Development of a dual channel detection system for pan-genotypic simultaneous quantification of hepatitis B and delta viruses.

Hepatitis B virus (HBV) infection remains a major public health problem and, in associated co-infection with hepatitis delta virus (HDV), causes the most severe viral hepatitis and accelerated liver disease progression. As a defective satellite RNA virus, HDV can only propagate in the presence of HBV infection, which makes HBV DNA and HDV RNA the standard biomarkers for monitoring the virological response upon antiviral therapy, in co-infected patients. Although assays have been described to quantify these viral nucleic acids in circulation independently, a method for monitoring both viruses simultaneously is not available, thus hampering characterization of their complex dynamic interactions. Here, we describe the development of a dual fluorescence channel detection system for pan-genotypic, simultaneous quantification of HBV DNA and HDV RNA through a one-step quantitative PCR. The sensitivity for both HBV and HDV is about 10 copies per microliter without significant interference between these two detection targets. This assay provides reliable detection for HBV and HDV basic research in vitro and in human liver chimeric mice. Preclinical validation of this system on serum samples from patients on or off antiviral therapy also illustrates a promising application that is rapid and cost-effective in monitoring HBV and HDV viral loads simultaneously.

Successful Treatment of Cutibacterium acnes Prosthetic Joint Infection With Single-Stage Exchange and Oral Antibiotics.

Interest has grown in less invasive surgical treatment and early use of oral antibiotics in the treatment of Cutibacterium acnes prosthetic joint infection. We report a series of patients who were successfully treated with single-stage exchange and an all-oral course of rifampin and linezolid.

Burkitt lymphoma presenting with fever of unknown origin and isolated hypoglossal nerve palsy.

Fever of unknown origin (FUO) continues to present a clinical conundrum for even expert practitioners. The syndrome of FUO has over 200 possible etiologies. Burkitt lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma with only 1,200 US adult cases reported annually. Fever, night sweats, and weight loss, otherwise known as B symptoms, are common early symptoms of BL. Nerve palsy, especially isolated hypoglossal nerve palsy (IHNP), is rarely seen as a presenting sign in any pathological condition. A case report of FUO and IHNP as the presenting manifestations of BL is presented. The rarity of IHNP and its clinical features delayed the recognition of this syndrome and emphasizes the value of a thorough understanding of the physical examination and the association of unusual clinical findings with a readily identifiable clinical syndrome.

Preclinical assessment of antiviral combination therapy in a genetically humanized mouse model for hepatitis delta virus infection.

Chronic delta hepatitis, caused by hepatitis delta virus (HDV), is the most severe form of viral hepatitis, affecting at least 20 million hepatitis B virus (HBV)-infected patients worldwide. HDV/HBV co- or superinfections are major drivers for hepatocarcinogenesis. Antiviral treatments exist only for HBV and can only suppress but not cure infection. Development of more effective therapies has been impeded by the scarcity of suitable small-animal models. We created a transgenic (tg) mouse model for HDV expressing the functional receptor for HBV and HDV, the human sodium taurocholate cotransporting peptide NTCP. Both HBV and HDV entered hepatocytes in these mice in a glycoprotein-dependent manner, but one or more postentry blocks prevented HBV replication. In contrast, HDV persistently infected hNTCP tg mice coexpressing the HBV envelope, consistent with HDV dependency on the HBV surface antigen (HBsAg) for packaging and spread. In immunocompromised mice lacking functional B, T, and natural killer cells, viremia lasted at least 80 days but resolved within 14 days in immunocompetent animals, demonstrating that lymphocytes are critical for controlling HDV infection. Although acute HDV infection did not cause overt liver damage in this model, cell-intrinsic and cellular innate immune responses were induced. We further demonstrated that single and dual treatment with myrcludex B and lonafarnib efficiently suppressed viremia but failed to cure HDV infection at the doses tested. This small-animal model with inheritable susceptibility to HDV opens opportunities for studying viral pathogenesis and immune responses and for testing novel HDV therapeutics.

Linkage to Care for Suburban Heroin Users with Hepatitis C Virus Infection, New Jersey, USA.

We identified a 41.4% prevalence of hepatitis C virus, absence of HIV, and unexpectedly high frequency of hepatitis C virus genotype 3 among suburban New Jersey heroin users 17-35 years of age during 2014-2015. Despite 2 clinicians prepared to engage these users, few were successfully linked to care and treated.