Machine learning versus multivariate logistic regression for predicting severe COVID-19 in hospitalized children with Omicron variant infection.

With the emergence of the Omicron variant, the number of pediatric Coronavirus Disease 2019 (COVID-19) cases requiring hospitalization and developing severe or critical illness has significantly increased. Machine learning and multivariate logistic regression analysis were used to predict risk factors and develop prognostic models for severe COVID-19 in hospitalized children with the Omicron variant in this study. Of the 544 hospitalized children including 243 and 301 in the mild and severe groups, respectively. Fever (92.3%) was the most common symptom, followed by cough (79.4%), convulsions (36.8%), and vomiting (23.2%). The multivariate logistic regression analysis showed that age (1-3 years old, odds ratio (OR): 3.193, 95% confidence interval (CI): 1.778-5.733], comorbidity (OR: 1.993, 95% CI:1.154-3.443), cough (OR: 0.409, 95% CI:0.236-0.709), and baseline neutrophil-to-lymphocyte ratio (OR: 1.108, 95% CI: 1.023-1.200), lactate dehydrogenase (OR: 1.993, 95% CI: 1.154-3.443), blood urea nitrogen (OR: 1.002, 95% CI: 1.000-1.003) and total bilirubin (OR: 1.178, 95% CI: 1.005-3.381) were independent risk factors for severe COVID-19. The area under the curve (AUC) of the prediction models constructed by multivariate logistic regression analysis and machine learning (RandomForest + TomekLinks) were 0.7770 and 0.8590, respectively. The top 10 most important variables of random forest variables were selected to build a prediction model, with an AUC of 0.8210. Compared with multivariate logistic regression, machine learning models could more accurately predict severe COVID-19 in children with Omicron variant infection.

Superbinder based phosphoproteomic landscape revealed PRKCD_pY313 mediates the activation of Src and p38 MAPK to promote TNBC progression.

Phosphorylation proteomics is the basis for the study of abnormally activated kinase signaling pathways in breast cancer, which facilitates the discovery of new oncogenic agents and drives the discovery of potential targets for early diagnosis and therapy of breast cancer. In this study, we have explored the aberrantly active kinases in breast cancer development and to elucidate the role of PRKCD_pY313 in triple negative breast cancer (TNBC) progression. We collected 47 pairs of breast cancer and paired far-cancer normal tissues and analyzed phosphorylated tyrosine (pY) peptides by Superbinder resin and further enriched the phosphorylated serine/threonine (pS/pT) peptides using TiO2 columns. We mapped the kinases activity of different subtypes of breast cancer and identified PRKCD_pY313 was upregulated in TNBC cell lines. Gain-of-function assay revealed that PRKCD_pY313 facilitated the proliferation, enhanced invasion, accelerated metastasis, increased the mitochondrial membrane potential and reduced ROS level of TNBC cell lines, while Y313F mutation and low PRKCD_pY313 reversed these effects. Furthermore, PRKCD_pY313 significantly upregulated Src_pY419 and p38_pT180/pY182, while low PRKCD_pY313 and PRKCD_Y313F had opposite effects. Dasatinib significantly inhibited the growth of PRKCD_pY313 overexpression cells, and this effect could be enhanced by Adezmapimod. In nude mice xenograft model, PRKCD_pY313 significantly promoted tumor progression, accompanied by increased levels of Ki-67, Bcl-xl and Vimentin, and decreased levels of Bad, cleaved caspase 3 and ZO1, which was opposite to the trend of Y313F group. Collectively, the heterogeneity of phosphorylation exists in different molecular subtypes of breast cancer. PRKCD_pY313 activates Src and accelerates TNBC progression, which could be inhibited by Dasatinib.

Neurological manifestations and risk factors associated with poor prognosis in hospitalized children with Omicron variant infection.

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

Impact of the COVID-19 pandemic on liver disease-related mortality rates in the United States.

