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Cureus Apr 2024In 2021 and 2022, there were noted to be clusters of pediatric acute hepatitis of unknown origin (AHUO) occurring across the globe. While there was not necessarily a... (Review)
Review
In 2021 and 2022, there were noted to be clusters of pediatric acute hepatitis of unknown origin (AHUO) occurring across the globe. While there was not necessarily a global increase in cases, understanding the pattern of liver injury in AHUO is crucial to properly identify cases of this unexplained phenomenon, especially since it occurred simultaneously with a global resurgence of COVID-19. The objective of this study was to contrast the patterns in liver-relevant biochemical data from COVID-19 patients and AHUO. Studies reporting liver chemistries for cases of AHUO and COVID-19 were identified by a systematic review and search of the literature. For each case, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, direct bilirubin, and international normalized ratio (INR) levels were extracted as available. These were normalized to multiples of the upper limit of normal by patient age. There were statistically significant greater elevations of ALT and AST in patients with AHUO than in those with COVID-19. Only a subset of patients with COVID-19 had an AST or ALT greater than the normal range. INR elevation could be substantial for both conditions but was also statistically higher in the AHUO group. Liver chemistry changes were not statistically correlated with age. The pattern of liver chemistry changes between AHUO and COVID-19 have some distinctions, which suggests that AHUO is not a phenomenon driven primarily by SARS-CoV-2 infection alone. Differentiating AHUO and COVID-19 would be challenging based on patterns of liver chemistry changes alone.
PubMed: 38752102
DOI: 10.7759/cureus.58307 -
Journal of Clinical Medicine Feb 2024HBV-specific T lymphocytes are pivotal in eliminating the hepatitis B virus (HBV) and regulating intrahepatic inflammatory reactions. Effective T cell responses curtail... (Review)
Review
HBV-specific T lymphocytes are pivotal in eliminating the hepatitis B virus (HBV) and regulating intrahepatic inflammatory reactions. Effective T cell responses curtail HBV infection; however, compromised immunity can result in persistent infection. Beyond the acute phase, the continued presence of antigens and inflammation leads to the increased expression of various inhibitory receptors, such as PD-1, CTLA-4, Tim-3, LAG3, 2B4, CD160, BTLA, and TIGIT. This escalates the dysfunction of and diminishes the immune and proliferative abilities of T cells. In this study, we reviewed English-language literature from PubMed, Web of Science, and Scopus up to 9 July 2023. This paper aims to elucidate the inhibitory effects of these receptors on HBV-specific T lymphocytes and how immune function can be rejuvenated by obstructing the inhibitory receptor signaling pathway in chronic HBV patients. We also summarize the latest insights into related anti-HBV immunotherapy. From 66 reviewed reports, we deduced that immunotherapy targeting inhibitory receptors on T cells is a reliable method to rejuvenate T cell immune responses in chronic HBV patients. However, comprehensive combination therapy strategies are essential for a functional cure. Targeting T cell suppressor receptors and combining immunotherapy with antiviral treatments may offer a promising approach towards achieving a functional cure, urging future research to prioritize effective combination therapeutic strategies for chronic HBV infection.
PubMed: 38592036
DOI: 10.3390/jcm13051210 -
Conflict and Health Apr 2024Conflict situations, armed or not, have been associated with emergence and transmission of infectious diseases. This review aims to identify the pathways through which... (Review)
Review
BACKGROUND
Conflict situations, armed or not, have been associated with emergence and transmission of infectious diseases. This review aims to identify the pathways through which infectious diseases emerge within conflict situations and to outline appropriate infectious disease preparedness and response strategies.
METHODS
A systematic review was performed representing published evidence from January 2000 to October 2023. Ovid Medline and Embase were utilised to obtain literature on infectious diseases in any conflict settings. The systematic review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis). No geographical restrictions were imposed.
