Safety and Immunogenicity After Primary and Booster Inactivated SARS-Cov-2 Vaccination in Patients with Autoimmune Liver Diseases.

Background and Aims: SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports. However, the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases (AILD) is still unknown. Methods: Eighty-four patients with AILD were prospectively followed up after the second dose (primary) of inactivated SARS-CoV-2 vaccine. Some of them received the third dose (booster) of inactivated vaccine. Adverse events (AEs), autoimmune activation, and liver inflammation exacerbation after primary and booster vaccination were recorded. Meanwhile, dynamics of antireceptor-binding-domain IgG (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD-specific B cells responses were evaluated. Results: The overall AEs in AILD patients after primary and booster vaccination were 26.2% and 13.3%, respectively. The decrease of C3 level and increase of immunoglobulin light chain κ and λ levels were observed in AILD patients after primary vaccination, however, liver inflammation was not exacerbated, even after booster vaccination. Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination. Notably, the antibody titers were significantly elevated after booster vaccination (10-fold in anti-RBD-IgG and 7.4-fold in NAbs, respectively), which was as high as in healthy controls. Unfortunately, the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants. Changes of atypical memory B cells were inversely related to antibody levels, which indicate that the impaired immune memory was partially restored partly by the booster vaccination. Conclusions: The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.

Use of metagenomic next-generation sequencing for diagnosis of peritonitis in end-stage liver disease.

Background: Conventional methods are low in positive rates and time-consuming for ascites pathogen detection in patients with end-stage liver disease (ESLD). With many advantages, metagenomic next-generation sequencing (mNGS) may be a good alternative method. However, the related studies are still lacking. Methods: Ascites from 50 ESLD patients were sampled for pathogen detection using mNGS and conventional methods (culture and polymorphonuclear neutrophils detection) in this prospective observational study. Results: Forty-two samples were detected positive using mNGS. 29 strains of bacteria, 11 strains of fungi, and 9 strains of viruses were detected. 46% of patients were detected to be co-infected with 2 or more pathogens by mNGS. Moreover, mNGS showed similar and high positive rates in ESLD patients with different clinical characteristics. Compared to conventional methods, mNGS had higher positivity rates (84% vs. 20%, P<0.001), sensitivity (45.2% vs. 23.8%, P=0.039), broader pathogen spectrum, shorter detection time (24 hours vs. 3-7 days), but lower specificity (25% vs 100%, P = 0.010). Furthermore, compared to conventional methods, mNGS showed similar consistence with final diagnosis (42% vs. 36%, P=0.539). Conclusions: mNGS may be a good supplement for conventional methods and helpful to early etiological diagnosis of peritonitis, and thus improve ESLD patients' survival.

Local tumor destruction and liver resection increase overall survival in intermediate/advanced hepatocellular carcinoma patients: evidence from a population-based study.

Background: Liver resection (LR) and local tumor destruction (LTD) are effective treatments, but not commonly recommended for patients with intermediate/advanced hepatocellular carcinoma (HCC). This study aimed to explore whether LR/LTD could improve overall survival (OS) of these patients, and to identify the patients who will most likely benefit from LR/LTD. Methods: Data of patients with intermediate/advanced HCC between 2001 and 2018 were extracted from Surveillance, Epidemiology, and End Results database. OS was compared between HCC patients who received LR/LTD and those who did not. A nomogram was constructed for predicting OS, and it was then validated. Results: A total of 535 eligible patients were included, among which 128 received LR/LTD while 407 did not. Significantly higher OS in patients who received LR/LTD was observed (P<0.001). Based on independent prognostic factors obtained from univariate and multivariate analyses, a nomogram was constructed. The C-indices of nomogram were higher than those of the TNM staging system (training cohort: 0.74 vs. 0.59; validation cohort: 0.78 vs. 0.61). Similarly, areas under receiver operating characteristic curves and calibration curves indicated good accuracy of the nomogram. Decision curve analysis curves revealed good clinical practicability of the nomogram. Furthermore, low-risk patients (nomogram score: 0-221.9) had higher OS compared with high-risk patients (nomogram score: higher than 221.9) (P<0.001). Conclusion: LR/LTD significantly improves OS in patients with intermediate/advanced HCC. The nomogram developed in the present study shows high predicating value for OS in patients with intermediate/advanced HCC, which might be useful in selecting patients who are most suitable for LR/LTD.

Humoral responses after primary and booster SARS-CoV-2 inactivated vaccination in patients with chronic hepatitis B virus infection: A longitudinal observational study.