BACKGROUND & AIMS: The pandemic has resulted in an increase of deaths not directly related to COVID-19 infection. We aimed to use a national death dataset to determine the impact of the pandemic on people with liver disease in the USA, focusing on alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). METHODS: Using data from the National Vital Statistic System from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform and ICD-10 codes, we identified deaths associated with liver disease. We evaluated observed vs. predicted mortality for 2020-2021 based on trends from 2010-2019 with joinpoint and prediction modelling analysis. RESULTS: Among 626,090 chronic liver disease-related deaths between 2010 and 2021, Age-standardised mortality rates (ASMRs) for ALD dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 3.5% to 17.6%, p <0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (15.67 vs. 13.04) and 2021 (17.42 vs. 13.41). ASMR for NAFLD also increased during the pandemic (APC: 14.5%), whereas the rates for hepatitis B and C decreased. Notably, the ASMR rise for ALD was most pronounced in non-Hispanic Whites, Blacks, and Alaska Indians/Native Americans (APC: 11.7%, 10.8%, 18.0%, all p <0.05), with similar but less critical findings for NAFLD, whereas rates were steady for non-Hispanic Asians throughout 2010-2021 (APC: 4.9%). The ASMR rise for ALD was particularly severe for the 25-44 age group (APC: 34.6%, vs. 13.7% and 12.6% for 45-64 and ≥65, all p <0.01), which were also all higher than pre-COVID-19 rates (all p <0.01). CONCLUSIONS: ASMRs for ALD and NAFLD increased at an alarming rate during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. IMPACT AND IMPLICATIONS: The pandemic has led to an increase of deaths directly and indirectly related to SARS-CoV-2 infection. As shown in this study, age-standardised mortality rates for alcohol-associated liver disease and non-alcoholic fatty liver disease substantially increased during the COVID-19 pandemic in the USA and far exceeded expected levels predicted from past trends, especially among the young, non-Hispanic White, and Alaska Indian/Native American populations. However, much of this increase was not directly related to COVID-19. Therefore, for the ongoing pandemic as well as its recovery phase, adherence to regular monitoring and care for people with chronic liver disease should be prioritised and awareness should be raised among patients, care providers, healthcare systems, and public health policy makers.

Effectiveness and tolerability of camrelizumab combined with molecular targeted therapy for patients with unresectable or advanced HCC.

There is a lack of effective programmed cell death protein 1 (PD-1)-targeted immunotherapy with good tolerability in patients with advanced hepatocellular carcinoma (HCC) and severely compromised liver function. We assessed patient outcomes after combined camrelizumab and molecular targeted therapy in a multicenter cohort study in China. The study included 99 patients with advanced HCC (58 Child-Pugh A and 41 Child-Pugh B), 84 of them received camrelizumab combined with molecular targeted therapy from January 10, 2019, to March 31, 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were assessed. The median follow-up was 12.1 months. For patients with Child-Pugh B, the OS probability at 12-months, ORR and DCR were 49.7%, 31.7% and 65.9%, respectively, and the median PFS was 5.1 months [95% confidence interval (CI) 3.0-7.1], which were comparable with Child-Pugh A patients, although median OS was shorter in Child-Pugh B patients (20.5 vs.13.4 months, P = 0.12). In multivariate analysis, macrovascular infiltration (MVI), but not sex, age, hepatitis B virus etiology, extrahepatic metastasis, Child-Pugh B, or AFP > 400 ng/ml, was associated with 12-months OS [hazard ratio (HR) 2.970, 95% CI 1.276-6.917, P = 0.012] and ORR (HR 2.906, 95% CI 1.18-7.16, P = 0.020). Grade 3/4 immune-related AEs occurred in 26.8% of Child-Pugh B patients, including one potentially treatment-related death. In both groups, the most common AEs were immune thrombocytopenia and hepatotoxicity. Camrelizumab combined with targeted therapy showed favorable effectiveness and tolerability with manageable toxicities in Chinese HCC patients, regardless of Child-Pugh A/B liver function. MVI was associated with suboptimal immunotherapy response and poor prognosis.

Racial and Ethnic Disparities in Years of Potential Life Loss Among Patients With Cirrhosis During the COVID-19 Pandemic in the United States.

INTRODUCTION: Our aim was to evaluate the impact of race/ethnicity on cirrhosis-related premature death during the COVID-19 pandemic. METHODS: We obtained cirrhosis-related death data (n = 872,965, January 1, 2012-December 31, 2021) from the US National Vital Statistic System to calculate age-standardized mortality rates and years of potential life lost (YPLL) for premature death aged 25-64 years. RESULTS: Significant racial/ethnic disparity in cirrhosis-related age-standardized mortality rates was noted prepandemic but widened during the pandemic, with the highest excess YPLL for the non-Hispanic American Indian/American Native (2020: 41.0%; 2021: 68.8%) followed by other minority groups (28.7%-45.1%), and the non-Hispanic White the lowest (2020: 20.7%; 2021: 31.6%). COVID-19 constituted >30% of the excess YPLLs for Hispanic and non-Hispanic American Indian/American Native in 2020, compared with 11.1% for non-Hispanic White. DISCUSSION: Ethnic minorities with cirrhosis experienced a disproportionate excess death and YPLLs in 2020-2021.

