Hepatic Infection Research Articles

Increasing trends in hepatitis E hospitalisations in Spain, 1997 to 2019.

BackgroundHepatitis E, a viral hepatitis caused mainly by the ingestion of raw or undercooked food, is not a notifiable disease in Spain.AimTo analyse the temporal trends, epidemiological characteristics and factors associated with severe disease from hepatitis E hospitalisations in Spain from 1997 to 2019.MethodsHospitalisation records were obtained from the Spanish National Hospital Discharge Database. Temporal trends and seasonality were analysed by Poisson regression in years 1997-2015 and 2016-19, given changes in hospital discharge databases. Multivariate logistic regression was used to identify factors associated with severe disease.ResultsHepatitis E hospitalisation incidence increased from 0.22 cases per 1,000,000 inhabitants in 1997 to a maximum of 2.95 in 2018. Seasonality was observed during 2016-19 period, with more cases in the second and third quarters of the year. The incidence was higher in men vs women, and in the population aged over 40 years. Factors independently associated with death were age ≥ 50 years (adjusted odds ratio (aOR): 2.43), chronic liver disease (aOR: 4.29), HIV infection (aOR: 3.00) and hepatitis B/C (aOR: 2.11).ConclusionsHepatitis E hospitalisations have increased in Spain in recent years, being more severe in cases with older age, chronic hepatic diseases and HIV infection. A greater incidence in men over 40 years and a possible seasonality were observed. Further studies are needed to assess the seasonality, geographical distribution and impact of the disease to guide public health actions for prevention and control.

Diagnostic Performance of 18-Fluorodeoxyglucose Positron-Emission Tomography-Computed Tomography (18F-FDG PET-CT) in the Detection of Autosomal Dominant Polycystic Kidney Disease Cyst Infections: A Meta-Analysis.

Diagnosing suspected renal or hepatic infections in autosomal dominant polycystic kidney disease (ADPKD) is difficult. Although 18-fluorodeoxyglucose positron-emission tomography-computed tomography (18F-FDG PET-CT) is recommended to aid in the diagnosis, there is no consensus about its diagnostic accuracy. We aimed to investigate its diagnostic performance. To further assess this, we performed a meta-analysis. A comprehensive literature search screening of PubMed/MEDLINE, Embase, and Cochrane library databases through February 2024 was performed. Pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and C-reactive protein (CRP) were estimated using the random effects model. Heterogeneity between studies was estimated using CochranQ and I2 statistics. A total of seven studies were included in the final analysis. The pooled sensitivity of 18F-FDG PET-CT in diagnosing kidney and hepatic cyst infection was 82.6% (95% CI: 73.8-88.9; I2 16.9%), specificity was 77.6% (95% CI: 66.7-85.7; I2 15.6%), PPV was 79.4% (95% CI: 62.4-89.9; I2 62.6%), and NPV was 81.3% (95% CI: 72.7-87.7; I2 0%). The mean CRP was 244.2 mg/L (95% CI: 209.1-279.1; I2 66%).The results showed that18F-FDG PET-CT demonstrated excellent pooled diagnostic performance in diagnosing renal and hepatic cyst infections in ADPKD.

Phase IB part of LOC-R01, a LOC network non-comparative randomized phase IB/II study testing R-MPV in combination with escalating doses of lenalidomide or ibrutinib for newly diagnosed primary central nervous system lymphoma (PCNSL) patients

BackgroundResults of conventional induction chemotherapies in primary central nervous system lymphoma (PCNSL) need to be improved. Ibrutinib, a BTK inhibitor, and lenalidomide, an immunomodulatory drug, have shown promising results at relapse, supporting to further assess their individual use in combination with high-dose methotrexate-based chemotherapy.MethodsPatients with newly diagnosed PCNSL were randomized to receive four 28-day cycles of ibrutinib or lenalidomide in combination with R-MPV (rituximab, methotrexate, procarbazine, vincristine and prednisone) in a 3 + 3 design. Responders then received a consolidation with R-Cytarabine and an intensive chemotherapy with autologous stem cell transplantation. The objective of the phase IB study was to define the recommended phase II dose (RP2D) based on the dose-limiting toxicity (DLT) occurring during the first induction cycle.ResultsTwenty-six patients (median age 52) were randomized. Four DLTs were observed: one grade 5 aspergillosis and pneumocystosis, one grade 4 catheter-related infection and two grade 3 increased alanine aminotransferase levels. RP2D of ibrutinib and lenalidomide were 560 mg daily (D3-14 and D17-28) and 15 mg daily (D1-21) respectively, in combination with R-MPV. In both arms, the most frequent grade ≥3 treatment-related adverse events were hepatic cytolysis, neutropenia and infections. One grade 4 Lyell’s syndrome was reported at cycle 2 in the lenalidomide arm. After 4 induction cycles, the overall response rates were 76.9% and 83.3% in the lenalidomide and ibrutinib arm, respectively.ConclusionTargeted induction therapies combining lenalidomide or ibrutinib with R-MPV are feasible for first-line PCNSL. The safety profile is consistent with the known safety profiles of R-MPV and both targeted therapies. The phase II part of the study is ongoing.Trial registrationNCT04446962.