FINDINGS
Our review identified 51 studies covering AIDS, Hepatitis B, Tuberculosis, Cholera, Coronavirus 2, Ebola, Poliomyelitis, Malaria, Leishmaniasis, Measles, Diphtheria, Dengue and Acute Bacterial Meningitis within conflict settings in Europe, Middle East, Asia, and Africa since October 2023. Key factors contributing to disease emergence and transmission in conflict situations included population displacement, destruction of vital infrastructure, reduction in functioning healthcare systems and healthcare personnel, disruption of disease control programmes (including reduced surveillance, diagnostic delays, and interrupted vaccinations), reduced access by healthcare providers to populations within areas of active conflict, increased population vulnerability due to limited access to healthcare services, and disruptions in the supply chain of safe water, food, and medication. To mitigate these infectious disease risks reported preparedness and response strategies included both disease-specific intervention strategies as well as broader concepts such as the education of conflict-affected populations through infectious disease awareness programmes, investing in and enabling health care in locations with displaced populations, intensifying immunisation campaigns, and ensuring political commitment and intersectoral collaborations between governments and international organisations.
CONCLUSION
Conflict plays a direct and indirect role in the transmission and propagation of infectious diseases. The findings from this review can assist decision-makers in the development of evidence-based preparedness and response strategies for the timely and effective containment of infectious disease outbreaks in conflict zones and amongst conflict-driven displaced populations.
FUNDING
European Centre for Disease Prevention and Control under specific contract No. 22 ECD.13,154 within Framework contract ECDC/2019/001 Lot 1B.
PubMed: 38584269
DOI: 10.1186/s13031-023-00568-z -
Journal of the International AIDS... Mar 2024Disengagement from antiretroviral therapy (ART) care is an important reason why people living with HIV do not achieve viral load suppression become unwell.
INTRODUCTION
Disengagement from antiretroviral therapy (ART) care is an important reason why people living with HIV do not achieve viral load suppression become unwell.
METHODS
We searched two databases and conference abstracts from January 2015 to December 2022 for studies which reported reasons for disengagement from ART care. We included quantitative (mainly surveys) and qualitative (in-depth interviews or focus groups) studies conducted after "treat all" or "Option B+" policy adoption. We used an inductive approach to categorize reasons: we report how often reasons were reported in studies and developed a conceptual framework for reasons.
RESULTS
We identified 21 studies which reported reasons for disengaging from ART care in the "Treat All" era, mostly in African countries: six studies in the general population of persons living with HIV, nine in pregnant or postpartum women and six in selected populations (one each in people who use drugs, isolated indigenous communities, men, women, adolescents and men who have sex with men). Reasons reported were: side effects or other antiretroviral tablet issues (15 studies); lack of perceived benefit of ART (13 studies); psychological, mental health or drug use (13 studies); concerns about stigma or confidentiality (14 studies); lack of social or family support (12 studies); socio-economic reasons (16 studies); health facility-related reasons (11 studies); and acute proximal events such as unexpected mobility (12 studies). The most common reasons for disengagement were unexpected events, socio-economic reasons, ART side effects or lack of perceived benefit of ART. Conceptually, studies described underlying vulnerability factors (individual, interpersonal, structural and healthcare) but that often unexpected proximal events (e.g. unanticipated mobility) acted as the trigger for disengagement to occur.
DISCUSSION
People disengage from ART care for individual, interpersonal, structural and healthcare reasons, and these reasons overlap and interact with each other. While HIV programmes cannot predict and address all events that may lead to disengagement, an approach that recognizes that such shocks will happen could help.
CONCLUSIONS
Health services should focus on ways to encourage clients to engage with care by making ART services welcoming, person-centred and more flexible alongside offering adherence interventions, such as counselling and peer support.
