Acute-on-chronic Liver Failure In Patients Research Articles

Enhancing ACLF prediction by integrating sarcopenia assessment and frailty in liver transplant candidates on the waiting list

Malnutrition, sarcopenia, and frailty are prevalent in cirrhosis. We aimed to assess the correlation between assessment tools for malnutrition, sarcopenia, and frailty in patients on the liver transplant (LT) waiting list (WL), and to identify a predictive model for acute-on-chronic liver failure (ACLF) development. This prospective single-center study enrolled consecutive patients with cirrhosis on the WL for LT (May 2019-November 2021). Assessments included subjective global assessment, CT body composition, skeletal muscle index (SMI), ultrasound thigh muscle thickness, sarcopenia HIBA score, liver frailty index (LFI), hand grip strength, and 6-minute walk test at enrollment. Correlations were analyzed using Pearson's correlation. Competing risk regression analysis was used to assess the predictive ability of the liver- and functional physiological reserve-related variables for ACLF. A total of 132 patients, predominantly with decompensated cirrhosis (87%), were included. Our study revealed a high prevalence of malnutrition (61%), sarcopenia (61%), visceral obesity (20%), sarcopenic visceral obesity (17%), and frailty (10%) among participants. Correlations between the assessment tools for sarcopenia and frailty were poor. Sarcopenia by SMI remained prevalent when frailty assessments were not usable. After a median follow-up of 10 months, 39% of the patients developed ACLF on WL, while 28% experienced dropouts without ACLF. Multivariate analysis identified MELD-Na, SMI, and LFI as independent predictors of ACLF on the WL. The predictive model MELD-Na-sarcopenia-LFI had a C-statistic of 0.85. The poor correlation between sarcopenia assessment tools and frailty underscores the importance of a comprehensive evaluation. The SMI, LFI, and MELD-Na independently predicted ACLF development in WL. These findings enhance our understanding of the relationship between sarcopenia, frailty, and ACLF in patients awaiting LT, emphasizing the need for early detection and intervention to improve WL outcomes. The relationship between sarcopenia and frailty assessment tools, as well as their ability to predict acute-on-chronic liver failure (ACLF) in patients on the liver transplant (LT) waiting list (WL), remains poorly understood. Existing objective frailty screening tests have limitations when applied to critically ill patients. The correlation between sarcopenia and frailty assessment tools was weak, suggesting that they may capture different phenotypes. Sarcopenia assessed by skeletal muscle index, frailty evaluated using the liver frailty index, and the model for end-stage liver disease-Na score independently predicted the development of ACLF in patients on the WL. Our findings support the integration of liver frailty index and skeletal muscle index assessments at the time of inclusion on the WL for LT. This combined approach allows for the identification of a specific patient subgroup with an increased susceptibility to ACLF, underscoring the importance of early implementation of targeted treatment strategies to improve outcomes for patients awaiting LT.

Proton pump inhibitor treatment is associated with acute-on-chronic liver failure in patients with advanced cirrhosis.

Acute-on-chronic liver failure (ACLF) is a fatal complication of cirrhosis. Hence, identification of risk factors for ACLF is crucial. Previous studies have linked proton pump inhibitor (PPI) treatment to complications of cirrhosis, however, a possible effect of PPI treatment on the risk of ACLF has not been investigated yet. Therefore, the present study aimed to characterize the impact of PPI treatment on ACLF development. A total of 642 patients hospitalized due to complications of cirrhosis were retrospectively identified, and PPI treatment during an observation period of 3 years following the hospitalization was reviewed. Subsequently, 74 patients with newly initiated PPI treatment at the time of hospitalization (PPI group) were 1:1 propensity score matched to 74 patients who received no PPI treatment (no-PPI group). Primary end point was the development of ACLF during the observation period, and secondary endpoints were mortality and upper gastrointestinal bleeding. PPI and no-PPI groups had comparably severe chronic liver disease at baseline. Nevertheless, the cumulative incidence of ACLF in the presence of death as competing risk was markedly higher in the PPI group compared with the no-PPI group. ACLF-related deaths contributed significantly to a higher 3-year mortality in the PPI group. Uni and multivariable competing risk regression models confirmed that PPI treatment was an independent predictor of ACLF in the study collective (subdistribution HR: 1.892, 95% CI: 1.092-3.281, p = 0.023). The impact of PPI treatment on ACLF development was particularly strong in patients with a model for end-stage liver disease score >12. Upper gastrointestinal bleeding was slightly less frequent in the PPI group. The present results indicate that PPI treatment could be a risk factor for ACLF in patients with advanced cirrhosis.

