P0496 : Impaired neutrophil function contributes to liver injury and positively correlates with clinical severity indices in acute-on-chronic liver failure

Liver failure occurs when loss of hepatic parenchymal function exceeds the capacity of hepatocytes to regenerate or repair liver injury. Acute liver failure is characterized by jaundice and prolongation of the prothrombin time in the context of recent acute liver injury, with hepatic encephalopathy occurring within 8 weeks of the first onset of liver disease. Acute-on-chronic liver failure is characterized by hepatic and/or extrahepatic organ failure in patients with cirrhosis associated with an identified or unidentified precipitating event. The commonest causes of acute liver failure are acute viral hepatitis and drugs. Acute-on-chronic liver failure is most commonly precipitated by infection, alcohol abuse, and superimposed viral infection. The main clinical manifestations are hepatic encephalopathy, coagulopathy, jaundice, renal dysfunction, and haemodynamic instability. Infection and systemic inflammation contribute to pathogenesis and critically contribute to prognosis. Specific therapy for the underlying liver disease is administered when available, but this is not possible for most causes of liver failure. Treatment is predominantly supportive, with particular emphasis on (1) correction or removal of precipitating factors; (2) if encephalopathy is present, using phosphate enemata, nonhydrolysed disaccharide laxatives, and/or rifaximin; (3) early detection and prompt treatment of complications such as hypoglycaemia, hypokalaemia, cerebral oedema, infection, and bleeding. The onset of organ failure should prompt discussion with a liver transplantation centre. The mortality of acute liver failure (without liver transplantation) is about 40%. Patients with acute liver failure who do not develop encephalopathy can be expected to recover completely. Those who recover from an episode of acute-on-chronic liver failure should be considered for liver transplantation because otherwise their subsequent mortality remains high.

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

Disease Markers ◽

10.1155/2020/8814841 ◽

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.

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Cefprozil as a Cause of Drug-Induced Liver Injury Leading to Acute-on-Chronic Liver Failure

The American Journal of Gastroenterology ◽

10.14309/00000434-201810001-02424 ◽

2018 ◽

Vol 113 (Supplement) ◽

pp. S1350-S1351

Author(s):

Majd Khasawneh ◽

Zaid Imam ◽

Fadi Odish ◽

Mohamad Rasm Al Sibae

Keyword(s):

Liver Injury ◽

Liver Failure ◽

Chronic Liver ◽

Chronic Liver Failure ◽

Drug Induced ◽

Drug Induced Liver Injury

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Hepatoprotective Effect of Yiqijianpi Formula (YQJPF) on Liver Failure Through Modulation of Hypoxic and Apoptosis Pathways

10.21203/rs.3.rs-122878/v1 ◽

2020 ◽

Author(s):

Li Tang ◽

Feixia Wang ◽

Lingyan Xiao ◽

Min Shen ◽

Siwei Xia ◽

...

Keyword(s):

Liver Injury ◽

Liver Failure ◽

Signaling Pathways ◽

Tunel Assay ◽

Chronic Liver ◽

Active Components ◽

Chronic Liver Failure ◽

Apoptosis Pathway ◽

L02 Cells

Abstract BackgroundAcute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis, which seriously endanger human life and health. Yiqijianpi decoction (YQJPF) is a Traditional Chinese Medicine (TCM) formula that has been widely used in the treatment of liver failure with significant effect. The purpose of this study was to investigate the active components and mechanism to ameliorate acute on chronic liver failure(ACLF).MethodsLPS combined with D-Gal was used to establish the rat model of ACLF, pathological examination was detected by H&E staining, liver function test was assayed by ELISA. LPS was used to induce hepatocytes injury in vitro. Cell proliferation assay, TUNEL assay were used in human hepatic L02 cells. The active components and putative targets of YQJPF were predicted by network pharmacology approach and GEO analysis. Functional and pathway enrichment analysis were presented by using String, Cytoscape and Metascape. Further, experimental validation was done to verify the effect of YQJPF on PI3K/AKT-HIF-1ɑ and apoptosis-related signaling pathways by using Immunohistochemistry and Western blotting.ResultsAfter being treated with YQJPF, the rat liver injury and fibrosis were alleviated, and Cell Counting Kit-8 assay, TUNEL assay indicated YQJPF also inhibited the apoptosis in hepatic L02 cells. Through network pharmacologic analysis, 135 active components in YQJPF decoction, 573 known therapeutic targets and 2940 liver failure-related human genes were identified. 163 gene symbols maybe the key for liver failure treatment by YQJPF decoction. VEGF-A was hub gene in PPI network. The KEGG pathway and GO enrichment analyses indicated that the PI3K/AKT, HIF-1 signaling pathways were the prominently enriched signaling pathways. In vivo, YQJPF upregulated the expression of PI3K/AKT-HIF1-ɑ and VEGF-A. Moreover apoptosis pathway were verified by up-regulating Bcl2 expression and down-regulating Bax expression in vivo and in vitro.ConclusionYQJPF is beneficial for alleviating liver failure, may regulate hypoxic liver injury through PI3K/AKT-HIF1α dependent apoptosis pathway.

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Acute liver injury, acute liver failure and acute on chronic liver failure: A clinical spectrum of poisoning due to Gyromitra esculenta

Annals of Hepatology ◽

10.1016/j.aohep.2018.11.009 ◽

2019 ◽

Vol 18 (3) ◽

pp. 514-516

Author(s):

Magdalena Arłukowicz-Grabowska ◽

Maciej Wójcicki ◽

Joanna Raszeja-Wyszomirska ◽

Monika Szydłowska-Jakimiuk ◽

Bernard Piotuch ◽

...

Keyword(s):

Liver Injury ◽

Liver Failure ◽

Acute Liver Failure ◽

Acute Liver Injury ◽

Chronic Liver ◽

Clinical Spectrum ◽

Chronic Liver Failure

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Evaluation of prognostic value of neutrophil-to-lymphocyte ratio in patients with acute-on-chronic liver failure or severe liver injury from chronic HBV infection

European Journal of Gastroenterology & Hepatology ◽

10.1097/meg.0000000000002207 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Jian Sun ◽

Hongying Guo ◽

Xueping Yu ◽

Jingwen Chen ◽

Haoxiang Zhu ◽

...

Keyword(s):

Liver Injury ◽

Liver Failure ◽

Prognostic Value ◽

Chronic Liver ◽

Hbv Infection ◽

Chronic Liver Failure ◽

Severe Liver ◽

Chronic Hbv Infection ◽

Lymphocyte Ratio ◽

Chronic Hbv

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

10.21203/rs.3.rs-408638/v1 ◽

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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