scholarly journals Dynamic Prognostication in Transplant Candidates with Acute-on-Chronic Liver Failure

2020 ◽  
Vol 10 (4) ◽  
pp. 230
Author(s):  
Cheng-Yueh Lu ◽  
Chi-Ling Chen ◽  
Cheng-Maw Ho ◽  
Chih-Yang Hsiao ◽  
Yao-Ming Wu ◽  
...  
Keyword(s):  
Liver Failure ◽  
Liver Transplant ◽  
Protective Factor ◽  
Multivariable Analysis ◽  
Chronic Liver ◽  
Clinical Markers ◽  
Chronic Liver Failure ◽  
Live Donors ◽  
Severity Scores ◽  
Tertiary Center

We aimed to extensively investigate clinical markers that are sufficiently dynamic for prognosis of acute-on-chronic liver failure (ACLF). Defined by the Asian Pacific Association for the Study of the Liver (APASL) criteria, patients with ACLF on the liver transplant waitlist in a tertiary center were retrospectively reviewed. Laboratory results and severity scores at three time points (days 1, 7, and 14 after admission) were analyzed. From 2015 to 2019, 64 patients with ACLF were enrolled, of which 24 received a liver transplant from 22 live donors. The hospital mortality rate was 31% (8% for transplant; 45% for nontransplant groups), and the 3-month survival was crucial for determining long-term outcomes. The number of significant variables for mortality, and, specifically, the hazards of international normalized ratio of prothrombin time (INR) and APASL ACLF Research Consortium (AARC) score were increased within two weeks. In multivariable analysis, INR and AARC score (D-14) were associated with poor survival and liver transplant was a protective factor in all patients, while AARC score (D-14) was significant in the nontransplant group. AARC score at day 14 is an independent risk factor for mortality in ACLF. Liver transplant from live donors reversed poor outcomes in patients with ACLF in a timely manner.

Systematic review with meta-analysis: liver transplant provides survival benefit in patients with acute on chronic liver failure

2020 ◽  
Vol 52 (2) ◽  
pp. 222-232 ◽  
Author(s):  
Mohamed A. Abdallah ◽  
Muhammad Waleed ◽  
Matthew G. Bell ◽  
Morgan Nelson ◽  
Robert Wong ◽  
...  
Keyword(s):  
Systematic Review ◽  
Liver Failure ◽  
Liver Transplant ◽  
Survival Benefit ◽  
Meta Analysis ◽  
Chronic Liver ◽  
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.

Iso and Xeno Fetal Liver Transplant Therapy for the Treatment of Acute and Chronic Liver Failure in Rats

1994 ◽  
Vol 3 (1_suppl) ◽  
pp. 29-30 ◽  
Author(s):  
Masao Hagihara ◽  
Tatsuo Shimura ◽  
Kentarou∕ Takebe ◽  
Munkhbatø Batømunkh ◽  
Kimiyoshi Tsuji
Keyword(s):  
Liver Failure ◽  
Liver Transplant ◽  
Fetal Liver ◽  
Chronic Liver ◽  
Chronic Liver Failure

scholarly journals Longitudinal Renal Function in Liver Transplant Recipients With Acute-on-Chronic Liver Failure

2020 ◽  
Vol 11 (6) ◽  
pp. e00185
Author(s):  
Masahiko Yazawa ◽  
Benedict Maliakkal ◽  
Satheesh Nair ◽  
Pradeep S. B. Podila ◽  
Uchenna A. Agbim ◽  
...  
Keyword(s):  
Renal Function ◽  
Liver Failure ◽  
Liver Transplant ◽  
Chronic Liver ◽  
Transplant Recipients ◽  
Chronic Liver Failure ◽  
Liver Transplant Recipients

scholarly journals pCLIF-SOFA is a reliable outcome prognostication score of critically ill children with cirrhosis: an ESPNIC multicentre study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline Claude ◽  
◽  
Akash Deep ◽  
Martin Kneyber ◽  
Salman Siddiqui ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Failure ◽  
Critically Ill ◽  
Sofa Score ◽  
Multivariable Analysis ◽  
Scoring Systems ◽  
Chronic Liver ◽  
Critically Ill Children ◽  
Composite Outcome ◽  
Chronic Liver Failure

