Associations of diet with infectious diseases in UK Biobank.

This research aims to utilize multivariate logistic regression to explore associations between the frequency of 13 food groups intake (or four diet groups) and infectious diseases. 487849 participants from the UK Biobank were enrolled, and 75209 participants were diagnosed with infectious diseases. Participants reporting the highest intake frequency of processed meat [odds ratio ( OR) = 1.0964; 95% CI: 1.0622-1.1318] and red meat ( OR = 1.0895; 95% CI: 1.0563-1.1239) had a higher risk of infectious diseases compared to those with the lowest intake frequency. Consuming fish 2.0-2.9 times ( OR = 0.8221; 95% CI: 0.7955-0.8496), cheese ≥5.0 times ( OR = 0.8822; 95% CI: 0.8559-0.9092), fruit 3.0-3.9 servings ( OR = 0.8867; 95% CI: 0.8661-0.9078), and vegetables 2.0-2.9 servings ( OR = 0.9372; 95% CI: 0.9189-0.9559) per week were associated with a lower risk of infection. Low meat-eaters ( OR = 0.9404; 95% CI: 0.9243-0.9567), fish-eaters ( OR = 0.8391; 95% CI: 0.7887-0.8919), and vegetarians ( OR = 0.9154; 95% CI: 0.8561-0.9778) had a lower risk of infectious diseases compared to regular meat-eaters. Mediation analysis was performed, revealing glycosylated hemoglobin, white blood cell counts, and body mass index were mediators in the relationships between diet groups and infectious diseases. This study suggested that intake frequency of food groups is a factor in infectious diseases and fish-eaters have a lower risk of infection.

Evaluating short-term and long-term liver fibrosis improvement in hepatitis C patients post-DAA treatment.

Despite achieving a high cure rate with direct-acting antivirals (DAAs) in hepatitis C treatment, further research is needed to identify additional benefits of the DAA therapy. The current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs, who also achieved sustained virologic response (SVR). Using the fibrosis-4 (FIB-4) index, patients were categorized based on their baseline fibrosis level, and improvements in fibrosis were analyzed in both the short-term (9-26 weeks) and long-term (≥ 36 weeks) follow-up. The results showed a significant decrease in the FIB-4 index, indicating an improvement in liver fibrosis, in 63.00% of the patients during the short-term follow-up and 67.56% during the long-term follow-up. Short-term improvement was associated with factors including ribavirin (RBV) usage, blood cholinesterase levels, alanine transaminase levels, albumin levels, and the baseline FIB-4 index. Additionally, long-term improvement was associated with factors such as aspartate transaminase levels, total protein level, and the baseline FIB-4 index. The current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis, providing crucial insights for enhancing patient care in hepatitis C management.

Epidemiology of acute hepatitis C and hepatitis C virus-related cirrhosis in reproductive-age women, 1990-2019: An analysis of the Global Burden of Disease study.

Background: The current study uniquely focuses on the global incidence and temporal trends of acute hepatitis C (AHC) and hepatitis C virus (HCV)-related cirrhosis among women of reproductive age (15-49 years) from 1990-2019. The risk of vertical transmission and adverse perinatal outcomes associated with HCV infection underscores the importance of prioritising these women in HCV prevention efforts. Methods: Leveraging the Global Burden of Disease 2019 data, we calculated age-standardised incidence rates (ASIR) and assessed temporal trends via the average annual percent change from joinpoint regression. The age-period-cohort model was employed to understand further the effects of age, period, and birth cohort. Results: Over the 30 years, global incidences of AHC and HCV-related cirrhosis in reproductive-age women increased by 46.45 and 72.74%, respectively. The ASIR of AHC was highest in low sociodemographic index regions but showed a declining trend. Conversely, the ASIR of HCV-related cirrhosis displayed unfavourable trends in low, low-middle, and high sociodemographic index regions. Special attention is necessary for sub-Saharan Africa, high-income North America, Eastern Europe, and Central Asia due to their high incidence rates or increasing trends of AHC and HCV-related cirrhosis. Notably, the age-period-cohort model suggests a recent resurgence in AHC and HCV-related cirrhosis risk. Conclusions: The current study is the first to thoroughly evaluate the trends of AHC and HCV-related cirrhosis among reproductive-age women, shedding light on previously unexplored aspects of HCV epidemiology. Our findings identify critical areas where health care systems must adapt to the changing dynamics of HCV infection. The detailed stratification by region and nation further enables the development of localised prevention and treatment strategies.

