Development of a novel prognostic assessment model for hepatitis B virus-related acute-on-chronic liver failure based on reexamination results.

Acute-on-chronic liver failure (ACLF) is a common clinical emergency and critical illness with rapid progression and poor prognosis. This study aims to establish a more efficient system for the prognostic assessment of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), which will provide a guiding scheme for subsequent treatment and improve the survival rate of patients. Data on 623 patients with HBV-ACLF were recorded. Univariate and multivariate analyses were performed to determine the discriminative abilities of the novel prognostic assessment model in predicting 90-day mortality. The area under the receiver operating characteristic curve was used to evaluate the accuracy of the models. Patients were divided into high- and low-scoring groups based on the best critical values, and survival rates were analyzed using Kaplan-Meier survival analysis and compared by applying log-rank tests. The area under the curve of the new scoring system established using the results of the first reexamination, the results of the first examination, the mean daily change in these results (MDCR) and the results of other first examinations were 0.911 (95% confidence interval [CI]: 0.889, 0.933), 0.893 (95% CI: 0.868, 0.917), and 0.895 (95% CI: 0.871, 0.919), respectively. The final prognostic scoring system established using the results of the first reexamination was chosen as a novel prognostic assessment model, and patients with lower scores (first reexamination results [FRER] score ≤ 3.65) had longer survival times (P < .001). The prognostic scoring system established using the FRER combined with other examination results can better assess the prognosis of HBV-ACLF at 90 days.

Limitations of current liver donor allocation systems and the impact of newer indications for liver transplantation.

Liver transplantation represents a life-saving treatment for patients with decompensated cirrhosis, a severe condition associated with a high risk of waiting list mortality. When decompensation occurs rapidly in the presence of extrahepatic organ failures, the condition is called acute-on-chronic liver failure, which is associated with an even higher risk of death, though liver transplantation can also markedly improve survival in affected patients. However, there are still gaps in our understanding of how to optimise prioritisation and organ allocation, as well as survival among patients with acute-on-chronic liver failure (both before and after transplant). Moreover, it is urgent to address inequalities in access to liver transplantation in patients with severe alcoholic hepatitis and non-alcoholic steatohepatitis. Several controversies still exist regarding gender and regional disparities, as well as the use of suboptimal donor grafts. In this review, we aim to provide a critical perspective on the role of liver transplantation in patients with decompensated cirrhosis and address areas of ongoing uncertainty.

Point-of-Care Echocardiography and Hemodynamic Monitoring in Cirrhosis and Acute-on-Chronic Liver Failure in the COVID-19 Era.

Point-of-Care (POC) transthoracic echocardiography (TTE) is transforming the management of patients with cirrhosis presenting with septic shock, acute kidney injury, hepatorenal syndrome and acute-on-chronic liver failure (ACLF) by correctly assessing the hemodynamic and volume status at the bedside using combined echocardiography and POC ultrasound (POCUS). When POC TTE is performed by the hepatologist or intensivist in the intensive care unit (ICU), and interpreted remotely by a cardiologist, it can rule out cardiovascular conditions that may be contributing to undifferentiated shock, such as diastolic dysfunction, myocardial infarction, myocarditis, regional wall motion abnormalities and pulmonary embolism. The COVID-19 pandemic has led to a delay in seeking medical treatment, reduced invasive interventions and deferment in referrals leading to "collateral damage" in critically ill patients with liver disease. Thus, the use of telemedicine in the ICU (Tele-ICU) has integrated cardiology, intensive care, and hepatology practices across the spectrum of ICU, operating room, and transplant healthcare. Telecardiology tools have improved bedside diagnosis when introduced as part of COVID-19 care by remote supervision and interpretation of POCUS and echocardiographic data. In this review, we present the contemporary approach of using POC echocardiography and offer a practical guide for primary care hepatologists and gastroenterologists for cardiac assessment in critically ill patients with cirrhosis and ACLF. Evidenced based use of Tele-ICU can prevent delay in cardiac diagnosis, optimize safe use of expert resources and ensure timely care in the setting of critically ill cirrhosis, ACLF and liver transplantation in the COVID-19 era.

