[This corrects the article DOI: 10.3389/fmed.2026.1843714.].

Background:The mortality rate of severe/critical coronavirus disease (COVID-19) is high in the elderly, and early prediction of its prognosis can facilitate timely treatment and reduce mortality. This study aims to identify early predictors of severe COVID-19 in elderly and construct a validated risk prediction model. Methods:This retrospective study included 722 elderly COVID-19 patients (those aged ≥60) who attended Nanfang Hospital of Southern Medical University between July 2022 and November 2023. They were categorized as mild/moderate or severe/critical according to the extent of their condition during hospitalization. Predictive models were constructed using logistic regression analysis and visualized using nomograms. Receiver operating characteristic (ROC) curves were used to assess the model's accuracy and predictive value. An external validation cohort containing 1,249 elderly COVID-19 patients who were admitted to Huashan Hospital of Fudan University between March and May 2022 was also collected. Results:In multivariable logistic regression analysis, respiratory rate, comorbid diabetes, C-reactive protein (CRP), lymphocyte percentage, and D-dimer were independently associated with severe and critical COVID-19. Based on these findings, the final severity prediction model was constructed using three laboratory markers: CRP, lymphocyte percentage, and D-dimer. This model achieved an area under the curve (AUC) of 0.753 (0.713-0.794). For mortality prediction, CRP and D-dimer emerged as the significant independent predictors; the model showed an AUC of 0.722 (0.653-0.791) in the internal validation cohort and 0.877 (0.833-0.921) in the external validation cohort. Conclusions:The predictive model incorporating features selected via logistic regression accurately predicts prognosis of severe COVID-19 in elderly, facilitating the implementation of early clinical interventions.

Background:Elderly patients remain at high risk for adverse outcomes from COVID-19 despite the generally reduced pathogenicity of the Omicron variant. Corticosteroids are commonly used in hospitalized patients with COVID-19, particularly in those with more severe disease, while antiviral agents inhibit viral replication. However, evidence comparing corticosteroid monotherapy with corticosteroid-antiviral combination therapy in elderly hospitalized patients remains limited. Methods:This multicenter retrospective cohort study included hospitalized patients aged ≥60 years with laboratory-confirmed COVID-19 at two tertiary hospitals in China, all of whom received systemic corticosteroid therapy during hospitalization. Patients were classified into either a corticosteroid monotherapy group or corticosteroid-antiviral combination therapy group. To reduce confounding, inverse probability of treatment weighting (IPTW) based on propensity scores was applied. The primary outcome was all-cause in-hospital mortality, and mechanical ventilation was assessed as a secondary outcome. Results:A total of 624 elderly hospitalized patients with COVID-19 who received systemic corticosteroid therapy were included in the IPTW analysis (290 in the corticosteroid group and 334 in the combination therapy group). After weighting, baseline characteristics were well balanced between groups. The weighted incidence of in-hospital mortality was lower in the combination therapy group than in the corticosteroid monotherapy group (8.09% vs 13.47%; OR 0.566, 95% CI 0.333-0.961; p = 0.035). No statistically significant difference was observed in the risk of mechanical ventilation between groups (OR 1.286, 95% CI 0.924-1.789; p = 0.136). Conclusions:Among elderly hospitalized patients with COVID-19 during the Omicron period who received systemic corticosteroid therapy corticosteroids combined with antiviral therapy were associated with lower in-hospital mortality compared with corticosteroid monotherapy, while no significant difference was observed in mechanical ventilation.

