Diagnostic Utility of Pre-Genomic Hepatitis B RNA in the Evaluation of HBV/HIV Coinfection.

Background: Newer biomarkers of Hepatitis B virus (HBV) infection and treatment response have not been well-characterized in individuals with HBV/HIV coinfection.

Methods: Pre-genomic RNA (pgRNA) and quantitative HBsAg (qHBsAg) were used to evaluate the associations with baseline characteristics. Participants included two separate groups - 236 with HBV/HIV coinfection enrolled in a cross-sectional cohort in Ghana and 47 from an HBV nucleoside/nucleotide treatment trial comparing tenofovir to adefovir in the United States.

Replication and Injury Associated With SARS-CoV-2 in Cultured Hepatocytes.

Background: Liver dysfunction is one of the hallmarks of SARS-CoV-2 infection. The mechanism(s) of hepatic injury in SARS-CoV-2 infection remains controversial with some reporting viral replication and cellular injury and others suggesting lack of replication and injury due to non-cytopathogenic etiologies. To investigate this further, we evaluated SARS-CoV-2 replication in immortalized hepatic cell lines and primary hepatocytes, examined whether cell injury was associated with apoptotic pathways, and also determined the effect of the antiviral remdesivir on these processes.

Humoral and T-cell-mediated immunity to SARS-CoV-2 vaccination in patients with liver disease and transplant recipients.

Background: SARS-CoV-2 vaccination induces a varied immune response among persons with chronic liver disease (CLD) and solid organ transplant recipients (SOTRs). We aimed to evaluate the humoral and T-cell-mediated immune responses to SARS-CoV-2 vaccination in these groups.

Methods: Blood samples were collected following the completion of a standard SARS-CoV-2 vaccination (2 doses of either BNT162b2 or mRNA-12732), and a subset of patients had a blood sample collected after a single mRNA booster vaccine.

Cocaine use associated gut permeability and microbial translocation in people living with HIV in the Miami Adult Study on HIV (MASH) cohort.

Objective: Determine if cocaine use impacts gut permeability, promotes microbial translocation and immune activation in people living with HIV (PLWH) using effective antiretroviral therapy (ART).

Methods: Cross-sectional analysis of 100 PLWH (ART ≥6 months, HIV-RNA <200 copies/mL) from the Miami Adult Studies on HIV (MASH) cohort. Cocaine use was assessed by self-report, urine screen, and blood benzoylecgonine (BE).

Soluble CD163 Identifies Those at Risk for Increased Hepatic Inflammation & Fibrosis.

Background: Liver disease remains a significant cause of morbidity and mortality in HIV-infected persons. Soluble CD163 is a marker of Kupffer cell activation that is highly associated with development of hepatic fibrosis. The relative contributions of HIV-associated systemic immune activation vs other etiologies of injury are poorly characterized.

PNPLA3 Single Nucleotide Polymorphism Prevalence and Association with Liver Disease in a Diverse Cohort of Persons Living with HIV.

In persons living with HIV (PLWH), there are multiple sources of liver injury. Gene polymorphisms of PNPLA3 (patatin-like phospholipase domain-containing protein 3) have been identified as an important cofactor for increased disease severity in both alcoholic and non-alcoholic steatohepatitis (NASH). We utilized a well-characterized cohort of ethnically and racially diverse patients with HIV to define the prevalence of PNPLA3 SNPs (single nucleotide polymorphism) (rs738409), and to determine the relationship to hepatic steatosis and liver fibrosis.

Hepatitis E Infection in a Longitudinal Cohort of Hepatitis C Virus and HCV/HIV Coinfected Persons.

Hepatitis E virus (HEV) is thought to be common in the United States with increased prevalence in those with concomitant hepatitis C virus (HCV) or HCV/HIV coinfection. Little is known regarding true prevalence, incidence, and antibody seroreversion in these populations. We sought to define these rates among HCV and HCV/HIV coinfected persons in the Washington, DC area.

The Enhanced Liver Fibrosis Index Predicts Hepatic Fibrosis Superior to FIB4 and APRI in HIV/HCV Infected Patients.

