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Clinical and Molecular Hepatology Jul 2023Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
METHODS
We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
RESULTS
We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88-95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27-0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
CONCLUSION
IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Liver Neoplasms; Hepatitis B virus; Antiviral Agents; Liver Cirrhosis; Fatty Liver; DNA, Viral
PubMed: 37157776
DOI: 10.3350/cmh.2023.0004 -
Archives of Virology Jan 2023Hand, foot, and mouth disease (HFMD) is a common infectious disease in children. Enterovirus A71 (EV-A71) is one of the main pathogens, and coxsackievirus A6 (CVA6) has... (Meta-Analysis)
Meta-Analysis Review
Hand, foot, and mouth disease (HFMD) is a common infectious disease in children. Enterovirus A71 (EV-A71) is one of the main pathogens, and coxsackievirus A6 (CVA6) has gradually become the dominant pathogen of HFMD in recent years. This study was conducted mainly to assess the serological prevalence of EV-A71 and CVA6 antibodies in people of different ages, sexes, and regions through a systematic review and meta-analysis. A comprehensive study was performed based on the EV-A71 and CVA6 serological literature published before May 2022. Heterogeneity analysis (Cochrane's Q test and the I statistic) and random effect models were adopted. Subgroup and meta-regression analyses were used to identify potential sources of heterogeneity in the data, and all analysis was performed using STATA version 16.0. This study included 71 studies involving 55,176 people from 13 countries that met the inclusion criteria. The serological prevalence of EV-A71 antibody in different studies was 4.31-88.8%, and that of CVA6 antibody was 40.8-80.9%. Meta-analysis results showed that the serum positive rate for EV-A71 antibody was 45.9% (95% CI: 37.6-54.1%). The rate in the Chinese population was 47.8% (95% CI: 42.4-53.2%), and in the other countries, it was 38% (95% CI: 23-55%). The serum positive rate for CVA6 antibody was 58.3% (95% CI: 46.5-70.2%). The rate in the Chinese population was 49.1% (95% CI: 38.3-59.9%), and in the other countries, it was 68% (95% CI: 51-83%). Subgroup analysis was also conducted. The seroprevalence of EV-A71 and CVA6 antibodies is related to age rather than gender or region. The rates of EV-A71 and CVA6 seropositivity are considerably lower in children younger than five years of age. However, the rates gradually increase with age. The findings of this study suggest that children under five years of age may be susceptible to EV-A71 and CVA6. Thus, safety education and vaccination should be strengthened accordingly. This study provides a basis for understanding the risk factors for EV-A71 and CVA6 infection in China and for deciding how to formulate standard preventive measures to prevent the spread of the virus.
Topics: Child; Humans; Child, Preschool; Hand, Foot and Mouth Disease; Seroepidemiologic Studies; Enterovirus; Enterovirus Infections; Antibodies, Viral; China; Enterovirus A, Human
PubMed: 36609748
DOI: 10.1007/s00705-022-05642-0 -
JHEP Reports : Innovation in Hepatology Jan 2023The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This...
BACKGROUND & AIMS
The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This systematic review and meta-analysis aimed to evaluate current literature on this issue.
METHODS
We searched PubMed, Embase, and Web of Science for NUC stop studies that noted clinical outcomes published between January 1, 2006 and August 18, 2022. We performed meta-research analyses to examine the relationships of reported outcomes with study designs and characteristics and also pooled studies with non-overlapping populations to provide risk estimates for the proportions of (1) severe hepatitis flares or hepatic decompensation or (2) hepatitis flare-related death or liver transplantation.
RESULTS
The meta-research analysis included 50 studies of highly heterogeneous designs and characteristics. We found that reporting of safety outcomes varied widely according to outcome definition, follow-up duration, and sample size. Only ten studies prespecified safety events as the study outcome, and only four had an outcome definition to include hepatic insufficiency, a follow-up duration >12 months, and a sample size >100 patients. We further pooled 15 studies with 4,525 individuals and estimated that severe hepatitis flares or decompensation would occur in 1.21% (95% CI 0.70-2.08%), with significant heterogeneity ( = 54%, <0.01), while hepatitis flare-related death or liver transplantation would occur in 0.37% (95% CI 0.20-0.67%), without significant heterogeneity ( = 0.00%, = 1.00).
CONCLUSIONS
Current literature on the risk of serious clinical outcomes following NUC cessation is very limited and highly heterogeneous. Pooled analyses of available data found approximately 1% of patients who stopped NUCs developed severe flares or hepatic decompensation.