IntroductionSARS-CoV-2/HBV coinfections are increasingly common as SARS-CoV-2 continues to evolve. The interferon (IFN) therapy for HBV infection might also have antiviral effects against SARS-CoV-2. To understand the effects of IFN on SARS-CoV-2 infection, we compared the clinical characteristics between IFN-treated chronic hepatitis B (CHB) patients and nucleo(s)tide analogs (NAs)-treated CHB patients during their SARS-CoV-2 infection.MethodsOur cohort study enrolled patients with primary SARS-CoV-2 infections among IFN-treated and NAs-treated CHB patients during the Omicron wave in Shanghai, China, from December 7 2022 to January 23 2023. Clinical characteristics and self-reported acute symptoms during SARS-CoV-2 infection were collected by telephone questionnaire in January 2023.ResultsThe four most common symptoms were fever, fatigue, cough and sore throat among all enrolled participants, regardless of their treatment. Interestingly, Pegylated interferon-alpha (Peg-IFNα) treated CHB patients had a significantly higher proportion of asymptomatic infection than NAs-treated CHB patients (14.53% vs. 2.70%, p = 0.002). Additionally, IFN-treated CHB patients had significantly lower duration of fever (p = 0.018), less usage of antipyretics (p < 0.0001), less occurrence of muscle and/or joint pain (p < 0.0001), less occurrence of headache (p < 0.0001) and less occurrence of runny nose (p < 0.0001) compared to NAs-treated CHB patients.ConclusionIn this real-world cohort of CHB patients infected with SARS-CoV-2 during the Omicron wave, Peg-IFNα treatment was associated with milder self-reported acute clinical manifestations, including a higher proportion of asymptomatic infection and reduced occurrence of several common symptoms.

Background & Aims: Nucleo(s)tide analogue (NUC) cessation can lead to hepatitis B surface antigen (HBsAg) clearance but also a high rate of virological relapse. However, the effect of pegylated interferon alpha-2a (PegIFN-alpha-2a) on virological relapse after NUC cessation is unknown. Therefore, this study aimed to evaluate the effect of switching from NUC to PegIFN-alpha-2a treatment for 48 weeks on virological relapse up to week 96. Methods: In this multicenter randomized-controlled clinical trial, 180 non-cirrhotic patients with HBeAg-negative chronic hepatitis B on continuous NUC therapy for >=-2.5 years, with HBV DNA levels <60 IU/ml, were randomized to discontinue NUC therapy (n = 90) or receive 48 weeks of PegIFN-alpha-2a treatment (n = 90). Patients were followed up for up to 96 weeks. The primary endpoint was the virological relapse rate up to week 96. Results: Intention-to-treat analysis revealed patients in the interferon monotherapy group had significantly lower cumulative virological relapse rates than the NUC cessation group until week 96 (20.8% vs. 53.6%, p <0.0001). Consistently, a significantly lower proportion of patients in the interferon monotherapy group had virological relapse than those in the NUC cessation group at 48 weeks off treatment (17.8% vs. 36.7%, p = 0.007). The virological relapse rate positively correlated with HBsAg levels in the NUC cessation group. The interferon monotherapy group had a lower cumulative clinical relapse rate (7.8% vs. 20.9%, p = 0.008) and a higher HBsAg loss rate (21.5% vs. 9.0%, p = 0.03) than the NUC cessation group. Conclusions: Switching from NUC to PegIFN-alpha-2a treatment for 48 weeks significantly reduces virological relapse rates and leads to higher HBsAg loss rates than NUC treatment cessation alone in patients with HBeAg-negative chronic hepatitis B. (c) 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Patients on immunosuppressive drugs or those who are critically ill are at high risk for invasive fungal infections (IFIs). The assessment of IFI risk and the initiation of prophylaxis in these patients remain unclear. A nomogram model was developed to evaluate clinical and immune indicators in relation to IFI risk and validated by immunocompromised patients. High-risk patients, as identified by the model, were selected for a prospective randomized study to assess the efficacy of the model and timing of fungal prophylaxis initiation. Patients deemed high risk received either fluconazole or a placebo until IFI occurrence or risk downgrade for 90 days. We compared the incidence of IFI and mortality between the two groups. The nomogram, created from a training cohort (n = 384), included age, IgG level, and CD4+ cell count as predictive indicators of IFI and was validated in a separate cohort (n = 281) with an area under the curve of 0.723. A total of 265 patients were recruited into the prospective study, with 163 high-risk patients randomly assigned to receive either fluconazole (n = 83) or a placebo (n = 80). The model had a positive predictive value of 48.8% and a negative predictive value of 90.2%. High-risk IFI defined by this model could be reduced to the low-risk cohort level with fluconazole prophylaxis (P < 0.01). This nomogram model reliably predicts the risk of IFI and timing of mycoprophylaxis in immunocompromised patients. Targeted mycoprophylaxis significantly reduces the incidence of IFI, particularly yeast infections, and may help to prevent fungal colonization. IMPORTANCE We still lack enough evidence to decide when and how to begin fungal prophylaxis in immunocompromised patients. A model based on immune function indicator is an effective tool for predicting risk of invasive fungal infection (IFI) in immunocompromised patients. Patients were collected to evaluate the performance of the model retrospectively and prospectively. CLINICAL TRIALS This study is registered with the Chinese Clinical Trial Registry as ChiCTR2400079810.

