Risk factors for sporadic hepatitis A infection: a systematic review and meta-analysis

Hepatitis A virus (HAV) is responsible for common acute viral hepatitis worldwide. Improvement in sanitation and use of efficient vaccines have reduced HAV incidence in developed countries. However, naive adult population are most susceptible to severe outcomes, and high endemic areas persist in developing regions. The transmission of HAV through the fecal-oral route is established. However, considering evolving consumption habits and global market exchange of food, investigations on risk factors associated with HAV infection are needed. Thus, a systematic review and a meta-analysis of case-control, cohort and transversal studies was performed to determine the main risk factors associated with sporadic HAV infection. Relevant scientific articles were identified through systematic literature search and subjected to a methodological quality assessment. Mixed-effects meta-analyses models were adjusted by population type to appropriate data partitions. HAV infections are defined by serological testing. The quality assessment stage selected 78 studies investigating risk factors for sporadic infections with hepatitis A conducted between 1985 and 2013. This meta-analysis confirmed that HAV infections are mostly related to inter-human transmissions, either due to contact with an ill person, through oral-anal sex practice, or lack of personal hygiene. Travel to endemic countries, occupational exposure such as working in child daycare, and exposure to wastewater were associated with HAV infection. As HAV can persist in the environment, it was not surprising that consumption of untreated drinking water, shellfish consumed raw, and crop products were risk factors. Food contamination could be due to the use of contaminated water (fruits, vegetables) or originate from infected food handlers at every point of the food chain (from picking to serving). Eating or drinking outside were associated with HAV infection. A lack of recent case-control studies was identified, with only three studies eligible between 2011 and 2017. Case-control studies required a more precise definition of risk factors such as type of crop product, and storing/preparation information (e.g. washed, frozen). The frequency of consumption or duration of environmental exposure could also better inform relationship between exposure and risk of infection. In a context of epidemiological change of HAV, international travel and trade of foods, future case-control studies are needed and should focus on populations at risk of severe infections and acute cases.U. Gonzales-Barron and V. Cadavez are grateful to the Foundation for Science and Technology (FCT, Portugal) and FEDER under programme PT2020 for the financial support to CIMO (UID/AGR/00690/2019).info:eu-repo/semantics/publishedVersio

Safety and efficacy of protease inhibitors to treat hepatitis C after liver transplantation: A multicenter experience

Background & Aims: Protease inhibitors (PI) with peginterferon/ ribavirin have significantly improved SVR rates in HCV G1 patients. Their use to treat HCV recurrence after liver transplantation (LT) is a challenge. Methods: This cohort study included 37 liver transplant recipients (male, 92%, age 57 ± 11 years), treated with boceprevir (n = 18) or telaprevir (n = 19). The indication for therapy was HCV recurrence (fibrosis stage PF2 (n = 31, 83%) or fibrosing cholestatic hepatitis (n = 6, 16%). Results: Eighteen patients were treatment-naive, five were relapsers and fourteen were non-responders to dual therapy after LT. Twenty-two patients received cyclosporine and fifteen tacrolimus. After 12 weeks of PI therapy, a complete virological response was obtained in 89% of patients treated with boceprevir, and 58% with telaprevir (p = 0.06). The end of treatment virological response rate was 72% (13/18) in the boceprevir group and 40% (4/10) in the telaprevir group (p = 0.125). A sustained virological response 12 weeks after treatment discontinuation was observed in 20% (1/5) and 71% (5/7) of patients in the telaprevir and boceprevir groups, respectively (p = 0.24). Treatment was discontinued in sixteen patients (treatment failures (n = 11), adverse events (n = 5)). Infections occurred in ten patients (27%), with three fatal outcomes (8%). The most common adverse effect was anemia (n = 34, 92%), treated with erythropoietin and/ or a ribavirin dose reduction; thirteen patients (35%) received red blood cell transfusions. The cyclosporine dose was reduced by 1.8 ± 1.1-fold and 3.4 ± 1.0-fold with boceprevir and telaprevir, respectively. The tacrolimus dose was reduced by 5.2 ± 1.5-fold with boceprevir and 23.8 ± 18.2-fold with telaprevir. Conclusions: Our results suggest that triple therapy is effective in LT recipients, particularly those experiencing a severe recurrence. The occurrence of anemia and drug-drug interactions, and the risk of infections require close monitoring.