IMPACT AND IMPLICATIONS
Current literature regarding the safety concerns surrounding NUC cessation for individuals with chronic hepatitis B is limited and heterogeneous in designs and characteristics, and thus should be interpreted with great caution. Based on currently available data, the proportion of patients that develop severe hepatitis flares or hepatic decompensation was estimated at 1.21% and that of flare-related death or liver transplantation at 0.37%. Our findings are important for individuals receiving nucleos(t)ide analogues for hepatitis B virus infection because we not only pooled currently available data to estimate the risk of serious clinical adverse events following treatment cessation but also uncovered critical limitations of existing literature regarding the safety of finite therapy.
PubMed: 36466989
DOI: 10.1016/j.jhepr.2022.100617 -
The Journal of Infectious Diseases Aug 2022Limited data are available on the economic costs of respiratory syncytial virus (RSV) infections among infants and young children in the United States.
BACKGROUND
Limited data are available on the economic costs of respiratory syncytial virus (RSV) infections among infants and young children in the United States.
METHODS
We performed a systematic literature review of 10 key databases to identify studies published between 1 January 2014 and 2 August 2021 that reported RSV-related costs in US children aged 0-59 months. Costs were extracted and a systematic analysis was performed.
RESULTS
Seventeen studies were included. Although an RSV hospitalization (RSVH) of an extremely premature infant costs 5.6 times that of a full-term infant ($10 214), full-term infants accounted for 82% of RSVHs and 70% of RSVH costs. Medicaid-insured infants were 91% more likely than commercially insured infants to be hospitalized for RSV treatment in their first year of life. Medicaid financed 61% of infant RSVHs. Paying 32% less per hospitalization than commercial insurance, Medicaid paid 51% of infant RSVH costs. Infants' RSV treatment costs $709.6 million annually, representing $187 per overall birth and $227 per publicly funded birth.
CONCLUSIONS
Public sources pay for more than half of infants' RSV medical costs, constituting the highest rate of RSVHs and the highest expenditure per birth. Full-term infants are the predominant source of infant RSVHs and costs.
Topics: Child; Child, Preschool; Databases, Factual; Hospitalization; Humans; Infant; Medicaid; Respiratory Syncytial Virus Infections; United States
PubMed: 35968875
DOI: 10.1093/infdis/jiac172 -
Exercise Immunology Review 2022There is a knowledge gap regarding the consequences of exercise during acute infections in humans and contradictory findings in animal studies, compromising public... (Meta-Analysis)
Meta-Analysis
There is a knowledge gap regarding the consequences of exercise during acute infections in humans and contradictory findings in animal studies, compromising public health advice on the potential benefits of physical activity for immunity. Here, we carried out a meta-analysis of studies of the effects of moderate exercise (ME) and exercise until fatigue (EF) on symptom severity, morbidity and mortality during viral infection in animal models. The systematic review on PubMed, Scopus, Embase, Web of Science, Cochrane and EBSCOhost (CINAHL and SPORT Discus) identified 8 controlled studies, with 15 subgroups within them. The studies exposed the animals (mice [7 studies] and monkeys [1 study]) to exercise immediately before or after viral inoculation (HSV-1, H1N1 influenza and B.K. virus) with follow-up for 21 days. ME significantly reduced morbidity (OR 0.43 [0.19; 0.98], P = 0.04) with no change for symptom severity (SMD -3.37 [-9.01; 2.28], P = 0.24) or mortality (OR 0.48 [0.08;3.03], P = 0.43). In contrast, EF gave a trend towards increased symptom severity (SMD 0.96 [-0.06; 1.98], P = 0.07) and mortality (OR 1.47 [0.96;2.28], P =0.08) with no change in morbidity (OR 1.22 [0.60;2.5], P = 0.58). We conclude that in animals moderate exercise during infection is advantageous, whilst exercise until fatigue should be avoided. Further research is required to determine if moderate exercise may also be beneficial in humans during infection.
Topics: Animals; Exercise Therapy; Fatigue; Humans; Influenza A Virus, H1N1 Subtype; Mice; Morbidity; Virus Diseases
PubMed: 35913495
DOI: No ID Found -
Frontiers in Medicine 2022Autoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage...
INTRODUCTION
Autoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage and serious long-term effects, like amyloidosis. Disease-specific anti-inflammatory therapeutic strategies are established for some AID. However, their clinical course frequently includes relapsing, uncontrolled conditions. Therefore, new therapeutic approaches are needed. Janus Kinase inhibitors (JAKi) block key cytokines of AID pathogenesis and can be a potential option.