B- and T-lymphocyte attenuator (BTLA) levels are increased in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This condition is characterized by susceptibility to infection and T-cell immune exhaustion. However, whether BTLA can induce T-cell immune exhaustion and increase the risk of infection remains unclear. Here, we report that BTLA levels are significantly increased in the circulating and intrahepatic CD4 + T cells from patients with HBV-ACLF, and are positively correlated with disease severity, prognosis, and infection complications. BTLA levels were upregulated by the IL-6 and TNF signaling pathways. Antibody crosslinking of BTLA activated the PI3K-Akt pathway to inhibit the activation, proliferation, and cytokine production of CD4 + T cells while promoting their apoptosis. In contrast, BTLA knockdown promoted their activation and proliferation. BTLA -/- ACLF mice exhibited increased cytokine secretion, and reduced mortality and bacterial burden. The administration of a neutralizing anti-BTLA antibody reduced Klebsiella pneumoniae load and mortality in mice with ACLF. These data may help elucidate HBV-ACLF pathogenesis and aid in identifying novel drug targets.

Background: The prognosis of patients with liver failure (LF) depends significantly on the etiology and clinical indicators. This analysis of these basic indicators can help provide a basis for the study of predictive outcome indicators. Methods: We collected the data from multiple centers in Southeast China, including subclasses of acute liver failure (ALF), subacute liver failure (SLF), acute-on-chronic liver failure (ACLF), subacute-on-chronic liver failure (SALF), and chronic liver failure (CLF). Multivariate logistic regression analysis was used to screen for clinical indicators of nonsurvivors. We analyzed receiver operating characteristic (ROC) curves and cutoff values to assess the prognostic criteria. Results: Hepatitis B virus (HBV) infection is the leading etiology of patients with LF (64.52% (411/637)). SALF (41.36%) and CLF (32.30%) are the main subclasses of the hepatitis B virus-related liver failure (HBV-LF) group and the non-HBV-related LF group in Southeast China, respectively. Between 2018 and 2020, the incidence of HBV-LF decreased significantly, ranging from 72.36% to 59.74%, and the spontaneous survival rates of patients with HBV-LF were substantially lower than those of non-HBV-LF patients (36.43%similar to 44.93% vs. 58.97%similar to 63.64%). Infection and cirrhosis were the leading causes of death in both groups. The age and total bilirubin value of the nonsurvivors with HBV-LF were significantly higher, and the number of days of hospitalization was significantly shorter than that of the survivors. The ages of the nonsurvivors in the non-HBV-LF group were significantly higher than those of the survivors. The prothrombin time-international normalized ratio (PT-INR) is 2.05, 1.92, or 2.11, and antithrombin III (AT III) is 24.50%, which are proposed as prognostic criteria for the HBV-SALF (hepatitis B virus-related subacute-on-chronic liver failure), non-HBV-SLF (non-hepatitis B virus-related subacute liver failure), non-HBV-ACLF (non-hepatitis B virus-related acute-on-chronic liver failure), and HBV-ALF (hepatitis B virus-related acute liver failure) subclasses, respectively. Conclusions: The incidence of HBV-LF is decreasing annually. AT III, as an independent prognostic criterion, has excellent discriminative ability for the outcomes of the HBV-ALF subclass.

