The impact of hepatitis B and C positive serologies on the outcomes of non-hepatic solid organ transplantation in the United States.

Chronic viral hepatitis B (HBV) and C (HCV) infection could negatively affect outcomes of non-hepatic solid organ transplantations due to the risk of viral reactivation in the presence of immunosuppression. This study aimed to determine post-transplant outcomes in patients with HBV or HCV positivity receiving non-hepatic solid-state organ transplant. Data was collected from the Scientific Registry of Transplant Recipients (SRTR) 2006-2021 for patients (≥18) who received a lung, heart, or kidney single organ transplant in the U.S. Hepatitis C positivity (HCV+) was determined as positive HCV Ab and hepatitis B positivity (HBV+) as positive HBsAg. We included N = 30,872 lung, N = 36,990 heart and N = 280,162 kidney transplant recipients. The prevalence of HBV+ was 1.3% in lung, 1.5% in heart and 1.7% in kidney patients, HCV+ was 2.2%, 2.2% and 5.0%, respectively. Post-transplant survival of patients with vs. without HBV+ was similar in all solid organ transplants (all p > .05). Similarly, there was no difference in post-transplant survival between lung transplant recipients with vs. without anti-HCV (all p > .05). Heart transplant recipients with HCV+ had higher crude post-transplant mortality (all p < .01). Similarly, there was higher post-transplant mortality in kidney transplant recipients with HCV+ (1-year: 6% vs. 3%; 5-year: 21% vs. 13%; 10-year: 47% vs. 31%; all p < .0001). In multivariate analysis controlling for confounders, only the association of HCV+ with higher post-kidney transplant mortality remained significant: adjusted hazard ratio (aHR) (95% CI) = 1.16 (1.12-1.20), p < .0001. There was no association of viral hepatitis seropositivity with the risk of graft failure in all groups (p > .05). In most cases, the presence of HBV or HCV serologies is not associated with adverse post-transplant outcomes in non-hepatic solid organ transplants. However, kidney transplant recipients who are positive for HCV serology have an increased risk for post-transplant mortality.

Overcome Health Inequities to Eliminate Viral Hepatitis.

This Viewpoint outlines the progress made toward eliminating hepatitis B and C but emphasizes the work that remains to prioritize diagnosis and treatment of populations disproportionately affected by viral hepatitis, including ensuring that there are systems in place to treat those infected and care for those at risk.

Current Approach to Renal Transplantation Candidates and Potential Donors with Viral Hepatitis.

Renal transplantation is the most beneficial treatment in patients with chronic kidney disease (CKD), increasing life expectancy and improving quality of life. A better understanding of organ and tissue functions, the development of surgical techniques, and new and effective immunosuppressive and antimicrobial drugs increase the success of transplantation. However, the number of renal transplantations from living and cadaveric donors is not at the desired frequency. Among the leading causes of the restrictions for transplantation are both the recipients' and donors' chronic diseases. While hepatitis B and C infections are a significant problem affecting the number and success of renal transplantations, the innovation of hepatitis C virus treatments has improved outcomes. Thus, the recipient and donor hepatitis B and C virus infections are no longer considered as relative contraindications for renal transplantation. This review discusses the management of patients and donors with hepatitis B and hepatitis C in renal transplantation.

Hepatitis aguda grave en niños de etiología no precisada y lo que es conocido, mayo 2022 / Severe acute hepatitis in children of unspecified etiology and what is known, May 2022

