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Turkish Journal of Haematology :... May 2024The survival rates of children with acute lymphoblastic leukemia (ALL) have improved over the years, but infections remain a significant cause of morbidity and...
OBJECTIVE
The survival rates of children with acute lymphoblastic leukemia (ALL) have improved over the years, but infections remain a significant cause of morbidity and mortality. Chemotherapy has a range of harmful side effects including the loss of protective antibodies against vaccine-preventable diseases. The objective of this study was to evaluate the serological status of pediatric ALL cases before and after the intensive chemotherapy.
MATERIALS AND METHODS
Children treated and followed up for ALL at Dokuz Eylül University were included in this retrospective cross-sectional study. Antibody levels against hepatitis A, hepatitis B, and rubella were routinely assessed both at the time of diagnosis and six months after completion of chemotherapy. However, measles, mumps, and varicella antibody levels were evaluated just six months after the treatment.
RESULTS
Seventy-eight children who completed chemotherapy for ALL were recruited. All participants had nonprotective antibody levels for at least one of the diseases. The highest seropositivity rate was found for hepatitis A (55.1%) and the lowest for measles (17.9%) after chemotherapy. Overall, 50.7%, 30.6%, and 45.7% of the patients significantly lost their humoral immunity against hepatitis B, hepatitis A, and rubella, respectively. Patients in the higher-risk group for ALL had a lower seropositivity rate than the other risk group patients. There were statistically significant relations between the protective antibody rates of hepatitis A and varicella and the age of the patients. Except for the hepatitis A vaccination, pre-chemotherapy vaccination did not affect post-chemotherapy serology. On the other hand, all children with a history of varicella before the diagnosis showed immunity after chemotherapy.
CONCLUSION
All patients, including those previously fully vaccinated, are at great risk of infection due to the decrease in protective antibody levels after chemotherapy. There is a need for routine post-chemotherapy serologic testing and re-vaccination based on the results obtained.
PubMed: 38801016
DOI: 10.4274/tjh.galenos.2024.2024.0150 -
Clinical Case Reports Jun 2024This case emphasizes the significance of COVID-19 in pediatric patients presenting with unusual hepatic manifestations, urging clinicians to broaden their diagnostic...
KEY CLINICAL MESSAGE
This case emphasizes the significance of COVID-19 in pediatric patients presenting with unusual hepatic manifestations, urging clinicians to broaden their diagnostic lens. The unexpected elevation of SARS-CoV-2 antibodies and the effective use of N-acetyl cysteine highlight the importance of adaptability in treatment strategies.
ABSTRACT
This case report presents a unique manifestation of severe hepatic involvement in a 4-year-old girl with thalassemia minor and COVID-19. Despite the absence of prominent respiratory symptoms, the patient exhibited jaundice, elevated liver enzymes, and coagulopathy. Initial suspicion of viral hepatitis was replaced by the discovery of significantly elevated SARS-CoV-2 antibodies. A multidisciplinary approach, including gastroenterology consultation and an extensive workup, was pivotal in ruling out alternative etiologies. Unconventional use of N-acetyl cysteine contributed to clinical improvement, highlighting the need for adaptable treatment strategies. This case underscores the importance of heightened awareness in recognizing atypical presentations of COVID-19 in pediatric patients, especially those with underlying health conditions. Further exploration into nuanced manifestations and treatment approaches is warranted for comprehensive clinical management.
PubMed: 38799536
DOI: 10.1002/ccr3.8955 -
Vaccines May 2024The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections....
The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991-1993 and in 1994-1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 ( < 0.001). The incidence in 2014-2021 was lower for regions that started adolescent vaccination in 1991-1993 rather than in 1994-1996 (IRR 0.76; 95% CI 0.72-0.83; < 0.001). In the 20-29 age group, incidence in regions that started adolescent vaccination in 1991-1993 was also lower (IRR 0.87; 95% CI 0.77-0.98; = 0.02 in 2005-2013 and IRR 0.71; 95% CI 0.56-0·90; < 0.001 in 2014-2021). Anti-HBc prevalence in the 35-39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant ( = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030.
PubMed: 38793738
DOI: 10.3390/vaccines12050488 -
Viruses May 2024An increase in the number of cases of acute hepatitis of unknown origin (HUO) in children was observed in 2021. Adenovirus and adeno-associated virus 2 (AAV2) infections...