Gut microbial features may influence antiviral IgG levels after vaccination against viral respiratory infectious diseases: the evidence from two-sample bidirectional mendelian randomization.

BACKGROUND: Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels. METHODS: We conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels. To make the results more reliable, we used four robust methods and performed comprehensive sensitivity analyses. RESULTS: The MR analyses revealed 26, 13, 20, and 18 causal associations of the gut microbial features influencing four IgG levels separately. ​Interestingly, ten microbial features, like genus Collinsella, species Bifidobacterium longum, and the biosynthesis of L-alanine have shown the capacity to regulate multiple IgG levels with consistent direction (rise or fall). The ​reverse MR analysis suggested several potential causal associations of IgG levels affecting microbial features. CONCLUSIONS: The human immune response against viral respiratory infectious diseases could be modulated by changing the abundance of gut microbes, which provided new approaches for the intervention of viral respiratory infections.

Leveraging baseline transcriptional features and information from single-cell data to power the prediction of influenza vaccine response.

Introduction: Vaccination is still the primary means for preventing influenza virus infection, but the protective effects vary greatly among individuals. Identifying individuals at risk of low response to influenza vaccination is important. This study aimed to explore improved strategies for constructing predictive models of influenza vaccine response using gene expression data. Methods: We first used gene expression and immune response data from the Immune Signatures Data Resource (IS2) to define influenza vaccine response-related transcriptional expression and alteration features at different time points across vaccination via differential expression analysis. Then, we mapped these features to single-cell resolution using additional published single-cell data to investigate the possible mechanism. Finally, we explored the potential of these identified transcriptional features in predicting influenza vaccine response. We used several modeling strategies and also attempted to leverage the information from single-cell RNA sequencing (scRNA-seq) data to optimize the predictive models. Results: The results showed that models based on genes showing differential expression (DEGs) or fold change (DFGs) at day 7 post-vaccination performed the best in internal validation, while models based on DFGs had a better performance in external validation than those based on DEGs. In addition, incorporating baseline predictors could improve the performance of models based on days 1-3, while the model based on the expression profile of plasma cells deconvoluted from the model that used DEGs at day 7 as predictors showed an improved performance in external validation. Conclusion: Our study emphasizes the value of using combination modeling strategy and leveraging information from single-cell levels in constructing influenza vaccine response predictive models.

Integrating single-cell RNA sequencing data to genome-wide association analysis data identifies significant cell types in influenza A virus infection and COVID-19.

With the global pandemic of COVID-19, the research on influenza virus has entered a new stage, but it is difficult to elucidate the pathogenesis of influenza disease. Genome-wide association studies (GWASs) have greatly shed light on the role of host genetic background in influenza pathogenesis and prognosis, whereas single-cell RNA sequencing (scRNA-seq) has enabled unprecedented resolution of cellular diversity and in vivo following influenza disease. Here, we performed a comprehensive analysis of influenza GWAS and scRNA-seq data to reveal cell types associated with influenza disease and provide clues to understanding pathogenesis. We downloaded two GWAS summary data, two scRNA-seq data on influenza disease. After defining cell types for each scRNA-seq data, we used RolyPoly and LDSC-cts to integrate GWAS and scRNA-seq. Furthermore, we analyzed scRNA-seq data from the peripheral blood mononuclear cells (PBMCs) of a healthy population to validate and compare our results. After processing the scRNA-seq data, we obtained approximately 70 000 cells and identified up to 13 cell types. For the European population analysis, we determined an association between neutrophils and influenza disease. For the East Asian population analysis, we identified an association between monocytes and influenza disease. In addition, we also identified monocytes as a significantly related cell type in a dataset of healthy human PBMCs. In this comprehensive analysis, we identified neutrophils and monocytes as influenza disease-associated cell types. More attention and validation should be given in future studies.

Accurate prediction of HCC risk after SVR in patients with hepatitis C cirrhosis based on longitudinal data.