Hepatitis aguda es el término empleado para describir una variedad de condiciones patológicas caracterizadas por la inflamación aguda del parénquima hepático que evoluciona a la normalización de las pruebas funcionales hepáticas en un período menor a seis meses. Puede variar en el rango de leve y autolimitada a enfermedad severa que requiere trasplante hepático. Etiológicamente, puede ser ocasionada por agentes tóxicos, drogas, factores ambientales, procesos autoinmunes o agentes infecciosos (bacterias, hongos, parásitos y virus). Los virus son considerados los agentes etiológicos más comunes de la hepatitis aguda. Los virus de la hepatitis A, B, C, D y E son reconocidos como los causantes de hepatitis viral y difieren entre ellos en modos de trasmisión, severidad de la enfermedad, distribución geográfica y métodos de prevención. Otros agentes virales pueden causar una hepatitis aguda: virus Epstein-Barr, citomegalovirus, virus herpes simplex, coxsackievirus, virus dengue, coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SARS-CoV-2, por sus siglas en inglés).1 El 5 de abril de 2022, el Punto Focal Nacional del Reglamento Sanitario Internacional de Escocia Central notificó al Reino Unido un aumento significativo e inesperado de casos (10) de hepatitis aguda grave en niños menores de 10 años, previamente sanos, en los que no se identificó asociación conocida con los viajes. En nueve de los casos, el inicio de los síntomas fue en marzo de 2022 y en uno, en enero de 2022. Los 10 casos detectados fueron hospitalizados. Como resultado de una investigación a nivel nacional, el 8 de abril de 2022, en el Reino Unido se habían identificado un total de 74 casos, estableciendo como definición de caso confirmado toda persona que hubiera presentado una hepatitis aguda (resultado negativo a los virus de hepatitis A a la E) con transaminasas séricas >500 UI/L (Aspartato Transaminasa-AST o Alanina Transaminasa -ALT), con 10 años de edad o menos, desde...(AU)

Hepatite de causa desconhecida em crianças / Hepatitis of unknown cause in children

Em 23 de abril de 2022, a Organização Mundial da Saúde ­ OMS divulgou que, até o dia 21 do mês em questão, foram notificados 169 casos de hepatite aguda de origem desconhecida entre crianças de 1 mês a 16 anos de idade em 11 países da Região Europeia da OMS (a maioria no Reino Unido ­ 114 casos) e em um país da Região das Américas (EUA ­ 9 casos) ­ Figura 1 (WHO, 2022). Até 29 de abril de 2022, mais de 200 casos haviam sido reportados no mundo. Houve relatos na Espanha, Israel, Estados Unidos, Dinamarca, Irlanda, Holanda, Itália, Noruega, França, Romênia, Bélgica e Argentina. No Brasil, em 06 de maio de 2022, sete casos suspeitos estavam sob investigação (INSTITUTO BUTANTAN, 2022).

On April 23, 2022, the World Health Organization (WHO) reported that, until the 21st of the month in question, 169 cases of acute hepatitis of unknown origin were reported among children aged 1 month to 16 years in 11 countries in the world. WHO European Region (most in the UK ­ 114 cases) and one country in the Region of the Americas (USA ­ 9 cases) ­ Figure 1 (WHO, 2022). As of April 29, 2022, more than 200 cases have been reported worldwide. There were reports in Spain, Israel, the United States, Denmark, Ireland, the Netherlands, Italy, Norway, France, Romania, Belgium and Argentina. In Brazil, on May 6, 2022, seven suspected cases were under investigation (INSTITUTO BUTANTAN, 2022).

Cardiovascular disease risk in liver transplant recipients transplanted due to chronic viral hepatitis.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of morbidity and mortality after liver transplantation, mostly in patients transplanted for nonalcoholic steatohepatitis, obesity and diabetes. Few data exist on cardiovascular diseases among patients transplanted for viral hepatitis. OBJECTIVE: Our aim is to clarify the cardiovascular risk and subclinical vascular damage among liver transplant recipients for chronic viral hepatitis (i.e. hepatits C virus, hepatis B virus and hepatitis D virus infection). METHODS: Adult patients (age ≥ 18 years) with orthotopic liver transplants (OLT) due to viral hepatitis who signed informed consent, and were admitted for a routine follow-up between June 2019 and September 2020 at the Infectious Disease outpatient clinic of the University of Campania Luigi Vanvitelli, Naples, Italy, were prospectively enrolled. An estimation of cardiovascular risk was assessed using three main risk charts, echocolor-Doppler of epiaortic vessels was performed to assess subclinical Intima-Media changes. RESULTS: A total of 161 patients were evaluated; of these 15 were excluded because not affected by viral hepatitis. 146 patients were considered. 83 patients (56.8%) were considered at high cardiovascular risk according to Framingham, 54 patients (36.9%) to American Heart Association Arteriosclerotic Cardiovascular Disease (ASCVD) score and 19 (13.0%) to Heart Score. Only 8 patients (5.4%) showed a normal carotid ultrasound, while 52 patients (35.6%) had a carotid artery Intima-Media Thickness (IMT) and 86 (58.9%) an atherosclerotic plaque. CONCLUSIONS: Liver transplant recipients for virus-related associated liver disease are, in light of the high percentage of carotid lesions, at high risk of CVD. Risk charts compared to subclinical carotid lesions which represent damage already established and a real localization of the disease, seem to underestimate the cardiovascular risk. A chronic inflammatory status, could play a key role. It's important to raise the awareness of cardiovascular risk in liver transplant patients to prevent cardiovascular diseases and improve the timing of early diagnosis of premature vascular lesions.

