Immunostaining for hepatitis B viral antigens in liver: Association with clinical, biochemical, and virologic features of disease.

Background And Aim: Staining for hepatitis B viral antigens is often done in liver biopsies from patients with chronic hepatitis B, but its correlates with clinical phenotypes are not well described.

Methods: Biopsies were collected from a large cohort of adults and children with chronic hepatitis B viral infection through the Hepatitis B Research Network. Immunohistochemical staining of sections was done for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) and then centrally read by the pathology committee.

Targeted delivery of an anti-inflammatory corticosteroid to Ly6C/G-positive cells abates severity of influenza A symptoms.

The distribution of Ly6C/G-positive cells in response to an infection of the mouse respiratory tract with influenza A virus was followed noninvasively over time by immuno-positron emission tomography. We converted nanobodies that recognize Ly6C and Ly6G, markers of neutrophils and other myeloid cells, as well as an influenza hemagglutinin-specific nanobody, into Zr-labeled PEGylated positron emission tomography (PET) imaging agents. The PET images showed strong accumulation of these imaging agents in the lungs of infected mice.

HBV transcription and translation persist despite viral suppression in HBV-HIV co-infected patients on antiretroviral therapy.

Background And Aims: Liver injury may persist in patients with HBV receiving antiviral therapy who have ongoing transcription and translation. We sought to assess ongoing HBV transcription by serum HBV RNA, translation by serum hepatitis B core related antigen (HBcrAg), and their associations with hepatic HBsAg and HBcAg staining in patients coinfected with HBV and HIV.

Methods: This is a cross-sectional study of 110 adults coinfected with HBV and HIV who underwent clinical assessment and liver biopsy.

Decreased Tissue Omega-6/Omega-3 Fatty Acid Ratio Prevents Chemotherapy-Induced Gastrointestinal Toxicity Associated with Alterations of Gut Microbiome.

Gastrointestinal toxicity (GIT) is a debilitating side effect of Irinotecan (CPT-11) and limits its clinical utility. Gut dysbiosis has been shown to mediate this side effect of CPT-11 by increasing gut bacterial β-glucuronidase (GUSB) activity and impairing the intestinal mucosal barrier (IMB). We have recently shown the opposing effects of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) on the gut microbiome.

Neutralization breadth of SARS-CoV-2 viral variants following primary series and booster SARS-CoV-2 vaccines in patients with cancer.

Patients with cancer are more likely to have impaired immune responses to SARS-CoV-2 vaccines. We study the breadth of responses against SARS-CoV-2 variants after primary vaccination in 178 patients with a variety of tumor types and after booster doses in a subset. Neutralization of alpha, beta, gamma, and delta SARS-CoV-2 variants is impaired relative to wildtype, regardless of vaccine type.

A Prospective Cohort Study of Novel Markers of Hepatitis B Virus Replication in Human Immunodeficiency Virus Coinfection.

Background & Aims: The contribution of the novel biomarkers, hepatitis B virus (HBV) RNA and HBV core-related antigen (HBcrAg), to characterization of HBV-human immunodeficiency virus (HIV) coinfection is unclear. We evaluated the longitudinal dynamics of HBV RNA and HBcrAg and their association with classical HBV serum biomarkers and liver histology and viral staining.

Methods: HBV-HIV co-infected adults from 8 North American centers entered a National Institutes of Health-funded prospective cohort study.

Evolution of Fatty Liver Disease and Relationship With Lipoproteins and Clinical Outcomes in Hepatitis B/Human Immunodeficiency Virus Coinfection.

Background: Fatty liver disease (FLD) and hepatitis B virus (HBV) infection occur commonly in human immunodeficiency virus (HIV). FLD resolution is associated with improvement in lipoproteins in HIV-uninfected patients. We evaluated changes in FLD in an HBV/HIV-coinfected cohort.

Hepatic Steatosis and Steatohepatitis in a Large North American Cohort of Adults With Chronic Hepatitis B.

Introduction: Fatty liver disease (FLD) influences liver disease progression and liver cancer risk. We investigated the impact of FLD on liver disease severity in a large North American cohort with chronic hepatitis B virus (HBV).

Methods: Liver biopsies from 420 hepatitis B surface antigen-positive adults enrolled in the Hepatitis B Research Network and who were not on HBV therapy in the previous month were evaluated for inflammation and fibrosis.

A Prospective Study Evaluating Changes in Histology, Clinical and Virologic Outcomes in HBV-HIV Co-infected Adults in North America.

Background And Aims: Histological and clinical outcomes in HBV-HIV coinfection in the era of combination antiretroviral therapy (cART) are poorly defined.

Approach And Results: Adult patients co-infected with HBV-HIV from eight North American sites were enrolled in this National Institutes of Health (NIH)-funded prospective observational study (n = 139). Demographic, clinical, serological, and virological data were collected at entry and every 24 weeks for ≤ 192 weeks.

Diagnostic Accuracy of Shear Wave Elastography as a Non-invasive Biomarker of High-Risk Non-alcoholic Steatohepatitis in Patients with Non-alcoholic Fatty Liver Disease.

In this study, we evaluated the diagnostic accuracy of shear wave elastography (SWE) for differentiating high-risk non-alcoholic steatohepatitis (hrNASH) from non-alcoholic fatty liver and low-risk non-alcoholic steatohepatitis (NASH). Patients with non-alcoholic fatty liver disease scheduled for liver biopsy underwent pre-biopsy SWE. Ten SWE measurements were obtained.

Immunologic Alterations Associated With Oral Delivery of Anti-CD3 (OKT3) Monoclonal Antibodies in Patients With Moderate-to-Severe Ulcerative Colitis.