Acute-on-chronic liver failure in patients with severe acute respiratory syndrome coronavirus 2 infection.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a significant impact on the lives of millions of people, especially those with other concomitant diseases, such as chronic liver diseases. To date, seven coronaviruses have been identified to infect humans. The main site of pathological action of these viruses is lung tissue. However, a substantial number of studies have proven that SARS-CoV-2 shows affinity towards several organs, including the gastrointestinal tract and the liver. The current state of evidence points to several proposed mechanisms of liver injury in patients with COVID-19 and their combination. Liver impairment is considered to be the result of the direct effect of the virus on the hepatic tissue cells, a systemic reaction consisting of inflammation, hypoxia and cytokine storm, drug-induced liver injury, with the possible contribution of a perturbed gut-liver axis. Reactivation of chronic hepatic disease could be another factor for liver impairment in patients with SARS-CoV-2 infection. Acute-on-chronic liver failure (ACLF) is a relatively new syndrome that occurs in 10%-30% of all hospitalized patients with chronic liver disease. It is crucial to recognize high-risk patients due to the increased morbidity and mortality in these cases. Several published studies have reported virus infection as a trigger factor for ACLF. However, to date, there are few relevant studies describing the presence of ACLF in patients with acute SARS-CoV-2 infection. In this minireview we summarize the current state of knowledge regarding the relation between ACLF and acute SARS-CoV-2 infection.

The Ratio of von Willebrand Factor Antigen to ADAMTS13 Activity: Usefulness as a Prognostic Biomarker in Acute-on-Chronic Liver Failure

Acute-on-chronic liver failure (ACLF) has a high risk of short-term mortality. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) is a metalloproteinase that specifically cleaves multimeric von Willebrand factor (VWF). Imbalance between ADAMTS13 and VWF is associated with portal hypertension, which induces ACLF development. A previous study reported that ADAMTS13 activity (ADAMTS13:AC) and VWF antigen (VWF:Ag) are predictive biomarkers of ACLF development in patients with cirrhosis. This study investigated the changes in ADAMTS13:AC and VWF:Ag levels from before to after the development of ACLF to determine their usefulness as a prognostic biomarker in patients with ACLF. In total, 101 patients with cirrhosis were enrolled in this study. The level of ADAMTS13:AC and VWF:Ag was determined by an enzyme-linked immunosorbent assay. Cox proportional hazard regression analysis was conducted to determine independent prognostic factors for patients with liver cirrhosis in the post-ACLF group. ADAMTS13:AC levels gradually decreased in the order of non-ACLF group, pre-ACLF group, and finally post-ACLF group. VWF:Ag and the ratio of VWF:Ag to ADAMTS13:AC (VWF:Ag/ADAMTS13:AC) levels gradually increased in the order of non-ACLF group, pre-ACLF group, followed by post-ACLF group. VWF:Ag/ADAMTS13:AC and CLIF-C ACLF scores were associated with prognosis in the post-ACLF group in multivariate analysis. The cumulative survival of the post-ACLF group was significantly lower for patients with high VWF:Ag/ADAMTS13:AC (>9) compared with those with low VWF:Ag/ADAMTS13:AC (≤9) (HR: 10.72, 95% confidence interval: 1.39-82.78, p < 0.05). The VWF:Ag/ADAMTS13:AC increased according to the progression of ACLF in patients with cirrhosis and predicted prognosis in patients with cirrhosis with ACLF.

Complement C3 Facilitates Stratification of Stages of Chronic Hepatitis B and Signifies Development of Acute-on-Chronic Liver Failure in Acute Decompensated Cirrhosis.

Patients with chronic hepatitis B (CHB) have a dynamic disease process and risk of end-stage liver disease. It is critical to unambiguously differentiate the stages of the disease and focus on therapy prior to onset of an irreversible clinical endpoint. We retrospectively analyzed a wide range of CHB patients at different stages. The predictive power of serum complement component 3 (C3) levels for the development of acute-on-chronic liver failure (ACLF) in patients with decompensated cirrhosis was established and validated. The decrease in serum C3 levels paralleled the severity of diseases related to hepatitis B virus. Patients with decompensated cirrhosis who developed ACLF had significantly lower serum C3 levels than others on admission (0.50 vs. 0.80g/L, P<0.001). Data analysis also revealed that low serum C3 was a significant risk factor for developing ACLF (hazard ratio=0.32, P<0.01). The area under the receiver operating characteristic curve (auROC) for serum C3 levels that predicted the development of ACLF in patients with decompensated cirrhosis was 0.90, which had sensitivity and specificity of 88.2% and 88.7%, respectively. A similar result was observed in the validation set (auROC=0.86 for predicting development of ACLF in patients with decompensated cirrhosis). Serum C3 levels are valuable in assessing the severity of CHB-related stages. Low C3 levels signifies the development of ACLF in patients with decompensated cirrhosis.