METHODS
A systematic review of the literature in accordance with the PRISMA guidelines was conducted. Three databases (MEDLINE, Embase and Cochrane Central Register of Controlled Trials) were searched for publications regarding the use of JAKi for AID. Data from the included publications was extracted and a narrative synthesis was performed. Criteria for defining treatment response were defined and applied.
RESULTS
We report data from 38 publications with a total of 101 patients describing the effects of JAKi in AID. Data on Type I Interferonopathies, Adult-Onset Still's Disease (AOSD), Systemic Juvenile Idiopathic Arthritis (sJIA), Familial Mediterranean Fever (FMF), and Behçet's Syndrome (BS) was identified. From a total of 52 patients with type I interferonopathies, in seven patients (7/52, 13.5%) a complete response was achieved, most (35/52, 67.3%) showed a partial response and a minority (10/52, 19.2%) showed no treatment response. For AOSD, a complete or a partial response was achieved by eleven (11/26, 42.3%) patients each. Two sJIA patients achieved complete response (2/4, 50%) and in two cases (2/4, 50%) a partial response was reported. Half of FMF patients showed a complete response and the other half had a partial one (3/6, 50.0%). Amongst BS patients most achieved a partial response (8/13, 61.5%). Five patients showed no response to therapy (5/13, 38.5%). Overall, the most frequent AEs were upper respiratory tract infections (17), pneumonia (10), BK virus viremia (10) and viruria (4), herpes zoster infection (5), viral gastroenteritis (2) and other infections (4).
CONCLUSION
The results from this systematic review show that JAKi can be beneficial in certain AID. The risk of AEs, especially viral infections, should be considered. To accurately assess the risk benefit ratio of JAKi for AID, clinical trials should be conducted.
PubMed: 35833101
DOI: 10.3389/fmed.2022.930071 -
Hepatology Communications Jul 2022Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have... (Meta-Analysis)
Meta-Analysis
Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have improved over time. We aimed to estimate pooled overall survival (OS), recurrence-free survival (RFS), and complication rates in patients with hepatocellular carcinoma (HCC) following curative surgical resection and to compare outcomes by region and by time period. In this systematic review and meta-analysis, we searched Pubmed, Embase, and Cochrane databases from inception to May 15, 2020. We selected studies reporting OS, RFS, and complications in adult patients with HCC undergoing curative surgical resection. Two authors independently searched the literature and extracted the data. We screened 6983 articles and included 110 eligible studies with 82,392 patients, with study periods spanning from 1980-2017. The global pooled 1-year and 5-year survival rates were 88.9% (95% confidence interval [CI] 87.1-90.4) and 56.2% (95% CI 52.8-59.6) for OS and 71.1% (95% CI 67.6-74.3) and 35.2% (95% CI 32.5-38.0) for RFS, respectively. Five-year OS was higher in Asia (57.03%) than in other regions (Europe 48.3%; North America 48.0%; and South America 49.5%); p = 0.002. Five-year RFS was higher in patients with hepatitis B virus versus patients with hepatitis C virus (34.8% vs. 24.1%; p = 0.02). There was no significant improvement in 5-year OS and RFS over time. The pooled rate for complications was 27.6% (95% CI 23.4-32.3), with 9.7% (95% CI 6.3-14.7) classified as major. One-year OS after surgical resection for HCC is excellent (~90%). However, 5-year OS (~55%) and RFS (~35%) are still poor, suggesting that long-term care is suboptimal. Greater efforts are required to improve survival through enhanced surveillance and preventing recurrence through antiviral therapy.
Topics: Adult; Carcinoma, Hepatocellular; Hepatectomy; Hepatitis B; Hepatitis C; Humans; Liver Neoplasms; Survival Analysis
PubMed: 35234371
DOI: 10.1002/hep4.1923 -
International Journal of Molecular... Sep 2021Extracellular vesicles (EVs) are nanoparticles that transmit molecules from releasing cells to target cells. Recent studies link urinary EVs (uEV) to diverse processes...
Extracellular vesicles (EVs) are nanoparticles that transmit molecules from releasing cells to target cells. Recent studies link urinary EVs (uEV) to diverse processes such as infection and rejection after kidney transplantation. This, and the unmet need for biomarkers diagnosing kidney transplant dysfunction, has led to the current high level of interest in uEV. uEV provide non-intrusive access to local protein, DNA, and RNA analytics without invasive biopsy. To determine the added value of uEV measurements for detecting allograft dysfunction after kidney transplantation, we systematically included all related literature containing directly relevant information, with the addition of indirect evidence regarding urine or kidney injury without transplantation. According to their varying characteristics, uEV markers after transplantation could be categorized into kidney-specific, donor-specific, and immune response-related (IR-) markers. A few convincing studies have shown that kidney-specific markers (PODXL, ion cotransporters, SYT17, NGAL, and CD133) and IR-markers (CD3, multi-mRNA signatures, and viral miRNA) could diagnose rejection, BK virus-associated nephropathy, and calcineurin inhibitor nephrotoxicity after kidney transplantation. In addition, some indirect proof regarding donor-specific markers (donor-derived cell-free DNA) in urine has been demonstrated. Together, this literature review provides directions for exploring novel uEV markers' profiling complications after kidney transplantation.
