Development and validation of a nomogram to predict failure of 14-day negative nucleic acid conversion in adults with non-severe COVID-19 during the Omicron surge: a retrospective multicenter study.

BACKGROUND: With the variability in emerging data, guidance on the isolation duration for patients with coronavirus disease 2019 (COVID-19) due to the Omicron variant is controversial. This study aimed to determine the predictors of prolonged viral RNA shedding in patients with non-severe COVID-19 and construct a nomogram to predict patients at risk of 14-day PCR conversion failure. METHODS: Adult patients with non-severe COVID-19 were enrolled from three hospitals of eastern China in Spring 2022. Viral shedding time (VST) was defined as either the day of the first positive test or the day of symptom onset, whichever was earlier, to the date of the first of two consecutively negative PCR tests. Patients from one hospital (Cohort I, n = 2033) were randomly grouped into training and internal validation sets. Predictors of 14-day PCR conversion failure were identified and a nomogram was developed by multivariable logistic regression using the training dataset. Two hospitals (Cohort II, n = 1596) were used as an external validation set to measure the performance of this nomogram. RESULTS: Of the 2033 patients from Cohort I, the median VST was 13.0 (interquartile range: 10.0‒16.0) days; 716 (35.2%) lasted > 14 days. In the training set, increased age [per 10 years, odds ratio (OR) = 1.29, 95% confidence interval (CI): 1.15‒1.45, P < 0.001] and high Charlson comorbidity index (OR = 1.25, 95% CI: 1.08‒1.46, P = 0.004) were independent risk factors for VST > 14 days, whereas full or boosted vaccination (OR = 0.63, 95% CI: 0.42‒0.95, P = 0.028) and antiviral therapy (OR = 0.56, 95% CI: 0.31‒0.96, P = 0.040) were protective factors. These predictors were used to develop a nomogram to predict VST > 14 days, with an area under the ROC curve (AUC) of 0.73 in the training set (AUC, 0.74 in internal validation set; 0.76 in external validation set). CONCLUSIONS: Older age, increasing comorbidities, incomplete vaccinations, and lack of antiviral therapy are risk factors for persistent infection with Omicron variant for > 14 days. A nomogram based on these predictors could be used as a prediction tool to guide treatment and isolation strategies.

The potential effect of HBV vaccination on off-treatment HBsAg reversion after interferon-induced HBsAg clearance.

Off-treatment HBsAg reversion occurs in a considerable number of chronic hepatitis B(CHB) patients after IFN(interferon)-induced HBsAg clearance. HBV vaccination protects the general population against HBV infection. However, it remains unclear whether HBV vaccination could prevent off-treatment HBsAg reversion in CHB patients with HBsAg clearance. CHB patients (n = 199) with HBsAg clearance were included in the current study, comprising spontaneous HBsAg clearance group (n = 51), NA (nucleoside/nucleotide analogues)-induced group (n = 36) and IFN-induced group (n = 112). Log-rank test was performed to compare the cumulative incidences of HBsAg reversion between groups. Cox regression model was used to identify the factors associated with off-treatment HBsAg reversion. The 5-year cumulative incidence of HBsAg reversion in IFN-induced group was significantly higher than that in NA-induced group or spontaneous group (27.6% vs. 3.3% vs. 8.1%, both p < .05). In IFN-induced group, 66.7% of CHB patients received HBV vaccination. The cumulative incidence of HBsAg reversion in individuals with strong responses to HBV vaccination (HBsAb level >100mIU/ml) was significantly lower than that in those with weak responses to HBV vaccination (HBsAb level ≤100mIU/ml) or without HBV vaccination in IFN-induced group (7.7% vs. 58.5% vs. 31.9%, both p < .05). Multivariate Cox regression analysis confirmed strong responses to HBV vaccination were independently associated with a lower cumulative incidence of HBsAg reversion after IFN-induced HBsAg clearance (HR = 0.246, 95%CI: 0.066-0.907, p = .035). HBV vaccination has potential to prevent off-treatment HBsAg reversion in CHB patients after IFN-induced HBsAg clearance via a sufficiently high level of HBsAb, helping clinicians optimize the clinical management of such patients.

Alteration of Bile Acids and Omega-6 PUFAs Are Correlated With the Progression and Prognosis of Drug-Induced Liver Injury.

Background & Aims: Drug-induced liver injury (DILI) is one of the leading causes of liver failure with some of the patients progressed to chronic DILI. The mechanisms underlying the severity and chronicity of DILI are poorly elucidated and the biomarkers are limited. Metabolites and gut microbiota played a crucial role in the development of various liver diseases. Herein, a systematic analysis of serum metabolites and gut microbiota was performed in DILI patients, aiming to identify metabolites correlated with the progression and clinical prognosis of DILI. Methods: Various serum metabolites were quantitated using a metabolite array technology in this prospective study. Gut microbiome compositions and the expression profiles of liver genes were determined in patients with DILI and healthy controls. Results: Metabolomic analysis revealed that bile acids (BAs) and polyunsaturated fatty acids (PUFAs) were closely related to DILI severity and chronicity respectively. The ratios of serum primary/secondary BAs and omega-6/omega-3 PUFAs were elevated in DILI patients. A model established by adrenic acid (AdA) and aspartic acid (Asp) exerts good performance for predicting the chronicity of DLIL. Hepatic transcriptome revealed enhanced expression of PUFA peroxidation and supressed expression of BA synthesis related genes in DILI patients. In addition, Lactic acid bacteria and BA converting bacteria were increased in gut of DILI patients. Besides, elevated serum malondialdehyde (MDA) and fibroblast growth factor 19 (FGF19) was observed in DILI patients. Conclusion: BAs and PUFAs could be potent markers for the severity and chronicity of DILI respectively. The panel of AdA and Asp could be ideal predictive model for the risk of chronicity at the acute stage of DILI. Gut microbiota might act as a negative feedback mechanism to maintain the homeostasis of BAs and PUFAs via FGF19 signalling and PUFA saturation, respectively. Our study revealed novel biomarkers for severe and chronic DILI and provided new therapeutic targets for DILI.