Clinical and Histopathologic Characteristics of Acute Severe Hepatitis Associated With Human Herpesvirus 6 Infection.

Acute severe hepatitis associated with active human herpesvirus 6 (HHV-6) infection is a rare life-threatening condition with unclear clinical course and histopathology. In this study, we retrospectively analyzed 5 patients with indeterminate acute severe hepatitis found to have active hepatic HHV-6 infection during care. All patients were previously healthy children presenting with a nonspecific prodrome. Four developed acute liver failure (ALF) and 3 received liver transplantation. The explanted livers and biopsies demonstrated a centrilobular pattern of necroinflammation characterized by moderate to marked central perivenulitis and confluent centrilobular to panlobular necrosis in 4 cases, accompanied by marked hepatocellular swelling and milder portal inflammation in 3. Central perivenulitis was more prominent in comparison to a control of group of ALF without HHV-6 ( P =0.01). When compared with the children with acute severe hepatitis associated with adenovirus encountered in the recent outbreak, both central perivenulitis and centrilobular necrosis were significant predictors for association with HHV-6 ( P <0.01). Liver immunohistochemistry detected HHV-6 structural protein in biliary epithelium in all cases and a predominance of CD8 + T cells in the perivenular inflammatory infiltrate. Among the 4 patients with ALF, one received early anti-HHV-6 therapy and had transplant-free survival, while the other 3 received either general prophylactic antiviral treatment only (n=2) or late anti-HHV-6 therapy (n=1) and needed liver transplantation. Our findings were similar to those in previously reported cases. In summary, acute severe hepatitis associated with HHV-6 tends to affect children, progress to ALF, and exhibit characteristic centrilobular necroinflammation which likely represents an immune-mediated process.

Female patients with hepatitis B may exhibit a reduced risk of breast cancer: A review of NHANES data.

Hepatic viral infections and breast cancer (BC) constitute major global health challenges, yet the interconnection between these hepatic infections and BC continues to be ambiguous. Conducting a comprehensive evaluation of the link between hepatitis virus infection and the incidence of BC and leveraging data from the National Health and Nutrition Examination Survey covering the period from 1999 to March 2022, we utilized logistic regression and subgroup analysis, among other methodologies, to execute a cross-sectional investigation. The univariate logistic regression analysis elucidates that individuals classified as non-Hispanic White exhibit a markedly higher incidence of BC at 2.620 (95% confidence interval [CI], 1.117-7.676; P = .045); moreover, advanced age at 1.063 (95% CI, 1.036-1.093; P < .001), elevated educational attainment at 1.962 (95% CI, 1.17-3.366; P = .012), and higher income levels at 2.835 (95% CI, 1.303-7.439; P = .017) emerge as significant predisposing factors for BC. In contrast, a greater number of live births significantly diminishes the risk of BC, reducing the incidence to 81.1% with each additional birth. Pertaining to hepatitis and vaccination status, our analysis distinctly demonstrates that only hepatitis B at 0.110 (95% CI, 0.018-0.353; P = .002) bears a significant inverse relationship with BC risk, suggesting a protective effect. The multivariate logistic regression analysis further reveals a negative association between hepatitis B infection and BC incidence, whereas hepatitis B vaccination shows a positive correlation with the disease incidence. After adjusting for all covariates, model 3 delineates odds ratios (95% CI) as follows: 0.14 (0.02-0.50; P = .009) and 1.92 (0.99-3.62; P = .046). Our investigation uncovers that within the general populace, there exists an inverse correlation between hepatitis B infection and BC incidence; in addition, the administration of the hepatitis B virus vaccine is potentially positively associated with the prevalence of BC.

