Abstract
Background
Hepatitis delta virus (HDV) coinfects with hepatitis B virus (HBV) causing the most severe form of viral hepatitis. However, its exact global disease burden remains largely ...obscure. We aim to establish the global epidemiology, infection mode-stratified disease progression, and clinical outcome of HDV infection.
Methods
We conducted a meta-analysis with a random-effects model and performed data synthesis.
Results
The pooled prevalence of HDV is 0.80% (95% confidence interval CI, 0.63–1.00) among the general population and 13.02% (95% CI, 11.96–14.11) among HBV carriers, corresponding to 48–60 million infections globally. Among HBV patients with fulminant hepatitis, cirrhosis, or hepatocellular carcinoma, HDV prevalence is 26.75% (95% CI, 19.84–34.29), 25.77% (95% CI, 20.62–31.27), and 19.80% (95% CI, 10.97–30.45), respectively. The odds ratio (OR) of HDV infection among HBV patients with chronic liver disease compared with asymptomatic controls is 4.55 (95% CI, 3.65–5.67). Hepatitis delta virus-coinfected patients are more likely to develop cirrhosis than HBV-monoinfected patients with OR of 3.84 (95% CI, 1.79–8.24). Overall, HDV infection progresses to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years, on average.
Conclusions
Findings suggest that HDV poses a heavy global burden with rapid progression to severe liver diseases, urging effective strategies for screening, prevention, and treatment.
Forty-eight to 60 million individuals are infected with HDV around the globe, and Asia and Africa are the worst-hit areas. HDV infection predisposes to rapid progression into severe liver diseases, particularly liver cirrhosis.
T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory receptor expressed on several types of lymphocytes. Efficacy of antibody blockade of TIGIT in cancer immunotherapy is currently ...widely being investigated in both pre-clinical and clinical studies. In multiple cancers TIGIT is expressed on tumor-infiltrating cytotoxic T cells, helper T cells, regulatory T cells and NK cells, and its main ligand CD155 is expressed on tumor-infiltrating myeloid cells and upregulated on cancer cells, which contributes to local suppression of immune-surveillance. While single TIGIT blockade has limited anti-tumor efficacy, pre-clinical studies indicate that co-blockade of TIGIT and PD-1/PD-L1 pathway leads to tumor rejection, notably even in anti-PD-1 resistant tumor models. Among inhibitory immune checkpoint molecules, a unique property of TIGIT blockade is that it enhances not only anti-tumor effector T-cell responses, but also NK-cell responses, and reduces the suppressive capacity of regulatory T cells. Numerous clinical trials on TIGIT-blockade in cancer have recently been initiated, predominantly combination treatments. The first interim results show promise for combined TIGIT and PD-L1 co-blockade in solid cancer patients. In this review, we summarize the current knowledge and identify the gaps in our current understanding of TIGIT's roles in cancer immunity, and provide, based on these insights, recommendations for its positioning in cancer immunotherapy.
Interferon-stimulated genes (ISGs) are a group of gene products that coordinately combat pathogen invasions, in particular viral infections. Transcription of ISGs occurs rapidly upon pathogen ...invasion, and this is classically provoked via activation of the Janus kinase/signal transducer and activator of transcription (JAK–STAT) pathway, mainly by interferons (IFNs). However, a plethora of recent studies have reported a variety of non-canonical mechanisms regulating ISG transcription. These new studies are extremely important for understanding the quantitative and temporal differences in ISG transcription under specific circumstances. Because these canonical and non-canonical regulatory mechanisms are essential for defining the nature of host defense and associated detrimental proinflammatory effects, we comprehensively review the state of this rapidly evolving field and the clinical implications of recently acquired knowledge in this respect.
As the central dogma of molecular biology, genetic information flows from DNA through transcription into RNA followed by translation of the message into protein by transfer RNAs (tRNAs). However, ...mRNA translation is not always perfect, and errors in the amino acid composition may occur. Mistranslation is generally well tolerated, but once it reaches superphysiological levels, it can give rise to a plethora of diseases. The key causes of mistranslation are errors in translational decoding of the codons in mRNA. Such errors mainly derive from tRNA misdecoding and misacylation, especially when certain codon-paired tRNA species are missing. Substantial progress has recently been made with respect to the mechanistic basis of erroneous mRNA decoding as well as the resulting consequences for physiology and pathology. Here, we aim to review this progress with emphasis on viral evolution and cancer development.