Given the pandemic of severe acute respiratory syndrome coronavirus 2 Omicron variants, booster vaccination (BV) using inactivated virus vaccines (the third dose) has been implemented in China. However, the immune responses after BV, especially those against Omicron, in patients with chronic hepatitis B virus (HBV) infection (CHB) are unclear. In this prospective longitudinal study, 114 patients with CHB and 68 healthy controls (HCs) were recruited after receiving inactivated vaccination. The anti-receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibodies (NAbs), neutralization against Omicron (BA2.12.1, BA.4/5), and specific B/T cells were evaluated. In patients, anti-RBD IgG was elevated significantly after BV; the titers were as high as those in HCs. Similar results were obtained for the NAbs. However, compared with that against wild type (WT), the neutralization against Omicron was compromised after BV. The frequency of RBD+ atypical memory B cells increased, but spike-specific cluster of differentiation 4+ /8+ T cells remained unchanged after BV. Moreover, no serious adverse events or HBV reactivation were observed after BV. These results suggest that BV significantly enhanced antibody responses against WT; however, it resulted in compromised antibody responses against Omicron in patients with CHB. Hence, new all-in-one vaccines and optimal vaccination strategies should be studied promptly.

Decreased antibody response to influenza vaccine with an enhanced antibody response to subsequent SARS-CoV-2 vaccination in patients with chronic hepatitis B virus infection.

INTRODUCTION: Influenza or SARS-CoV-2 vaccination is especially recommended for people with underlying diseases. For the large number of patients with chronic hepatitis B virus infection (CHB), studies on their immune responses to these vaccines are still lacking. METHODS: A total of 57 CHB patients and 19 healthy controls (HCs) receiving inactivated influenza vaccination were prospectively followed up. Influenza-specific immunoglobulin G (IgG) antibodies (anti-H1N1, anti-H3N2, and anti-B IgG), antibody-secreting cells (ASCs), and circulating T follicular helper cells were assessed simultaneously. Eight CHB patients subsequently got inactivated SARS-CoV-2 vaccination during 1-year follow-up, and levels of serum antibodies against SARS-CoV-2 were further analyzed. RESULTS: On day 28 after influenza vaccination, three influenza antibodies levels appeared to be lower in CHB patients than in HCs. And anti-H1N1 IgG level was significantly decreased in cirrhotic patients (p < .05). Anti-H1N1 IgG levels (day 28) were positively correlated with ASC frequencies (day 7) (p < .05), and negatively correlated with cirrhosis and hepatitis B surface antigen levels (p < .05). Anti-SARS-CoV-2 antibodies were higher in patients with influenza vaccination history than in patients without the history (p < .05). Moreover, positive correlations existed between influenza vaccination history and anti-SARS-CoV-2 antibody levels (p < .01). CONCLUSIONS: CHB patients, especially those with cirrhosis, appeared to have a decreased antibody response to inactivated influenza vaccine. A history of inactivated influenza vaccination within 1 year before inactivated SARS-CoV-2 vaccination might induce stronger anti-SARS-CoV-2 antibody response.

Dynamic Humoral Immune Response to Primary and Booster Inactivated SARS-CoV-2 Vaccination in Patients with Cirrhosis.

Background and Aims: Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) booster vaccination in cirrhotic patients who had received the primary series. Methods: We performed a longitudinal assessment in 48 patients with cirrhosis, 57 patients with chronic hepatitis B (CHB) and 68 healthy controls (HCs) to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times. A pseudovirus neutralization assay was used to determine neutralization against Omicron subvariants BA.2.12.1, BA.4 and BA.5 from serum samples collected from three cohorts. Results: Serum anti-receptor-binding domain (RBD) immunoglobulin (Ig)G and neutralizing antibody (NAb) levels in cirrhotic patients were elevated within 15-45 days after completing the primary series before rapidly declining and reaching a valley at around 165-195 days. After receiving the booster dose, both antibody levels were significantly increased to levels comparable to patients with CHB and HCs. Subgroup analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated cirrhosis. The SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibro-cirrhosis grade. However, compared with the primary series, the booster dose did not result in an evident improvement of neutralization activity against the Omicron subvariants BA.2.12.1 and BA.4, and was followed by a significant decrease in the titer against BA.5. Conclusions: A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the Omicron subvariants. Repeated vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.