MicroRNAs modulate SARS-CoV-2 infection of primary human hepatocytes by regulating the entry factors ACE2 and TMPRSS2.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) preferentially infects the respiratory tract; however, several studies have implicated a multi-organ involvement. Hepatic dysfunctions caused by SARS-CoV-2 infection have been increasingly recognized and described to correlate with disease severity. To elucidate molecular factors that could contribute towards hepatic infection, we concentrated on microRNAs (miRNAs), a class of small non-coding RNAs that modulate various cellular processes and which are reported to be differentially regulated during liver injury. We aimed to study the infection of primary human hepatocytes (PHH) with SARS-CoV-2 and to evaluate the potential of miRNAs for modulating viral infection. We analysed liver autopsies from a coronavirus disease 19 (COVID-19)-positive cohort for the presence of viral RNA using Nanopore sequencing. PHH were used for the infection with SARS-CoV-2. The candidate miRNAs targeting angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) were identified using in silico approaches. To discover the potential regulatory mechanism, transfection experiments, qRT-PCRs, western blots and luciferase reporter assays were performed. We could detect SARS-CoV-2 RNA in COVID-19-positive liver autopsies. We show that PHH express ACE2 and TMPRSS2 and can be readily infected with SARS-CoV-2, resulting in robust replication. Transfection of selected miRNA mimics reduced SARS-CoV-2 receptor expression and SARS-CoV-2 burden in PHH. In silico and biochemical analyses supported a potential direct binding of miR-141-3p to the SARS-CoV-2 genome. We confirm that PHH are susceptible to SARS-CoV-2 infection and demonstrate selected miRNAs targeting SARS-CoV-2 entry factors and/or the viral genome reduce viral loads. These data provide novel insights into hepatic susceptibility to SARS-CoV-2 and associated dysfunctions in COVID-19.

A liver immune rheostat regulates CD8 T cell immunity in chronic HBV infection

Chronic hepatitis B virus (HBV) infection affects 300 million patients worldwide1,2, in whom virus-specific CD8 T cells by still ill-defined mechanisms lose their function and cannot eliminate HBV-infected hepatocytes3–7. Here we demonstrate that a liver immune rheostat renders virus-specific CD8 T cells refractory to activation and leads to their loss of effector functions. In preclinical models of persistent infection with hepatotropic viruses such as HBV, dysfunctional virus-specific CXCR6+ CD8 T cells accumulated in the liver and, as a characteristic hallmark, showed enhanced transcriptional activity of cAMP-responsive element modulator (CREM) distinct from T cell exhaustion. In patients with chronic hepatitis B, circulating and intrahepatic HBV-specific CXCR6+ CD8 T cells with enhanced CREM expression and transcriptional activity were detected at a frequency of 12–22% of HBV-specific CD8 T cells. Knocking out the inhibitory CREM/ICER isoform in T cells, however, failed to rescue T cell immunity. This indicates that CREM activity was a consequence, rather than the cause, of loss in T cell function, further supported by the observation of enhanced phosphorylation of protein kinase A (PKA) which is upstream of CREM. Indeed, we found that enhanced cAMP–PKA-signalling from increased T cell adenylyl cyclase activity augmented CREM activity and curbed T cell activation and effector function in persistent hepatic infection. Mechanistically, CD8 T cells recognizing their antigen on hepatocytes established close and extensive contact with liver sinusoidal endothelial cells, thereby enhancing adenylyl cyclase–cAMP–PKA signalling in T cells. In these hepatic CD8 T cells, which recognize their antigen on hepatocytes, phosphorylation of key signalling kinases of the T cell receptor signalling pathway was impaired, which rendered them refractory to activation. Thus, close contact with liver sinusoidal endothelial cells curbs the activation and effector function of HBV-specific CD8 T cells that target hepatocytes expressing viral antigens by means of the adenylyl cyclase–cAMP–PKA axis in an immune rheostat-like fashion.

The suppressive role of NLRP6 in host defense against Streptococcus suis infection

Streptococcus suis (S. suis) disease is a prevalent zoonotic infectious threat that elicits a systemic inflammatory response in both swine and humans, frequently culminating in high mortality rates. The excessive inflammation triggered by S. suis infection can precipitate tissue damage and sudden death; however, a comprehensive strategy to mitigate this inflammatory response remains elusive. Our study examines the role of NLRP6 in S. suis infection, with a particular focus on its involvement in pathogen regulation. A marked upregulation of NLRP6 was observed in peritoneal macrophages post-infection with S. suis SC19 strain, consequently activating the NLRP6 inflammasome. Furthermore, SC19 infection was found to augment the secretion of pro-inflammatory cytokines IL-1β via NLRP6 activation, while NLRP6 deficiency mitigates the invasion and adhesion of SC19 to macrophages. In vivo models revealed that NLRP6 deletion enhanced survival rates of SC19-infected mice, alongside a reduction in tissue bacterial load and inflammatory cytokine levels. NLRP6-/- mice were shown to exhibit attenuated inflammatory responses in pulmonary, hepatic, and splenic tissues post-SC19 infection, as evidenced by lower inflammation scores. Flow cytometry analyses further substantiated that NLRP6 is involved in modulating macrophage and neutrophil recruitment during infection. Our findings suggest that NLRP6 negatively regulates host resistance against S. suis infection; its absence results in reduced mortality, bacterial colonization, and a milder inflammatory response. Elucidating the mechanism of NLRP6 in S. suis-induced inflammation provides novel insights and theoretical underpinnings for the prophylaxis and therapeutics of S. suis diseases.

