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Journal of Hepatology Apr 2023Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein,...
BACKGROUND & AIMS
Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein, we performed a systematic review to determine its clinical utility.
METHODS
We evaluated the biological pathway of HBcrAg and performed a systematic review of PubMed for clinical trials, cohort studies, and case-control studies that evaluated the clinical utility of HBcrAg. The effectiveness of HBcrAg in predicting HBV-specific clinical events (e.g. HBeAg seroconversion, phases of CHB, HBsAg loss, treatment response, and relapse after stopping therapy) was examined using receiver-operating characteristic curves. The correlation coefficients of HBcrAg with HBV DNA, quantitative HBsAg (qHBsAg), HBV RNA, and cccDNA were summarised from published studies. Median values were used as estimates.
RESULTS
HBcrAg consists of three precore/core protein products: HBcAg, HBeAg, and a 22 kDa precore protein. HBcrAg assays have been associated with false-positive rates of 9.3% and false-negative rates of between 12-35% for CHB. The new iTACT-HBcrAg is more sensitive but does not reduce the false-positive rate. A PubMed search found 248 papers on HBcrAg, of which 59 were suitable for analysis. The clinical performance of HBcrAg was evaluated using AUROC analyses, with median AUROCs of 0.860 for HBeAg seroconversion, 0.867 for predicting HBeAg(-) hepatitis, 0.645 for HBsAg loss, 0.757 for treatment response, and 0.688 for relapse after stopping therapy. The median correlation coefficient (r) was 0.630 with HBV DNA, 0.414 with qHBsAg, 0.619 with HBV RNA and 0.550 with cccDNA. Correlation decreased during antiviral therapy, but combined biomarkers improved performance.
CONCLUSIONS
HBcrAg has a mixed performance and has a poor correlation with HBsAg loss and antiviral therapy, hence HBcrAg results should be interpreted with caution.
IMPACT AND IMPLICATIONS
Hepatitis B core-related antigen (HBcrAg) has been used to assess management of patients with chronic hepatitis B (CHB) without a systematic and critical Sreview of its performance. Our finding that HBcrAg had a false-positive rate of 9% and a false-negative rate of 12-35% raises concerns, although larger studies are needed for validation. A systematic review showed that the performance of HBcrAg was variable depending on the CHB endpoint; it was excellent at predicting HBeAg seroconversion and HBeAg-negative chronic hepatitis (vs. chronic infection), which should be its main use, but it was poor for relapse after stopping antiviral therapy and for HBsAg loss. HBcrAg results should be interpreted with considerable caution, particularly by physicians, researchers, guideline committees and agencies that approve diagnostic tests.
Topics: Humans; Hepatitis B Core Antigens; Hepatitis B, Chronic; Hepatitis B Surface Antigens; Hepatitis B e Antigens; DNA, Viral; Biomarkers; Antiviral Agents; RNA; Hepatitis B virus
PubMed: 36586590
DOI: 10.1016/j.jhep.2022.12.017 -
Traffic (Copenhagen, Denmark) Dec 2021Endoplasmic reticulum (ER)-to-Golgi trafficking is an essential and highly conserved cellular process. The coat protein complex-II (COPII) arm of the trafficking... (Review)
Review
Endoplasmic reticulum (ER)-to-Golgi trafficking is an essential and highly conserved cellular process. The coat protein complex-II (COPII) arm of the trafficking machinery incorporates a wide array of cargo proteins into vesicles through direct or indirect interactions with Sec24, the principal subunit of the COPII coat. Approximately one-third of all mammalian proteins rely on the COPII-mediated secretory pathway for membrane insertion or secretion. There are four mammalian Sec24 paralogs and three yeast Sec24 paralogs with emerging evidence of paralog-specific cargo interaction motifs. Furthermore, individual paralogs also differ in their affinity for a subset of sorting motifs present on cargo proteins. As with many aspects of protein trafficking, we lack a systematic and thorough understanding of the interaction of Sec24 with cargoes. This systematic review focuses on the current knowledge of cargo binding to both yeast and mammalian Sec24 paralogs and their ER export motifs. The analyses show that Sec24 paralog specificity of cargo (and cargo receptors) range from exclusive paralog dependence or preference to partial redundancy. We also discuss how the Sec24 secretion system is hijacked by viral (eg, VSV-G, Hepatitis B envelope protein) and bacterial (eg, the enteropathogenic Escherichia coli type III secretion system effector NleA/EspI) pathogens.
