Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis: A case report of 3 patients.

Short-term administration of the entry inhibitor myrcludex-B (MyrB) has been shown to be safe and effective in phase II studies in patients coinfected with hepatitis B virus (HBV) and hepatitis delta virus (HDV). However, its effectiveness and safety are unknown during long-term and high-dose treatment of patients with compensated cirrhosis in real-life settings. Herein, we describe the first 3 European patients with HDV-related compensated cirrhosis who were treated with MyrB 10 mg/day for 48 weeks as a compassionate therapy. Liver function tests, bile acids, and virological markers were monitored every 4 weeks. HBV/HDV-specific T cell quantity (up to 48 and 36 weeks) and HBV RNA levels were also assessed in 2 cases. During MyrB treatment, HDV RNA levels progressively declined from 4.4 and 5.6 logs IU/ml to undetectability in 2 cases, and from 6.8 log copies/ml to 500 copies/ml for the other patient. Alanine aminotransferase normalised after 20, 12 and 28 weeks, respectively. A significant improvement in features of portal hypertension, liver function tests and alpha-fetoprotein levels were documented in 2 cases. In the male patient with histological and clinical stigmata of autoimmune hepatitis, IgG and immunoglobulins rapidly normalised. No significant changes in HBV surface antigen levels and circulating HBV/HDV-specific T cells were demonstrated; HBV DNA and HBV RNA levels remained undetectable throughout the study period. MyrB was well tolerated; patients remained fully asymptomatic despite a significant increase of bile acids. In conclusion, this report shows excellent safety and effectiveness of a 48-week course of MyrB 10 mg/day, combined with tenofovir disoproxil fumarate, for the treatment of HDV-related compensated cirrhosis.

Emergence of divergent enterovirus (EV) D68 sub-clade D1 strains, northern Italy, September to October 2018.

Between September and October 2018, an enterovirus D68 (EV-D68) outbreak occurred in patients hospitalised with severe acute respiratory infection in northern Italy; 21 laboratory-confirmed cases were reported. Phylogenetic analysis revealed that 16/20 of the EV-D68 sequences belonged to a divergent group within the sub-clade D1. Since its upsurge, EV-D68 has undergone rapid evolution with the emergence of new viral variants, emphasising the need for molecular surveillance that include outpatients with respiratory illness.

HEV and HAV seroprevalence in men that have sex with men (MSM): An update from Milan, Italy.

Hepatitis E virus (HEV) is a feco-orally transmitted pathogen and one of the most common cause of acute hepatitis worldwide. Recent studies in developed countries suggested that a direct human-to-human contact such as for sexually transmitted diseases may play a significant role in the HEV spread. The aim of this study was to investigate the seroprevalence of HEV and HAV in a group of MSM, including subjects HIV, and Treponema infected, in Milan, Italy. The overall anti HEV IgG seroprevalence in MSM was 10.2% (65/636), instead in the control group the detection rate was 5.2% (15/288) (P < 0.05); the anti HAV seroprevalence was 42.8% in MSM, when in the control group the positivity rate was 29.2% (P < 0.05). The rate of coinfection HEV/HAV was 14.6% in MSM and 1% in control group (P < 0.05). In the future, sexual history, HIV status, and STI risk might address specific investigations to prevent spread of pathogens such HEV in MSM, before becoming a substantial public health problem like for HAV outbreaks.

Epidemiologic and Molecular Study of EVs in Hospitalized Children With Severe Acute Respiratory Infection.

BACKGROUND: To evaluate the enterovirus (EV)-positivity rate in respiratory samples collected from children ≤15 years hospitalized with severe acute respiratory infections (SARIs) and to describe the epidemiologic and molecular characteristics of EVs. METHODS: Respiratory samples were collected from 2468 children hospitalized with SARI at a university and research hospital in Milan (September 1, 2014 to August 31, 2017). EV and EV-D68 RNA were detected using a commercial multiplex and a specific real-time RT-PCR assay, respectively. The EV-D68-negative samples were then characterized by partial sequencing of the VP1 gene. RESULTS: EV-RNA was detected in 9% (222/2468) of SARI cases, 77% were children ≤3 years, almost 13% of whom required intensive care. EVs circulated all-year-round in 2 distinct epidemic waves (May-August and November-December). An EV-D68 outbreak, responsible for 14.8% of EV-positive-SARIs, occurred in 2016 and 5 newly emerging EV types were identified. Twenty-two EV types were detected and remarkable heterogeneity was observed in species distribution and between different pediatric age groups. CONCLUSIONS: This study showed that EV-positivity rate for our SARI series was 9%. The molecular detection and characterization of EVs allowed for the rapid detection of an EV-D68 outbreak and revealed the presence of emerging EV types that may pose a public health threat. The lack of routine screening and EV characterization in respiratory tract infections hampers the assessment of their epidemiologic and molecular features.