CLIF-SOFA and CLIF-C scores for the prognostication of acute-on-chronic liver failure and acute decompensation of cirrhosis: A systematic review

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by decompensation in individuals with chronic liver disease, generally secondary to one or more extra-hepatic organ failures, implying an elevated mortality rate. Acute decompensation (AD) is the term used for one or more significant consequences of liver disease in a short time and is the most common reason for hospital admission in cirrhotic patients. The European Association for the Study of Liver-Chronic-Liver Failure (EASL-CLIF) Group modified the intensive care Sequential Organ Failure Assessment score into CLIF-SOFA, which detects the presence of ACLF in patients with or without AD, classifying it into three grades. To investigate the role of the EASL-CLIF definition for ACLF and the ability of CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD scores for prognosticating ACLF or AD. This study is a literature review using a standardized search method, conducted using the steps following the guidelines for reporting systematic reviews set out by the PRISMA statement. For specific keywords, relevant articles were found by searching PubMed, ScienceDirect, and BioMed Central-BMC. The databases were searched using the search terms by one reviewer, and a list of potentially eligible studies was generated based on the titles and abstracts screened. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/). Most of the included studies used the EASL-CLIF definition for ACLF to identify cirrhotic patients with a significant risk of short-term mortality. The primary outcome in all reviewed studies was mortality. Most of the study findings were based on an area under the receiver operating characteristic curve (AUROC) analysis, which revealed that CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD scores were preferable to other models predicting 28-d mortality. Their AUROC scores were higher and able to predict all-cause mortality at 90, 180, and 365 d. A total of 50 articles were included in this study, which found that the CLIF-SOFA, CLIF-C ACLF and CLIF-C AD scores in more than half of the articles were able to predict short-term and long-term mortality in patients with either ACLF or AD. CLIF-SOFA score surpasses other models in predicting mortality in ACLF patients, especially in the short-term. CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD are accurate short-term and long-term mortality prognosticating scores.

Transjugular intrahepatic portosystemic shunt vs conservative treatment for recurrent ascites: A propensity score matched comparison.

Transjugular intrahepatic portosystemic shunt (TIPS) placement is an effective intervention for recurrent tense ascites. Some studies show an increased risk of acute on chronic liver failure (ACLF) associated with TIPS placement. It is not clear whether ACLF in this context is a consequence of TIPS or of the pre-existing liver disease. To better understand the risks of TIPS in this challenging setting and to compare them with those of conservative therapy. Two hundred and fourteen patients undergoing their first TIPS placement for recurrent tense ascites at our tertiary-care center between 2007 and 2017 were identified (TIPS group). Three hundred and ninety-eight patients of the same time interval with liver cirrhosis and recurrent tense ascites not undergoing TIPS placement (No TIPS group) were analyzed as a control group. TIPS indication, diagnosis of recurrent ascites, further diagnoses and clinical findings were obtained from a database search and patient records. The in-hospital mortality and ACLF incidence of both groups were compared using 1:1 propensity score matching and multivariate logistic regressions. After propensity score matching, the TIPS and No TIPS groups were comparable in terms of laboratory values and ACLF incidence at hospital admission. There was no detectable difference in mortality (TIPS: 11/214, No TIPS 13/214). During the hospital stay, ACLF occurred more frequently in the TIPS group than in the No TIPS group (TIPS: 70/214, No TIPS: 57/214, P = 0.04). This effect was confined to patients with severely impaired liver function at hospital admission as indicated by a significant interaction term of Child score and TIPS placement in multivariate logistic regression. The TIPS group had a lower ACLF incidence at Child scores < 8 points and a higher ACLF incidence at ≥ 11 points. No significant difference was found between groups in patients with Child scores of 8 to 10 points. TIPS placement for recurrent tense ascites is associated with an increased rate of ACLF in patients with severely impaired liver function but does not result in higher in-hospital mortality.