Topics: Animals; COP-Coated Vesicles; Endoplasmic Reticulum; Golgi Apparatus; Mammals; Membrane Proteins; Protein Transport; Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Secretory Pathway
PubMed: 34533884
DOI: 10.1111/tra.12817 -
BMC Infectious Diseases Jul 2019The differential diagnosis of Fever of Unknown Origin (FUO) is very extensive, and includes infectious diseases (ID), neoplasms and noninfectious inflammatory diseases...
BACKGROUND
The differential diagnosis of Fever of Unknown Origin (FUO) is very extensive, and includes infectious diseases (ID), neoplasms and noninfectious inflammatory diseases (NIID). Many FUO remain undiagnosed. Factors influencing the final diagnosis of FUO are unclear.
METHODS
To identify factors associated with FUO diagnostic categories, we performed a systematic review of classical FUO case-series published in 2005-2015 and including patients from 2000. Moreover, to explore changing over time, we compared these case-series with those published in 1995-2004.
RESULTS
Eighteen case-series, including 3164 patients, were included. ID were diagnosed in 37.8% of patients, NIID in 20.9%, and neoplasm in 11.6%, FUO were undiagnosed in 23.2%. NIIDs significantly increased over time. An association exists between study country income level and ID (increasing when the income decreases) and undiagnosed FUO (increasing when the income increases); even if not significant, the use of a pre-defined Minimal Diagnostic Work-up to qualify a fever as FUO seems to correlate with a lower prevalence of infections and a higher prevalence of undiagnosed FUO. The multivariate regression analysis shows significant association between geographic area, with ID being more frequent in Asia and Europe having the higher prevalence of undiagnosed FUO. Significant associations were found with model of study and FUO defining criteria, also.
CONCLUSIONS
Despite advances in diagnostics, FUO still remains a challenge, with ID still representing the first cause. The main factors influencing the diagnostic categories are the income and the geographic position of the study country.
Topics: Adult; Asia; Communicable Diseases; Diagnosis, Differential; Europe; Female; Fever of Unknown Origin; Humans; Inflammation; Male; Middle Aged; Neoplasms; Prevalence
PubMed: 31331269
DOI: 10.1186/s12879-019-4285-8 -
Food and Environmental Virology Sep 2023One of the most frequent causes of acute viral hepatitis is hepatitis E virus (HEV) causing 20 million infections worldwide each year and 44,000 deaths. Studies on HEV... (Review)
Review
One of the most frequent causes of acute viral hepatitis is hepatitis E virus (HEV) causing 20 million infections worldwide each year and 44,000 deaths. Studies on HEV in the Iberian Peninsula have been increasing through time with HEV infection being identified in humans and animals. The aim of the present systematic review was to compile and evaluate all the published data on HEV from studies performed in humans, animals and environmental samples in the Iberian Peninsula. The electronic databases Mendeley, PubMed, Scopus, and Web of Science were thoroughly searched, and research published up until February 01, 2023 were included. Resulting in a total of 151 eligible papers by full reading and application of PRISMA exclusion/inclusion criteria. Overall, the present review shows that several HEV genotypes, namely HEV-1, 3, 4, and 6 as well as Rocahepevirus, are circulating in humans, animals, and in the environment in the Iberian Peninsula. HEV-3 was the most common genotype circulating in humans in Portugal and Spain, as expected for developed countries, with HEV-1 only being detected in travelers and emigrants from HEV endemic regions. Spain is the biggest pork producer in Europe and given the high circulation of HEV in pigs, with HEV-3 being primarily associated to zoonotic transmission through consumption of swine meat and meat products, in our opinion, the introduction of an HEV surveillance system in swine and inclusion of HEV in diagnostic routines for acute and chronic human hepatitis would be important. Additionally, we propose that establishing a monitoring mechanism for HEV is crucial in order to gain a comprehensive understanding of the prevalence of this illness and the various strains present in the Iberian Peninsula, as well as their potential impact on public health.
