scholarly journals Identification and validation of circulating miRNAs as potential new biomarkers for severe liver disease in patients with leptospirosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257805
Author(s):  
Natthaya Chuaypen ◽  
Umaporn Limothai ◽  
Pattapon Kunadirek ◽  
Pornchai Kaewsapsak ◽  
Patipark Kueanjinda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Expression Profiles ◽  
Clinical Manifestations ◽  
High Sensitivity ◽  
Liver Involvement ◽  
Severe Liver ◽  
Serum Samples ◽  
Poor Overall Survival

Background Leptospirosis, a global zoonotic infectious disease, has various clinical manifestations ranging from mild self-limiting illness to life-threatening with multi-organ damage, including liver involvement. This study was aimed at identifying circulating microRNAs (miRNAs) as novel biomarkers for predicting severe liver involvement in patients with leptospirosis. Methods In a discovery set, 12 serum samples of patients with anicteric and icteric leptospirosis at initial clinical presentation were used for miRNA profiling by a NanoString nCounter miRNA assay. In a validated cohort, top candidate miRNAs were selected and further tested by qRT-PCR in serum samples of 81 and 16 individuals with anicteric and icteric leptospirosis, respectively. Results The discovery set identified 38 significantly differential expression miRNAs between the two groups. Among these, miR-601 and miR-630 were selected as the top two candidates significantly up-regulated expressed in the icteric group. The enriched KEGG pathway showed that these miRNAs were mainly involved in immune responses and inflammation. In the validated cohort, miR-601 and miR-630 levels were significantly higher in the icteric group compared with the anicteric group. Additionally, these two miRNAs displayed good predictors of subsequent acute liver failure with a high sensitivity of 100%. On regression analysis, elevated miR-601 and miR-630 expression were also predictive of multi-organ failures and poor overall survival. Conclusion Our data indicated that miRNA expression profiles were significantly differentiated between the icteric and anicteric groups. Serum miR-601 and miR-630 at presentation could potentially serve as promising biomarkers for predicting subsequent acute liver failure and overall survival in patients with leptospirosis.

Acute liver failure is associated with altered cerebral expression profiles of long non-coding RNAs

2017 ◽  
Vol 656 ◽  
pp. 58-64 ◽  
Author(s):  
Vinícius R. Silva ◽  
Rodrigo Secolin ◽  
Raghu Vemuganti ◽  
Iscia Lopes-Cendes ◽  
Alan S. Hazell
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Expression Profiles ◽  
Non Coding Rnas

scholarly journals Prognosis and treatment options in cases of acute liver failure caused by mushroom poisoning due to Amanita phalloides

2020 ◽  
Vol 7 (5) ◽  
pp. 875
Author(s):  
Anant Parasher ◽  
Akshay Aggrawal
Keyword(s):  
Liver Transplantation ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Orthotopic Liver Transplantation ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Amanita Phalloides ◽  
Penicillin G ◽  
Mushroom Poisoning ◽  
Mushroom Ingestion

Poisoning due to mushroom ingestion is a relatively rare but deadly cause of acute liver failure (ALF). Consumption of the poisonous mushroom Amanita phalloides, also known as ‘death cap’, is one of the most common causes of mushroom poisoning worldwide, being involved in the majority of human fatalities caused due to mushroom ingestion. A major portion of the liver damage due to Amanita phalloides is related to powerful toxins known as amanitins, which cause impairment in protein synthesis and subsequent cell necrosis by the inhibition of RNA polymerase II. Initially the presentation is that of an asymptomatic lag phase, followed by gastrointestinal symptoms and hepato-renal involvement. Amatoxin poisoning may progress into fulminant hepatic failure and eventually death if liver transplantation is not performed. It is based on a careful assessment of history of type and duration of mushroom ingestion, as well as the clinical manifestations. Diagnosis can be confirmed by laboratory tests measuring urinary amatoxin levels and identification of the mushroom. Although N-Acetyl Cysteine and Penicillin-G have proven to be effective therapeutic agents, Orthotopic Liver Transplantation (OLT) or Auxiliary Partial Orthotopic Liver Transplantation (APOLT) is the only treatment option for most of the cases carrying a poor prognosis.

Liver failure

2020 ◽  
pp. 3089-3100
Author(s):  
Jane Macnaughtan ◽  
Rajiv Jalan
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Hepatic Encephalopathy ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Organ Failure ◽  
Clinical Manifestations ◽  
Chronic Liver ◽  
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.

scholarly journals Identification of Hub Genes and Potential Molecular Mechanisms in Patients with HBV-Associated Acute Liver Failure

2020 ◽  
Vol 16 ◽  
pp. 117693432094390
Author(s):  
Ying Sun ◽  
Haitao Yu ◽  
Fangfang Li ◽  
Liqiang Lan ◽  
Daxin He ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Division ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Antigen Processing ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Killer Cell ◽  
Cyclin B1 ◽  
Hub Genes

Hepatitis B virus (HBV) infection is a major cause of acute liver failure (ALF) in China, and mortality rates are high among patients who do not receive a matched liver transplant. This study aimed to determine potential mechanisms involved in HBV-ALF pathogenesis. Gene expression profiles under access numbers GSE38941 and GSE14668 were downloaded from the Gene Expression Omnibus database, including cohorts of HBV-ALF liver tissue and normal samples. Differentially expressed genes (DEGs) with false discovery rates (FDR) <0.05 and |log2(fold change)| >1 as thresholds were screened using the Limma package. Gene modules associated with stable disease were mined using weighed gene co-expression network analysis (WGCNA). A co-expression network was constructed and DEGs were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A gene-based network was constructed to explore major factors associated with disease progression. We identified 2238 overlapping DEGs as crucial gene cohorts in ALF development. Based on a WGCNA algorithm, 10 modules (modules 1-10) were obtained that ranged from 75 to 1078 genes per module. Cyclin-dependent kinase 1 ( CDK1), cyclin B1 ( CCNB1), and cell-division cycle protein 20 ( CDC20) hub genes were screened using the co-expression network. Furthermore, 17 GO terms and 6 KEGG pathways were identified, such as cell division, immune response process, and antigen processing and presentation. Two overlapping signaling pathways that are crucial factors in HBV-ALF were screened using the Comprehensive Toxicogenomics Database (CTD). Several candidate genes including HLA-E, B2M, HLA-DPA1, and SYK were associated with HBV-ALF progression. Natural killer cell-mediated cytotoxicity and antigen presentation contributed to the progression of HBV-ALF. The HLA-E, B2M, HLA-DPA1, and SYK genes play critical roles in the pathogenesis and development of HBV-ALF.

scholarly journals Viral Surveillance in Serum Samples From Patients With Acute Liver Failure By Metagenomic Next-Generation Sequencing

2017 ◽  
Vol 65 (9) ◽  
pp. 1477-1485 ◽  
Author(s):  
Sneha Somasekar ◽  
Deanna Lee ◽  
Jody Rule ◽  
Samia N Naccache ◽  
Mars Stone ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Next Generation ◽  
Serum Samples ◽  
Viral Surveillance ◽  
Generation Sequencing

scholarly journals Demographics, aetiology and outcome of paediatric acute liver failure in Singapore

2021 ◽  
Author(s):  
FK Chiou ◽  
V Logarajah ◽  
CWW Ho ◽  
LSH Goh ◽  
SV Karthik ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Hepatitis A ◽  
Spontaneous Recovery ◽  
Acute Liver Injury ◽  
Single Centre ◽  
Poor Overall Survival ◽  
One Year ◽  
Viral Hepatitis A ◽  
Overall Mortality

Introduction: The aetiology of paediatric acute liver failure (PALF) varies widely according to age, and geographic and socioeconomic factors. This study aimed to examine the epidemiology, aetiology and outcome of PALF in Singapore at a single centre. Methods: A retrospective review was performed of patients aged 0–18 years who were diagnosed with PALF from 2007 to 2019. PALF was defined by: absence of chronic liver disease; biochemical evidence of acute liver injury; and coagulopathy, non-correctible by vitamin K, defined as prothrombin time (PT) ≥ 20 seconds or international normalised ratio (INR) ≥ 2.0 regardless of hepatic encephalopathy (HE) or PT ≥ 15 seconds or INR ≥ 1.5 in the presence of HE. Results: 34 patients were included. Median age at diagnosis was 10 months (range 7 days to 156 months). The top three causes of PALF were indeterminate (41.2%), metabolic (26.5%) and infectious (26.5%) aetiologies. A metabolic disorder was the most frequent aetiology in infants < 12 months (38.9%), whereas an indeterminate cause was the most common in children > 12 months (50%). No cases of viral hepatitis A or B presenting with PALF were detected. Overall spontaneous recovery rate (survival without liver transplantation [LT]) was 38.2%, and overall mortality rate was 47.1%. Six patients underwent living-donor LT, and the post-transplant survival at one year was 83.3%. Conclusion: The aetiologic spectrum of PALF in Singapore is similar to that in developed Western countries, with indeterminate aetiology accounting for the majority. PALF is associated with poor overall survival; hence, timely LT for suitable candidates is critical to improve survival outcomes.

scholarly journals Multiplex Qpcr Facilitates Identification Of Betaherpesviruses In Patients With Acute Liver Failure Of Unknown Etiology

2019 ◽  
Author(s):  
Jéssica Vasques Raposo ◽  
Arthur Daniel Rocha Alves ◽  
Alexandre Dos Santos Da Silva ◽  
Damião Carlos Dos Santos ◽  
Juliana Gil Melgaço ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Real Time ◽  
Liver Enzyme ◽  
Real Time Pcr ◽  
Dual Infection ◽  
Unknown Etiology ◽  
Hepatic Enzyme ◽  
Serum Samples ◽  
Multiplex Qpcr

Abstract Background: The etiology of acute liver failure (ALF) is often unknown and reported to be associated with herpesviruses in a number of cases. In this study, we examined for betaherpesviruses infections in patients with ALF of unknown etiology using a multiplex qPCR to Betaherpesviruses subfamily. Methods: Liver and serum samples from 27 patients with ALF of unknown etiology were analyzed with the aid of multiplex qPCR to identify betaherpesviruses. All positive samples were sequenced to confirm herpes infection and liver enzyme levels evaluated. Results: Betaherpesviruses infection was effectively detected using multiplex qPCR. Seven (26%), two (7%) and three (11%) cases were positive for HHV-6, HHV-7 and HCMV, respectively. Two cases of dual infection (HHV-7/HHV-6 and HHV-7/HCMV) were additionally identified. Interestingly, HHV-7 was only detected in the presence of other betaherpesviruses. Sequencing information confirmed betaherpesviruses infection. High hepatic enzyme levels and INR values>1.4 were determined in all betaherpesvirus-positive patients. Conclusions: Multiplex qPCR facilitated efficient quantification, indicating that differentiation between betaherpesviruses is possible with the sole use of real-time PCR. Liver and serum samples were positive for some betaherpesviruses, suggesting an association with ALF. Coinfection of HHV-7 with HHV-6 or HCMV was additionally detected, suggesting that the precursor betaherpesviruses infection can trigger HHV-7 infection. Based on these results, we propose that ALF patients should be screened for the presence of betaherpesviruses.

scholarly journals MULTIPLEX qPCR FACILITATES IDENTIFICATION OF BETAHERPESVIRUSES IN PATIENTS WITH ACUTE LIVER FAILURE OF UNKNOWN ETIOLOGY