Folic acid supplementation is associated with a decreased mortality and reduced hospital readmission in patients with decompensated alcohol-related liver cirrhosis

Background and AimsThiamine and folic acid malnutrition is highly frequent in patients with decompensated alcohol-related liver cirrhosis (aLC). Current guidelines therefore recommend vitamin supplementation in these patients. However, implementation and its impact on the clinical outcome remains unknown. Therefore, we aimed to analyze the use of thiamine and folic acid and their effects on mortality and morbidity in patients with decompensated aLC. MethodsA number of 289 consecutive patients with decompensated aLC who received a paracentesis at Hannover Medical School between 2011 and 2023 were retrospectively investigated. The use of folic acid and thiamine-containing supplements was assessed in the discharge medication. Patients were followed for up to one year regarding liver transplant (LTx)-free survival and the incidence of hepatic encephalopathy, infections and hepatic decompensation requiring rehospitalization. ResultsMedian baseline MELD was 15, median age 56.6 years. 73.0% (n=211) were male patients. At hospital discharge, thiamine-containing supplements and folic acid were prescribed to 48.1% (n=139) and 18.0% (n=52) patients, respectively. Neither thiamine nor folic acid prescription were linked to improved clinical outcomes within 90 days. However, folic acid intake was associated with a higher one-year LTx-free survival (HR=0.48; p=0.04) in the multivariable analysis. Furthermore, folic acid substitution was linked to a decreased risk of rehospitalization within one year (HR=0.55; p=0.01) in the multivariable competing risk model. In contrast, thiamine prescription did neither affect LTx-free survival nor the here investigated liver-related complications. ConclusionFolic acid, but not thiamine substitution was linked to an improved outcome in patients with decompensated aLC.

Lasting differential gene expression of circulating CD8 T cells in chronic HCV infection with cirrhosis identifies a role for Hedgehog signaling in cellular hyperfunction.

The impact of chronic hepatic infection on antigen non-specific immune cells in circulation remains poorly understood. We reported lasting global hyperfunction of peripheral CD8 T cells in HCV-infected individuals with cirrhosis. Whether gene expression patterns in bulk CD8 T cells are associated with the severity of liver fibrosis in HCV infection is not known. RNA sequencing of blood CD8 T cells from treatment naïve, HCV-infected individuals with minimal (Metavir F0-1 ≤ 7.0 kPa) or advanced fibrosis or cirrhosis (F4 ≥ 12.5 kPa), before and after direct-acting antiviral therapy, was performed. CD8 T cell function was assessed by flow cytometry. In CD8 T cells from pre-DAA patients with advanced compared to minimal fibrosis, Gene Ontology analysis and Gene Set Enrichment Analysis identified differential gene expression related to cellular function and metabolism, including upregulated Hedgehog (Hh) signaling, IFN-α, -γ, TGF-β response genes, apoptosis, apical surface pathways, phospholipase signaling, phosphatidyl-choline/inositol activity, and second-messenger-mediated signaling. In contrast, genes in pathways associated with nuclear processes, RNA transport, cytoskeletal dynamics, cMyc/E2F regulation, oxidative phosphorylation, and mTOR signaling, were reduced. Hh signaling pathway was the top featured gene set upregulated in cirrhotics, wherein hallmark genes GLI1 and PTCH1 ranked highly. Inhibition of Smo-dependent Hh signaling ablated the expression of IFN-γ and perforin in stimulated CD8 T cells from chronic HCV-infected patients with advanced compared to minimal fibrosis. CD8 T cell gene expression profiles post-DAA remained clustered with pre-DAA profiles and disparately between advanced and minimal fibrosis, suggesting a persistent perturbation of gene expression long after viral clearance. This analysis of bulk CD8 T cell gene expression in chronic HCV infection suggests considerable reprogramming of the CD8 T cell pool in the cirrhotic state. Increased Hh signaling in cirrhosis may contribute to generalized CD8 T cell hyperfunction observed in chronic HCV infection. Understanding the lasting nature of immune cell dysfunction may help mitigate remaining clinical challenges after HCV clearance and more generally, improve long term outcomes for individuals with severe liver disease.