Topics: Humans; Animals; Swine; Hepatitis E virus; Hepatitis E; Europe; Public Health; Meat; Genotype; Swine Diseases; Phylogeny
PubMed: 37434079
DOI: 10.1007/s12560-023-09560-5 -
Digestive Diseases and Sciences Nov 2021Chronic viral hepatitis is associated with a wide range of extrahepatic diseases; however, evidence on a link between chronic viral hepatitis and colorectal neoplasia is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic viral hepatitis is associated with a wide range of extrahepatic diseases; however, evidence on a link between chronic viral hepatitis and colorectal neoplasia is still lacking.
AIMS
To analyze the association between chronic viral hepatitis and prevalence of colorectal neoplasia.
METHODS
A systematic review of articles published in the MEDLINE, EMBASE, and Cochrane Library between 2000 and 2020 was performed. Subgroup analyses based on the types of colorectal neoplasia and the etiology of chronic viral hepatitis were conducted.
RESULTS
Twelve eligible studies with 48,428 hepatitis B virus (HBV) patients and 46,561 hepatitis C virus (HCV) patients were included. Chronic viral hepatitis was significantly associated with an increased risk of both colorectal adenoma (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.16-2.02; I = 83%) and colorectal cancer (CRC) (OR, 1.32; 95% CI, 1.08-1.61; I = 94%). The etiology of chronic viral hepatitis was an independent factor related to heterogeneity for CRC subgroup analysis revealed an increased risk of CRC in both HBV (OR, 1.18; 95% CI, 1.09-1.27; I = 37%) and HCV (OR, 1.88; 95% CI, 1.78-1.97; I = 0%). HCV was associated with an increased risk of colorectal adenoma (OR, 1.48; 95% CI, 1.22-1.79; I = 0%); however, HBV was not associated with an increased risk of colorectal adenoma and had considerable heterogeneity (OR, 1.65; 95% CI, 0.88-3.09; I = 90%).
CONCLUSION
Our meta-analysis showed that chronic viral hepatitis is associated with an increased risk of colorectal neoplasia. The strategy of stricter screening colonoscopy may benefit from patients with chronic viral hepatitis.
Topics: Colorectal Neoplasms; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Risk Factors
PubMed: 33433792
DOI: 10.1007/s10620-020-06745-x -
World Journal of Orthopedics Nov 2022Although the impact of microbial infections on orthopedic clinical outcomes is well recognized, the influence of viral infections on the musculoskeletal system might...
BACKGROUND
Although the impact of microbial infections on orthopedic clinical outcomes is well recognized, the influence of viral infections on the musculoskeletal system might have been underestimated.
AIM
To systematically review the available evidence on risk factors and musculoskeletal manifestations following viral infections and to propose a pertinent classification scheme.
METHODS
We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), the Reference Citation Analysis (RCA), and Scopus for completed studies published before January 30, 2021, to evaluate risk factors and bone and joint manifestations of viral infection in animal models and patient registries. Quality assessment was performed using SYRCLE's risk of bias tool for animal studies, Moga score for case series, Wylde score for registry studies, and Newcastle-Ottawa Scale for case-control studies.
RESULTS
Six human and four animal studies were eligible for inclusion in the qualitative synthesis. Hepatitis C virus was implicated in several peri- and post-operative complications in patients without cirrhosis after major orthopedic surgery. Herpes virus may affect the integrity of lumbar discs, whereas Ross River and Chikungunya viruses provoke viral arthritis and bone loss.
CONCLUSION
Evidence of moderate strength suggested that viruses can cause moderate to severe arthritis and osteitis. Risk factors such as pre-existing rheumatologic disease contributed to higher disease severity and duration of symptoms. Therefore, based on our literature search, the proposed clinical and pathogenetic classification scheme is as follows: (1) Viral infections of bone or joint; (2) Active bone and joint inflammatory diseases secondary to viral infections in other organs or tissues; and (3) Viral infection as a risk factor for post-surgical bacterial infection.