More rapid blood interferon α2 decline in fatal versus surviving COVID-19 patients

BackgroundThe clinical outcome of COVID-19 pneumonia is highly variable. Few biological predictive factors have been identified. Genetic and immunological studies suggest that type 1 interferons (IFN) are essential to control SARS-CoV-2 infection.ObjectiveTo study the link between change in blood IFN-α2 level and plasma SARS-Cov2 viral load over time and subsequent death in patients with severe and critical COVID-19.MethodsOne hundred and forty patients from the CORIMUNO-19 cohort hospitalized with severe or critical COVID-19 pneumonia, all requiring oxygen or ventilation, were prospectively studied. Blood IFN-α2 was evaluated using the Single Molecule Array technology. Anti-IFN-α2 auto-Abs were determined with a reporter luciferase activity. Plasma SARS-Cov2 viral load was measured using droplet digital PCR targeting the Nucleocapsid gene of the SARS-CoV-2 positive-strand RNA genome.ResultsAlthough the percentage of plasmacytoid dendritic cells was low, the blood IFN-α2 level was higher in patients than in healthy controls and was correlated to SARS-CoV-2 plasma viral load at entry. Neutralizing anti-IFN-α2 auto-antibodies were detected in 5% of patients, associated with a lower baseline level of blood IFN-α2. A longitudinal analysis found that a more rapid decline of blood IFN-α2 was observed in fatal versus surviving patients: mortality HR=3.15 (95% CI 1.14–8.66) in rapid versus slow decliners. Likewise, a high level of plasma SARS-CoV-2 RNA was associated with death risk in patients with severe COVID-19.ConclusionThese findings could suggest an interest in evaluating type 1 IFN treatment in patients with severe COVID-19 and type 1 IFN decline, eventually combined with anti-inflammatory drugs.Clinical trial registrationhttps://clinicaltrials.gov, identifiers NCT04324073, NCT04331808, NCT04341584

Development of a World Health Organization International Reference Panel for different genotypes of hepatitis E virus for nucleic acid amplification testing.

Globally, hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Epidemiology and clinical presentation of hepatitis E vary greatly by location and are affected by the HEV genotype. Nucleic acid amplification technique (NAT)-based assays are important for the detection of acute HEV infection as well for monitoring chronic cases of hepatitis E. The aim of the study was to evaluate a panel of samples containing different genotypes of HEV for use in nucleic NAT-based assays. The panel of samples comprises eleven different members including HEV genotype 1a (2 strains), 1e, 2a, 3b, 3c, 3e, 3f, 4c, 4g as well as a human isolate related to rabbit HEV. Each laboratory assayed the panel members directly against the 1 World Health Organization (WHO) International Standard (IS) for HEV RNA (6329/10) which is based upon a genotype 3 a strain. The samples for evaluation were distributed to 24 laboratories from 14 different countries and assayed on three separate days. Of these, 23 participating laboratories returned a total of 32 sets of data; 17 from quantitative assays and 15 from qualitative assays. The assays used consisted of a mixture of in-house developed and commercially available assays. The results showed that all samples were detected consistently by the majority of participants, although in some cases, some samples were detected less efficiently. Based on the results of the collaborative study the panel (code number 8578/13) was established as the "1st International Reference Panel (IRP) for all HEV genotypes for NAT-based assays" by the WHO Expert Committee on Biological Standardization. This IRP will be important for assay validation and ensuring adequate detection of different genotypes and clinically important sub-genotypes of HEV

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection