ABSTRACT
The incidence of drug-induced liver injury (DILI) has risen considerably in recent years. Drug-induced liver failure tends to have severe conditions, limited therapeutic strategy, and a high mortality rate and should thus be taken seriously by clinicians. N-acetyl-p-aminophenol is the most common cause of acute liver failure (ALF) in Western countries; for ALF associated with idiosyncratic DILI (iDILI), since there is little in-deep understanding of host susceptibility and pathogenesis, it is difficult to identify ALF caused by iDILI in the early stage, and due to a low rate of spontaneous recovery and poor prognosis, it has become a major indication for emergency liver transplantation in many countries. A comprehensive understanding of the clinical features and prognostic prediction of drug-induced liver failure and the search for new reliable diagnostic methods and effective treatment strategies are of vital importance in reducing the disease burden of drug-induced liver failure.
ABSTRACT
The coronavirus disease 2019 (COVID-19) has caused global public health and economic crises. Thus, new therapeutic strategies and effective vaccines are urgently needed to cope with this severe pandemic. The development of a broadly neutralizing antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the attractive treatment strategies for COVID-19. Currently, the receptor-binding domain (RBD) of the spike (S) protein is the main target of neutralizing antibodies when SARS-CoV-2 enters human cells through an interaction between the S protein and the angiotensin-converting enzyme 2 expressed on various human cells. A single monoclonal antibody (mAb) treatment is prone to selective pressure due to increased possibility of targeted epitope mutation, leading to viral escape. In addition, the antibody-dependent enhancement effect is a potential risk of enhancing the viral infection. These risks can be reduced using multiple mAbs that target nonoverlapping epitopes. Thus, a cocktail therapy combining two or more antibodies that recognize different regions of the viral surface may be the most effective therapeutic strategy.
Subject(s)
Humans , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , SARS-CoV-2 , Spike Glycoprotein, CoronavirusABSTRACT
The 2019 European Association for the Study of the Liver (EASL) Clinical Practice Guidelines (hereinafter referred to as the EASL Guidelines) extracted the required evidence from detailed research materials, and rigorously graded and condensed the varying strengths of evidence into 32 recommendations and 14 statements (recommendations and reminders) for drug-induced Liver Injury (DILI). This guideline has important reference values for helping clinicians to further improve their understanding of DILI and the level of clinical diagnosis, treatment and prevention; however, there are still several issues worthy of further discussion.
ABSTRACT
Objective To measure the expression of circulating microRNA (miRNA)in patients with hepatitis B virus (HBV)-related liver failure and its relationship with disease prognosis.Methods The miRNA expressions in serum of 5 patients with HBV-related liver failure and 5 healthy control subjects were compared using Exiqon miRCURY LNATM miRNA microarray.The sera from 20 patients with chronic hepatitis B (CHB),20 patients hepatitis B related cirrhosis,50 patients with HBV-related liver failure and 40 healthy persons in Ruijin Hospital were collected.The relative expression of miRNA-595 was measured using quantitative real-time polymerase chain reaction (PCR).The relative expressions of miRNAs among groups were analyzed using student t test,the correlations were analyzed by Pearson and Spearman correlation.Results Microarray informed that 92 miRNAs changed significantly in patients with HBV-related liver failure,and miRNA-595 increased most significantly.The results of real-time PCR showed that the relative expressions of miRNA-595 ,miRNA-300 and miRNA-122 were 6.03 (t=3.134, P =0.003),3.12 (t=7.221 ,P <0.01)and 2.77 (t=2.671 ,P =0.021),which were higher compared to those in healthy control group.In the analysis of the relationship between miRNA-595 expression and disease prognosis in patients with HBV-related liver failure,the relative expressions of miRNA-595 in patients with CHB,hepatitis B related cirrhosis and HBV-related liver failure were 2.26 (t =3.780,P =0.001),3.32 (t = 6.111 ,P < 0.01)and 6.03 (t = 3.134,P = 0.003),respectively,which were all increased compared to that of the healthy control.The relative expression of miRNA-595 of patients with HBV-related liver failure was 2.66 times (t=2.450,P =0.043)higher than that of patients with CHB. When dividing patients according to prothrombin activity,miRNA-595 increased significantly in patients with early stage liver failure.When dividing patients according to model of end-stage liver disease (MELD) score,MELD score was positive correlated with the expression of miRNA-595 when MELD score was under 30 (r=0.673,P =0.004).The expression of serum miRNA-595 in survival group (11 .08,n=23) was higher than that in non-survival group (3.67,n = 27,t =4.309,P =0.041).Conclusions The expressions of miRNA595 ,miRNA-300 and miRNA-122 are all increased in patients with HBV-related liver failure,especially the expression of circulating miRNA-595 at early stage of the disease.The miRNA-595 may be used as a new serum biomarker for monitoring the severity of disease.
ABSTRACT
Objective To explore the expressions of circulating microRNAs (miRNAs) in acute liver failure mice induced by D-galactosamine (GalN)/lipopolysaccharides (LPS) and the correlation with miRNAs in the liver.Methods Forty clean grade Balb/C mice,with 32 in the model group and 8 in the control group were enrolled in the study.Liver failure was induced by intraperitoneally injection of D-GalN and LPS in mice of the model group,while mice of the control group were intraperitoneally injected with 1 mL 0.9 ％ sodium chloride solution.Serum and liver samples were collected at 0,3,5,7 hours following administration,and eight mice should be supplied to each sample,and changes of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and histopathology of the liver were observed.miRNA from both the serum and the liver was extracted,miRNA expression profile in the liver at 0,5,7 hours by locked nucleic acid (LNA)-miRNA microarray was analyzed and miRNA by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) was detected.Means of the two groups were compared using one-way ANOVA and correlation analyses were performed using Pearson and Spearman correlation.Results Expression of miRNAs in the liver tissue changed significantly over time with the occurrence of acute liver failure in the mice.Twenty-one miRNAs were up-regulated and 27 were down-regulated,among which miRNA-122 and miRNA-1187 were down-regulated while miRNA-146a and miRNA-155 were up-regulated.It was confirmed by the PCR assay that the expression of miRNA-122 and miRNA-1187 in the liver gradually decreased,while those in the serum were up-regulated over time.However,the expressions of inflammation associated miRNA-155 and miRNA-146a were up-regulated both in the serum and the liver after administration.The expressions of miRNA-122 and miRNA-1187 were negatively correlated between serum and liver (r=-0.477,P=0.0089,r=-0.420,P=0.231),while the expressions of miRNA-155 in serum and liver were positively correlated (r=0.678,P=0.0001).Moreover,the expressions of miRNA-122 (r=0.571,0.554) and miRNA-1187 (r=0.471,0.542) were also positively correlated with serum levels of ALT and AST (all P＜0.05).Liver and serum levels of miRNA-122 and miRNA-1187 changed significantly at 5 hours after administration,which preceded the changes of ALT/AST.Conclusions The expressions of miRNA-122 and miRNA-1187 in serum are well inversely correlated with the corresponding expressions in liver tissues during acute liver failure in mice.The changes of miRNA-122 and miRNA-1187 in the serum precede those of ALT/AST.These data suggest that serum miRNA-122 and miRNA-1187 might be the candidate serum biomarkers for early prediction of liver injury.