BACKGROUND: Most existing predictive models of hepatocellular carcinoma (HCC) risk after sustained virologic response (SVR) are built on data collected at baseline and therefore have limited accuracy. The current study aimed to construct an accurate predictive model incorporating longitudinal data using a novel modeling strategy. The predictive performance of the longitudinal model was also compared with a baseline model. METHODS: A total of 400 patients with HCV-related cirrhosis who achieved SVR with direct-acting antivirals (DAA) were enrolled in the study. Patients were randomly divided into a training set (70%) and a validation set (30%). Informative features were extracted from the longitudinal variables and then put into the random survival forest (RSF) to develop the longitudinal model. A baseline model including the same variables was built for comparison. RESULTS: During a median follow-up time of approximately 5 years, 25 patients (8.9%) in the training set and 11 patients (9.2%) in the validation set developed HCC. The areas under the receiver-operating characteristics curves (AUROC) for the longitudinal model were 0.9507 (0.8838-0.9997), 0.8767 (0.6972,0.9918), and 0.8307 (0.6941,0.9993) for 1-, 2- and 3-year risk prediction, respectively. The brier scores of the longitudinal model were also relatively low for the 1-, 2- and 3-year risk prediction (0.0283, 0.0561, and 0.0501, respectively). In contrast, the baseline model only achieved mediocre AUROCs of around 0.6 (0.6113, 0.6213, and 0.6480, respectively). CONCLUSIONS: Our longitudinal model yielded accurate predictions of HCC risk in patients with HCV-relate cirrhosis, outperforming the baseline model. Our model can provide patients with valuable prognosis information and guide the intensity of surveillance in clinical practice.

Using multi-tissue transcriptome-wide association study to identify candidate susceptibility genes for respiratory infectious diseases.

Objective: We explore the candidate susceptibility genes for influenza A virus (IAV), measles, rubella, and mumps and their underlying biological mechanisms. Methods: We downloaded the genome-wide association study summary data of four virus-specific immunoglobulin G (IgG) level data sets (anti-IAV IgG, anti-measles IgG, anti-rubella IgG, and anti-mumps virus IgG levels) and integrated them with reference models of three potential tissues from the Genotype-Tissue Expression (GTEx) project, namely, whole blood, lung, and transformed fibroblast cells, to identify genes whose expression is predicted to be associated with IAV, measles, mumps, and rubella. Results: We identified 19 significant genes (ULK4, AC010132.11, SURF1, NIPAL2, TRAP1, TAF1C, AC000078.5, RP4-639F20.1, RMDN2, ATP1B3, SRSF12, RP11-477D19.2, TFB1M, XXyac-YX65C7_A.2, TAF1C, PCGF2, and BNIP1) associated with IAV at a Bonferroni-corrected threshold of p < 0.05; 14 significant genes (SOAT1, COLGALT2, AC021860.1, HCG11, METTL21B, MRPL10, GSTM4, PAQR6, RP11-617D20.1, SNX8, METTL21B, ANKRD27, CBWD2, and TSFM) associated with measles at a Bonferroni-corrected threshold of p < 0.05; 15 significant genes (MTOR, LAMC1, TRIM38, U91328.21, POLR2J, SCRN2, Smpd4, UBN1, CNTROB, SCRN2, HOXB-AS1, SLC14A1, AC007566.10, AC093668.2, and CPD) associated with mumps at a Bonferroni-corrected threshold of p < 0.05; and 13 significant genes (JAGN1, RRP12, RP11-452K12.7, CASP7, AP3S2, IL17RC, FAM86HP, AMACR, RRP12, PPP2R1B, C11orf1, DLAT, and TMEM117) associated with rubella at a Bonferroni-corrected threshold of p < 0.05. Conclusions: We have identified several candidate genes for IAV, measles, mumps, and rubella in multiple tissues. Our research may further our understanding of the pathogenesis of infectious respiratory diseases.

The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study.