HIV-related mortality in the United States during the COVID-19 pandemic: A population-based study.

BACKGROUND: US progress toward ending the HIV epidemic was disrupted during the COVID-19 pandemic. OBJECTIVES: To determine the impact of the pandemic on HIV-related mortality and potential disparities. METHODS: Using data from the Centers for Disease Control and Prevention and the United States (US) Census Bureau, HIV-related mortality data of decedents aged ≥25 years between 2012 and 2021 were analyzed. Excess HIV-related mortality rates were estimated by determining the difference between observed and projected mortality rates during the pandemic. The trends of mortality were quantified with joinpoint regression analysis. RESULTS: Of the 79,725 deaths documented in adults aged 25 years and older between 2012 and 2021, a significant downward trend was noted in HIV-related mortality rates before the pandemic, followed by a surge during the pandemic. The observed mortality rates were 18.8% (95% confidence interval [CI]: 13.1%-25.5%) and 25.4% (95%CI: 19.9%-30.4%) higher than the projected values in 2020 and 2021, respectively. Both of these percentages were higher than that in the general population in 2020 (16.4%, 95%CI: 14.9%-17.9%) and 2021 (19.8%, 95%CI: 18.0%-21.6%), respectively. Increased HIV-related mortality was observed across all age subgroups, but those aged 25-44 years demonstrated the greatest relative increase and the lowest COVID-19-related deaths when compared to middle- and old-aged decedents. Disparities were observed across racial/ethnic subgroups and geographic regions. CONCLUSIONS: The pandemic led to a reversal in the attainments made to reduce the prevalence of HIV. Individuals living with HIV were disproportionately affected during the pandemic. Thoughtful policies are needed to address the disparity in excess HIV-related mortality.

Excess risk for acute myocardial infarction mortality during the COVID-19 pandemic.

The COVID-19 pandemic has had a detrimental impact on the healthcare system. Our study armed to assess the extent and the disparity in excess acute myocardial infarction (AMI)-associated mortality during the pandemic, through the recent Omicron outbreak. Using data from the CDC's National Vital Statistics System, we identified 1 522 669 AMI-associated deaths occurring between 4/1/2012 and 3/31/2022. Accounting for seasonality, we compared age-standardized mortality rate (ASMR) for AMI-associated deaths between prepandemic and pandemic periods, including observed versus predicted ASMR, and examined temporal trends by demographic groups and region. Before the pandemic, AMI-associated mortality rates decreased across all subgroups. These trends reversed during the pandemic, with significant rises seen for the youngest-aged females and males even through the most recent period of the Omicron surge (10/2021-3/2022). The SAPC in the youngest and middle-age group in AMI-associated mortality increased by 5.3% (95% confidence interval [CI]: 1.6%-9.1%) and 3.4% (95% CI: 0.1%-6.8%), respectively. The excess death, defined as the difference between the observed and the predicted mortality rates, was most pronounced for the youngest (25-44 years) aged decedents, ranging from 23% to 34% for the youngest compared to 13%-18% for the oldest age groups. The trend of mortality suggests that age and sex disparities have persisted even through the recent Omicron surge, with excess AMI-associated mortality being most pronounced in younger-aged adults.

Isothermal nucleic acid amplification technology for rapid detection of virus.

While the research field and industrial market of in vitro diagnosis (IVD) thrived during and post the COVID-19 pandemic, the development of isothermal nucleic acid amplification test (INAAT) based rapid diagnosis was engendered in a global wised large measure as a problem-solving exercise. This review systematically analyzed the recent advances of INAAT strategies with practical case for the real-world scenario virus detection applications. With the qualities that make INAAT systems useful for making diagnosis relevant decisions, the key performance indicators and the cost-effectiveness of enzyme-assisted methods and enzyme-free methods were compared. The modularity of nucleic acid amplification reactions that can lead to thresholding signal amplifications using INAAT reagents and their methodology design were examined, alongside the potential application with rapid test platform/device integration. Given that clinical practitioners are, by and large, unaware of many the isothermal nucleic acid test advances. This review could bridge the arcane research field of different INAAT systems and signal output modalities with end-users in clinic when choosing suitable test kits and/or methods for rapid virus detection.

