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.

scholarly journals Serum Clusterin: A Potential Marker for Assessing the Clinical Severity and Short-Term Prognosis of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Huimin Liu ◽  
Yuxin Li ◽  
Fangyuan Gao ◽  
Peipei Meng ◽  
Hao Yu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Liver Failure ◽  
Chronic Liver ◽  
Clinical Severity ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Potential Biomarker ◽  
B Virus ◽  
Normal Controls

Background. Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by acute deterioration of liver function and high short-term mortality. Clusterin, with biological functions similar to small heat shock proteins, can protect cells from apoptosis induced by various stressors. The aim of this study was to detect the level of serum clusterin in hepatitis B virus- (HBV-) related ACLF and to assess the predictive value of clusterin for the short-term prognosis of HBV-ACLF. Methods. We detected serum clusterin by ELISA in 108 HBV-ACLF patients, 63 HBV-non-ACLF patients, and 44 normal controls. Results. Serum clusterin was markedly lower in HBV-ACLF patients (median, 51.09 μg/mL) than in HBV-non-ACLF patients (median, 188.56 μg/mL) and normal controls (median, 213.45 μg/mL; all P < 0.05 ). Nonsurviving HBV-ACLF patients who died within 90 days had much lower clusterin levels than did surviving patients, especially those who died within 28 days (nonsurvival group vs. survival group: 39.82 ± 19.34 vs. 72.26 ± 43.52 , P < 0.001 ; survival time ≤ 28 vs. survival time > 28 : median 28.39 vs. 43.22, P = 0.013 ). The results showed that for identifying HBV-ACLF, the sensitivity of clusterin (93.7%) was similar to the sensitivities of the international normalized ratio (INR; 94.4%) and total bilirubin (TBIL; 94.8%), but its specificity (90.7%) was higher than that of prothrombin activity (PTA; 65.8%) and TBIL (69.8%) and was similar to INR (88.9%). As the concentration of clusterin increased, the mortality of HBV-ACLF patients decreased significantly from 59.3% to 7.0%. Clusterin had better ability for predicting the prognosis of HBV-ACLF patients than did the model for end-stage liver disease (MELD) score and the chronic liver failure consortium (CLIF-C) ACLF score (MELD vs. clusterin: P = 0.012 ; CLIF-C ACLF vs. clusterin: P = 0.031 ). Conclusion. Serum clusterin is a potential biomarker for HBV-ACLF which can be used to assess clinical severity and the short-term prognosis of patients with this disease and may help clinicians identify HBV-ACLF with greater specificity and improved prognostic accuracy than existing prognostic markers.

scholarly journals Copeptin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival

Critical Care ◽  
2017 ◽  
Vol 21 (1) ◽  
Author(s):  
Annarein J. C. Kerbert ◽  
◽  
Hein W. Verspaget ◽  
Àlex Amorós Navarro ◽  
Rajiv Jalan ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Failure ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Term Survival ◽  
Acute Decompensation ◽  
Short Term Survival

scholarly journals Value of Liver Regeneration in Predicting Short-Term Prognosis for Patients with Hepatitis B-Related Acute-on-Chronic Liver Failure

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Xiaoping Wang ◽  
Mengying Sun ◽  
Xianjun Yang ◽  
Liucun Gao ◽  
Min Weng ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Hepatitis B ◽  
Liver Failure ◽  
Scoring System ◽  
Chronic Liver ◽  
Hepatic Regeneration ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Term Survival ◽  
Hepatocyte Regeneration

Background and Aims. The value of hepatocyte regeneration in predicting the outcomes of hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) is not fully assessed. The present study was aimed at establishing a novel scoring system to predict patients’ outcomes within 3 months by applying serological indicators of hepatic regeneration and liver injury. Methods. Patients with chronic hepatitis B who had a rapid deterioration were investigated. Patients were observed for 90 days, and the endpoint of follow-up was death or liver transplantation. Serum parameters were estimated on the diagnosis of acute-on-chronic liver failure (ACLF). Cox proportional hazard regression was used to identify independent prognostic factors and create a novel prognostic scoring system, and a receiver operating characteristic (ROC) curve was used to analyze the performance of the model. Results. A total of 308 patients with HBV-ACLF were incorporated and divided into the training cohort (n=206) and testing cohort (n=102) randomly. Creatine (Cre), age, total bilirubin (TBil), alpha-fetoprotein (AFP), and international normalized ratio (INR) were found to be independent prognostic factors. According to the results of Cox regression analysis, a new prognostic model (we named it the TACIA score) was calculated. The areas under ROC (AUROC) for the new model were 0.861 and 0.763 in the training and testing cohorts, respectively, and patients with lower TACIA scores (<4.34) would survive longer (P<0.001). Conclusions. A pertinent prognostic scoring system for patients with HBV-ACLF was established in our study, and the novel model could predict patients’ short-term survival effectively.

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.

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