The persistent global burden of hepatitis B virus (HBV) infection has prompted ongoing investigations into host determinants of viral control. In this study, we investigate the regulatory influence of the host gene cleavage stimulation factor subunit 2 (CSTF2) on HBV replication dynamics. We demonstrate differential CSTF2 expression across the spectrum of HBV infection phases, with upregulated expression noted during the immune-reactive and inactive carrier states compared with the immune-tolerant phase. Notably, dose-responsive attenuation of HBV DNA, as well as surface and core protein levels, is observed subsequent to CSTF2 overexpression, whereas HBV RNA levels remain unaffected. Upon HBV transfection, a notable alteration in CSTF2 subcellular localization is discerned, suggesting active relocalization to the cytoplasm, potentially mediated through interaction with the HBV posttranscriptional regulatory element (PRE). This interaction appears to impede the nuclear export of HBV RNA. Additionally, distinct antiviral efficacies are attributed to the functional domains of the CSTF2 protein, indicating a multifaceted host defense mechanism. These insights increase the understanding of host-virus interplay and identify CSTF2 as a candidate for antiviral therapeutic strategies.

Hepatic encephalopathy (HE) represents a critical complications of end-stage liver disease, serving as an independent predictor of mortality among patients with cirrhosis. Despite effective treatment with rifaximin, some patients with HE still progress to recurrent episodes, posing a significant therapeutic challenge. Recurrent HE is defined as experiencing two or more episodes within a 6-month period. Previous research has suggested that FMT may emerge as a promising treatment for recurrent HE. However, there remains a critical need to explore the optimal dosage. This trial aims to abscess the efficacy and safety of two FMT dosages: 800 ml or 400 ml total bacterial count, including mortality and quality of life. This multicenter, prospective, randomized controlled trial will enroll 100 eligible patients from 31 hospitals in China. Participants will be randomly assigned in a 1:1 ratio to either the high-dose group (800 ml total bacterial count) or the low-dose group (400 ml total bacterial count). The primary objective is to assess the efficacy and safety of both dosages on outcomes at 24 and 48 weeks, including mortality and quality of life. If either or both dosages of FMT demonstrate safe and effective treatment of recurrent HE, leading to improve quality of life and survival at 24 and 48 weeks, this trial would address a significant gap in the management of recurrent HE, carrying innovative and clinically significant implications. NCT05669651 on ClinicalTrials.gov. Registered on 29 December 2022. CHiCTR2200067135 on China Registered Clinical Trial Registration Center. Registered on 27 December 2022.

We evaluated the diagnostic accuracy of various international guideline criteria for identifying HBeAg-positive chronic HBV infection patients with no significant liver disease. A total of 1108 HBeAg-positive CHB patients were retrospectively enrolled. The guidelines assessed included those from the European Association for the Study of the Liver (EASL) 2017, the American Association for the Study of the Liver Disease (AASLD) 2018, the Asian Pacific Association for the Study of the Liver (APASL) 2015 and the Chinese Society of Hepatology (CSH) 2022. The CSH criteria demonstrated a higher proportion of patients with G0-1 and S0-1 (82.9%) compared to the EASL (75.9%), AASLD (75.3%) and APASL groups (58.8%). Additionally, the CSH criteria exhibited a significantly higher predictive value (AUC 0.782, 95% CI 0.754-0.809) than the EASL (AUC 0.765, 95% CI 0.737-0.793), AASLD (AUC 0.749, 95% CI 0.720-0.778) and APASL (AUC 0.720, 95% CI 0.690-0.750) criteria for identifying G0-1 and S0-1. Adding quantitative HBsAg levels (> 104 IU/mL) to the EASL, AASLD and APASL criteria improved diagnostic performance. Consequently, the CSH guideline thresholds showed higher accuracy in identifying Chinese HBeAg-positive patients with no significant liver disease compared to EASL, AASLD and APASL criteria, emphasising the importance of considering quantitative HBsAg in the evaluation of HBeAg-positive chronic HBV infection.