Noninvasive assessment of liver fibrosis for predicting acute-on-chronic liver failure in patients with chronic hepatitis B.

BACKGROUND AND AIM: The aim of this study was to evaluate the accuracy of serum markers of liver fibrosis for predicting progression to acute-on-chronic liver failure (ACLF) in patients with acute exacerbation (AE) and severe AE (SAE) of chronic hepatitis B virus (HBV) infection. METHODS: The predictive accuracy of aminotransferase-to-platelet ratio index (APRI), Fibrosis-4, Lok index, and Forns index for progression to ACLF was evaluated via receiver operating characteristic (ROC) curve and area under the ROC (AUROC) in 441 and 130 patients with AE and SAE. RESULTS: After admission, 24 (5.8%) and 25 (19.2%) patients with AE and SAE, respectively, progressed to ACLF. The Lok index was one of the independent risk factors associated with progression to ACLF in patients with AE and SAE. The AUROC of Lok index for diagnosing liver cirrhosis was 0.815 (0.774-0.851) in patients with AE and 0.715 (0.629-0.791) in patients with SAE. The AUROC of Lok index for predicting progression to ACLF in patients with AE and SAE was 0.756 (0.711-0.797) and 0.866 (0.795-0.919), respectively. In patients with AE and SAE, the cut-off values of the Lok index for predicting ACLF were higher and lower, respectively, than those for diagnosing liver cirrhosis. CONCLUSION: The Lok index has predictive accuracy regarding progression to ACLF in patients with AE and SAE. Different thresholds of liver fibrosis are needed for determining progression to ACLF in patients with different severity of liver injury during acute exacerbation of chronic HBV infection.

Acute-on-chronic liver failure: A comparison of three different diagnostic criteria.

INTRODUCTION AND AIM: Different criteria are applied for the diagnosis of acute-on-chronic liver failure (ACLF). Our aim was to compare the performance of different ACLF diagnostic criteria for predicting mortality. MATERIALS AND METHODS: This was a prospective cohort study of adult cirrhotic patients admitted to a tertiary hospital for acute decompensation (AD) of cirrhosis. The evaluated outcome was mortality at 28 and 90 days, according to the different ACLF diagnostic criteria: Chronic Liver Failure Consortium (CLIF-C), Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC) and North American Consortium for the Study of End-Stage Liver Disease (NACSELD). Prognostic performance was evaluated using receiver operating characteristic (ROC) curves. RESULTS: 146 patients were included. 43 (29.5%) with ACLF according to CLIF-C definition, 14 (9.6%) with ACLF by AARC definition, and 6 (4.1%) by NACSELD definition. According to Kaplan-Meier survival analyses median survival of patients with ACLF by CLIF-C definition was 27.0 days, median survival of patients with ACLF by AARC definition was 27.0 days, and median survival of patients with ACLF by NACSELD definition was 4.0 days. The areas under the ROC curves for performance evaluation in predicting mortality at 28 days for CLIF-C, AARC and NACSELD criteria were, respectively, 0.710, 0.560 and 0.561 (p=0.002). Regarding 90-day mortality, the areas under the ROC curves were 0.760, 0.554 and 0.555 respectively (p<0.001). CONCLUSION: ACLF definition proposed by CLIF-C had better performance in predicting mortality at 28 and 90 days when compared to criteria proposed by AARC and NACSELD.

NASH Is the Most Rapidly Growing Etiology for Acute-on-Chronic Liver Failure-Related Hospitalization and Disease Burden in the United States: A Population-Based Study.