A prominent mucinous phenotype is observed in 10–15% of all colorectal cancers (CRCs). They are associated with a proximal location, and more commonly observed among tumors with mismatch repair ...defects and a promoter CpG methylator phenotype. However, none of these features has been clearly linked mechanistically to this mucinous subtype. Here, we propose that bacterial biofilms could represent a currently unappreciated contributor to mucinous CRC formation. The colonic microbiome and biofilms in particular, are emerging as important factors in tumor initiation and progression. Intriguingly, biofilms preferentially accompany proximal tumors, suggesting that there may be a direct mechanistic link with mucinous CRCs.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology updated from non-alcoholic fatty liver disease (NAFLD). In this study, we aim to estimate the global prevalence of ...MAFLD specifically in overweight and obese adults from the general population by performing a systematic review and meta-analysis through mining the existing epidemiological data on fatty liver disease.
We searched Medline, Embase, Web of Science, Cochrane and google scholar database from inception to November, 2020. DerSimonian-Laird random-effects model with Logit transformation was performed for data analysis. Sensitivity analysis and meta-regression were used to explore predictors of MAFLD prevalence in pooled statistics with high heterogeneity.
We identified 116 relevant studies comprised of 2,667,052 participants in general population with an estimated global MAFLD prevalence as 50.7% (95% CI 46.9-54.4) among overweight/obese adults regardless of diagnostic techniques. Ultrasound was the most commonly used diagnostic technique generating prevalence rate of 51.3% (95% CI, 49.1-53.4). Male (59.0%; 95% CI, 52.0-65.6) had a significantly higher MAFLD prevalence than female (47.5%; 95% CI, 40.7-54.5). Interestingly, MAFLD prevalence rates are comparable based on classical NAFLD and non-NAFLD studies in general population. The pooled estimate prevalence of comorbidities such as type 2 diabetes and metabolic syndrome was 19.7% (95% CI, 12.8-29.0) and 57.5% (95% CI, 49.9-64.8), respectively.
MAFLD has an astonishingly high prevalence rate in overweight and obese adults. This calls for attention and dedicated action from primary care physicians, specialists, health policy makers and the general public alike.
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Intermittent fasting is a popular dietary intervention with perceived relatively easy compliance and is linked to various health benefits, including weight loss and improvement in blood glucose ...concentrations. The mechanistic explanations underlying the beneficial effects of intermittent fasting remain largely obscure but may involve alterations in the gut microbiota.
We sought to establish the effects of 1 mo of intermittent fasting on the gut microbiome.
We took advantage of intermittent fasting being voluntarily observed during the Islamic faith-associated Ramadan and sampled feces and blood, as well as collected longitudinal physiologic data in 2 cohorts, sampled in 2 different years. The fecal microbiome was determined by 16S sequencing. Results were contrasted to age- and body weight–matched controls and correlated to physiologic parameters (e.g., body mass and calorie intake).
We observed that Ramadan-associated intermittent fasting increased microbiome diversity and was specifically associated with upregulation of the Clostridiales order–derived Lachnospiraceae no fasting 24.6 ± 13.67 compared with fasting 39.7 ± 15.9 in relative abundance (%); linear discriminant analysis = 4.9, P < 0.001 by linear discriminant analysis coupled with effect size measurements and Ruminococcaceae no fasting 13.4 ± 6.9 compared with fasting 23.2 ± 12.9 in relative abundance (%); linear discriminant analysis = 4.7, P < 0.001 by linear discriminant analysis coupled with effect size measurements bacterial families. Microbiome composition returned to baseline upon cessation of intermittent feeding. Furthermore, changes in Lachnospiraceae concentrations mirrored intermittent fasting–provoked changes in physiologic parameters.
Intermittent fasting provokes substantial remodeling of the gut microbiome. The intermittent fasting–provoked upregulation of butyric acid–producing Lachnospiraceae provides an obvious possible mechanistic explanation for health effects associated with intermittent fasting.
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Intestinal microbiota have emerged as an important factor in colorectal cancer (CRC) initiation and progression. The currently prominent view on bacterial tumorigenesis is that CRC initiation is ...triggered by local mucosal colonization with specific pathogens (drivers), and that subsequent changes in the peritumoral environment allow colonization by opportunistic (passenger) microbes, further facilitating disease progression. Screening for CRC ‘driver-passenger’ microorganisms might thus allow early CRC diagnosis or preventive intervention. Such efforts are now being revolutionized by the notion that CRC initiation and progression require organization of bacterial communities into higher-order structures termed biofilms. We explore here the concept that a polymicrobial biofilm promotes pro-carcinogenic activities that may partially underlie progression along the adenoma–CRC axis.
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