Immunotherapy responses in viral hepatitis-induced hepatocellular carcinoma: A meta-analysis.

e16223 Background: The advent of immunotherapy has ushered in a paradigm shift in the management of advanced hepatocellular carcinoma (HCC). The distinctive etiological profiles of HCC, characterized by HBV predominance in Asia and HCV/nonviral prevalence in the West, may impart intricacies in the immunological milieu, thereby influencing treatment outcomes. This meta analysis delves into the immunotherapeutic outcomes in patients with hepatitis-induced HCC. Methods: A systematic search was conducted by applying the Boolean logic (and/or) in PubMed (MEDLINE), Embase and Cochrane Library until February 3, 2024. This study investigates the outcomes of patients with HCC complicated by hepatic infection, focusing on overall survival (OS) and progression-free survival (PFS). A meta-analysis was conducted, combining data from 6 studies for OS and 5 studies for PFS. Statistical analyses were conducted using R (v.4.3.2., Vienna). Results: A total of 6 clinical trials pooling in 2958 patients were included in this meta analysis. For OS, the random effects model estimated the cumulative survival across the studies to be 18.3950 months (95% CI [16.3869; 20.4032]). Quantifying heterogeneity revealed a tau-squared value of 5.1789 and Higgins I-squared of 72.7% [41.2%; 87.3%]. The test of heterogeneity indicated significant variability among the studies (Q = 21.99, df = 6, p = 0.0012). For PFS, the random effects model estimated the combined progression-free survival to be 5.9906 months (95% CI [4.2889; 7.6923]). Quantifying heterogeneity revealed a tau-squared value of 3.4995 and Higgins I-squared of 95.4% [91.9%; 97.4%]. The test of heterogeneity indicated significant variability among the studies (Q = 87.66, df = 4, p &lt; 0.0001). Conclusions: The intricate relationship between HCC, hepatic infection, and treatment outcomes necessitates tailored therapeutic strategies for this patient population. Unveiling the heterogeneity in our analysis prompts a comprehensive exploration of potential factors, spanning both biological variances and clinical parameters. This inquiry fuels scientific discourse, urging an in-depth investigation into the immunological nuances influencing therapeutic responses in hepatitis-induced HCC. By addressing these complexities, we can optimize patient care and advance our understanding of effective treatment modalities for this challenging disease.

Infection-Related Readmissions Are Rising among Patients with Hepatorenal Syndrome: A Nationwide Analysis

Hepatorenal syndrome (HRS) is a unique form of renal dysfunction that results from circulatory hemodynamic dysfunction in advanced liver disease. We aimed to determine longitudinal trends in both all-cause and cause-specific readmissions for HRS in the United States. Using the National Readmission Database (2010–2018), we identified adult HRS patients during index admission via ICD codes. Fisher’s exact test and Cox regression analysis were used to compare proportions and compute adjusted p-values, respectively. Regression models were adjusted for gender, age, the Charlson comorbidity index, median household income, and hospital factors. A total of 169,522 HRS patients were included in the analysis (overall mean age 58.97 years). The incidence of HRS hospitalization increased from 5.30% in 2010 to 5.84% in 2018 (p &lt; 0.01). Over the same duration, all-cause readmission at 30 days showed an overall increasing trend from 19.81% to 19.99% (trend p &lt; 0.01). HRS-specific readmission at 30 days following an index hospitalization ranged from 13.60 to 15.98, with an overall increasing trend in the study period (2010–2018). While cirrhosis, hepatic failure, and infection were uniformly the three most common causes of readmission throughout the study period, cirrhosis and infection showed an upward trend. Rising readmissions, especially with hepatic failure and infection, in HRS patients signal a need for national strategies to manage and prevent HRS towards reducing its healthcare burden.

CURRENT CHALLENGES OF HEPATITIS A IN UKRAINE DURING WARTIME: A LITERATURE REVIEW

Goal: to analyze the situation of the incidence of hepatitis A in Ukraine during wartime. Materials and methods. The literature review was carried out using search engines on the platforms PubMed and Google Scholar, abstract database of scientific literature Scopus. Articles in both English and Ukrainian languages were sought. Employing bibliographic and analytical methods, approximately 50 literary sources were scrutinized. These included review articles, randomized and cohort studies, as well as international recommendations for antiviral drug prescriptions, directives, Ukrainian and European protocols for managing hepatic infection. Results. Fulminant hepatitis is a rare occurrence, accounting for less than 1% of cases, although cholestatic forms and recurrent hepatitis have also been documented. Recurrent hepatitis typically manifests in about 3–20% of patients, usually occurring 3–12 weeks following the initial episode, with symptoms generally less severe than the initial presentation. Unlike other hepatitis viruses, HAV does not establish chronic infections. While extrahepatic manifestations of acute hepatitis A are uncommon, they may include neurological symptoms such as Guillain-Barré syndrome, rash, pancreatitis, arthritis, myocarditis, acute kidney injury, and hematologic disorders such as hemolysis and cryoglobulinemia. Numerous studies have indicated that disease severity and mortality associated with HAV infection are heightened among individuals with chronic liver disease, encompassing hepatitis B or C virus coinfection, alcoholic cirrhosis, and fatty liver disease. Chronic liver disease is prevalent in HIV patients due to factors such as coinfection with HBV or HCV, hepatotoxicity from antiviral medications, or alcoholic liver disease. This population may also face an elevated risk of acute or chronic liver failure. HAV infections represent the predominant cause of viral hepatitis globally. The epidemiology of HAV has undergone significant changes due to globalization and improved sanitation. Person-to-person transmission, particularly among high-risk populations such as men who have sex with men (MSM), individuals who use psychoactive substances, and those experiencing homelessness, predominates in high-income countries. Conclusion. However, outbreaks still occur despite the availability of safe, effective vaccines and long-term HGA vaccination recommendations for these individuals. Efforts should be made to develop resources aimed at raising awareness of HAV among high-risk populations and promoting vaccination. Additionally, the development of a specific antiviral treatment for HAV could be very helpful in preventing outbreaks of the virus.