Acute-on-chronic liver failure (ACLF) is characterized by multiple organ failure (OF) with high short-term mortality. There is lack of population-based data on trends on etiology specific ACLF related burden. National Inpatient Sample (2006-2014) was queried using ICD-09 codes for admissions with cirrhosis and ACLF (≥2 extrahepatic OF). Of 1,928,764 admissions for cirrhosis between 2006 and 2014, 112,174 (5.9%) had ACLF (4.5%, 1.2%, and 0.2% with ACLF 1, 2, and 3, respectively). The brain was the most common OF in 11.9%, followed by respiratory failure in 7.7%, cardiac failure in 6.3%, and renal failure in 5.6%. ACLF increased by 24% between 2006 and 2014 with a 63% increase in 179,104 patients with nonalcoholic steatohepatitis (NASH) cirrhosis (3.5% to 5.7%); a 28% increase in patients with 429,306 alcoholic cirrhosis (5.6% to 7.2%); a 25% increase in patients with 1,091,053 with other etiologies (5.2% to 6.5%); and no significant change in 229,301 patients with viral hepatitis (VH) (4.0% to 4.1%). In-hospital mortality was higher among ACLF patients compared with patients without ACLF (44% versus 4.7%; P < 0.0001). Each NASH-related ACLF patient compared with other etiologies had a longer mean length of stay (14 versus 12 days), was associated with higher median total charges (US $151,196 versus US $134,597), and had more frequent use of dialysis (45% versus 36%) and longterm care (32% versus 26%; P < 0.0001 for all). Results remained similar in a subgroup analysis after including half of admissions with cryptogenic cirrhosis as NASH. In conclusion, NASH cirrhosis is the most rapidly growing indication for ACLF-related hospitalization and use of hospital resources. In the setting of improved treatment options for chronic hepatitis, the health care burden of chronic viral-related liver disease remains stable. Population-based strategies are needed to reduce the health care burden of cirrhosis, particularly related to NASH.

Applicability of Sepsis-3 criteria and quick Sequential Organ Failure Assessment in patients with cirrhosis hospitalised for bacterial infections.

BACKGROUND & AIMS: An algorithm including Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) was recently proposed to predict severity of infection in cirrhosis. However, its applicability among patients without a baseline SOFA available for Sepsis-3 definition is unknown. We sought to investigate the applicability and prognostic value of qSOFA and Sepsis-3 criteria in patients with cirrhosis hospitalised for bacterial infections, without pre-hospitalisation SOFA. METHODS: In this cohort study, 164 patients were followed up to 30 days. Data collection, including the prognostic models, was performed at admission and at day-3. RESULTS: All patients fulfilled Sepsis-3 criteria (admission SOFA ≥ 2) and, therefore, admission Sepsis-3 was not included in further analysis. Admission qSOFA was an independent predictor of survival (HR = 2.271, P = 0.015). For patients initially classified as high risk by qSOFA, Chronic Liver Failure - Sequential Organ Failure Assessment (CLIF-SOFA) was the only prognostic predictor. Among patients initially classified as low risk by qSOFA, the following parameters evaluated at day-3 were independent predictors of survival: qSOFA, acute-on-chronic liver failure, and Child-Pugh classification. Although not independently related to survival, Sepsis-3 criteria at day-3 was associated with lower 30-day survival in Kaplan-Meier analysis (66% vs 85%, P = 0.008). However, prognosis was better predicted by day-3 qSOFA, with 30-day Kaplan-Meier survival probability of 88% when qSOFA < 2 and 24% among those with qSOFA ≥ 2. CONCLUSION: Sepsis-3 criteria evaluated at admission are very limited in infected patients with cirrhosis without baseline SOFA. qSOFA was independently related to survival and appears to be a valuable tool for determining severity of infection and to follow patients initially classified as low risk.

Assessment of scoring systems for acute-on-chronic liver failure at predicting short-term mortality in patients with alcoholic hepatitis.