BACKGROUND AND AIMS
An increase in the number of cases of acute hepatitis of unknown origin (HUO) in children was observed in 2021. Adenovirus and adeno-associated virus 2 (AAV2) infections have been suggested as possible triggers. However, the potential etiology is still unclear. We aimed to characterize a cohort of children with HUO in Israel in view of the COVID-19 pandemic.
METHOD
Demographics, clinical data, and laboratory results on the children compatible with the CDC criteria for HUO were collected by the established registry of the Ministry of Health. Available specimens were sent to the Central Virology Laboratory.
RESULTS
A total of 39 children were included in the registry. A total of 20 were enrolled prospectively, in which human herpes virus 6 (HHV6) infection or reactivation was identified in 11/19, adenovirus was found in 4/19 of the cases, and AAV2 was detected in 2/16. Past COVID-19 exposure was recorded for 24/39 of the children. A total of 10 children underwent liver biopsy, and 8 were successfully treated with steroids and 2 underwent liver transplantation.
CONCLUSIONS
The COVID-19 pandemic and the related containment measures combined with reactivation or active infection with other viruses could have been a trigger for the HUO outbreak. In our cohort, HHV6 was the most abundant finding.
Topics: Humans; COVID-19; Child; Female; Male; Child, Preschool; Infant; Israel; SARS-CoV-2; Adolescent; Herpesvirus 6, Human; Disease Outbreaks; Prospective Studies; Acute Disease; Pandemics
PubMed: 38793689
DOI: 10.3390/v16050808 -
Viruses May 2024Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but...
INTRODUCTION
Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but has also been reported to be transmitted through blood transfusion. Although most HEV infections, including those via blood products, are usually self-limiting, they may become chronic in immunocompromised persons. It is thus essential to identify HEV-infected blood donations to prevent transmission to vulnerable recipients.
AIMS
Prior to the decision whether to introduce HEV RNA screening for all Swiss blood donations, a 2-year nationwide prevalence study was conducted.
METHODS
All blood donations were screened in pools of 12-24 samples at five regional blood donation services, and HEV RNA-positive pools were subsequently resolved to the individual donation index donation (X). The viral load, HEV IgG and IgM serology, and HEV genotype were determined. Follow-up investigations were conducted on future control donations (X + 1) and previous archived donations of the donor (X - 1) where available.
RESULTS
Between October 2018 and September 2020, 541,349 blood donations were screened and 125 confirmed positive donations were identified (prevalence 1:4331 donations). At the time of blood donation, the HEV RNA-positive individuals were symptom-free. The median viral load was 554 IU/mL (range: 2.01-2,500,000 IU/mL). Men (88; 70%) were more frequently infected than women (37; 30%), as compared with the sex distribution in the Swiss donor population (57% male/43% female, < 0.01). Of the 106 genotyped cases (85%), all belonged to genotype 3. Two HEV sub-genotypes predominated; 3h3 (formerly 3s) and 3c. The remaining sub-genotypes are all known to circulate in Europe. Five 3ra genotypes were identified, this being a variant associated with rabbits. In total, 85 (68%) X donations were negative for HEV IgM and IgG. The remaining 40 (32%) were positive for HEV IgG and/or IgM, and consistent with an active infection. We found no markers of previous HEV in 87 of the 89 available and analyzed archive samples (X - 1). Two donors were HEV IgG-positive in the X - 1 donation suggesting insufficient immunity to prevent HEV reinfection. Time of collection of the 90 (72%) analyzed X + 1 donations varied between 2.9 and 101.9 weeks (median of 35 weeks) after X donation. As expected, none of those tested were positive for HEV RNA. Most donors (89; 99%) were positive for anti-HEV lgG/lgM (i.e., seroconversion). HEV lgM-positivity (23; 26%) indicates an often-long persistence of lgM antibodies post-HEV infection.
CONCLUSION
The data collected during the first year of the study provided the basis for the decision to establish mandatory HEV RNA universal screening of all Swiss blood donations in minipools, a vital step in providing safer blood for all recipients, especially those who are immunosuppressed.
Topics: Humans; Hepatitis E; Blood Donors; Switzerland; Hepatitis E virus; Male; Female; Adult; Prevalence; Middle Aged; RNA, Viral; Genotype; Hepatitis Antibodies; Immunoglobulin M; Young Adult; Immunoglobulin G; Viral Load; Aged; Adolescent
PubMed: 38793625
DOI: 10.3390/v16050744 -
Journal of Personalized Medicine May 2024Sepsis remains a major health challenge worldwide, characterized by a dysregulated host response to infection, leading to high mortality and morbidity in intensive care...
