Progress on clinical prognosis assessment in liver failure

Liver failure is a group of clinical syndromes with a mortality rate of>50%.The accurate evaluation of severity in patients with liver failure has been a meaningful and hot topic in clinical research and an important guide for liver transplantation.Numerous prognosis studies have emerged in recent years with high accuracy and adequate validity.Nonetheless,different models utilize distinct parameters and have unequal efficiencies,leading to a specific value and unique application situations for each model.This review focused on the progress in recent prognostic studies including the model for end-stage liver disease,sequential organ failure assessment and its derivative models,the Chinese Group on the Study of Severe Hepatitis B Acute-on-Chronic Liver Failure,the Tongji prognostic predictor model,and other emerging prognostic models and predictors.This review aims to assist clinicians understand the framework of recent models and choose the appropriate model and treatment.

A novel nomogram based on routine clinical indicators for screening for Wilson's disease

Background and aims:There is currently no single model for predicting Wilson's disease(WD).We aimed to create a nomogram using daily clinical parameters to improve the accuracy of WD diagnosis in patients with abnormal liver function.Methods:Between July 2016 and December 2020,we identified 90 WD patients with abnormal liver function who had homozygous or compound heterozygous mutations in the ATP7B gene.The control group included 128 patients with similar liver function but no WD during the same time period.To create a nomogram,we screened potential predictive variables using the least absolute shrinkage and selection operator model and multivariate logistic regression.Results:We developed a nomogram for screening for WD based on six predictive factors:serum copper,direct bilirubin,uric acid,cholinesterase,prealbumin,and reticulocyte percentage.In the training cohort,the area under curve(AUC)of the nomogram reached 0.967(95%confidence interval(CI)0.946e0.988),while the area under the precision-recall curve was 0.961.Based on the optimal cutpoint of 213.55,our nomogram performed well,with a sensitivity of 96%and a specificity of 87%.In the validation cohort,the AUC of the nomogram was as high as 0.991(95%CI 0.970e1.000).Conclusions:We developed a nomogram that can predict the risk of WD prior to the detection of serum ceruloplasmin or urinary copper,greatly increasing screening efficiency for patients with abnormal liver function.

Expression and Regulatory Network Analysis of Function of Small Nucleolar RNA Host Gene 4 in Hepatocellular Carcinoma

Background and Aims:Long non-coding RNA small nucleolar RNA host genes(SNHGs)play a critical role in the occurrence and development of tumors.In this study,we aimed to investigate the role of SNHG4 in hepatocellular carcinoma(HCC)and its underlining mechanism.Methods:Datasets were acquired from The Cancer Genome Atlas(TCGA)database.lncLocator 2.0 was used to identify the distribution of SNHG4 in HCC cells.Gene expression,Kaplan-Meier survival,microRNA and transcription factor target analyses were performed with the University of Alabama Cancer(UALCAN)Database,Kaplan-Meier Plotter,LinkedOmics,WebGestalt and gene set enrichment analysis,respectively.Gene Ontology and pathway enrichment analyses and assessment of RNA binding proteins were performed by R software,circlncRNAnet and Encyclopedia of RNA Interactomes(EN-CORI).In addition,CirclncRNAnet and ENCORI were used to find the correlation between SNHG4 and important proteins,while the prognostic value was assessed with the Human Protein Atlas database and Kaplan-Meier Plotter.Results:Expression of SNHG4 in HCC is higher in HCC tissue than in normal healthy liver tissues and is mainly distributed in the nucleus.SNHG4 positively correlated with poor prognosis(p<0.01 for overall survival and recurrence-free survival).Functional enrichment analysis revealed SNHG4 involve-ment with regulation of ribosomal RNA synthesis and the RNA processing and surveillance pathway.SNHG4 is closely associated with miR-154 and miR-206,transcription factor target E2F family and the signaling pathway for MAPK/ERK and mTOR.U2 auxiliary factor 2(U2AF2)showed strong correlation with SNHG4,while low-expression of U2AF2 showed good prognosis.Conclusions:Based on our find-ings,we infer SNHG4 may play a role in the formation of HCC via regulation of tumor-related pathways.

A Prognostic Nomogram with High Accuracy Based on 2D-SWE in Patients with Acute-on-chronic Liver Failure

Background and Aims:Acute-on-chronic liver failure(ACLF)is associated with very high mortality.Accurate prediction of prognosis is critical in navigating optimal treatment decisions to improve patient survival.This study was aimed to develop a new nomogram integrating two-dimensional shear wave elastography(2D-SWE)values with other independent prognostic factors to improve the precision of predicting ACLF patient outcomes.Methods:A total of 449 consecutive patients with ACLF were recruited and randomly allocated to a training cohort(n=315)or a test cohort(n=134).2D-SWE values,conventional ultrasound features,laboratory tests,and other clinical characteristics were included in univariate and multivariate analysis.Factors with prognostic value were then used to construct a novel prognostic nomogram.Receiver operating curves(ROCs)were generated to evaluate and compare the performance of the novel and published models including the Model for EndStage Liver Disease(MELD),MELD combined with sodium(MELD-Na),and Jin’s model.The model was validated in a prospective cohort(n=102).Results:A ACLF prognostic nomogram was developed with independent prognostic factors,including 2D-SWE,age,total bilirubin(TB),neutrophils(Neu),and the international normalized ratio(INR).The area under the ROC curve(AUC)was 0.849 for the new model in the training cohort and 0.861 in the prospective validation cohort,which were significantly greater than those for MELD(0.758),MELD-Na(0.750),and Jin’s model(0.777,all p<0.05).Calibration curve analysis revealed good agreement between the predicted and observed probabilities.The new nomogram had superior overall net benefit and clinical utility.Conclusions:We established and validated a 2D-SWE-based noninvasive nomogram to predict the prognosis of ACLF patients that was more accurate than other prognostic models.

Association between the nasopharyngeal microbiome and metabolome in patients with COVID-19

SARS-CoV-2,the causative agent for COVID-19,infect human mainly via respiratory tract,which is heavily inhabited by local microbiota.However,the interaction between SARS-CoV-2 and nasopharyngeal microbiota,and the association with metabolome has not been well characterized.Here,metabolomic analysis of blood,urine,and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients,and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19.Results showed lactic acid,L-proline,and chlorogenic acid methyl ester(CME)were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones.Nasopharyngeal commensal bacteria including Gemella morbillorum,Gemella haemolysans and Leptotrichia hofstadii were notably depleted in the pharynges of COVID-19 patients,while Prevotella histicola,Streptococcus sanguinis,and Veillonella dispar were relatively increased.The abundance of G.haemolysans and L.hofstadii were significantly positively associated with serum CME,which might be an anti-SARS-CoV-2 bacterial metabolite.This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility.The findings were based on a very limited number of patients enrolled in this study;a larger size of cohort will be appreciated for further investigation.

Real-world effectiveness and safety of OBT/PTV/r and dasabuvir for patients with chronic HCV genotype 1b infection in China:A multicenter prospective observational study

Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients.Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(ITT)and modified ITT(mITT)populations were used in the analysis.Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diagnosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment.Conclusions:The rate of SVR12 was consistent with Phase III clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.