PubMed: 36439372
DOI: 10.5312/wjo.v13.i11.1015 -
Viruses Jul 2023Hepatitis delta virus (HDV) is the smallest known human virus and causes the most severe form of human viral hepatitis, yet it is still not fully understood how the... (Review)
Review
Hepatitis delta virus (HDV) is the smallest known human virus and causes the most severe form of human viral hepatitis, yet it is still not fully understood how the virus replicates and how it interacts with many host proteins during replication. This review aims to provide a systematic review of all the host factors currently known to interact with HDV and their mechanistic involvement in all steps of the HDV replication cycle. Finally, we discuss implications for therapeutic development based on our current knowledge of HDV-host protein interactions.
Topics: Humans; Hepatitis Delta Virus; Virus Replication
PubMed: 37515216
DOI: 10.3390/v15071530 -
EClinicalMedicine Dec 2023Monitoring progress towards the WHO global target to eliminate hepatitis C virus (HCV) infection by 2030, entails reliable prevalence estimates for HCV infection in...
BACKGROUND
Monitoring progress towards the WHO global target to eliminate hepatitis C virus (HCV) infection by 2030, entails reliable prevalence estimates for HCV infection in different populations. Little is known about the global burden of HCV infection in pregnant women. Here, for the first time to our knowledge, we estimated the global and regional seroprevalence of HCV antibody (Ab) and determinants in pregnant women.
METHODS
In this systematic review and meta-analysis study, we searched PubMed/MEDLINE, Web of Science, Embase, Scopus, and SciELO databases for peer-reviewed observational studies between January 1, 2000 and April 1, 2023, without language or geographical restrictions. Pooled global seroprevalence (and 95% confidence interval, CI) were estimated using random-effects meta-analysis and seroprevalences were categorised according to World Health Organization regions and subregions, publishing year, countries' income and human development index (HDI) levels. We used sensitivity analysis to assess the effect of four large sample size studies on pooled global prevalence through the "leave-one-out" method. We also investigated the association of potential risk factors with HCV seropositivity in pregnant women by subgroup and meta-regression analyses. The Protocol was registered in PROSPERO CRD42023423259.
FINDINGS
We included 192 eligible studies (208 datasets), with data for 148,509,760 pregnant women from 53 countries. The global seroprevalence of HCV Ab in pregnant women was 1.80% (95% CI, 1.72-1.89%) and 3.29% (3.01-3.57%) in overall and sensitivity analyses, respectively. The seroprevalence was highest in the Eastern Mediterranean region (6.21%, 4.39-8.29%) and lowest in the Western Pacific region (0.75%, 0.38-1.22%). Subgroup analysis indicated that the seroprevalence of HCV Ab among pregnant women was significantly higher for those with opioid use disorder (51.94%, 95% CI: 37.32-66.39) and HIV infection (4.34%, 95% CI: 2.21-7.06%) than for the general population of pregnant women (1.08%, 95% CI: 1.02-1.15%), as confirmed by multivariable meta-regression (p < 0.001). A significant decreasing trend was observed with increasing human development index levels. Other important risk factors for HCV seropositivity included older age, lower educational levels, poly sexual activity, history of blood transfusion, hospitalization, surgery, abortion and sexual transmitted diseases, having scarification/tattoo or piercing, and testing hepatitis B positive.
INTERPRETATION
This meta-analysis showed relatively high burden of exposure to HCV infection (2.2-5.3 million) in pregnant women globally. However, due to substantial heterogeneity between studies, our estimates might be different than the true seroprevalence. Our findings highlighted the need to expand HCV screening for women of reproductive age or during pregnancy, particularly in countries with high prevalence; as well as for more studies that assess safety of existing therapeutic drugs during pregnancy or potentially support development of drugs for pregnant women.
FUNDING
There was no funding source for this study.