AIM: To assess the performance of proposed scores specific for acute-on-chronic liver failure in predicting short-term mortality among patients with alcoholic hepatitis. METHODS: We retrospectively collected data from 264 patients with clinically diagnosed alcoholic hepatitis from January to December 2013 at 21 academic hospitals in Korea. The performance for predicting short-term mortality was calculated for Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), CLIF Consortium Organ Failure score (CLIF-C OFs), Maddrey's discriminant function (DF), age, bilirubin, international normalized ratio and creatinine score (ABIC), Glasgow Alcoholic Hepatitis Score (GAHS), model for end-stage liver disease (MELD), and MELD-Na. RESULTS: Of 264 patients, 32 (12%) patients died within 28 d. The area under receiver operating characteristic curve of CLIF-SOFA, CLIF-C OFs, DF, ABIC, GAHS, MELD, and MELD-Na was 0.86 (0.81-0.90), 0.89 (0.84-0.92), 0.79 (0.74-0.84), 0.78 (0.72-0.83), 0.81 (0.76-0.86), 0.83 (0.78-0.88), and 0.83 (0.78-0.88), respectively, for 28-d mortality. The performance of CLIF-SOFA had no statistically significant differences for 28-d mortality. The performance of CLIF-C OFs was superior to that of DF, ABIC, and GAHS, while comparable to that of MELD and MELD-Na in predicting 28-d mortality. A CLIF-SOFA score of 8 had 78.1% sensitivity and 79.7% specificity, and CLIF-C OFs of 10 had 68.8% sensitivity and 91.4% specificity for predicting 28-d mortality. CONCLUSION: CLIF-SOFA and CLIF-C OF scores performed well, with comparable predictive ability for short-term mortality compared to the commonly used scoring systems in patients with alcoholic hepatitis.

Child-Pugh, MELD, and ALBI scores for predicting the in-hospital mortality in cirrhotic patients with acute-on-chronic liver failure.

OBJECTIVES: Our study aimed to evaluate the discriminative abilities of Child-Pugh, model for end-stage liver disease (MELD), and albumin-bilirubin (ALBI) scores in predicting the in-hospital mortality in cirrhotic patients with acute-on-chronic liver failure (ACLF). METHODS: Cirrhotic patients with ACLF admitted between 2010 January and 2014 June were retrospectively reviewed. Areas under the receiver operating characteristic curves (AUROCs) with 95% confidence intervals (CIs) were calculated. RESULTS: One hundred patients were eligible for the Asia-Pacific Association for the Study of the Liver (APASL) criteria. AUROCs of Child-Pugh, MELD, and ALBI scores in predicting the in-hospital mortality was 0.63 (95%CI: 0.52-0.72, P = 0.05), 0.75 (95%CI: 0.65-0.83, P < 0.0001), and 0.53 (95%CI: 0.42-0.63, P = 0.69), respectively. Eighty-eight patients were eligible for the EASL/AASLD criteria. AUROCs of Child-Pugh, MELD, and ALBI scores in predicting the in-hospital mortality were 0.59 (95%CI: 0.48-0.69, P = 0.14), 0.57 (95%CI: 0.46-0.68, P = 0.26), and 0.57 (95%CI: 0.46-0.67, P = 0.29), respectively. There was no significant difference among them. CONCLUSION: Child-Pugh, MELD, and ALBI scores might be ineffective in predicting the in-hospital mortality of cirrhosis with ACLF.

Allocation of patients with liver cirrhosis and organ failure to intensive care: Systematic review and a proposal for clinical practice.

AIM: To propose an allocation system of patients with liver cirrhosis to intensive care unit (ICU), and developed a decision tool for clinical practice. METHODS: A systematic review of the literature was performed in PubMed, MEDLINE and EMBASE databases. The search includes studies on hospitalized patients with cirrhosis and organ failure, or acute on chronic liver failure and/or intensive care therapy. RESULTS: The initial search identified 660 potentially relevant articles. Ultimately, five articles were selected; two cohort studies and three reviews were found eligible. The literature on this topic is scarce and no studies specifically address allocation of patients with liver cirrhosis to ICU. Throughout the literature, there is consensus that selection criteria for ICU admission should be developed and validated for this group of patients and multidisciplinary approach is mandatory. Based on current available data we developed an algorithm, to determine if a patient is candidate to intensive care if needed, based on three scoring systems: premorbid Child-Pugh Score, Model of End stage Liver Disease score and the liver specific Sequential Organ Failure Assessment score. CONCLUSION: There are no established systems for allocation of patients with liver cirrhosis to the ICU and no evidence-based recommendations can be made.