Epidemiological profile of viral hepatitis infection in the population treated at a reference hospital in Alagoas / Perfil epidemiológico da infecção por hepatite viral na população atendida em hospital de referência em Alagoas

Viral hepatitis are widely spread infectious diseases caused by a variety of etiological agents that displays liver tropism as a common characteristic. A descriptive, cross-sectional, observational and retrospective study was conducted through the analysis of viral hepatitis medical records treated and diagnosed from 2010 to 2015. The relationship between the variables were made through the chi-square test. 632 viral hepatitis medical records were analyzed. The highest number of cases happened in 2011. Hepatitis A virus (HAV) infection was predominant. The most affected age group was < 20 years and the highest number of cases observed in this age group was related to HAV (p<0.001). The acute clinical form was predominant, with 70.2% of the cases. 92.3% of which corresponded to HAV infection (p<0.001). Most of the cases occurred in the brown race and male gender. Moreover, regarding the probable source/mechanism of infection, the contact with suspicious water/food for hepatitis A cases was highlighted. The sexual form predominated in HBV infection and previous history of blood transfusion in cases of hepatitis C. Most cases were spotted in the mesoregion of Eastern Alagoas, especially in the capital Maceió. It must be observed the importance of knowing the profile of this disease in order to understand its dissemination and thus have subsidies for the creation of actions and strategies to combat the infection.

A hepatite viral é uma doença infecciosa amplamente difundida causada por uma variedade de agentes etiológicos que exibem o tropismo hepático como uma característica comum. Um estudo descritivo, transversal, observacional e retrospectivo foi realizado por meio da análise de prontuários de hepatites virais tratados e diagnosticados de 2010 a 2015. A relação entre as variáveis foi feita através do teste qui-quadrado. Foram analisados 632 prontuários de hepatite sustero. O maior número de casos aconteceu em 2011. A infecção pelo vírus da hepatite A (HAV) foi predominante. A faixa etária mais atingida foi < 20 anos e o maior número de casos observados nessa faixa etária foi relacionado ao HAV (p<0,001). A forma clínica aguda foi predominante, com 70,2% dos casos. 92,3% dos quais corresponderam à infecção por HAV (p<0,001). A maioria dos casos ocorreu na raça parda e no sexo masculino. Além disso, quanto à provável fonte/mecanismo de infecção, foi destacado o contato com água/alimento suspeitos para os casos de hepatite A. A forma sexual predominou na infecção pelo HbV e histórico anterior de transfusão de sangue em casos de hepatite C. A maioria dos casos foi avistada na mesorregião do Leste de Alagoas, especialmente na capital Maceió. Deve-se observar a importância de conhecer o perfil dessa doença para entender sua disseminação e, assim, contar com subsídios para a criação de ações e estratégias de combate à infecção.

Bioengineered Liver Cell Models of Hepatotropic Infections.

Hepatitis viruses and liver-stage malaria are within the liver infections causing higher morbidity and mortality rates worldwide. The highly restricted tropism of the major human hepatotropic pathogens-namely, the human hepatitis B and C viruses and the Plasmodium falciparum and Plasmodium vivax parasites-has hampered the development of disease models. These models are crucial for uncovering the molecular mechanisms underlying the biology of infection and governing host-pathogen interaction, as well as for fostering drug development. Bioengineered cell models better recapitulate the human liver microenvironment and extend hepatocyte viability and phenotype in vitro, when compared with conventional two-dimensional cell models. In this article, we review the bioengineering tools employed in the development of hepatic cell models for studying infection, with an emphasis on 3D cell culture strategies, and discuss how those tools contributed to the level of recapitulation attained in the different model layouts. Examples of host-pathogen interactions uncovered by engineered liver models and their usefulness in drug development are also presented. Finally, we address the current bottlenecks, trends, and prospect toward cell models' reliability, robustness, and reproducibility.

