibiotic therapy as initial empirical antibiotic therapy (P=.005). This study confirmed the EASL-CLIF-Consortium definition of ACLF as strong predictor of mortality in patients with acute decompensation of cirrhosis. However, we have observed a remarkably higher mortality in infection-triggered ACLF compared to other precipitating events.

FRI-421 - Acute on chronic liver failure (ACLF) – combining CLIF-SOFA criteria with APASL definition of ACLF enhances prediction of mortality at 1, 3 and 6 months

FRI-421 - Acute on chronic liver failure (ACLF) – combining CLIF-SOFA criteria with APASL definition of ACLF enhances prediction of mortality at 1, 3 and 6 months

Acute-on-chronic liver failure in India: The Indian National Association for Study of the Liver consortium experience.

The aim of this study was to analyze etiologies and frequency of hepatic and extrahepatic organ failures (OFs) and outcome of acute-on-chronic liver failure (ACLF) at 10 tertiary centers in India. In this retrospective study (2011-2014), patients satisfying Asian Pacific Association for the Study of the Liver definition of ACLF were included. Etiology of acute precipitating insult and chronic liver disease and outcomes were assessed. Occurrence and severity of OF were assessed by chronic liver failure-sequential organ failure assessment score. The mean (±SD) age of 1049 consecutive ACLF patients was 44.7 ± 12.2 years; Eighty-two percent were men. Etiology of acute precipitants included alcohol 35.7%, hepatitis viruses (hepatitis A, hepatitis B, and hepatitis E) 21.4%, sepsis 16.6%, variceal bleeding 8.4%, drugs 5.7%, and cryptogenic 9.9%. Among causes of chronic liver disease, alcohol was commonest 56.7%, followed by cryptogenic and hepatitis viruses. Predictors of survival were analyzed for a subset of 381 ACLF patients; OF's liver, renal, coagulation, cerebral, respiratory, and failure were seen in 68%, 32%, 31.5%, 22.6%, 14.5%, and 15%, respectively. Fifty-seven patients had no OF, whereas 1, 2, 3, 4, and 5 OFs were recorded in 126, 86, 72, 28, and 12 patients, respectively. The mortality increased progressively with increasing number of OFs (12.3% with no OF, 83.3% with five OFs). During a median hospital stay of 8 days, 42.6% (447/1049) of patients died. On multivariate analysis by Cox proportional hazard model, elevated serum creatinine (hazard ratio [HR] 1.176), advanced hepatic encephalopathy (HR 2.698), and requirement of ventilator support (HR 2.484) were independent predictors of mortality. Alcohol was the commonest etiology of ACLF. Within a mean hospital stay of 8 days, 42% patients died. OFs independently predicted survival.

Pediatric Acute-on-Chronic Liver Failure in a Specialized Liver Unit: Prevalence, Profile, Outcome, and Predictive Factors.

The aim of the study was to assess the prevalence, profile, outcome, and predictive factors of pediatric acute-on-chronic liver failure (ACLF). All children 3 months to 18 years satisfying the Asia Pacific Association for the Study of Liver Diseases definition of ACLF were included. Data were both extracted from records (January 2011 to December 2014) and prospectively collected (January to October 2015). Successful outcome was defined as survival with native liver at 90 days, whereas poor outcome included those who died or received liver transplantation. Of the 499 children with chronic liver disease (CLD), 56 (11.2%) presented as ACLF, with a mean age of 9.35 (±4.39) years. Wilson disease and autoimmune hepatitis were the commonest underlying CLDs accounting for 24 (42.8%) and 18 (32.1%) cases, respectively. The most frequent events precipitating ACLF were a flare up of the underlying disease in 27 (48.2%) and acute viral hepatitis in 17 (30%). Poor outcome occurred in 22 (39.3%) children: 17 (30.4%) died and 5 (8.9%) received liver transplantation. Poor outcome was associated with grades 3 to 4 hepatic encephalopathy, bilirubin ≥17.5, international normalized ratio ≥3.5, and presence of 2 or more organ failures. On multivariate analysis, a Chronic Liver Failure-Sequential Organ Failure Assessment score ≥10 best predicted mortality (odds ratio 20.45, 95% confidence interval 3.9-106.7). ACLF is present in 11.2% of childhood CLD, with a 90-day native liver survival of 61%. A Chronic Liver Failure-Sequential Organ Failure Assessment score of ≥10 best predicts mortality at day 90.

Predisposing Factors in Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality in patients with chronic liver disease. The definition of ACLF has been addressed recently in many publications, and despite regional differences the number and severity of organ failures are decisive for the presence and severity of ACLF. However, the predisposition of patients to develop ACLF has not been addressed in prospective studies. Several predisposing factors for ACLF have been mentioned, but still clear-cut analysis and the sequential processes have not been explored. One reason is that different factors might predispose in one setting and might be the precipitating event in another, thus rendering the generalization of predisposing factors difficult. However, genetic factors, lifestyle, past medical history, aging, latent chronic infections, and the severity of the liver disease and portal hypertension might predispose for the development of ACLF after proper injury and response.