Sarcopenia in cirrhosis: epidemiology, diagnosis, management and prognosis.

PURPOSE OF REVIEW: With the development of many international guidelines, research on sarcopenia has increased rapidly, showing that sarcopenia is predictive of adverse outcomes, including increased mortality and impaired mobility, in patients with cirrhosis. The purpose of this article is to review the current evidence concerning the epidemiology, diagnosis, management and predictive value of sarcopenia on the prognosis of patients with cirrhosis. RECENT FINDINGS: Sarcopenia is a frequent and lethal complication of cirrhosis. Currently, abdominal computed tomography imaging is the most commonly used method to diagnose sarcopenia. In clinical practice, assessing muscle strength and physical performance, such as by measuring handgrip strength and gait speed, is of increasing interest. In addition to the necessary pharmacological therapy, adequate intake of protein, energy and micronutrients, as well as regular moderate-intensity exercise, can help to minimize sarcopenia. Sarcopenia has been shown to be a strong predictor of prognosis in patients with severe liver disease. SUMMARY: A global consensus is needed on the definition and operational parameters for the diagnosis of sarcopenia. Further research should focus on developing standardized screening, management and treatment protocols for sarcopenia. Adding sarcopenia to existing models may better exploit the effect of sarcopenia on prognosis in patients with cirrhosis, which should be investigated further.

[Prevalence Survey of Functional Dyspepsia and Irritable Bowel Syndrome in Chinese College Students Based on Rome â £ Diagnostic Criteria].

Objective: To investigate the prevalence and risk factors of functional dyspepsia (FD) and irritable bowel syndrome (IBS) among college students in China. Methods: An online questionnaire survey of college students aged 17-35 from across China was conducted. The online questionnaire survey was supplemented by an offline survey. A total of 2025 valid samples were included for statistical analysis. χ 2 test and logistic regression were performed for statistical analysis. Results: The prevalence of FD among college students who met the Rome Ⅳ diagnostic criteria was 5.5% (112/2025), with most of them, or 66.1% (74/112), suffering from postprandial discomfort syndrome (PDS). Smoking (odds ratio [ OR]=2.334, 95% confidence interval [ CI]: 1.187-4.589, P=0.014), depression ( OR=2.447, 95% CI: 1.421-4.214, P=0.001), and insomnia ( OR=1.947, 95% CI: 1.291-2.937, P=0.001) were positively correlated with the prevalence of FD. The prevalence of IBS was 1.9% (38/2025), with IBS-diarrhea dominant (IBS-D) being the most important subtype that accounted for 44.7%. Anxiety ( OR=3.63, 95% CI: 1.34-9.88, P=0.012) and insomnia ( OR=2.35, 95% CI: 1.18-4.68, P=0.015) were positively correlated with the prevalence of IBS. Conclusion: Based on Rome Ⅳ criteria, IBS and FD are not uncommon among Chinese university students. Psychological disorders and some related lifestyle factors may be related to the development of the disease. In the future, more series of studies based on different diagnostic criteria, different regions, and multiple factors should be conducted in China.

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Sofosbuvir-based therapy for late pregnant women and infants with severe chronic hepatitis C: A case series study.

Data on sofosbuvir-based therapy for pregnant women and infants with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant Women 1 and 2 and Infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant Women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant Women 1 and 2 and Infant 3 had hepatitis C virus (HCV) RNA levels of 139 000, 198 000, and 8 450 000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively. All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti-HCV antibody during the 1-year follow-up after birth. Additionally, two newborns and Infant 3 had normal growth parameters during the follow-up year one. In conclusion, this case series study found that sofosbuvir-based therapy for pregnant women and infants with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir-based therapy as a reference when similar severe CHC situations are encountered during clinical practice.

COVID-19 epidemic in New York City: development of an age group-specific mathematical model to predict the outcome of various vaccination strategies.