Sleep can affect nonalcoholic fatty liver disease (NAFLD). We investigated the association between sleep duration, sleep quality, and NAFLD. From January to December 2018, 1,073 patients (age: 37.94 ± 10.88, Body Mass Index (BMI): 22.85 ± 3.27) were enrolled. Pittsburgh Sleep Quality Index Questionnaire and Munich Chronotype Questionnaire were used to assess sleep duration, quality, and habits. Ultrasonography was used to diagnose NAFLD. Multivariate logistic regression models were used to calculate the odds ratio (OR) and 95% confidence interval (CI) of the risk of NAFLD by different types of sleep duration and sleep quality. No significant differences in sleep time, sleep quality, and sleep habits between the NAFLD and the non-NAFLD groups were observed (P > 0.05). There was no correlation between sleep duration and NAFLD in the whole cohort. After adjusting for age, exercise, fasting plasma glucose, and BMI, the group with long sleep duration showed a decreased risk of NAFLD in men (OR = 0.01, 95% CI: 0.001-0.27, P = 0.032). However, in all four adjusted models, no correlation between sleep duration, quality, and NAFLD was found in women. In conclusion, sleep duration was significantly and negatively associated with NAFLD in men but not women. Prospective studies are required to confirm this association.

Genetic variants of IFIH1 and DHX58 affect the chronicity of hepatitis C in the Chinese Han population.

Hepatitis C remains a major public health problem in the world. The host immune system plays a key role in viral clearance. This study aimed to investigate the connection between retinoic acid-inducible gene I-like (RIG-I-like) receptor gene polymorphism and hepatitis C chronicity in the Chinese Han population. The current study genotyped three SNPs (IFIH1 rs10930046 and DHX58 rs2074158, rs2074160) to assess their association with the chronicity of hepatitis C virus (HCV) infection among 1,590 participants (590 spontaneous HCV clearance cases and 1,000 persistent infection patients). Our research shows that DHX58 rs2074158-G allele (dominant model: adjusted OR = 1.53, 95% CI [1.20-1.95], P = 0.001; additive model: adjusted OR = 1.50, 95% CI [1.27-1.78], P < 0.001) and IFIH1 rs10930046-C allele (additive model: adjusted OR = 1.26, 95% CI [1.07-1.49], P = 0.005) were associated with chronic hepatitis C (CHC). And the risk of CHC increased in people carrying more unfavorable genotypes (rs2074158-AG/GG or rs10930046-CC), with the chronic rates for genotypes number from zero to two in 60.69%, 57.33%, and 85.93%, respectively (adjusted OR = 3.64, 95% CI [2.18-6.08]; P < 0.001). Genetic polymorphism of IFIH1 and DHX58 may be related to CHC in the Chinese Han population. Furthermore, the risk of CHC increases as the number of unfavorable genotypes carried by the HCV-infected person increases. IFIH1 rs10930046, DHX58 rs2074158, age, ALT, and AST levels were all independent predictors of CHC.

Associations of socioeconomic status with infectious diseases mediated by lifestyle, environmental pollution and chronic comorbidities: a comprehensive evaluation based on UK Biobank.

BACKGROUND: Socioeconomic status (SES) inequity was recognized as a driver of some certain infectious diseases. However, few studies evaluated the association between SES and the burden of overall infections, and even fewer identified preventable mediators. This study aimed to assess the association between SES and overall infectious diseases burden, and the potential roles of factors including lifestyle, environmental pollution, chronic disease history. METHODS: We included 401,009 participants from the UK Biobank (UKB) and defined the infection status for each participant according to their diagnosis records. Latent class analysis (LCA) was used to define SES for each participant. We further defined healthy lifestyle score, environment pollution score (EPS) and four types of chronic comorbidities. We used multivariate logistic regression to test the associations between the four above covariates and infectious diseases. Then, we performed the mediation and interaction analysis to explain the relationships between SES and other variables on infectious diseases. Finally, we employed seven types of sensitivity analyses, including considering the Townsend deprivation index as an area level SES variable, repeating our main analysis for some individual or composite factors and in some subgroups, as well as in an external data from the US National Health and Nutrition Examination Survey, to verify the main results. RESULTS: In UKB, 60,771 (15.2%) participants were diagnosed with infectious diseases during follow-up. Lower SES [odds ratio (OR) = 1.5570] were associated with higher risk of overall infections. Lifestyle score mediated 2.9% of effects from SES, which ranged from 2.9 to 4.0% in different infection subtypes, while cardiovascular disease (CVD) mediated a proportion of 6.2% with a range from 2.1 to 6.8%. In addition, SES showed significant negative interaction with lifestyle score (OR = 0.8650) and a history of cancer (OR = 0.9096), while a significant synergy interaction was observed between SES and EPS (OR = 1.0024). In subgroup analysis, we found that males and African (AFR) with lower SES showed much higher infection risk. Results from sensitivity and validation analyses showed relative consistent with the main analysis. CONCLUSIONS: Low SES is shown to be an important risk factor for infectious disease, part of which may be mediated by poor lifestyle and chronic comorbidities. Efforts to enhance health education and improve the quality of living environment may help reduce burden of infectious disease, especially for people with low SES.