2019 ◽  
Author(s):  
Jéssica Vasques Raposo ◽  
Arthur Daniel Rocha Alves ◽  
Alexandre Dos Santos Da Silva ◽  
Damião Carlos Dos Santos ◽  
Juliana Gil Melgaço ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Enzyme ◽  
Real Time Pcr ◽  
The Other ◽  
Unknown Etiology ◽  
Hepatic Enzyme ◽  
Serum Samples ◽  
Multiplex Qpcr ◽  
Dual Infections

Abstract Background: The etiology of acute liver failure (ALF) is often unknown and reported to be associated with herpesviruses in a number of cases. In this study, we examined for betaherpesviruses infections in patients with ALF of unknown etiology using a multiplex qPCR to Betaherpesviruses subfamily. Methods: Liver explant and serum samples from 27 patients with ALF of unknown etiology were analyzed with the aid of multiplex qPCR to identify betaherpesviruses. All positive samples were sequenced to confirm herpes infection and liver enzyme levels evaluated. Results: Betaherpesviruses infection was effectively detected using multiplex qPCR. Six (22%) HHV-6, one (3%) HCMV and two (7%) dual infections (one with HHV-7/HHV-6, and the other with HHV-7/ HCMV). Interestingly, HHV-7 was only detected in the presence of other betaherpesviruses. Sequencing information confirmed betaherpesviruses infection. High hepatic enzyme levels and INR values>1.5 were determined in all betaherpesvirus-positive patients. Conclusions: Multiplex qPCR facilitated efficient quantification, indicating that differentiation between betaherpesviruses is possible with the sole use of real-time PCR. Liver explant and serum samples were positive for some betaherpesviruses, and coinfection of HHV-7 with HHV-6 and HCMV was additionally detected. Based on these results, we propose that ALF patients should be screened for the presence of betaherpesviruses.

scholarly journals Proteomics Indicates Lactate Dehydrogenase is Prognostic in Acetaminophen-induced Acute Liver Failure Patients and Reveals a Role for LKB1-AMPK Signaling

2021 ◽  
Author(s):  
Joel H. Vazquez ◽  
Stefanie Kennon-McGill ◽  
Stephanie D. Byrum ◽  
Samuel G. Mackintosh ◽  
Hartmut Jaeschke ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Operating Characteristic ◽  
Proteomics Data ◽  
Serum Samples ◽  
Ampk Signaling ◽  
Promising Therapeutic Target ◽  
Measured Activity ◽  
End Stage ◽  
Time Point

ABSTRACTBetter biomarkers to predict death early in acute liver failure (ALF) are needed. To that end, we obtained early (study day 1) and later (day 3) serum samples from transplant-free survivors (n=28) and non-survivors (n=30) of acetaminophen (APAP)-induced ALF from the NIH-sponsored Acute Liver Failure Study Group, and from control volunteers (n=10). To identify proteins that increase early in serum during ALF, we selected individuals from this cohort for whom ALT was lower on day 1 than day 3, indicating a time point before the peak of injury (n=10/group). We then performed untargeted proteomics on their day 1 samples. Out of 1,682 quantifiable proteins, 79 were elevated ≥4-fold in ALF patients vs. controls and 23 of those were further elevated ≥4-fold in non-survivors vs. survivors, indicating potential to predict death. Interestingly, the biomarker with best performance was LDH. To confirm the prognostic potential of LDH, we measured activity in all day 1 and 3 samples from all 58 ALF patients. LDH was elevated in the non-survivors vs. survivors on both days. In addition, receiver operating characteristic (ROC) curve analyses revealed that LDH alone performed similarly to the model for end-stage liver disease (MELD), while a combination of MELD and LDH outperformed either alone. Finally, Upstream Analysis of our proteomics data indicated activation of LKB1-AMPK signaling in liver regeneration after APAP overdose and we confirmed that in mice. Overall, we conclude LDH can predict death in APAP-induced ALF and that LKB1-AMPK signaling may be a promising therapeutic target to improve survival.

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