Acute CMV hepatitis in an immunocompetent patient.

A previously well and immunocompetent 64-year-old woman presented with fever of unknown origin and acute hepatitis. Besides headache and nausea, she had no other symptoms. Her clinical examination was unremarkable with no clear focus of infection. She was thoroughly investigated and her biochemical profile suggested a viral or autoimmune aetiology. Multiple imaging modalities gave no further insight. Her serology and subsequent nucleic acid amplification indicated reactivation of latent cytomegalovirus (CMV). Her symptoms resolved with supportive care and no anti-viral therapy was needed. This case report highlights CMV reactivation leading to acute hepatitis in a well, immunocompetent patient.

A Qualitative Community Assessment of Racial/Ethnic Sexual Gender Minority Young Adults: Principles for Strategies to Motivate Action(s) for Realistic Tasks (SMART Thinking) Addressing HIV/AIDS, Viral Hepatitis, Mental Health, and Substance Abuse.

HIV/STI, substance use, and mental health issues disproportionately affect racial/ethnic sexual minority young adults. These health vulnerabilities intensify across the life course, most notably when young adults are independent college students. To identify the perspectives of racial/ethnic sexual gender minorities living on or near an urban university, we implemented an intersectionality-informed SWOT (strengths, weakness, opportunities, and threats) analysis, as a qualitative community assessment situated within in a campus-community setting. The community needs assessment was the first step in the strategic prevention framework (SPF) to co-locate substance abuse, mental health, viral hepatitis, and HIV prevention care services for Latinx and Black/African American sexual gender minority young adults at a minority-serving institution. The SWOT analysis identified principles for selecting, adapting, and implementing an evidence-based intervention. The significance of these principles demonstrates the value of intersectionality in evidence-based interventions to influence health education and behavior among racial/ethnic sexual gender minorities.

COVID-19 and gastrointestinal injury: a brief systematic review and data from Bulgaria.

In December 2019, a new Coronavirus (SARS-CoV-2) emerged in China, causing the pandemic disease COVID-19. The clinical presentation is variable, but the predominant symptoms are those of the upper respiratory tract. AIM: The aim of the current study is to describe the incidence and type of the gastrointestinal injury (GI) in COVID-19, as well as their prognostic value. MATERIALS AND METHODS: We conducted a coincidental search on this topic in PubMed, Web of Science and EMBASE. We also followed a group of 31 Bulgarian COVID-19 patients throughout the course of their disease and analyzed their symptoms (catarrhal and other) and outcome. RESULTS: The publications concerning our survey followed a total of 1509 COVID-19 patients. In the Bulgarian cohort, only 14 from the 31 patients were laboratory-confirmed COVID-19 cases. Approximately 1/3 of the infected individuals presented with GI. In some patients this was the first, or only, symptom of the disease. It was also indicative of a more severe disease course. CONCLUSION: GI may be an important symptom and prognostic factor in COVID-19. Therefore, patients with acute gastrointestinal symptoms must be actively tested for SARS-CoV-2.

Risk of hepatic failure in COVID-19 patients. A systematic review and meta-analysis.