Diversity of Circulating NKT Cells in Defense against Carbapenem-Resistant Klebsiella Pneumoniae Infection.

Nosocomial infection caused by carbapenem-resistant Klebsiella pneumonia (CRKP) infection has become a global public health problem. Human NK and NKT cells in peripheral immune responses are recognized as occupying a critical role in anti-bacterial immunity. Through performed scRNA-seq on serial peripheral blood samples from 3 patients with CRKP undergoing colonization, infection, and recovery conditions, we were able to described the immune responses of NK and NKT cells during CRKP infection and identified a mechanism that could contribute to CRKP clearance. The central player of CRKP infection process appears to be the NKT subset and CD56hiNKT subset which maintained immune competence during CRKP colonization. With time, CRKP leads to the loss of NK and CD160hiNKT cells in peripheral blood, resulting in suppressed immune responses and increased susceptibility to opportunistic infection. In summary, our study identified a possible mechanism for the CRKP invasion and to decipher the clues behind the host immune response that influences CRKP infection pathogenesis.

Trajectories of De Ritis ratio with risk of hepatocellular carcinoma and liver-related mortality following direct-acting antivirals for HCV: a retrospective longitudinal study up to 10 years.

The De Ritis ratio has good diagnostic accuracy in patients with chronic viral liver disease. However, its prognostic utility has remained controversial. This study was to identify different trajectories of De Ritis ratio in those hepatitis C patients cured and analyze the relationship between trajectory groups and risk of hepatocellular carcinoma (HCC) with liver-related mortality by the retrospective cohort study. This retrospective longitudinal cohort included 1241 patients with hepatitis C who underwent antiviral therapy since follow-up in 2012. De Ritis ratio trajectories were identified by the latent class growth mixed model. Patients were grouped into subgroups by De Ritis ratio according to longitudinal trajectories. The endpoints were HCC and liver-related mortality. Three distinct trajectory groups were characterized for serum De Ritis ratio: low-stable, middle-stable and high-rising. Fifty-one HCC and 11 liver-related mortality were recorded and tracked. Compared to the low-stable group, the adjusted hazard ratios (HRs) and 95% confidence interval (CI) associated with HCC and liver-related mortality were 2.02 (1.12 to 3.63), 9.36 (3.61 to 24.29), for the middle-stable, and high-rising group, respectively. Notably, the high-rising trajectory group still had prognostic significance after adjusting for preoperative levels. Likewise, for the high-rising trajectory group of sustained virological response, the HRs (95% CI) were 2.85 (1.03 to 10.75) for HCC and liver-related mortality, and in patients with cirrhosis, the HRs (95% CI) were 3.44 (1.64 to 7.19) and 4.35 (1.27 to 14.84) in the middle-stable trajectory group and the high-rising trajectory group, respectively. The dynamic measurements of De Ritis ratio are recommended to monitor the prognosis of Hepatitis C patients.

Identifying and Exploring the Candidate Susceptibility Genes of Cirrhosis Using the Multi-Tissue Transcriptome-Wide Association Study.