A cholangiocyte organoid system for Cryptosporidium parvum cultivation and transcriptomic studies of biliary cryptosporidiosis

Biliary cryptosporidiosis caused by Cryptosporidium is life-threatening in immunocompromised individuals, particularly those with acquired immune deficiency syndrome (AIDS), resulting in AIDS cholangiopathy. However, studies of biliary cryptosporidiosis have lagged due to the lack of in vitro models that allow complete pathogen development. Here we describe procedures for the generation of mouse cholangiocyte organoids (Chol-orgs). The Chol-orgs, which expressed stem and biliary cell markers, could be clonally expanded for three months and stored in liquid nitrogen for more than one year. Combined with cell differentiation using the air-liquid interface (ALI) approach, we established a culture system for C. parvum. ALI cultures using Chol-orgs have supported ∼50-fold amplification of the pathogen and generated viable oocysts in vitro. In addition, we analyzed the transcriptome of Chol-ALI cultures infected with the IId subtype of C. parvum to characterize host cell responses. RNA-seq analysis revealed that C. parvum upregulated immune and inflammatory responses and downregulated metabolic and cell proliferation signaling pathways in Chol-orgs. A similar system using bovine cholangiocytes also supported the complete development of C. parvum in vitro. These in vitro models provide convenient methods to study biliary cryptosporidiosis and other hepatic infections and to develop effective therapies for AIDS cholangiopathy.

Profile of Homosexuals, Bisexuals, and Transgender People in Kinshasa, the Democratic Republic of the Congo: A Cross-Sectional Study

&amp;lt;i&amp;gt;Introduction&amp;lt;/i&amp;gt;: It has been established that homosexuality plays a considerable role in the persistence of the Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) infections, but data related to their extent remains paradoxically fragmentary. &amp;lt;i&amp;gt;Objectives&amp;lt;/i&amp;gt;: This study aimed to determine the prevalence and determinants of viral infection (Human Immunodeficiency Virus and hepatic viral infections) among homosexuals, bisexuals, and transgenders in Kinshasa, Democratic Republic of the Congo. &amp;lt;i&amp;gt;Methods&amp;lt;/i&amp;gt;: Between February 1 and March 30, 2022, an analytical cross-sectional study was conducted among Kinshasa&amp;apos;s homosexual, bisexual, and transgender populations. The snowball method was used to choose participants from homosexuals’ organisations. Sociodemographic information and the prevalence of viral infections (HIV, HBV, and HCV) were included as study parameters. The determinants of viral infections were found using multivariate logistic regression. &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt;: A total of 555 participants (mean age: 28.5±7.8 years, unmarried: 44.9%) were enrolled. Human immunodeficiency virus, hepatitis B, and hepatitis C infection rates were, respectively, 31.5%, 6.3%, and 9.7% prevalent. HIV-HCV, HIV-HBV, and HIV-HBV-HCV coinfection rates were 4.7%, 4.1%, and 0.7%, respectively. HIV and HBV infection had the same risk factors namely piercing, incarceration, prostitution, and non-condom usage. HCV infection was more pronounced among individuals with piercing, STIs and a previous occurrence of jaundice. &amp;lt;i&amp;gt;Conclusion&amp;lt;/i&amp;gt;: In Kinshasa, HIV, HBV, and HCV infections were widespread among homosexuals, bisexuals, and transgender people. Actions targeting LBGTs are essential to reduce HIV, HCV and HBV infections transmission in the community.