Liver injury has been reported to occur during the disease in severe cases. Therefore, this meta-analysis study aims to investigate the incidence of liver injury among published literature from 2019-Jan-01 to 2020-April-03 to provide an outline for further studies on the liver injury of COVID-19. Four databases including Pubmed, Embase, Web of Science, and the Scopus were searched for studies published from 2019-Jan-01 to 2020-April-03. Data analysis and drawing of charts were performed using the Comprehensive Meta-Analysis Software Version 2.2 (Biostat, USA). The search yielded 450 publications, of which 64 potentially eligible studies were identified for full-text review and 21 studies fulfilling the inclusion criteria remained. A total of 4191 COVID-19 patients were included in our meta-analysis. The pooled prevalence of liver injury was 19.5% (95% CI: 14.3-26.1). According to our results, there was significant heterogeneity among the 19 studies (X2 = 738.5; p < 0.001; I2 = 94.34%). Among 288 death cases, the pooled prevalence of liver injury was 22.8% (95% CI: 11.7-39.8). In summary, the COVID-19 disease itself can result in severe and even fatal respiratory diseases and even may lead to ARDS and multiple organ failure. The results of this systematic review highlight the importance of liver injury that may assist clinicians anywhere in the globe in controlling COVID-19-related infection and complications. Moreover, the prevalence of liver injury can be higher in severe cases than in mild cases.

Viral Hepatitis and Iron Dysregulation: Molecular Pathways and the Role of Lactoferrin.

The liver is a frontline immune site specifically designed to check and detect potential pathogens from the bloodstream to maintain a general state of immune hyporesponsiveness. One of the main functions of the liver is the regulation of iron homeostasis. The liver detects changes in systemic iron requirements and can regulate its concentration. Pathological states lead to the dysregulation of iron homeostasis which, in turn, can promote infectious and inflammatory processes. In this context, hepatic viruses deviate hepatocytes' iron metabolism in order to better replicate. Indeed, some viruses are able to alter the expression of iron-related proteins or exploit host receptors to enter inside host cells. Lactoferrin (Lf), a multifunctional iron-binding glycoprotein belonging to the innate immunity, is endowed with potent antiviral activity, mainly related to its ability to block viral entry into host cells by interacting with viral and/or cell surface receptors. Moreover, Lf can act as an iron scavenger by both direct iron-chelation or the modulation of the main iron-related proteins. In this review, the complex interplay between viral hepatitis, iron homeostasis, and inflammation as well as the role of Lf are outlined.

Cytokine Expression in Dengue Fever and Dengue Hemorrhagic Fever Patients with Bleeding and Severe Hepatitis.

Dengue is the most common mosquito-borne flaviviral infection in the world today. Several factors contribute and act synergistically to cause severe infection. One of these is dysregulated host immunological mediators that cause transient pathophysiology during infection. These mediators act on the endothelium to increase vascular permeability, which leads to plasma leakage compromising hemodynamics and coagulopathy. We conducted a prospective study to explore the expression of pro- and anti-inflammatory cytokines and how they relate to clinical dengue manifestations, by assessing their dynamics through acute dengue infection in adults admitted to the Hospital for Tropical Diseases, Bangkok, Thailand. We performed cytokine analysis at three phases of infection for 96 hospitalized adults together with serotyping of confirmed dengue infection during the outbreaks of 2015 and 2016. The serum concentrations of seven cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha, and interferon gamma) were measured in duplicate using a commercial kit (Bio-Plex Human Cytokine Assay). In this study, the cytokine profile was suggestive of a T-helper 2 response. Most patients had secondary infection, and the levels of viremia were higher in patients with plasma leakage than those without plasma leakage. In addition, we observed that bleeding and hepatitis were associated with significantly higher levels of IL-8 during the early phases of infection. Furthermore, IL-6 levels in the early phase of infection were also elevated in bleeding patients with plasma leakage. These results suggest that IL-6 and IL-8 may act in synergy to cause bleeding in patients with plasma leakage.

Complications of measles: a case series.

Measles, which was once thought to be a disappearing viral infection due to effective vaccination, has been re-emerging globally, with increasing cases in adolescents and adults. This has been attributed to anti-vaccination campaigning in the early 21st century, which has resulted in a drop in overall herd immunity. In this case series we report three patients with complications secondary to measles who presented to a hospital in Malta in 2019. Through this series, we discuss the range of possible complications caused by the measles virus, ranging from mild viraemic symptoms to multiorgan involvement which could possibly lead to high-dependency care and may even be fatal. We also highlight recent global statistics which reflect the exponential increase in the incidence of measles, with a special focus on Europe. It is emphasised that vaccine education and compliance with the two-dose measles vaccine should be implemented worldwide.