Topics: Adolescent; Female; Humans; Male; Pregnancy; Anti-Retroviral Agents; Developing Countries; HIV Infections; Sexual and Gender Minorities; Medication Adherence; Patient Dropouts
PubMed: 38494657
DOI: 10.1002/jia2.26230 -
Cureus Jan 2024Dialysis in pediatric groups is complicated by a wide range of factors that can affect long-term prognosis. The purpose of this meta-analysis and systematic review is to... (Review)
Review
Dialysis in pediatric groups is complicated by a wide range of factors that can affect long-term prognosis. The purpose of this meta-analysis and systematic review is to better understand the demographic and clinical factors that affect dialysis success in children. We searched a variety of databases for relevant articles and included 14 reports that dealt with the case studies of pediatric patients undergoing dialysis for a wide range of renal diseases. Patients' demographics, clinical presentations, laboratory findings, and treatment outcomes were the primary areas of data collection. To get a better sense of the overall prevalence of certain outcomes and to spot noteworthy trends or patterns in the disease process, we conducted a meta-analysis. Variations in dialysis efficacy and outcomes are highlighted throughout a wide range of ages in the pediatric dialysis cohort, from neonates to teenagers. Acute kidney injuries (AKI) tended to impact more boys, but chronic kidney diseases (CKD), such as lupus nephritis, disproportionately afflicted girls. Many different ethnic groups were represented, and there was evidence that some diseases having a hereditary component were more common in some areas than others. However, the potential for long-term consequences remained a concern. Hemodialysis was found to be effective in controlling end-stage renal disease (ESRD) and AKI, with some patients going on to have a kidney transplant. At the same time, peritoneal dialysis was associated with an increased risk of infection. This comprehensive analysis highlights the importance of demographic and clinical parameters in determining pediatric dialysis outcomes. A 14.47% mortality rate and gender disparities are revealed by this meta-analysis of pediatric renal diseases, which included a cohort of 235 patients with conditions like lupus nephritis and hepatitis C infection. The findings stress the necessity for individualized treatment techniques and suggest that demographic characteristics should be addressed in prognostic models. For better patient outcomes, the study also suggests standardized reporting in pediatric dialysis studies.
PubMed: 38344624
DOI: 10.7759/cureus.51978 -
Journal of Clinical Medicine Jan 2024Acute esophageal variceal bleeding accounts for up to 70% of upper-gastrointestinal bleeding in cirrhotic patients. About 10-20% of patients with acute variceal... (Review)
Review
Acute esophageal variceal bleeding accounts for up to 70% of upper-gastrointestinal bleeding in cirrhotic patients. About 10-20% of patients with acute variceal bleeding have refractory bleeding that is not controlled by medical or endoscopic therapy, and this condition can be life-threatening. Balloon tamponade is a long-standing therapy which is only effective temporarily and has several complications, while transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation may not be readily available at some centers. The use of self-expandable metal stents (SEMSs) in refractory esophageal variceal bleeding has been studied for effectiveness and adverse events and has been recommended for use as a bridge to a more definitive treatment. To investigate the effectiveness and safety of SEMSs in managing refractory variceal bleeding. A systematic search of the MEDLINE, EMBASE, and Cochrane library databases was performed from inception to October 2022 using the following terms: "esophageal stent", "self-expandable metal stents", "endoscopic hemostasis", "refractory esophageal varices", and "esophageal variceal bleeding". Studies were included in the meta-analysis if they met the following criteria: (1) patients' age older than 18 and (2) a study (or case series) that has at least 10 patients in the study. Exclusion criteria included (1) non-English publications, (2) in case of overlapping cohorts, data from the most recent and/or most appropriate comprehensive report were collected. DerSimonian-Laird random-effects meta-analysis was performed using the meta package in R statistical software(version 4.2.2). Twelve studies involving 225 patients with 228 stents were included in the analyses. The mean age and/or median age ranged from 49.4 to 69 years, with a male-to-female ratio of 4.4 to 1. The median follow-up period was 42 days. The mean SEMS dwell time was 9.4 days. The most common cause of acute refractory variceal bleeding in chronic liver disease patients included alcohol use followed by viral hepatitis. The pooled rate of immediate bleeding control was 91% (95% CI 82-95%, = 0). The pooled rate of rebleeding was 17% (95% CI 8-32%, = 69). The pooled rate of stent ulceration was 7% (95% CI 3-13%, = 0), and the pooled rate of stent migration was 18% (95% CI 9-32%, = 38). The pooled rate of all-cause mortality was 38% (95% CI 30-47%, = 34). SEMSs should be primarily considered as salvage therapy when endoscopic band ligation and sclerotherapy fail and can be used as a bridge to emergent TIPS or definitive therapy, such as liver transplantation.