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

Bacterial Infections Confer a Risk of Progression to Acute-on-Chronic Liver Failure in Patients with HBV-Related Compensated Cirrhosis During Severe Hepatitis Flares.

The aims of this study were to investigate the risk factors for bacterial infections (BIs) and the association of BIs with the progression to acute-on-chronic liver failure (ACLF) in patients with hepatitisB virus (HBV)-related compensated liver cirrhosis and severe hepatitis flares. A total of 237 patients were retrospectively reviewed. Baseline biochemical characteristics were compared between patients with and without the occurrence of BIs and progression to ACLF. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for ACLF before and after 1:1 propensity score matching. Forty-eight (20.3%) patients progressed to ACLF after admission. Additionally, 136 (57.4%) patients progressed to hepatic decompensation (HD) and 52 (21.9%) patients had BIs before the development of ACLF. Patients with BIs had significantly higher incidences of HD (84.6%) and ACLF (46.2%) than those without BIs (49.7% and 13.0%, respectively; P < 0.01). CTP score (OR1.660, 95%CI 1.267-2.175) and MELD-Na score (OR1.082, 95%CI 1.010-1.160) were independent risk factors for BIs. BIs (OR4.037, 95%CI 1.808-9.061), CLIF-SOFA score (OR2.007, 95%CI 1.497-2.691), and the MELD-Na score (OR1.167, 95%CI 1.073-1.260) were independent risk factors for the progression to ACLF. BIs (OR4.730, 95%CI 1.520-14.718) were also an independent risk factor for the progression to ACLF after propensity score matching. High CTP and MELD-Na scores are risk factors for BIs, and BIs are risk factors for the progression to ACLF in patients with HBV-related compensated liver cirrhosis and severe hepatitis flares.

Con: Patients With Acute-on-Chronic Liver Failure Should Not Receive Priority on the Waiting List.

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Gastrointestinal hemorrhage as an acute-on-chronic liver failure trigger in cirrhotic patients.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with organ failures and very high short-term mortality. To assess the incidence and factors predisposing to ACLF in patients with liver cirrhosis hospitalized due to acute gastrointestinal bleeding (GIB). We collected and retrospectively analyzed the data of 89 consecutive patients (59 males (66.2%), median age 53 years (range: 44-62 years), mean Model for End-Stage Liver Disease (MELD) score 14.42 ±6.5, median Child-Turcotte-Pugh score 10 (range: 8-11), and acute GIB (72 variceal bleeding and 17 non-variceal bleeding cases). Acute-on-chronic liver failure was diagnosed based on European Association for the Study of the Liver - Chronic Liver Failure Consortium definition. Twenty-seven (30.33%) patients met the criteria of ACLF during hospitalization: 8 (30%) had ACLF grade 1, 13 (48%) had ACLF grade 2 and 6 (22%) had ACLF grade 3. The most frequent organ failures were respiratory (22 (25%)), kidney (18 (20.23%)) and brain (17 (19.1%)) failure. The MELD score value, creatinine level and presence of hepatic encephalopathy (HE) on admission were significant predictors of ACLF in the multivariate logistic regression model with optimal cutoff point for MELD score of 18.313 and optimal cutoff point for creatinine level of 1.35 mg/dL. In-hospital risk of ACLF in cirrhotic patients hospitalized for acute gastrointestinal hemorrhage is high despite successful arrest of bleeding. Elevated creatinine level, MELD score and the presence of HE on admission are the best predictors of ACLF during hospitalization in such patients.

