Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis

Gut ◽  
2021 ◽  
pp. gutjnl-2020-322161
Author(s):  
Gabriel Mezzano ◽  
Adria Juanola ◽  
Andres Cardenas ◽  
Esteban Mezey ◽  
James P Hamilton ◽  
...  
Keyword(s):  
South America ◽  
Liver Failure ◽  
South Asia ◽  
Chronic Liver ◽  
Sensitivity Analyses ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Global Prevalence ◽  
Statistical Heterogeneity ◽  
Organ Failures

Background and aimsAcute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations of ACLF across the world in terms of prevalence, mortality, aetiology of chronic liver disease (CLD), triggers and organ failures.MethodsWe searched EMBASE and PubMed from 3/1/2013 to 7/3/2020 using the ACLF-EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) criteria. Two investigators independently conducted the abstract selection/abstraction of the aetiology of CLD, triggers, organ failures and prevalence/mortality by presence/grade of ACLF. We grouped countries into Europe, East/South Asia and North/South America. We calculated the pooled proportions, evaluated the methodological quality using the Newcastle-Ottawa Scale and statistical heterogeneity, and performed sensitivity analyses.ResultsWe identified 2369 studies; 30 cohort studies met our inclusion criteria (43 206 patients with ACLF and 140 835 without ACLF). The global prevalence of ACLF among patients admitted with decompensated cirrhosis was 35% (95% CI 33% to 38%), highest in South Asia at 65%. The global 90-day mortality was 58% (95% CI 51% to 64%), highest in South America at 73%. Alcohol was the most frequently reported aetiology of underlying CLD (45%, 95% CI 41 to 50). Infection was the most frequent trigger (35%) and kidney dysfunction the most common organ failure (49%). Sensitivity analyses showed regional estimates grossly unchanged for high-quality studies. Type of design, country health index, underlying CLD and triggers explained the variation in estimates.ConclusionsThe global prevalence and mortality of ACLF are high. Region-specific variations could be explained by the type of triggers/aetiology of CLD or grade. Health systems will need to tailor early recognition and treatment of ACLF based on region-specific data.

The Prediction of in‐Hospital Mortality in Decompensated Cirrhosis with Acute‐on‐Chronic Liver Failure

2021 ◽  
Author(s):  
Florence Wong ◽  
K Rajender Reddy ◽  
Puneeta Tandon ◽  
Jennifer C Lai ◽  
Nishita Jagarlamudi ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Liver Failure ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure

scholarly journals Inhibition of glutamine synthetase in monocytes from patients with acute-on-chronic liver failure resuscitates their antibacterial and inflammatory capacity

Gut ◽  
2018 ◽  
Vol 68 (10) ◽  
pp. 1872-1883 ◽  
Author(s):  
Hannelie Korf ◽  
Johannie du Plessis ◽  
Jos van Pelt ◽  
Sofie De Groote ◽  
David Cassiman ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Liver Failure ◽  
Bacterial Infections ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Phenotypic Characterisation ◽  
Severity Scores ◽  
Aclf Patient

ObjectiveAcute-on-chronic liver failure (ACLF) is associated with dysfunctional circulating monocytes whereby patients become highly susceptible to bacterial infections. Here, we identify the pathways underlying monocyte dysfunction in ACLF and we investigate whether metabolic rewiring reinstates their phagocytic and inflammatory capacity.DesignFollowing phenotypic characterisation, we performed RNA sequencing on CD14+CD16− monocytes from patients with ACLF and decompensated alcoholic cirrhosis. Additionally, an in vitro model mimicking ACLF patient-derived features was implemented to investigate the efficacy of metabolic regulators on monocyte function.ResultsMonocytes from patients with ACLF featured elevated frequencies of interleukin (IL)-10-producing cells, reduced human leucocyte antigen DR isotype (HLA-DR) expression and impaired phagocytic and oxidative burst capacity. Transcriptional profiling of isolated CD14+CD16− monocytes in ACLF revealed upregulation of an array of immunosuppressive parameters and compromised antibacterial and antigen presentation machinery. In contrast, monocytes in decompensated cirrhosis showed intact capacity to respond to inflammatory triggers. Culturing healthy monocytes in ACLF plasma mimicked the immunosuppressive characteristics observed in patients, inducing a blunted phagocytic response and metabolic program associated with a tolerant state. Metabolic rewiring of the cells using a pharmacological inhibitor of glutamine synthetase, partially restored the phagocytic and inflammatory capacity of in vitro generated- as well as ACLF patient-derived monocytes. Highlighting its biological relevance, the glutamine synthetase/glutaminase ratio of ACLF patient-derived monocytes positively correlated with disease severity scores.ConclusionIn ACLF, monocytes feature a distinct transcriptional profile, polarised towards an immunotolerant state and altered metabolism. We demonstrated that metabolic rewiring of ACLF monocytes partially revives their function, opening up new options for therapeutic targeting in these patients.