PubMed: 38256491
DOI: 10.3390/jcm13020357 -
Revista Espanola de Enfermedades... Jan 2024Research on the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients with autoimmune hepatitis (AIH) has produced...
BACKGROUND
Research on the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients with autoimmune hepatitis (AIH) has produced varied results, and the determinants of the immunological response remain largely elusive.
METHODS
A comprehensive search of three primary databases (PubMed, Embase, and Web of Science) yielded pertinent studies on the topic. The data extraction was a collaborative effort among three independent researchers, who subsequently reconvened to validate the key data that were collated. The primary outcomes were the magnitudes of humoral and cellular immune responses to the vaccines. The secondary outcomes were related to factors affecting the humoral immune response post-vaccination.
RESULT
Our systematic review incorporated eight studies, and the meta-analysis involved three. The average antibody response rates after one, two, and three doses of the SARS-CoV-2 vaccine were 86%, 82%, and 91%, respectively. Unexpectedly, the antibody concentrations of seropositive patients were markedly lower than those of their healthy counterparts. The cellular immune response rates after two and three vaccine doses were 74% and 56%, respectively. Treatment with mycophenolate mofetil and corticosteroids was associated with a notable decrease in seropositivity [pooled odds ratio (95% confidence interval): 2.62 (2.12-3.25) and 2.4 (1.51-3.82), respectively]. In contrast, azathioprine had no discernable impact on the humoral response.
CONCLUSION
In patients with AIH, the immune response to COVID-19 vaccination is attenuated. Specific immunosuppressive agents, such as steroids and MMF, have been found to reduce antibody responses. Recognizing these determinants is foundational to formulating individualized vaccination strategies for patients with AIH. Further research with an emphasis on post-vaccination cellular immunity will be essential to refine the vaccination approaches for this demographic.
PubMed: 38235657
DOI: 10.17235/reed.2024.10053/2023 -
Frontiers in Pediatrics 2023In April 2022, the World Health Organization (WHO) declared a global outbreak of acute hepatitis of unknown etiology (AHUE) with a high risk of severe outcomes, for... (Review)
Review
In April 2022, the World Health Organization (WHO) declared a global outbreak of acute hepatitis of unknown etiology (AHUE) with a high risk of severe outcomes, for which various etiologies have been proposed by the literature. This study examines primary reports of pediatric AHUE cases and summarizes the proposed etiologies. This systematic review collected and evaluated published peer-reviewed articles, official data, and clinical reports of AHUE cases that met the WHO working case definition. 19 hypothesized etiologies for AHUE were identified from 36 sources, which fell into eight categories. While human adenovirus (HAdV) infection, viral infection, and immune-mediated responses were commonly suspected as causes of AHUE, no definitive etiology or epidemiological link has been established. However, recent evidence implicates adeno-associated virus-2 (AAV2) as a likely significant contributor. Conducting a comprehensive literature review following outbreaks is necessary for developing responsive strategies and protocols.
PubMed: 38089685
DOI: 10.3389/fped.2023.1285348 -
BMC Public Health Nov 2023Hepatitis E can potentially progress to HEV-related acute liver failure (HEV-ALF). East and South Asia bear a substantial burden of HEV infection, with Bangladesh,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis E can potentially progress to HEV-related acute liver failure (HEV-ALF). East and South Asia bear a substantial burden of HEV infection, with Bangladesh, China, and India facing the most severe threat in this region. Therefore, we conducted a systematic review and meta-analysis to evaluate the burden of HEV-ALF in these three high-risk countries.