Topics: Allografts; Biomarkers; Extracellular Vesicles; Graft Rejection; Humans; Kidney; Kidney Transplantation
PubMed: 34638835
DOI: 10.3390/ijms221910499 -
Food and Environmental Virology Sep 2021Water and wastewater virological quality is a significant public health issue. Viral agents include emerging and re-emerging pathogens characterized by extremely small... (Review)
Review
Water and wastewater virological quality is a significant public health issue. Viral agents include emerging and re-emerging pathogens characterized by extremely small size, and high environmental stability. Since the mainly used conventional disinfection methods are usually not able to achieve complete disinfection of viral and other microbial targets, in real water and wastewater matrices, effective strategies for the treatment, use and reuse of water and the development of next-generation water supply systems are required. The scope of the present systematic review was to summarize research data on the application of advanced oxidation processes (AOPs) for viral disinfection of water and wastewater. A literature survey was conducted using the electronic databases PubMed, Scopus, and Web of Science. This comprehensive research yielded 23 records which met the criteria and were included and discussed in this review. Most of the studies (14/23) used only MS2 bacteriophage as an index virus, while the remaining studies (9/23) used two or more viral targets, including phages (MS2, T4, T7, phiX174, PRD-1, S2, ϕB124-14, ϕcrAssphage) and/or Adenovirus, Aichivirus, Norovirus (I, II, IV), Polyomavirus (JC and BK), Sapovirus, Enterovirus, Coxsackievirus B3, Echovirus, and Pepper mild mottle virus. The vast majority of the studies applied a combination of two or more treatments and the most frequently used process was ultraviolet light-hydrogen peroxide (UV/HO) advanced oxidation. The review is expected to highlight the potential of the AOPs for public health protection from the waterborne viral exposure.
Topics: Disinfection; Hydrogen Peroxide; Ultraviolet Rays; Wastewater; Water; Water Purification
PubMed: 34125359
DOI: 10.1007/s12560-021-09481-1 -
Journal of Clinical Virology : the... Jul 2021BK virus (BKV) infection after kidney transplantation can cause BKV nephropathy (BKVAN) resulting in graft dysfunction and allograft loss. The treatment for BKVAN is... (Meta-Analysis)
Meta-Analysis
BK virus (BKV) infection after kidney transplantation can cause BKV nephropathy (BKVAN) resulting in graft dysfunction and allograft loss. The treatment for BKVAN is reduction of the immunosuppressive load which increases the risk of kidney transplant rejection. There is no biomarker to monitor BKV activity besides BK viral load. The value of the Enzyme-Linked Immunosorbent Spot (ELISPOT) assay as a tool to monitor the recipient's anti-BKV immune response after transplantation was investigated systematically. Electronic databases, including MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials were searched for studies of ELISPOT evaluating the immune response against BKV. BKV status was categorized as "active BKV infection" and as "resolving BKV infection". Random-effects model meta-analysis was performed to determine the diagnostic performance of the ELISPOT assay, after stratifying patients into groups based on positive and negative ELISPOT results. One-hundred twenty-seven articles were identified of which nine were included. Patients with negative ELISPOT had an increased risk of having active BKV replication (odds ratio of 71.9 (95%-CI 31.0-167.1). Pooled sensitivity was 0.95 (95%-CI 0.89-0.98) and specificity was 0.88 (95%-CI 0.78-0.94). The standardized mean difference of the number of IFN-γ producing cells between patients with active BKV infection compared with patients who had resolving BKV infection was -2.09 (95%-CI -2.50, -1.68). The ELISPOT assay is a useful tool for BKV risk assessment and in combination with BKV load may support clinicians in guiding immunosuppressive therapy in patients with BKV replication.
Topics: BK Virus; Enzyme-Linked Immunospot Assay; Humans; Immunity; Immunosorbents; Kidney Diseases; Kidney Transplantation; Polyomavirus Infections; Tumor Virus Infections
PubMed: 33979739
DOI: 10.1016/j.jcv.2021.104848