Objective: We identify and explore the candidate susceptibility genes for cirrhosis and their underlying biological mechanism. Methods: We downloaded the genome-wide association studies summary data of 901 cirrhosis cases and 451,363 controls and integrated them with reference models of five potential tissues from the Genotype-Tissue Expression (GTEx) Project, including whole blood, liver, pancreas, spleen, and thyroid, to identify genes whose expression is predicted to be associated with cirrhosis. Then, we downloaded gene expression data of individuals with hepatocellular carcinoma from TCGA database to conduct differential expression analysis to validate these identified genes and explored their possible role in driving cirrhosis via functional enrichment and gene set enrichment analysis (GSEA). Results: We identified 10 significant genes (SKIV2L, JPH4, UQCC2, RP11-91I8.3, MAU2, ERAP1, PUS3, ZNF677, ARHGAP40, and SHANK3) associated with cirrhosis at a Bonferroni-corrected threshold of p < 0.01, among which two (SKIV2L and JPH4) were identified in the liver and five (SKIV2L, JPH4, MAU2, SHANK3, and UQCC2) were validated by differential expression analysis at an FDR-corrected threshold of p < 0.01. The enrichment analysis showed that the degradation process of RNA, which is enriched by 58 genes, is significantly under-enriched in liver cancer tissues (p = 0.0268). Conclusion: We have identified several candidate genes for cirrhosis in multiple tissues and performed differential genetic analysis using the liver cancer database to verify the significant genes. We found that the genes SKIV2L and JPH4 identified in the liver are of particular concern. Finally, through enrichment analysis, we speculate that the process of mRNA transcription and RNA degradation may play a role in cirrhosis.

Genetic and hosts characterization of hantaviruses in port areas in Hainan Province, P. R. China.

BACKGROUND: Hantaviruses (HVs) are major zoonotic pathogens in China that cause hemorrhagic fever with renal syndrome (HFRS) posing a major threat to people's health. Hainan Province, an island located in Southeast China, is an ideal region for sea ports. The unique tropical monsoon climate in Hainan provides sufficient living conditions for rodents, which help spread HVs and other rodent-borne diseases. In the routine monitoring of hantavirus, there was no evidence that rodents in Hainan carried hantavirus. No patients infected with hantavirus were found in the past. However, the surveillance of HVs-carrying rodents covering the whole territory of Hainan has not stopped. METHODOLOGY/PRINCIPAL FINDINGS: For the monitoring of the prevalence of HVs in rodents and the search for theoretical reference for rodent control and HFRS prevention, a total of 60 rodents from 6 monitoring spots were trapped around main ports in Hainan between 2016 and 2019. HV positive samples were identified by a specific kit and sequenced. The data indicated that seven rodents (Rattus norvegicus) were positive for hantavirus with a positivity rate of 11.67%. Phylogenetic analysis suggested that the two complete sequence strains HN1 and HN4 in this research were highly similar to the sequence strains GZRn36 and GZRn148 isolated in Guangdong Province, and they located in the same phylogenetic tree branch which belongs to S2 subtype. Although the two partial sequences HT1 and HT2 isolated in Xisha Islands belong to S2 subtype according to the phylogenetic tree of L segment, they showed a great nucleotide difference with HN1 and HN4. We also found 13 amino acid variations compared with SEOV 80-39 and 6 amino acid mutations related to epitope, and the variations may reduce the effectiveness of the current HFRS vaccines used in humans. CONCLUSIONS/SIGNIFICANCE: The study indicated HVs carried by rodents found in Hainan Province may be transmitted from Guangdong Province through trading ports and carriage of goods by sea. So it is of great significance to strengthen the surveillance of rodents in port areas especially capture and eliminate rodents on ship. Timely elimination of host animals of hantavirus in port areas is necessary to prevent an outbreak of HVs disease.

Repeated Measurement of FIB-4 to Predict Long-Term Risk of HCC Development Up to 10 Years After SVR.