Exploring the utility of circulating miRNAs as diagnostic biomarkers of fasciolosis

Effective management and control of parasitic infections on farms depends on their early detection. Traditional serological diagnostic methods for Fasciola hepatica infection in livestock are specific and sensitive, but currently the earliest detection of the parasite only occurs at approximately three weeks post-infection. At this timepoint, parasites have already entered the liver and caused the tissue damage and immunopathology that results in reduced body weight and loss in productivity. Here, we investigated whether the differential abundance of micro(mi)miRNAs in sera of F. hepatica-infected sheep has potential as a tool for the early diagnosis of infection. Using miRNA sequencing analysis, we discovered specific profiles of sheep miRNAs at both the pre-hepatic and hepatic infection phases in comparison to non-infected sheep. In addition, six F. hepatica-derived miRNAs were specifically identified in sera from infected sheep. Thus, a panel of differentially expressed miRNAs comprising four sheep (miR-3231-3p; miR133-5p; 3957-5p; 1197-3p) and two parasite miRNAs (miR-124-3p; miR-Novel-11-5p) were selected as potential biomarkers. The expression of these candidates in sera samples from longitudinal sheep infection studies collected between 7 days and 23 weeks was quantified using RT-qPCR and compared to samples from age-matched non-infected sheep. We identified oar-miR-133-5p and oar-miR-3957-5p as promising biomarkers of fasciolosis, detecting infection as early as 7 days. The differential expression of the other selected miRNAs was not sufficient to diagnose infection; however, our analysis found that the most abundant forms of fhe-miR-124-3p in sera were sequence variants (IsomiRs) of the canonical miRNA, highlighting the critical importance of primer design for accurate diagnostic RT-qPCR. Accordingly, this investigative study suggests that certain miRNAs are biomarkers of F. hepatica infection and validates miRNA-based diagnostics for the detection of fasciolosis in sheep.

Clinical study on the relationship between liver cirrhosis, ascites, and hyponatremia.

Cirrhosis is a common liver disease, and ascites is one of the common clinical conditions. However, the clinical manifestations of ascites combined with hyponatremia as a high-risk condition and its relationship to patient prognosis have not been fully studied. To explore the clinical manifestations, prognostic factors, and relationships of ascites with hyponatremia in patients with cirrhosis to provide better diagnostic and treatment strategies. In this study, we retrospectively analyzed the clinical data of 150 patients diagnosed with cirrhosis and ascites between 2017 and 2022. Patients were divided into two groups: ascites combined with hyponatremia group and ascites group. We compared the general characteristics, degree of hyponatremia, complications, treatment, and prognosis between the two groups. In the study results, patients in the ascites combined with hyponatremia group showed an older average age (58.2 ± 8.9 years), 64.4% were male, and had a significantly longer hospitalization time (12.7 ± 5.3 d). Hyponatremia was more severe in this group, with a mean serum sodium concentration of 128.5 ± 4.3 mmol/L, which was significantly different from the ascites group of 137.6 ± 2.1 mmol/L. Patients with ascites and hyponatremia were more likely to develop hepatic encephalopathy (56.2% vs 39.0%), renal impairment (45.2% vs 28.6%) and infection (37.0% vs 23.4%). Regarding treatment, this group more frequently used diuretics (80.8% vs 62.3%) and salt supplements (60.3% vs 38.9%). Multiple logistic regression analysis identified older age [Odds ratio (OR) = 1.06, P = 0.025] and male gender (OR = 1.72, P = 0.020) as risk factors for hyponatremia combined with ascites. Overall, patients with ascites and hyponatremia present a clear high-risk status, accompanied by severe complications and poor prognosis. In patients with cirrhosis, ascites with hyponatremia is a high-risk condition that is often associated with severe complications.

Histopathological effects of Cryptococcus neoformans on liver and kidney in mice

This study provides a brief review of approaches for the detection of histopathological effects of Cryptococcus neoformans on the liver and kidney in mice that were injected I/P with 105 yeast cells of C. neoformans suspended in 1 ml phosphate-buffered saline at a single dose. After 14 days, the mice were sacrificed, and histopathological sections from the liver and kidney were prepared and stained with Haematoxylin and Eosin by the P.A.S. method. The results show that the liver was infiltrated with inflammatory cells, primarily mononuclear cells, in the portal. In addition to the activation of Kupffer cells and vacillation of hepatocytes, most blood vessels were congested. The section of the kidney shows sluffing of epithelia lining tubules and destruction of glomeruli, in addition to infiltration of mononuclear cells. These results suggested that the fungus invasiveness of mice has substantial effects on vital organs and may lead to death. Keywords: Cryptococcus neoformans, Hepatic cryptococcal infection, Cryptococcus

The association between hepatic viral infections and cancers: a cross-sectional study in the Taiwan adult population