METHODS
A systematic literature search was performed utilizing PubMed, the Cochrane Library, Medline, Embase, and Web of Science databases. Studies in English or Chinese that reported data on the burden of HEV-ALF in Bangladesh, China and India were included. Outcomes were pooled with meta-analysis utilizing R software. Estimates were calculated with random-effects models, and subgroup analysis and sensitivity analysis were conducted to address heterogeneity. Egger's test and Begg's test were performed to assess publication bias.
RESULTS
A total of 20 eligible studies were included in this study. The pooled HEV-attributable proportion of viral-related acute liver failure was estimated to be 40.0% (95% CI: 0.28-0.52), 30.0% (95% CI: 0.18-0.44), and 61.0% (95% CI: 0.49-0.72) among non-pregnant individuals in India, China and Bangladesh, while in Indian pregnant females, it was 71.0% (95% CI: 0.62-0.79). The combined prevalence among non-pregnant HEV-infected participants was 28.0% (95% CI: 0.20-0.37) and 10.0% (95% CI: 0.01-0.28) in India and China, and it was 34.0% (95% CI: 0.27-0.42) in Indian pregnant females with HEV infection. The overall mortality of HEV-ALF was estimated to be 32.0% (95% CI: 0.23-0.42) and 64.0% (95% CI: 0.50-0.77) among the non-pregnant and the pregnant participants in India, and it was 23.0% (95% CI: 0.14-0.34) in Chinese non-pregnant participants.
CONCLUSIONS
The burden of HEV-ALF in Bangladesh, China, and India is non-negligible despite geographic and population heterogeneity. The prevention of HEV infection and early recognition of HEV-ALF are of great significance, especially in high-risk countries and populations.
REGISTRATION
PROSPERO registration ID is CRD42022382101.
Topics: Pregnancy; Female; Humans; Bangladesh; Hepatitis E virus; Liver Failure, Acute; India; China
PubMed: 38031080
DOI: 10.1186/s12889-023-17302-2 -
Mediterranean Journal of Hematology and... 2023In patients with SCD, chronic liver damage is a common manifestation. More than 50% of SCD patients have elevated liver enzymes. Common underlying aetiologies include... (Review)
Review
In patients with SCD, chronic liver damage is a common manifestation. More than 50% of SCD patients have elevated liver enzymes. Common underlying aetiologies include sickle cell hepatic crisis, viral hepatitis, sickle cell intrahepatic cholestasis and hepatic sequestration in the acute setting, and cholelithiasis and iron overload in the chronic setting. Autoimmune hepatitis (AIH) is a rare disease that appears to occur more commonly in the sickle cell disease (SCD) population than in the general population. There are many schools of thought as to why this is the case, including the phosphatidylserine hypothesis, the heme inflammatory hypothesis, the complement generation hypothesis, and the transfusion alloimmunization hypothesis. Due to the natural history of the two illnesses, SCD is almost always diagnosed first in cases of dual pathology. Symptoms such as jaundice, fatigue, and abdominal pain are common in SCD, as are abnormal liver function tests (LFTs). These abnormalities, attributed to the other more frequent liver involvements in SCD, can lead to delays in AIH diagnosis in this population. Corticosteroids, sometimes with other immunosuppressive agents, such as azathioprine, are the cornerstone of acute AIH treatment. However, corticosteroid use in the SCD population has been shown to carry an increased risk of vaso-occlusive crises, providing a treatment dilemma. The following is a review of AIH in the SCD population, where we explore the pathophysiology behind the association between the two disorders, discuss an approach to investigating abnormal LFTs in SCD, and examine treatment options in this population with co-existing diseases.
PubMed: 38028400
DOI: 10.4084/MJHID.2023.060