Purpose: It is unclear whether and how the long-term risk of hepatocellular carcinoma (HCC) will change in hepatitis C virus (HCV) infected patients who have reached sustained virologic response (SVR) with direct-acting antivirals (DAA). In this study, we assessed the long-term risk of HCC up to 10 years after SVR using fibrosis 4 score (FIB-4) and its dynamic changes. Patients and Methods: A total of 701 DAA-treated patients who achieved SVR between January 2012 to October 2020 were enrolled in the study. The FIB-4 score of each patient was measured at the date of SVR and each follow-up visit annually. Patients were followed until December 31, 2021, with the longest follow-up time being 9.82 years. Results: Following SVR, 27 cases of HCC were observed. The annual incidence rate of HCC remained stable with no obvious downward trend. Patients with a FIB-4 >3.25 at baseline or anytime during follow-up were at a higher risk of developing HCC than those whose FIB-4 remained below 3.25. Patients with cirrhosis and patients with no cirrhosis but a FIB-4 >3.25 were at higher risk of developing HCC than patients with no cirrhosis and a FIB-4 ≦3.25. Conclusion: FIB-4 >3.25 measured at SVR or any time post-SVR was associated with HCC risks. The repeated measurement of FIB-4 revealed a better predictive ability of HCC risks than the simple measurement of FIB-4 at baseline. The additional stratification of patients by combining FIB-4 and cirrhosis leads to more accurately identifying high-risk patients. Surveillance of HCC is recommended for virologically cured patients with a FIB-4 >3.25 at SVR or anytime afterward and patients diagnosed with cirrhosis.

The Causal Effects of Primary Biliary Cholangitis on Thyroid Dysfunction: A Two-Sample Mendelian Randomization Study.

Background: Primary biliary cholangitis (PBC) is an autoimmune disease and is often accompanied by thyroid dysfunction. Understanding the potential causal relationship between PBC and thyroid dysfunction is helpful to explore the pathogenesis of PBC and to develop strategies for the prevention and treatment of PBC and its complications. Methods: We used a two-sample Mendelian randomization (MR) method to estimate the potential causal effect of PBC on the risk of autoimmune thyroid disease (AITD), thyroid-stimulating hormone (TSH) and free thyroxine (FT4), hyperthyroidism, hypothyroidism, and thyroid cancer (TC) in the European population. We collected seven datasets of PBC and related traits to perform a series MR analysis and performed extensive sensitivity analyses to ensure the reliability of our results. Results: Using a sensitivity analysis, we found that PBC was a risk factor for AITD, TSH, hypothyroidism, and TC with odds ratio (OR) of 1.002 (95% CI: 1.000-1.005, p = 0.042), 1.016 (95% CI: 1.006-1.027, p = 0.002), 1.068 (95% CI: 1.022-1.115, p = 0.003), and 1.106 (95% CI: 1.019-1.120, p = 0.042), respectively. Interestingly, using reverse-direction MR analysis, we also found that AITD had a significant potential causal association with PBC with an OR of 0.021 (p = 5.10E-4) and that the other two had no significant causal relation on PBC. Conclusion: PBC causes thyroid dysfunction, specifically as AITD, mild hypothyroidism, and TC. The potential causal relationship between PBC and thyroid dysfunction provides a new direction for the etiology of PBC.

Willingness of Chinese Men Who Have Sex With Men to Use Smartphone-Based Electronic Readers for HIV Self-testing: Web-Based Cross-sectional Study.

BACKGROUND: The need for strategies to encourage user-initiated reporting of results after HIV self-testing (HIVST) persists. Smartphone-based electronic readers (SERs) have been shown capable of reading diagnostics results accurately in point-of-care diagnostics and could bridge the current gaps between HIVST and linkage to care. OBJECTIVE: Our study aimed to assess the willingness of Chinese men who have sex with men (MSM) in the Jiangsu province to use an SER for HIVST through a web-based cross-sectional study. METHODS: From February to April 2020, we conducted a convenience web-based survey among Chinese MSM by using a pretested structured questionnaire. Survey items were adapted from previous HIVST feasibility studies and modified as required. Prior to answering reader-related questions, participants watched a video showcasing a prototype SER. Statistical analysis included descriptive analysis, chi-squared test, and multivariable logistic regression. P values less than .05 were deemed statistically significant. RESULTS: Of 692 participants, 369 (53.3%) were aged 26-40 years, 456 (65.9%) had ever self-tested for HIV, and 493 (71.2%) were willing to use an SER for HIVST. Approximately 98% (483/493) of the willing participants, 85.3% (459/538) of ever self-tested and never self-tested, and 40% (46/115) of unwilling participants reported that SERs would increase their HIVST frequency. Engaging in unprotected anal intercourse with regular partners compared to consistently using condoms (adjusted odds ratio [AOR] 3.04, 95% CI 1.19-7.74) increased the odds of willingness to use an SER for HIVST. Participants who had ever considered HIVST at home with a partner right before sex compared to those who had not (AOR 2.99, 95% CI 1.13-7.90) were also more willing to use an SER for HIVST. Playing receptive roles during anal intercourse compared to playing insertive roles (AOR 0.05, 95% CI 0.02-0.14) was associated with decreased odds of being willing to use an SER for HIVST. The majority of the participants (447/608, 73.5%) preferred to purchase readers from local Centers of Disease Control and Prevention offices and 51.2% (311/608) of the participants were willing to pay less than US $4.70 for a reader device. CONCLUSIONS: The majority of the Chinese MSM, especially those with high sexual risk behaviors, were willing to use an SER for HIVST. Many MSM were also willing to self-test more frequently for HIV with an SER. Further research is needed to ascertain the diagnostic and real-time data-capturing capacity of prototype SERs during HIVST.