BACKGROUND: Since December 14, 2020, New York City (NYC) has started the first batch of COVID-19 vaccines. However, the shortage of vaccines is currently an inevitable problem. Therefore, optimizing the age-specific COVID-19 vaccination is an important issue that needs to be addressed as a priority. OBJECTIVE: Combined with the reported COVID-19 data in NYC, this study aimed to construct a mathematical model with five age groups to estimate the impact of age-specific vaccination on reducing the prevalence of COVID-19. METHODS: We proposed an age-structured mathematical model and estimated the unknown parameters based on the method of Markov Chain Monte Carlo (MCMC). We also calibrated our model by using three different types of reported COVID-19 data in NYC. Moreover, we evaluated the reduced cumulative number of deaths and new infections with different vaccine allocation strategies. RESULTS: Compared with the current vaccination strategy in NYC, if we gradually increased the vaccination coverage rate for only one age groups from March 1, 2021 such that the vaccination coverage rate would reach to 40% by June 1, 2021, then as of June 1, 2021, the cumulative deaths in the 75-100 age group would be reduced the most, about 72 fewer deaths per increased 100,000 vaccinated individuals, and the cumulative new infections in the 0-17 age group would be reduced the most, about 21,591 fewer new infections per increased 100,000 vaccinated individuals. If we gradually increased the vaccination coverage rate for two age groups from March 1, 2021 such that the vaccination coverage rate would reach to 40% by June 1, 2021, then as of June 1, 2021, the cumulative deaths in the 65-100 age group would be reduced the most, about 36 fewer deaths per increased 100,000 vaccinated individuals, and the cumulative new infections in the 0-44 age group would be reduced the most, about 17,515 fewer new infections per increased 100,000 vaccinated individuals. In addition, if we had an additional 100,000 doses of vaccine for 0-17 and 75-100 age groups as of June 1, 2021, then the allocation of 80% to the 0-17 age group and 20% to the 75-100 age group would reduce the maximum numbers of new infections and deaths simultaneously in NYC. CONCLUSIONS: The COVID-19 burden including deaths and new infections would decrease with increasing vaccination coverage rate. Priority vaccination to the elderly and adolescents would minimize both deaths and new infections.

Incidence of mother-to-child transmission of hepatitis B in relation to maternal peripartum antiviral prophylaxis: A systematic review and meta-analysis.

INTRODUCTION: Mother-to-child transmission (MTCT) of the hepatitis B virus (HBV) is a serious public health challenge. Estimating HBV MTCT incidence by region under different prophylaxis regimens is critical to understanding the regional disease burden and prioritizing interventions. This study aimed to calculate HBV MTCT incidence under different prophylaxis regimens globally and regionally and identify the HBV DNA threshold for maternal peripartum antiviral prophylaxis. MATERIAL AND METHODS: This review was registered in advance in PROSPERO (CRD 42019120567). We searched PubMed, Embase, China National Knowledge Infrastructure, ClinicalTrials.gov, and Cochrane Library databases for studies on MTCT in pregnant women with chronic HBV infection from their inception until June 13, 2022. MTCT was defined as hepatitis B surface antigen (HBsAg) or HBV DNA seropositivity in infants aged 6-12 months. We calculated the pooled HBV MTCT incidence using the DerSimonian-Laird random-effects model. RESULTS: Among 300 studies, 3402 of 63 293 infants had HBV due to MTCT. Without prophylaxis regimens, the pooled HBV MTCT incidence was 31.3%, ranging from 0.0% (95% confidence interval [CI] 0.0%-6.0%; European Region) to 46.1% (95% CI 29.7%-63.0%; Western Pacific Region). Following the introduction of the hepatitis B vaccine, the HBV MTCT incidence decreased from 82.9% to 15.9% in HBeAg-positive women and from 10.3% to 2.3% in HBeAg-negative women. Maternal peripartum antiviral treatment alongside infant immunoprophylaxis further decreased MTCT incidence to 0.3% (95% CI 0.1%-0.5%). Despite infant immunoprophylaxis, the incidences of MTCT at maternal HBV DNA levels of <2.30, 2.00-3.29, 3.00-4.29, 4.00-5.29, 5.00-6.29, 6.00-7.29 and ≥7.00 log10  IU/ml were 0.0% (95% CI 0.0%-0.0%), 0.0% (95% CI 0.0%-0.0%), 0.0% (95% CI 0.0%-0.5%), 0.6% (95% CI 0.0%-2.6%), 1.0% (95% CI 0.0%-3.1%), 4.3% (95% CI 1.8%-7.5%), and 9.6% (95% CI 7.0%-12.5%), respectively. CONCLUSIONS: HBV MTCT incidence varies across regions. The Western Pacific Region bears the heaviest burden. Peripartum antiviral prophylaxis plus infant immunoprophylaxis is promising for interrupting HBV MTCT. Regarding the HBV DNA threshold for peripartum antiviral prophylaxis, maternal HBV DNA of 4.00 log10  IU/ml or greater seems justified.