scholarly journals Septic shock after liver transplantation successfully treated with endotoxin and cytokine adsorption continuous renal replacement therapy: a case report and literature review

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052094043
Author(s):  
Yining Li ◽  
Linshan Zhou ◽  
Lingzhi Yang ◽  
Fang Yuan
Keyword(s):  
Septic Shock ◽  
Liver Transplantation ◽  
Renal Replacement Therapy ◽  
Liver Failure ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Chronic Liver ◽  
Inflammatory Factors ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure

Endotoxins and cytokines play an important role in multiple organ failure pathogenesis in patients with severe Gram-negative bacterial infection. We present a clinical case where an oXiris hemofilter was used for continuous renal replacement therapy (CRRT) treatment in a patient with septic shock after liver transplantation. A 35-year-old man with a 20-year history of hepatitis B presented with jaundice, loss of appetite, and decreased urine output. He was diagnosed with decompensated cirrhosis with acute-on-chronic liver failure, and liver transplantation was indicated. The day after surgery, he developed hyperthermia, hypotension, anuria, and a progressive increase in blood inflammatory markers and creatinine. Combined with the donor source and blood culture results, septic shock after transplantation was considered. The patient was immediately treated with endotoxin and cytokine adsorption CRRT (oXiris hemofilter) with tigecycline, caspofungin, and ganciclovir as anti-infectives. After 48 hours on CRRT, his blood pressure gradually stabilized, the CLIF Consortium Acute-on-Chronic Liver Failure score decreased from 63 to 43. Procalcitonin, endotoxin, and the inflammatory factors interleukin (IL)-6 and IL-10 also decreased gradually. The patient’s liver and kidney functions were completely restored. Our experience suggests that oXiris CRRT combined with antibacterial therapy is an effective treatment for septic shock after liver transplantation.

Acute-on-chronic liver failure: to admit to intensive care or not?

2020 ◽  
Vol 81 (9) ◽  
pp. 1-6
Author(s):  
Asif Arshad ◽  
Lylah Irshad ◽  
Theodore Nabavi ◽  
Tony Whitehouse
Keyword(s):  
Liver Failure ◽  
Organ Failure ◽  
Gastrointestinal Haemorrhage ◽  
Chronic Liver ◽  
Organ Support ◽  
Chronic Liver Failure ◽  
Short Term Mortality ◽  
Organ Failures ◽  
Clinical Scoring ◽  
Excessive Alcohol

Acute-on-chronic liver failure is used to describe an acute decline in liver function in a patient with existing liver disease combined with other organ failure. Acute-on-chronic liver failure is associated with high short-term mortality, and the greater the number and severity of organ failures, the higher the mortality. The most commonly identified precipitants of acute-on-chronic liver failure include bacterial infection, gastrointestinal haemorrhage, viral hepatitis and recent excessive alcohol intake. Since some of these aetiologies are treatable, organ failure may return to pre-decompensation levels in up to 55% of patients. As a result, a trial of critical care treatment may be appropriate for many of these patients. Clinical scoring tools may help clinicians recognise futility, allowing timely withdrawal of organ support and shifting the focus of care toward palliation.

Coagulation Failure in Patients With Acute-on-Chronic Liver Failure and Decompensated Cirrhosis: Beyond the International Normalized Ratio

Hepatology ◽  
2018 ◽  
Vol 68 (6) ◽  
pp. 2325-2337 ◽  
Author(s):  
Annabel Blasi ◽  
Andrea Calvo ◽  
Verónica Prado ◽  
Enric Reverter ◽  
Juan Carlos Reverter ◽  
...  
Keyword(s):  
Liver Failure ◽  
International Normalized Ratio ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure
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