BACKGROUND:Low-level viremia is usually defined as a detectable but lower than 2000 IU/mL hepatitis B virus DNA level after 12 months or longer duration of antiviral therapy in chronic hepatitis B patients. In this study, we aimed to clarify the factors associated with lowlevel viremia in patients during long-term monotherapy with tenofovir disoproxil fumarate or entecavir. METHODS:Chronic hepatitis B patients having received entecavir or tenofovir disoproxil fumarate treatment for 12 months or more were enrolled from October 2019 to October 2021 at a tertiary hospital in Shanghai, China. In accordance with their hepatitis B virus DNA levels, chronic hepatitis B patients were grouped into 3 categories, hepatitis B virus DNA > 2000 IU/mL, low-level viremia, and complete virological response (hepatitis B virus DNA < 10 IU/mL). Compared with complete virological response patients, factors related to lowlevel viremia were evaluated. RESULTS:This study enrolled a total of 160 chronic hepatitis B patients, whose duration of treatment ranged from 12 to 144 months. In total, 107 patients achieved complete virological response, 51 showed low-level viremia, and 2 showed hepatitis B virus DNA > 2000 IU/mL. After multivariate logistic regression analysis, hepatitis e antigen-positivity (odds ratio = 6.479, 95% CI: 2.480-16.922, P = .000), entecavir treatment (odds ratio = 4.742, 95% CI: 1.855-12.118, P = .001), and duration of therapy (odds ratio = 0.168, 95% CI: 0.072-0.388, P = .000) were independently associated with low-level viremia. CONCLUSION:Having received long-term antiviral treatment, low-level viremia still occurred in 31.9% of patients. Longer duration of therapy was a protective factor, and HBeAg-positivity and entecavir treatment were risk factors for low-level viremia.

Abstract Background The prognosis of patients with liver failure (LF) depends significantly on the etiologies and clinical indicators. Methods The retrospective cohort study included 637 LF patients between 2018 and 2020, including the subclasses of acute liver failure (ALF), subacute liver failure (SLF), acute-on-chronic liver failure (ACLF), subacute-on-chronic liver failure (SALF), and chronic liver failure (CLF). Multivariate logistic regression analysis was used to screen clinical indicators of death patients. We analyzed the receiver operating characteristic curves (ROCs) and cut-off values to assess prognosis criteria. Results HBV infection was present in 64.52% of LF patients. SALF (41.36%) is the main subclass of the hepatitis B virus-related LF (HBV-LF) group, while chronic liver failure (32.30%) is the main subclass of the non-HBV-related LF group in southeast China. Between 2018 and 2020, the incidence of HBV-LF decreased significantly, ranging from 72.36–59.74%, and the spontaneous survival rates of HBV-LF patients were substantially lower than those of the non-HBV-LF group (36.43 ~ 44.93% vs. 58.97 ~ 63.64%). Infection and cirrhosis were the primary causes of both groups. The age and total bilirubin value of the HBV-LF dead patients were significantly higher, and the number of days of hospitalization was significantly shorter than those of the survivors. The ages of the dead patients of the non-HBV-LF group were significantly higher than those of the survivors. The prothrombin time-international normalized ratio (PT-INR) of 2.05, 1.92, or 2.11, and antithrombin III (AT III) of 24.50%, which were proposed as prognostic criteria for the HBV-SALF, non-HBV-subacute liver failure, non-HBV-acute-on-chronic liver failure, and HBV-acute liver failure subclasses, respectively. Conclusions The incidence of HBV-LF is decreasing yearly. AT III, as a new prognostic criterion, has an excellent discriminative ability on the outcomes of the HBV-ALF subclass.