Predicting the Onset of Hepatitis B Virus–Related Acute-on-Chronic Liver Failure

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome with rapid progression. This study aimed to develop and validate a prognostic score to predict the onset of ACLF in hepatitis B virus (HBV) etiology. The prospective clinical data of 1373 patients with acute deterioration of HBV-related chronic liver disease were used to identify clinical characteristics and develop a prognostic score for the onset of ACLF. Of the patients assessed using the Chinese Group on the Study of Severe Hepatitis B (COSSH)-ACLF criteria, 903 patients with non-ACLF at admission (1 received transplantation at 5 days) were stratified: 71 with progression to ACLF and 831 without progression to ACLF at 7 days. Four predictors (total bilirubin, international normalized ratio, alanine aminotransferase, and ferritin) were associated significantly with ACLF onset at 7 days. The COSSH-onset-ACLF score was constituted as follows: (0.101× ln [alanine aminotransferase]+ 0.819× ln [total bilirubin]+ 2.820× ln [international normalized ratio]+ 0.016× ln [ferritin]). The C-indexes of the new score for 7-/14-/28-day onset (0.928/0.925/0.913) were significantly higher than those of 5 other scores (Chronic Liver Failure Consortium ACLF development score/Model for End-stage Liver Disease score/Model for End-stage Liver Disease sodium score/COSSH-ACLF score/Chronic liver failure Consortium ACLF score; all P < .001). The improvement in predictive errors, time-dependent receiver operating characteristic, probability density function evaluation, and calibration curves of the new score showed the highest predictive value for ACLF onset at 7/14/28 days. Risk stratification of the new score showed 2 strata with high and low risk (≥6.3/<6.3) of ACLF onset. The external validation group further confirmed the earlier results. A new prognostic score based on 4 predictors can accurately predict the 7-/14-/28-day onset of ACLF in patients with acute deterioration of HBV-related chronic liver disease and might be used to guide clinical management.

From the Editor’s desk…

From the Editor’s desk…

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.

Cystatin C and interleukin-6 for prognosticating patients with acute decompensation of cirrhosis.

Background and AimSystemic inflammation and organ dysfunction/failure can complicate acute decompensation (AD) of cirrhosis with progression to acute‐on‐chronic liver failure (ACLF), leading to increased mortality. There are few studies on serum biomarkers predicting renal dysfunction (RD) or ACLF in AD. Serum cystatin C (CysC) and interleukin‐6 (IL‐6) were evaluated for predicting RD, ACLF, and mortality in AD patients.MethodsConsecutive AD patients seen from January 2018 to June 2019 were included. IL‐6 and CysC were measured in serum at the time of index presentation. Patients were followed for 90 days or until primary (development of RD) or secondary outcomes (development of ACLF or mortality). Multivariate analysis was performed to find whether CysC and IL‐6 can independently predict primary and secondary outcomes.ResultsA total of 124 patients were screened; 88 patients were included. On follow up, 22 (27.3%) developed RD, 11 (11/57, 19.3%) developed ACLF, and 21 (24%) died. The CysC predicted RD (odds ratio [OR] 7.97, 95% confidence interval [CI] 2.70–23.53, P = 0.001) and ACLF (OR 5.486, 95% CI 1.456–20.6, P = 0.012) development. IL‐6 was not an independent predictor of RD (P = 0.315), ACLF (P = 0.168), and mortality (P = 0.225).ConclusionSerum CysC can predict the development of RD and ACLF in patients of cirrhosis with AD.

From the Editor's Desk…

Bacterial infections are a well-known precipitating factor of organ failure/s and acute-on-chronic liver failure (ACLF) in patients with cirrhosis. In this post hoc analysis, Wong and coworkers aimed to evaluate regional differences in bacterial infection-related ACLF in patients with decompensated cirrhosis. They analysed data from 1,175 patients from across the world: 333 patients (28%) had ACLF at infection diagnosis, while 230 patients developed ACLF after infection diagnosis, resulting in an overall rate of bacterial infection induced-ACLF of 48%.

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

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. 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. 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. 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.

Prognostic Role of Bacterial and Fungal Infections in Patients With Liver Cirrhosis With and Without Acute-on-Chronic Liver Failure: A Prospective 2-Center Study.

BackgroundBacterial and fungal infections (BFIs) are frequent in patients with cirrhosis and often trigger acute-on-chronic liver failure (ACLF). This prospective observational study aims to describe the interactions between BFI and ACLF in terms of mortality and related risk factors.MethodsWe performed a 2-center prospective observational study enrolling hospitalized patients with cirrhosis admitted for acute decompensation. Data were recorded at admission and during hospitalization. Survival was recorded up to 1 year.ResultsAmong the 516 patients enrolled, 108 (21%) were infected at admission, while an additional 61 patients (12%) developed an infection during hospital stay. In the absence of ACLF, the 1-year mortality rate of patients with BFI did not differ from that of patients without BFI (33% vs 31%; P = .553). In contrast, those with ACLF triggered or complicated by BFI had a significantly higher mortality rate than those who remained free from BFI (75% vs 54%; P = .011). Competing risk analysis showed that the negative impact of ACLF-related BFI on long-term prognosis was independent from Model for End-stage Liver Disease (MELD) incorporating serum sodium concentration score, comorbidity, and basal C-reactive protein level. Finally, multivariable logistic regression showed that higher MELD score (P < .001), QuickSOFA score ≥2 points (P = .007), and secondary bloodstream (P = .022) and multidrug-resistant pathogen isolation (P = .030) were independently associated with ACLF in patients with BFI.ConclusionsThis large prospective study indicated that the adverse impact of BFI on long-term survival in decompensated cirrhosis is not universal but is limited to those patients who also develop ACLF. Both disease severity and microbiological factors predispose infected decompensated patients to ACLF.

Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure

Bacterial infections can trigger the development of organ failure(s) and acute-on-chronic liver failure (ACLF). Geographic variations in bacteriology and clinical practice could lead to worldwide differences in ACLF epidemiology, phenotypes and associated outcomes. Herein, we aimed to evaluate regional differences in bacterial infection-related ACLF in patients with cirrhosis admitted to hospital. This post hoc analysis included 1,175 patients with decompensated cirrhosis (with bacterial infection on admission or nosocomial infection) from 6 geographic regions worldwide. Clinical, laboratory and microbiological data were collected from the diagnosis of infection. Patients were followed-up for organ failure(s) and ACLF development according to the EASL-CLIF criteria from enrolment to discharge/death. A total of 333 patients (28%) had ACLF at diagnosis of infection, while 230 patients developed ACLF after diagnosis of infection, resulting in an overall rate of bacterial infection related-ACLF of 48%, with rates differing amongst different geographic regions (38% in Southern Europe vs. 75% in the Indian subcontinent). Bacterial infection related-ACLF more frequently developed in younger patients (55 ± 13 vs. 58 ± 14 years), males (73% vs. 62%), patients with alcohol-related cirrhosis (59% vs. 45%) and those with a higher baseline MELD score (25 ± 11 vs. 16 ± 5) (all p <0.001). Spontaneous bacterial peritonitis, pneumonia or infections caused by extensively drug resistant (XDR) bacteria were more frequently associated with ACLF development. More patients with ACLF had a positive quick sequential organ failure assessment score and septic shock, resulting in a lower infection resolution rate (all p <0.001). Bacterial infections, especially with XDR organisms, are associated with the highest risk of ACLF development, accounting for almost half of cases globally. Geographic differences result in variable epidemiology and clinical outcomes. Bacterial infections can trigger a sudden deterioration in an otherwise stable cirrhotic patient, a condition known as acute-on-chronic liver failure or ACLF. This study has found that the development of ACLF following bacterial infection occurs most commonly in the Indian subcontinent and less so in Southern Europe. The common infections that can trigger ACLF include infection of the abdominal fluid, known as spontaneous bacterial peritonitis, pneumonia and by bacteria that are resistant to multiple antibiotics. Patients who develop ACLF following a bacterial infection have high death rates and are frequently unable to clear the infection.

The course and survival of patients with liver cirrhosis and acute liver failure on the background of chronic

Aims. We comparative investigated the frequency, precipitating factors, lifetimes and predictive factors of survival in patients with liver cirrhosis (LC) and acute-on-chronic liver failure (ACLF). Material and methods. We collected data from 310 hospitalized patients with LC. Patients divided into groups: 1 — patients with compensation of LC; 2 — patients with decompensation of LC, but without organ failure (OF) and 3 — patients with ACLF. Diagnostic criteria for ACLF based on consensus recommendations of EASL. Survival was assessed according to the Kaplan-Meier method. Results. 48 patients with LC reported clinical signs of ACLF. 28-day mortality was in 4,8% of patients without ACLF and in 42,0% of patients with ACLF. 90-day mortality of patients with ACLF was 50% versus 11.6% in patients without ACLF. 6-month survival rate of patients with the development of acute decompensation with organ failure was only 33,3%. The lifetimes of patients with ACLF was only 136,65 ± 18,96 days. The predictive factors of survival of patients with LC and ACLF are: the number of organ failure, indicators of CLIF-SOFA and MELD, Child-Pugh score, degree of hepatic encephalopathy, leukocytosis, hyperbilirubinemia, hypercreatininemia and increased INR. Conclusion. The prevalence of ACLF in patients with LC is 15,5% and develops against a background of stable compensated or decompensated CP. The frequent trigger of ACLF is infection, which causes acute decompensation with the development of multiple organ failure and a high incidence of short-term mortality. The 28-day mortality rate in patients with ACLF was 8.7 times greater than the mortality rate in patients with decompensated LC without ACLF.