BACKGROUND
Sepsis remains a major health challenge worldwide, characterized by a dysregulated host response to infection, leading to high mortality and morbidity in intensive care units (ICUs). The Fibrosis 4 (FIB-4) index, originally developed to assess liver fibrosis in hepatitis C patients, has recently been explored for its potential prognostic value in sepsis patients.
METHOD
this study retrospectively analyzed 309 sepsis patients admitted to the Internal Medicine and An-aesthesia ICUs between 12 December 2021 and 15 December 2023 to investigate the relationship between FIB-4 levels, the Acute Physiology and Chronic Health Evaluation (APACHE), the Sequential Organ Failure Assessment (SOFA), and clinical outcomes.
RESULTS
This study found that higher FIB-4 measurements were statistically significantly associated with increased 28-day mortality, with a cut-off value of 4.9, providing a sensitivity of 54.92% and specificity of 74.25%. Logistic regression analysis indicated that elevated FIB-4 levels were a significant predictor of early mortality, suggesting that the FIB-4 index could serve as a valuable prognostic tool in assessing the severity and prognosis of sepsis patients.
CONCLUSIONS
by elucidating the potential role of the FIB-4 index in sepsis prognosis, this study contributes to the ongoing efforts to improve risk stratification and enhance patient care in sepsis management.
PubMed: 38793113
DOI: 10.3390/jpm14050531 -
Journal of Personalized Medicine May 2024This Editorial precedes the Special Issue entitled "Novel Challenges and Therapeutic Options for Liver Diseases". Following a historical outline of the roots of...
This Editorial precedes the Special Issue entitled "Novel Challenges and Therapeutic Options for Liver Diseases". Following a historical outline of the roots of hepatology, we provide a brief insight into our colleagues' contributions in this issue on the current developments in this discipline related to the prevention of liver diseases, the metabolic dysfunction-associated steatotic liver disease (or non-alcoholic fatty liver disease, respectively), liver cirrhosis, chronic viral hepatitides, acute-on-chronic liver failure, liver transplantation, the liver-microbiome axis and microbiome transplantation, and telemedicine. We further add some topics not covered by the contributions herein that will likely impact future hepatology. Clinically, these comprise the predictive potential of organokine crosstalk and treatment options for liver fibrosis. With regard to promising developments in basic research, some current findings on the genetic basis of metabolism-associated chronic liver diseases, chronobiology, metabolic zonation of the liver, aspects of the aging liver against the background of demography, and liver regeneration will be presented. We expect machine learning to thrive as an overarching topic throughout hepatology. The largest study to date on the early detection of liver damage-which has been kicked off on 1 March 2024-is highlighted, too.
PubMed: 38793074
DOI: 10.3390/jpm14050492 -
Microorganisms May 2024The repeated failure to treat patients chronically infected with hepatitis E (HEV) and C (HCV) viruses, despite the absence of resistance-associated substitutions (RAS),...
The repeated failure to treat patients chronically infected with hepatitis E (HEV) and C (HCV) viruses, despite the absence of resistance-associated substitutions (RAS), particularly in response to prolonged treatments with the mutagenic agents of HEV, suggests that quasispecies structure may play a crucial role beyond single point mutations. Quasispecies structured in a flat-like manner (referred to as flat-like) are considered to possess high average fitness, occupy a significant fraction of the functional genetic space of the virus, and exhibit a high capacity to evade specific or mutagenic treatments. In this paper, we studied HEV and HCV samples using high-depth next-generation sequencing (NGS), with indices scoring the different properties describing flat-like quasispecies. The significance of these indices was demonstrated by comparing the values obtained from these samples with those from acute infections caused by respiratory viruses (betacoronaviruses, enterovirus, respiratory syncytial viruses, and metapneumovirus). Our results revealed that flat-like quasispecies in HEV and HCV chronic infections without RAS are characterized by numerous low-frequency haplotypes with no dominant one. Surprisingly, these low-frequency haplotypes (at the nucleotide level) exhibited a high level of synonymity, resulting in much lower diversity at the phenotypic level. Currently, clinical approaches for managing flat-like quasispecies are lacking. Here, we propose methods to identifying flat-like quasispecies, which represents an essential initial step towards exploring alternative treatment protocols for viruses resistant to conventional therapies.