PubMed: 38045801
DOI: 10.1016/j.eclinm.2023.102327 -
Research in Veterinary Science Nov 2021This systematic review and meta-analysis summarize the available information on Hepatitis E virus (HEV) -specific antibody seroprevalence and HEV RNA prevalence in wild... (Review)
Review
This systematic review and meta-analysis summarize the available information on Hepatitis E virus (HEV) -specific antibody seroprevalence and HEV RNA prevalence in wild boar, one of the most abundant game species worldwide. A literature search (CAB Abstracts, Web of Science, Embase and Scopus) was performed to find relevant peer-reviewed works published during the period 1990-2020. A random-effect model was carried out to calculate the pooled HEV-specific antibody seroprevalence and HEV RNA prevalence estimates with 95% confidence intervals, and I statistic was used to assess the heterogeneity of the data. Values by subgroups were compared according to the geographical area, age class (≤ 12 months old and > 12 months old), and sample type (bile, faeces, liver, meat/muscle, serum). Sixty-nine publications were selected, with the majority of the studies from Southern Europe (n = 27). The pooled HEV-specific antibody seroprevalence in wild boar was 28% (CI 23-34) and the HEV RNA prevalence 8% (CI 6-10). The analysis highlighted a significant heterogeneity among the estimates from the included studies (I = 98% and I = 95% for HEV-specific antibody seroprevalence and viral prevalence respectively). The moderator analysis indicated a statistically significant difference (p-value = 0.03) for the HEV RNA prevalence according to the sample type, with the highest value in bile (17%, CI 9-27), followed by liver (10%, CI 7-14), serum (7%, CI 4-10), faeces (5%, CI 2-9), and meat/muscle (3%, CI 0.04-10). Finally, the HEV RNA prevalence in Europe (8.7, CI 6.7-11) was significantly (p-value = 0.04) higher than in Asia (4, CI 0.6-8). The analysis highlights the important role of wild boar in the epidemiology of HEV.
PubMed: 34864434
DOI: 10.1016/j.rvsc.2021.11.015 -
Clinical Gastroenterology and... Jun 2021Chronic viral hepatitis is a leading cause of worldwide liver-related morbidity and mortality, despite the availability of effective treatments that reduce or prevent... (Review)
Review
BACKGROUND & AIMS
Chronic viral hepatitis is a leading cause of worldwide liver-related morbidity and mortality, despite the availability of effective treatments that reduce or prevent complications in most patients. Electronic-health (eHealth) technologies have potential to intervene along the whole cascade of care. We aimed to summarize available literature on eHealth interventions with respect to conventional screening, diagnostic and treatment outcomes in chronic hepatitis B (HBV) and hepatitis C (HCV).
METHODS
We systematically reviewed MEDLINE, EMBASE, Cochrane Library and international conference abstracts, including studies published from 2009 - 2020. Overall 80 studies were included, covering electronic medical record (EMR) interventions (n=39), telemedicine (n=20), mHealth (n=5), devices (n=4), clinical decision support (n=3), web-based (n=5), social media (n=1) and electronic communication (n=3).
RESULTS
Compared to standard care, EMR alerts increase screening rates in eligible populations including birth cohort screening in HCV, universal HCV screening in Emergency Departments, ethnic groups with high HBV prevalence, and HBV screening prior to immunosuppression. Direct messaging alerts to providers and automated testing may have a greater effect. No significant difference was found in sustained virological response outcomes between telemedicine and face-to-face management for community, rural and prison cohorts in HCV in the direct acting antiviral era of treatment, with higher patient satisfaction in telemedicine groups.
CONCLUSIONS
EMR alerts significantly increase screening rates in eligible cohorts in both chronic HBV and HCV. Telemedicine is equally efficacious to face-to-face care in HCV treatment. Other eHealth technologies show promise; however rigorous studies are lacking.
Topics: Antiviral Agents; Electronics; Hepatitis C, Chronic; Humans; Mass Screening; Telemedicine
PubMed: 32896632
DOI: 10.1016/j.cgh.2020.09.011