Acute kidney injury in acute on chronic liver failure.

Acute on chronic liver failure (ACLF) is a distinct clinical entity; however, there is still debate in the way it is defined in the East as compared to the West, especially with respect to incorporation of kidney dysfunction or failure in the definition of ACLF. Kidney dysfunction is defined as serum creatinine between 1.5 and 1.9mg/dl and kidney failure as serum creatinine of more than 2mg/dl or requirement of renal replacement therapy according to the EASL-CLIF Consortium. Kidney dysfunction or failure is universally present in patients with ACLF according to the definition by the EASL-CLIF Consortium while on the contrary the APASL definition of ACLF does not incorporate kidney dysfunction or failure in its definition. Recently, both the diagnosis and management of renal failure in patients with cirrhosis has changed with the advent of the acute kidney injury (AKI) criteria defined as an abrupt decline in renal functions, characterized by an absolute increase in serum creatinine of 0.3mg/dl within 48h or an increase of more than 50% from baseline, which is known or presumed to have occurred in the previous 7days. Further, recent studies in patients with cirrhosis have shown the utility of biomarkers for the diagnosis of AKI. The present review covers the pathogenetic mechanisms, diagnosis, prognosis as well as management of AKI in patients with ACLF from both a Western as well as an Eastern perspective. The review identifies an unmet need to diagnose AKI and prevent this ominous complication in patients with ACLF.

Acute-on-chronic liver failure: a prospective study to determine the clinical profile, outcome, and factors predicting mortality.

Acute-on-chronic liver failure (ACLF), defined differently by different associations, lacks consensus on clinical profile, precipitating events and factors predicting mortality. This prospective multicentric study was conducted to determine the relevance of European Association for Study of Liver (EASL) and Asia Pacific Association for Study of Liver (APASL) definitions and to determine prognostic factors predicting the survival. Consecutive patients over a 3-month period with any form of acute deterioration were evaluated for presence of ACLF, as defined by APASL or EASL-Chronic Liver Failure (CLIF) criteria. Those enrolled underwent complete evaluation for identifying the acute insults, underlying chronic etiologies, presence of organ failures, and short-term survival. Sixty-two patients (median age 53 years, 51 males) who presented with either raised bilirubin (n = 52), international normalized ratio (INR) >1.5 (n = 46), new onset ascites (n = 53), or hepatic encephalopathy (n = 39) were included in study. Forty-four patients (36 males, 25 alcoholics) satisfied APASL definition of ACLF, with a mortality rate of 43.1 %. Hepatic encephalopathy (p-value 0.022) was significantly associated with mortality. By CLIF-Sequential Organ Failure Assessment (SOFA) score criteria for organ failure, 50 patients (80.6 %) had at least 1 organ failure whereas 15 had ≥3 organ failures (mortality rate >75 %). Twenty-nine patients classified as ACLF (1, 2, or 3) as per EASL-CLIF criteria. Bacterial infection, >1 precipitating event, additional organ failure, total leukocyte count, INR, and serum creatinine were significantly higher in patients with ACLF across all grades. Mortality rates were 6.6 and >60 % in patients with ACLF only by APASL criteria vs. by both criteria, respectively. ACLF, as defined by APASL in terms of liver failure, identified some patients with better survival rates as compared to EASL-CLIF definition which identifies presence of additional organ failures and high mortality.

Defining acute-on-chronic liver failure: East, West or Middle ground?

Acute-on-chronic liver failure (ACLF), a newly recognized clinical entity seen in hospitalized patients with chronic liver disease including cirrhosis, is associated with high short- and medium term morbidity and mortality. None of the definitions of ACLF proposed so far have been universally accepted, the two most commonly used being those proposed by the Asia-Pacific Association for the Study of Liver (APASL) and the European Association for the Study of Liver - Chronic Liver Failure (EASL-CLIF) consortium. On paper both definitions and diagnostic criteria appear to be different from each other, reflecting the differences in cut-off values for individual parameters used in diagnosis, the acute insult or precipitating event and the underlying chronic liver disease. Data directly comparing these two criteria are limited, and available studies reveal different outcomes when the two are applied to the same set of patients. However a review of the literature suggests that both definitions do not seem to identify the same set of patients. The definition given by the APASL consortium is easier to apply in day-to-day practice but the EASL-CLIF criteria appear to better predict mortality in ACLF. The World Gastroenterology Organization working party have proposed a working definition of ACLF which will identify patients from whom relevant data can be collected so that the similarities and the differences between the two regions, if any, can be clearly defined.

Acute-on-chronic liver failure: Pathogenesis, prognostic factors and management.

Acute-on-chronic liver failure (ACLF) is increasingly recognized as a complex syndrome that is reversible in many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure (OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept (Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies.

Liver: Acute-on-chronic liver failure--no longer an entity without definition.

Although clinicians instinctively recognise acute-on-chronic liver failure (ACLF), heretofore we have had no way of accurately studying the syndrome, as no definition of this entity existed. A consortium of European centres has finally offered a definition of ACLF and proposed a prognostic index based upon easily obtained features of patients with decompensated cirrhosis.