Impact of Physical Activity on COVID-19.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is seriously endangering human health worldwide. This study finds effective intervention modalities of physical activity on COVID-19 through a narrative review. METHODS: In this study, 41 papers were selected for a narrative literature review after a comprehensive database search from 20 December 2019, to 30 August 2022. RESULTS: 41 articles meet the established criteria, and in this review, we comprehensively describe recent studies on exercise and COVID-19, including the impact and recommendations of exercise on COVID-19 prevention, patients with COVID-19, and noninfected populations. CONCLUSIONS: The literature suggests that physical activity (PA) contributes to the prevention and treatment of COVID-19, can promote recovery of physical function, alleviate post-acute COVID-19 syndrome, and improve patients' psychological well-being. It is recommended to develop appropriate exercise prescriptions for different populations under the guidance of a physician.

Safety and antibody response to inactivated COVID-19 vaccine in patients with chronic hepatitis B virus infection.

BACKGROUND AND AIMS: The safety and antibody responses of coronavirus disease 2019 (COVID-19) vaccination in patients with chronic hepatitis B (CHB) virus infection is still unclear, and exploration in safety and antibody responses of COVID-19 vaccination in CHB patients is significant in clinical practice. METHODS: 362 adult CHB patients and 87 healthy controls at an interval of at least 21 days after a full-course vaccination (21-105 days) were enrolled. Adverse events (AEs) were collected by questionnaire. The antibody profiles at 1, 2 and 3 months were elucidated by determination of anti-spike IgG, anti-receptor-binding domain (RBD) IgG, and RBD-angiotensin-converting enzyme 2 blocking antibody. SARS-CoV-2 specific B cells were also analysed. RESULTS: All AEs were mild and self-limiting, and the incidence was similar between CHB patients and controls. Seropositivity rates of three antibodies were similar between CHB patients and healthy controls at 1, 2 and 3 months, but CHB patients had lower titers of three antibodies at 1 month. Compared to healthy controls, HBeAg-positive CHB patients had higher titers of three antibodies at 3 months (all P < .05) and a slower decline in antibody titers. Frequency of RBD-specific B cells was positively correlated with titers of anti-RBD IgG (OR = 1.067, P = .004), while liver cirrhosis, antiviral treatment, levels of HBV DNA, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total bilirubin (TB) were not correlated with titers of anti-RBD IgG. CONCLUSIONS: Inactivated COVID-19 vaccines were well tolerated, and induced effective antibody response against SARS-CoV-2 in CHB patients.

A Web-Based Prediction Model for Cancer-Specific Survival of Elderly Patients With Early Hepatocellular Carcinoma: A Study Based on SEER Database.

Background: Primary liver cancer is a common malignant tumor primarily represented by hepatocellular carcinoma (HCC). The number of elderly patients with early HCC is increasing, and older age is related to a worse prognosis. However, an accurate predictive model for the prognosis of these patients is still lacking. Methods: Data of eligible elderly patients with early HCC in Surveillance, Epidemiology, and End Results database from 2010 to 2016 were downloaded. Patients from 2010 to 2015 were randomly assigned to the training cohort (n = 1093) and validation cohort (n = 461). Patients' data in 2016 (n = 431) was used for external validation. Independent prognostic factors were obtained using univariate and multivariate analyses. Based on these factors, a cancer-specific survival (CSS) nomogram was constructed. The predictive performance and clinical practicability of our nomogram were validated. According to the risk scores of our nomogram, patients were divided into low-, intermediate-, and high-risk groups. A survival analysis was performed using Kaplan-Meier curves and log-rank tests. Results: Age, race, T stage, histological grade, surgery, radiotherapy, and chemotherapy were independent predictors for CSS and thus were included in our nomogram. In the training cohort and validation cohort, the concordance indices (C-indices) of our nomogram were 0.739 (95% CI: 0.714-0.764) and 0.756 (95% CI: 0.719-0.793), respectively. The 1-, 3-, and 5-year areas under receiver operating characteristic curves (AUCs) showed similar results. Calibration curves revealed high consistency between observations and predictions. In external validation cohort, C-index (0.802, 95%CI: 0.778-0.826) and calibration curves also revealed high consistency between observations and predictions. Compared with the TNM stage, nomogram-related decision curve analysis (DCA) curves indicated better clinical practicability. Kaplan-Meier curves revealed that CSS significantly differed among the three different risk groups. In addition, an online prediction tool for CSS was developed. Conclusions: A web-based prediction model for CSS of elderly patients with early HCC was constructed and validated, and it may be helpful for the prognostic evaluation, therapeutic strategy selection, and follow-up management of these patients.