Aim: The aim of this study was to determine the immunologic effects and safety of oral anti-CD3 in patients with ulcerative colitis (UC).

Methods: An open-label pilot study of orally delivered anti-CD3 was performed in patients with moderate-to-severe UC. The primary end points were changes in immunologic parameters and evaluation for safety.

Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice.

Background: Understanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS.

Results: Here we show that gut microbiome mediates the preventive effect of estrogen (17β-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17β-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals.

Experimental Validation of Longitudinal Speed of Sound Estimates in the Diagnosis of Hepatic Steatosis (Part II).

This study validates a non-invasive, quantitative technique to diagnose steatosis within tissue. The proposed method is based on two fundamental concepts: (i) the speed of sound in a fatty liver is lower than that in a healthy liver and (ii) the quality of an ultrasound image is maximized when the beamformer's speed of sound matches the speed in the medium under examination. The method uses image brightness and sharpness as quantitative image-quality metrics to predict the true sound speed and capture the effects of fat infiltration, while accounting for the transmission through subcutaneous fat.

Ultrasound Shear Wave Elastography: Variations of Liver Fibrosis Assessment as a Function of Depth, Force and Distance from Central Axis of the Transducer with a Comparison of Different Systems.

We evaluated variation in fibrosis staging caused by depth, pre-load force and measurement off-axis distance on different ultrasound shear wave elastography (SWE) systems prospectively in 20 patients with diffuse liver disease. Shear wave speed (SWS) was measured with transient elastography, acoustic radiation force impulse (ARFI) and 2-D shear wave elastography (SWE). ARFI and 2-D-SWE measurements were obtained at different depths (3, 5 and 7 cm), with different pre-load forces (4, 7 and 10N and variable) and at 0, 2 and 4cm off the central axis of the transducer.

Diagnostic Performance of Shear Wave Elastography in Patients With Autoimmune Liver Disease.

Objectives: To assess performance of shear wave elastography for evaluation of fibrosis and the histologic stage in patients with autoimmune liver disease (ALD) and to validate previously established advanced fibrosis cutoff values in this cohort.

Methods: Shear wave elastography was performed on patients with ALD with an Aixplorer ultrasound system (SuperSonic Imagine, Aix-en-Provence, France) using an SC6-1 transducer. The median estimated tissue Young modulus was calculated from sets of 8 to 10 elastograms.

is a colitis risk gene that regulates stability of epithelial adherens junctions.

Polymorphisms in are associated with increased risk of inflammatory bowel disease (IBD). However, the function of C1orf106 and the consequences of disease-associated polymorphisms are unknown. Here we demonstrate that C1orf106 regulates adherens junction stability by regulating the degradation of cytohesin-1, a guanine nucleotide exchange factor that controls activation of ARF6.

PD-L1 is an activation-independent marker of brown adipocytes.

Programmed death ligand 1 (PD-L1) is expressed on a number of immune and cancer cells, where it can downregulate antitumor immune responses. Its expression has been linked to metabolic changes in these cells. Here we develop a radiolabeled camelid single-domain antibody (anti-PD-L1 VHH) to track PD-L1 expression by immuno-positron emission tomography (PET).

Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells.

Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy.

Intestinal Alkaline Phosphatase Attenuates Alcohol-Induced Hepatosteatosis in Mice.

Background And Aims: Bacterially derived factors from the gut play a major role in the activation of inflammatory pathways in the liver and in the pathogenesis of alcoholic liver disease. The intestinal brush-border enzyme intestinal alkaline phosphatase (IAP) detoxifies a variety of bacterial pro-inflammatory factors and also functions to preserve gut barrier function. The aim of this study was to investigate whether oral IAP supplementation could protect against alcohol-induced liver disease.

Validation of Shear Wave Elastography Cutoff Values on the Supersonic Aixplorer for Practical Clinical Use in Liver Fibrosis Staging.

The purpose of this study was to determine the validity of previously established ultrasound shear wave elastography (SWE) cut-off values (≥F2 fibrosis) on an independent cohort of patients with chronic liver disease. In this cross-sectional study, approved by the institutional review board and compliant with the Health Insurance Portability and Accountability Act, 338 patients undergoing liver biopsy underwent SWE using an Aixplorer ultrasound machine (SuperSonic Imagine, Aix-en-Provence, France). Median SWE values were calculated from sets of 10 elastograms.

Metagenomic Characterization of Microbial Communities Within the Deeper Layers of the Ileum in Crohn's Disease.

Background & Aims: Microbial dysbiosis and aberrant host-microbe interactions in the gut are believed to contribute to the development and progression of Crohn's disease (CD). Microbiome studies in CD typically have focused on microbiota in feces or superficial mucosal layers of the colon because accessing DNA from deeper layers of the bowel is challenging. In this study, we analyzed the deep tissue microbiome in patients who underwent surgical resection of the small intestine.

TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation.

Significant insights into disease pathogenesis have been gleaned from population-level genetic studies; however, many loci associated with complex genetic disease contain numerous genes, and phenotypic associations cannot be assigned unequivocally. In particular, a gene-dense locus on chromosome 11 (61.5-61.

Interleukin 1β Mediates Intestinal Inflammation in Mice and Patients With Interleukin 10 Receptor Deficiency.

Interleukin 10 receptor (IL10R)-deficient mice develop spontaneous colitis and, similarly, patients with loss-of-function mutations in IL10R develop severe infant-onset inflammatory bowel disease. Loss of IL10R signaling in mouse and human macrophages is associated with increased production of interleukin 1β. We demonstrated that innate immune production of IL1β mediates colitis in IL10R-deficient mice.