BackgroundHepatitis B (HBV) and hepatitis C (HCV) viruses are diseases of global public health concern and are associated with liver cancer. Recent studies have revealed associations between hepatic viral infections and extrahepatic cancers. This study aimed to explore the associations between hepatitis B and C viruses and cancer at baseline in the Taiwan Biobank database while controlling for a wide range of confounding variables.MethodsIn a cross-sectional study of adults aged > 20 years, we compared the distribution of demographic factors, lifestyle, and comorbidities between viral and nonviral hepatic groups using the chi-square test. Univariate and multivariate logistic regressions were performed to observe the associations between hepatitis B and C viral infections and cancers by estimating the odds ratio (OR) and 95% confidence interval (CI). Multivariate regression analysis was adjusted for sociodemographic factors, lifestyle, and comorbidities.ResultsFrom the database, 2955 participants were identified as having HCV infection, 15,305 as having HBV infection, and 140,108 as the nonviral group. HBV infection was associated with an increased likelihood of liver cancer (adjusted OR (aOR) = 6.60, 95% CI = 3.21–13.57, P < 0.001) and ovarian cancer (aOR = 4.63, 95% CI = 1.98–10.83, P = 0.001). HCV infection was observed to increase the likelihood of liver cancer (aOR = 4.90, 95% CI = 1.37–17.53, P = 0.015), ovarian cancer (aOR = 8.50, 95% CI = 1.78–40.69, P = 0.007), and kidney cancer (aOR = 12.89, 95% CI = 2.41–69.01, P = 0.003).ConclusionOur findings suggest that hepatic viral infections are associated with intra- and extrahepatic cancers. However, being cross-sectional, causal inferences cannot be made. A recall-by-genotype study is recommended to further investigate the causality of these associations.

The impact of concomitant infective endocarditis in patients with spondylodiscitis and isolated spinal epidural empyema and the diagnostic accuracy of the modified duke criteria.

The co-occurrence of infective endocarditis (IE) and primary spinal infections (PSI) like spondylodiscitis (SD) and isolated spinal epidural empyema (ISEE) has been reported in up to 30% of cases and represents a life-threatening infection that requires multidisciplinary management to be successful. Therefore, we aimed to characterize the clinical phenotypes of PSI patients with concomitant IE and furthermore to assess the accuracy of the modified Duke criteria in this specific population. We conducted a retrospective cohort study in consecutive SD and ISEE patients treated surgically at our University Spine Center between 2002 and 2022 who have undergone detailed phenotyping comprising demographic, clinical, imaging, laboratory, and microbiologic assessment. Comparisons were performed between PSI patients with IE (PSICIE) and without IE (PSIWIE) to identify essential differences. Methicillin-susceptible Staphylococcus aureus (MSSA) was the most common causative pathogen in PSICIE group (13 patients, 54.2%) and aortic valve IE was the most common type of IE (12 patients, 50%), followed by mitral valve IE (5 patients, 20.8%). Hepatic cirrhosis (p < 0.011; OR: 4.383; 95% CI: 1.405-13.671), septic embolism (p < 0.005; OR: 4.387; 95% CI: 1.555-12.380), and infection with Streptococcus spp. and Enterococcus spp. (p < 0.003; OR: 13.830; 95% CI: 2.454-77.929) were identified as significant independent risk factors for the co-occurrence of IE and PSI in our cohort. The modified Duke criteria demonstrated a sensitivity of 100% and a specificity of 66.7% for the detection of IE in PSI patients. Pathogens were detected more frequently via blood cultures in the PSICIE group than in the PSIWIE group (PSICIE: 23, 95.8% vs. PSIWIE: 88, 62.4%, p < 0.001). Hepatic cirrhosis (PSICIE: 10, 41.7% vs. PSIWIE: 33, 21.6%, p = 0.042), pleural abscess (PSICIE: 9, 37.5% vs. PSIWIE: 25, 16.3%, p = 0.024), sepsis (PSICIE: 20, 83.3% vs. PSIWIE: 67, 43.8%, p < 0.001), septic embolism (PSICIE: 16/23, 69.6% vs. PSIWIE: 37/134, 27. 6%, p < 0.001) and meningism (PSICIE: 8/23, 34.8% vs. PSIWIE: 21/152, 13.8%, p = 0.030) occurred more frequently in PSICIE than in PSIWIE patients. PSICIE patients received longer intravenous antibiotic therapy (PSICIE: 6 [4-7] w vs. PSIWIE: 4 [2.5-6] w, p < 0.001) and prolonged total antibiotic therapy overall (PSICIE: 11 [7.75-12] w vs. PSIWIE: 8 [6-12] w, p = 0.014). PSICIE patients spent more time in the hospital than PSIWIE (PSICIE: 43.5 [33.5-53.5] days vs. PSIWIE: 31 [22-44] days, p = 0.003). We report distinct clinical, radiological, and microbiological phenotypes in PSICIE and PSIWIE patients and further demonstrate the diagnostic accuracy of the modified Duke criteria in patients with PSI and concomitant IE. In the high-risk population of PSI patients, the modified Duke criteria might benefit from amending pleural abscess, meningism, and sepsis as minor criteria and hepatic cirrhosis as major criterion.