The impact of COVID-19 on the cascade of care of HCV in the US and China.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic imperiled the global health system. We aimed to determine the impact of COVID-19 on the care continuum of HCV-infected patients. MATERIAL AND METHODS: Two hundred and fifty-six patients who were prescribed a course of DAA therapy at three tertiary medical centers in the US and China between January 1, 2019 to June 30, 2020 were included. We assessed the proportions of patients who completed DAA therapy and had HCV RNA testing during and after the end of therapy. We also assessed the impact of utilization of telemedicine. RESULTS: The proportion of patients undergoing HCV RNA testing during DAA treatment decreased from >81.7% before pandemic to 67.8% during the pandemic (P=0.006), with a more prominent decrease in the US. There were significant decreases in HCV RNA testing >12 (P<0.001) and >20 weeks (P<0.001) post-treatment during COVID-19 era. Compared to pre-COVID period, post-treatment clinic encounters during COVID-19 era decreased significantly in China (Xi'an: 13.6% to 7.4%; Nanjing: 16.7% to 12.5%) but increased in the US (12.5% to 16.7%), mainly due to the use of telemedicine. There was a 4-fold increase in utilization of telemedicine in the US. CONCLUSIONS: COVID-19 pandemic carried profound impact on care for HCV patients in both the US and China. HCV cure rate assessment decreased by half during COVID era but the proportion of patients finishing DAA therapy was not significantly affected. Increased utilization of telemedicine led to increased compliance with DAA therapy but did not encourage patients to have their laboratory assessment for HCV cure.

Tenofovir Alafenamide to Prevent Perinatal Hepatitis B Transmission: A Multicenter, Prospective, Observational Study.

BACKGROUND: Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200 000 IU/mL who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24-35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. RESULTS: In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants' physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. CONCLUSIONS: Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%.

Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study.

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.

High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b.

BACKGROUND AND AIM: Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3. METHODS: The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index). RESULTS: We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naïve, and 2.5% HBsAg+ . The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin). CONCLUSIONS: In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.

Silencing of long noncoding RNA HOXD-AS1 inhibits proliferation, cell cycle progression, migration and invasion of hepatocellular carcinoma cells through MEK/ERK pathway.

Accumulating findings reveal that long noncoding RNAs (lncRNAs) as crucial regulatory molecules serve vital functions in the progression of hepatocellular carcinoma (HCC). This study aims to investigate the biological roles and mechanisms of lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in HCC cells based on transcriptome analysis. The Cancer Genome Atlas data analysis and experimental validation showed that HOXD-AS1 was increased in HCC tissues/cell lines and positively relevant to histologic grade. The subcellular localization results indicated HOXD-AS1 was dispersed both in the nucleus as well as the cytoplasm of HCC cells. In vitro loss-of-function experiments revealed that silencing of HOXD-AS1 could dramatically suppress the proliferation, migration, and invasion, and induce S or/and G2/M phase cell cycle arrest as well as apoptosis of Bel-7402 and MHCC97H cells accompanying the changes in expression levels of cyclin B1, cyclin D1, BCL-2, BAX, and MMP2. In vivo assay also showed that HOXD-AS1 silencing could markedly reduce xenograft tumor volume and weight of HCC cells. Transcriptome and bioinformatic analysis indicated that a total of 1103 genes were significantly altered by HOXD-AS1 silencing, of which 132 genes exhibited a significant correlation with HOXD-AS1 expression in HCC tissues. Gene Ontology (GO) enrichment analysis revealed differentially expressed genes were remarkably enriched in several cancer-related biological processes (cell proliferation, cell cycle, apoptosis, migration, angiogenesis, and hypoxic response). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that HOXD-AS1 has the potential to affect p53, tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK) pathway, and Western blot results further validated that HOXD-AS1 silencing could inhibit the MEK/ERK pathway in Bel-7402 cells. Collectively, HOXD-AS1, as an oncogenic lncRNA, might exert crucial functions in HCC progression and serve as a potential diagnostic biomarker and therapeutic target for HCC.