PubMed: 38792840
DOI: 10.3390/microorganisms12051011 -
Cellular and Molecular Gastroenterology... May 2024There is limited information on how the liver-to-gut axis contributes to alcohol-associated liver disease (AALD). We previously identified that high-mobility group box-1...
BACKGROUND & AIMS
There is limited information on how the liver-to-gut axis contributes to alcohol-associated liver disease (AALD). We previously identified that high-mobility group box-1 (HMGB1) undergoes oxidation in hepatocytes and demonstrated elevated serum levels of oxidized HMGB1 ([O] HMGB1) in alcoholic patients. Since interleukin-1 beta (IL-1B) increases in AALD, we hypothesized hepatocyte-derived [O] HMGB1 could interact with IL-1B to activate a pro-inflammatory program that, besides being detrimental to the liver, drives intestinal barrier dysfunction.
RESULTS
Alcohol-fed Rage mice exhibited decreased nuclear factor kappa B signaling, a pro-inflammatory signature, and reduced total intestinal permeability, resulting in protection from AALD. In addition, [O] HMGB1 bound and signaled through the receptor for advanced-glycation end-products (RAGE) in myeloid cells, driving hepatic inflammation, intestinal permeability, and increased portal blood lipopolysaccharide in AALD. We identified that [O] HMGB1 formed a complex with IL-1B, which was found in the livers of patients with acute alcoholic hepatitis and mice with AALD. This complex originated from the liver, because it was absent in the intestine when hepatocytes did not produce [O] HMGB1. Mechanistically, the complex bound RAGE in Kupffer cells and macrophages induces a pro-inflammatory program. Moreover, it bound RAGE in intestinal macrophages and epithelial cells, leading to intestinal inflammation, altered intestinal epithelial cell tight junction protein expression, increased intestinal permeability, and elevated portal blood lipopolysaccharide, enhancing AALD pathogenesis.
CONCLUSIONS
We identified a protein complex of liver origin that amplifies the pro-inflammatory feedback loop in AALD; therefore, targeting this complex could have significant therapeutic potential.
PubMed: 38788899
DOI: 10.1016/j.jcmgh.2024.05.010 -
Renal Failure Dec 2024Glycyrrhizin (GL) has immunoregulatory effects on various inflammatory diseases including hepatitis and nephritis. However, the mechanisms underlying the...
Glycyrrhizin (GL) has immunoregulatory effects on various inflammatory diseases including hepatitis and nephritis. However, the mechanisms underlying the anti-inflammatory effect of GL on renal inflammation are not fully understood. Hepatorenal syndrome (HRS) is a functional acute renal impairment that occurs in severe liver disease, and we found that kidney injury also occurs in Con A-induced experimental hepatitis in mice. We previously found that GL can alleviate Con A-induced hepatitis by regulating the expression of IL-25 in the liver. We wanted to investigate whether GL can alleviate Con A-induced nephritis by regulating IL-25. IL-25 regulates inflammation by modulating type 2 immune responses, but the mechanism by which IL-25 affects kidney disease remains unclear. In this study, we found that the administration of GL enhanced the expression of IL-25 in renal tissues; the latter promoted the generation of type 2 macrophages (M2), which inhibited inflammation in the kidney caused by Con A challenge. IL-25 promoted the secretion of the inhibitory cytokine IL-10 by macrophages but inhibited the expression of the inflammatory cytokine IL-1β by macrophages. Moreover, IL-25 downregulated the Con A-mediated expression of Toll-like receptor (TLR) 4 on macrophages. By comparing the roles of TLR2 and TLR4, we found that TLR4 is required for the immunoregulatory effect of IL-25 on macrophages. Our data revealed that GL has anti-inflammatory effects on Con A-induced kidney injury and that the GL/IL-25/M2 axis participates in the anti-inflammatory process. This study suggested that GL is a potential therapeutic for protecting against acute kidney injury.
Topics: Animals; Glycyrrhizic Acid; Mice; Disease Models, Animal; Macrophages; Male; Kidney; Toll-Like Receptor 2; Interleukins; Anti-Inflammatory Agents; Inflammation; Interleukin-10; Toll-Like Receptor 4; Signal Transduction; Interleukin-1beta; Hepatorenal Syndrome; Mice, Inbred C57BL; Nephritis
PubMed: 38785317
DOI: 10.1080/0886022X.2024.2356023