目的:评估中国重症乙型肝炎研究学组(COSSH)慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)2.0(COSSH ACLFⅡ)评分对乙肝病毒相关ACLF(HBV-ACLF)患者短期预后评估和病情分级的应用价值.方法:回顾性分析皖南医学院附属第一医院2017年1月-2021年12月收治的114例HBV-ACLF患者的临床资料和生存信息.根据患者90 d生存情况分为存活组(n=67)和死亡组(n=47),比较两组基线特征的差异.采用受试者工作特征曲线下面积(area under curve,AUC)比较COSSH ACLF Ⅱ评分和COSSH ACLF评分、慢性肝衰竭联盟(CLIF-C)ACLF评分、CLIF-C脏器衰竭(CLIF-C OF)评分、终末期肝病模型(MELD)评分、MELD联合血清钠(MELD-Na)评分和Child-Turcotte-Pugh(CTP)评分预测患者90 d死亡的价值.分别按照 COSSH ACLF 分级(ACLF-1,n=83;ACLF-2,n=23;ACLF-3,n=8)和 COSSH ACLF Ⅱ 危险分层(＜7.4,n=82;7.4～＜8.4,n=21;≥8.4,n=11)将患者分组,Kaplan-Meier法比较各组90d生存率的差异.结果:死亡组的年龄、肝性脑病或细菌感染的发生率、白细胞计数、中性粒细胞计数、国际标准化比值、总胆红素、血肌酐、血尿素氮以及以上7种预后评分均高于存活组(P均＜0.05),凝血衰竭和中枢衰竭的发生率以及ACLF-1患者比例亦高于存活组(P均＜0.01).COSSH ACLF Ⅱ 评分预测患者90 d死亡的 AUC(0.892)大于CLIF-C ACLF评分(AUC=0.853,P=0.089)、COSSH ACLF评分(AUC=0.841,P＜0.05)、CLIF-C OF 评分(AUC=0.813,P＜0.05)、MELD-Na评分(AUC=0.771,P＜0.01)、MELD 评分(AUC=0.792,P＜0.01)和CTP评分(AUC=0.655,P＜0.001).患者90d生存率随ACLF分级和COSSH ACLF Ⅱ危险分层上升均呈递减趋势(73.5％vs.26.1％vs.0％,P均＜0.001;72.0％vs.38.1％vs.0％,P均＜0.01).结论:COSSH ACLF Ⅱ 评分对HBV-ACLF患者短期预后的预测价值较高,采用COSSH ACLF Ⅱ危险分层有助于简化HBV-ACLF患者病情分级.

During March 2022 to January 2023, two Omicron waves hit Shanghai and caused a massive number of reinfections. To better understand the incidence and clinical characteristics of SARS-CoV-2 reinfection in Shanghai, China, we conducted a multicenter cohort study. COVID-19 patients first infected with BA.2 (March 1, 2022-May 23, 2022) who were quarantined in Huashan Hospital, Renji Hospital, and Shanghai Jing'an Central Hospital were followed up for reinfection from June 1, 2022 to January 31, 2023. Of 897 primary infections, 148 (16.5%) experienced reinfection. Incidence rate of reinfection was 0.66 cases per 1000 person-days. Female gender (adjusted odds ratio [aOR]= 2.19, 95% confidence interval [CI]: 1.29-3.83) was a risk factor for reinfection. The four most common symptoms of reinfections during the circulation of BA.5 sublineages were cough (62.59%), sore throat (54.42%), fatigue (48.98%), and fever (42.57%). Having received a booster vaccination was not associated with reduced severity of reinfection in comparison with not having received booster vaccination. After matched 1:1 by age and sex, we found that reinfections with BA.5 sublineages had significantly lower occurrence and severity of fever, fatigue, sore throat, and cough, as compared to primary infections with BA.5 sublineages. SARS-CoV-2 Omicron reinfections were less severe than Omicron primary infections during the circulation of the same subvariant. Protection offered by both vaccination and previous infection was poor against SARS-CoV-2 reinfection.