Genetic Mutations in TNFSF11 Were Associated With the Chronicity of Hepatitis C Among Chinese Han Population.

Background: Recently, several studies have reported that the host immune response can be related to the RANKL/RANK/OPG signaling pathway. However, the associations of TNFSF11, TNFRSF11A, and TNFRSF11B gene polymorphisms in the RANKL/RANK/OPG pathway with hepatitis C virus (HCV) infection outcomes remain unclear. Methods: In this case-control study, 768 persistent HCV infection and 503 spontaneous HCV clearance cases, and 1,259 control subjects were included. The Taman-MGB probe method was utilized to detect TNFSF11 rs9525641, TNFRSF11A rs8686340, and TNFRSF11B rs2073618 genotypes. The distribution of three single nucleotide polymorphisms (SNPs) genotypes was analyzed using stata14.0. Results: SNPs rs9525641, rs8086340, and rs2073618 genotype frequencies followed the Hardy-Weinberg natural population equilibrium (p = 0.637, 0.250, and 0.113, respectively). Also, rs9525641 was significantly associated with HCV chronicity risk in recessive (OR = 1.203, 95% CI: 1.018-1.420, p = 0.030) and additive models (OR = 1.545, 95% CI: 1.150-2.075, p = 0.004). The stratified analysis showed that rs9525641 variant genotypes were associated with HCV chronicity among people older than 50 years (OR =1.562, 95% CI: 1.079-2.262, p = 0.018), females (OR = 1.667, 95% CI: 1.145-2.429, p = 0.008), ALT <40 U/L (OR = 1.532, 95% CI: 1.074-2.286, p = 0.018), and AST < 40 U/L (OR = 1.552, 95% CI: 1.095-2.201, p = 0.014). Conclusion: TNFRSF11 rs9525641 was significantly associated with HCV chronicity in the Chinese population.

The Causal Effects of Insomnia on Bipolar Disorder, Depression, and Schizophrenia: A Two-Sample Mendelian Randomization Study.

Psychiatric disorder, including bipolar disorder (BD), major depression (MDD), and schizophrenia (SCZ), affects millions of persons around the world. Understanding the disease causal mechanism underlying the three diseases and identifying the modifiable risk factors for them hold the key for the development of effective preventative and treatment strategies. We used a two-sample Mendelian randomization method to assess the causal effect of insomnia on the risk of BD, MDD, and SCZ in a European population. We collected one dataset of insomnia, three of BD, one of MDD, and three of SCZ and performed a meta-analysis for each trait, further verifying the analysis through extensive complementarity and sensitivity analysis. Among the three psychiatric disorders, we found that only insomnia is causally associated with MDD and that higher insomnia increases the risk of MDD. Specifically, the odds ratio of MDD increase of insomnia is estimated to be 1.408 [95% confidence interval (CI): 1.210-1.640, p = 1.03E-05] in the European population. The identified causal relationship between insomnia and MDD is robust with respect to the choice of statistical methods and is validated through extensive sensitivity analyses that guard against various model assumption violations. Our results provide new evidence to support the causal effect of insomnia on MDD and pave ways for reducing the psychiatric disorder burden.