Abstract Background and aims Data on outcome of critically ill children with cirrhosis are scarce. We aimed to evaluate the prognostic accuracy of sequential organs scoring systems in children with cirrhosis admitted to Paediatric Intensive Care Units (PICU). Methods We performed a multicentre retrospective analysis of children with cirrhosis admitted into four European PICUs between 2011 and 2016. Investigators were members of the ESPNIC liver failure and support working group. Paediatric End-Stage Liver Disease (PELD) and paediatric chronic liver failure sequential organ failure assessment score (pCLIF-SOFA) diagnostic accuracy for 28- and 60-day liver transplantation, 28-day mortality and 60-day composite outcome (ie. death or liver transplantation) were tested. Results One-hundred-and-thirty children were included. The main causes for PICU admission were acute-on-chronic liver failure (ACLF), gastrointestinal bleeding and sepsis. Twenty-nine percent died and 22.3% were transplanted by day-60 after PICU admission. On multivariable analysis, pCLIF-SOFA was the only predictor of mortality at day-28 and of composite outcome. Both pCLIF-SOFA and ACLF were independently associated with emergent liver transplantation. The pCLIF-SOFA score higher than 9 well predicted a 28-day mortality with a sensitivity of 87.8% and a specificity of 77.3%. A pCLIF-SOFA score higher than 7 was independently associated with liver transplantation on day-60. Stage 3 AKI assessed with KDIGO classification was significantly associated with 28-day mortality. Conclusions Half of critically ill cirrhotic children admitted to PICU either died or were transplanted within the initial 28-day period. On admission pCLIF-SOFA score accurately identify patients transplanted at day-28 and day-60 to those alive without LT and is associated with 28-day mortality and composite outcome at day-60.

scholarly journals Derivation and Validation of a Nomogram for Predicting 90-Day Survival in Patients With HBV-Related Acute-on-Chronic Liver Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Jun-feng Chen ◽  
Wei-zhen Weng ◽  
Miao Huang ◽  
Xiao-hua Peng ◽  
Jian-rong He ◽  
...  
Keyword(s):  
Liver Failure ◽  
Calibration Curve ◽  
Retrospective Cohort ◽  
Predictive Accuracy ◽  
Multivariable Analysis ◽  
Scoring Systems ◽  
Chronic Liver ◽  
Prognostic Models ◽  
Chronic Liver Failure ◽  
Derivation Cohort

Background: Conventional prognostic models do not fully reflect the severity of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). This study aimed to establish an effective and convenient nomogram for patients with HBV-related ACLF.Methods: A nomogram was developed based on a retrospective cohort of 1,353 patients treated at the Third Affiliated Hospital of Sun Yat-sen University from January 2010 to June 2016. The predictive accuracy and discriminatory ability of the nomogram were determined by a concordance index (C-index) and calibration curve, and were compared with current scoring systems. The results were validated using an independent retrospective cohort of 669 patients consecutively treated at the same institution from July 2016 to March 2018. This study is registered at ClinicalTrials.gov (NCT03992898).Results: Multivariable analysis of the derivation cohort found that independent predictors of 90-day survival were age, white blood cell (WBC) count, hemoglobin (Hb), aspartate aminotransferase (AST), total bilirubin (TBil), international normalized ratio, serum creatinine (Cr), alpha fetoprotein (AFP), serum sodium (Na), hepatic encephalopathy (HE), pre-existing chronic liver disease(PreLD), and HBV DNA load. All factors were included in the nomogram. The nomogram calibration curve for the probability of 90-day survival indicated that nomogram-based predictions were in good agreement with actual observations. The C-index of the nomogram was 0.790, which was statistically significantly greater than those for the current scoring systems in the derivation cohort (P < 0.001). The results were confirmed in the validation cohort.Conclusions: The proposed nomogram is more accurate in predicting the 90-day survival of patients with HBV-related ACLF than current commonly used methods.

Fecal Microbiota Transplantation in Alcohol-Associated Acute on Chronic Liver Failure: An Open-label Clinical Trial

2021 ◽  
Author(s):  
Anima Sharma ◽  
Akash Roy ◽  
Madhumita Premkumar ◽  
Ajay Duseja ◽  
Sunil Taneja ◽  
...  
Keyword(s):  
Liver Failure ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Chronic Liver ◽  
Clinical Severity ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Open Label ◽  
Term Survival ◽  
Severity Scores

Abstract Background: Severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Alteration of gut microbiota is a crucial component implicated in its pathogenesis, whose modulation has been suggested as a potential therapeutic tool. We evaluated the safety of fecal microbiota transplantation (FMT) and its efficacy in improving short-term survival and clinical severity scores in patients with SAH-ACLF.Methods: Thirty-three patients [13 in the FMT arm;20 in the standard of care arm (SOC] with SAH-ACLF were included in this open-label study. A single FMT session was administered as a freshly prepared stool suspension from pre-identified healthy family member stool donors through a nasojejunal tube. Patients were followed up on days seven, twenty-eight, and ninety. Results: Survival at twenty-eight and ninety days was significantly better in the FMT arm (100% versus 60%, P=0.01; 53.84% versus 25%, P=0.02). Hepatic encephalopathy resolved in 100% versus 57.14% (FMT versus SOC, P=0.11) patients, while ascites resolved in 100% versus 40% survivors (P=0.04). Major adverse event rates, including spontaneous bacterial peritonitis and gastrointestinal bleeding, were similar in both groups (P=0.77; P=0.70). Median IL1beta decreased by21.39% (IQR -73.67-7.63) in the FMT group, whereas it increased in the SOC by 27.44% (IQR -0.88-128.11) (P=0.01). Percentage changes in bilirubin and ALT between baseline and day seven emerged as predictors of ninety-day mortality.Conclusion: FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH-ACLF.

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