Background: Accurate noninvasive biomarkers of fibrotic progression are important for hepatitis C virus (HCV) management, but commonly used modalities may have decreased efficacy in human immunodeficiency virus (HIV)/HCV-coinfected persons. The enhanced liver fibrosis (ELF) index is a highly sensitive noninvasive marker of hepatic fibrosis that has had limited assessment in the HIV/HCV population. We compared ELF index performance to FIB4 and aspartate to platelet ratio index (APRI) at different stages of liver fibrosis as determined by liver histology, and validated the efficacy of the three noninvasive biomarkers in HIV/HCV-coinfected versus HCV-monoinfected.

CCR5 receptor antagonism inhibits hepatitis C virus (HCV) replication in vitro.

Background And Aim: The hepatitis C virus (HCV) is a single-strand RNA virus that infects millions of people worldwide. Recent advances in therapy have led to viral cure using two- and three- drug combinations of direct acting inhibitors of viral replication. CCR5 is a chemokine receptor that is expressed on hepatocytes and represents a key co-receptor for HIV.

Validation and Refinement of Noninvasive Methods to Assess Hepatic Fibrosis: Magnetic Resonance Elastography Versus Enhanced Liver Fibrosis Index.

Background: Noninvasive fibrosis markers are routinely used in patients with liver disease. Magnetic resonance elastography (MRE) is recognized as a highly accurate methodology, but a reliable blood test for fibrosis would be useful. We examined performance characteristics of the Enhanced Liver Fibrosis (ELF) Index compared to MRE in a cohort including those with HCV, HIV, and HCV/HIV.

Hepatitis C virus antigens enzyme immunoassay for one-step diagnosis of hepatitis C virus coinfection in human immunodeficiency virus infected individuals.

Background: Current diagnosis of hepatitis C virus (HCV) infection requires two sequential steps: testing for anti-HCV followed by HCV RNA PCR to confirm viremia. We have developed a highly sensitive and specific HCV-antigens enzyme immunoassay (HCV-Ags EIA) for one-step diagnosis of viremic HCV infection.

Aim: To assess the clinical application of the HCV-Ags EIA in one-step diagnosis of viremic HCV infection in human immunodeficiency virus (HIV)-coinfected individuals.

Zika virus replication and cytopathic effects in liver cells.

Zika virus (ZIKV) has emerged globally as an important pathogen, since it has been recognized as a cause of microcephaly and other neurologic processes and sequalae in newborns. The virus shares homology with Hepaciviruses and therefore may be a cause of hepatitis. We sought to characterize ZIKV replication in hepatocyte-derived cell lines.

HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles.

Background: Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to their shared routes of transmission, approximately 10% of HIV-infected patients worldwide are chronically coinfected with HBV. Additionally, liver disease has become a major cause of morbidity and mortality in HBV/HIV coinfected patients due to prolonged survival with the success of antiretroviral therapy.

Improvement in Hepatic Fibrosis Biomarkers Associated With Chemokine Receptor Inactivation Through Mutation or Therapeutic Blockade.

Background: The C-C chemokine receptor Type 5 (CCR5) is a key receptor for human immunodeficiency virus type 1 (HIV-1) entry into T-cells and a variant allele, CCR5 delta-32, is associated with decreased viral replication and disease progression. Active HIV-1 replication is highly associated with accelerated rates of hepatic fibrosis. We postulated that CCR5 plays a role in the development of hepatic fibrosis and evaluated the longitudinal effect of natural or drug-induced CCR5 mutation and blockade on biomarkers of liver fibrosis in HIV-1 patients.

PNPLA3 Gene Polymorphisms in HCV/HIV-Coinfected Individuals.

Background And Aims: The patatin-like phospholipase domain-containing 3 (PNPLA3) gene has been associated with the development of alcoholic and nonalcoholic steatohepatitis. Using a newly developed and validated assay for PNPLA3, we explored the prevalence of gene polymorphisms in a cohort of HCV/HIV-coinfected individuals to determine whether there was an association with insulin resistance or hepatic fibrosis.

Methods: A high-resolution melting point (HRM) assay was developed and validated.

Zika Virus Exposure in an HIV-Infected Cohort in Ghana.

Objective: To determine the prevalence and epidemiologic associations of Zika Virus (ZIKV) in HIV-infected patients in Ghana, West Africa.

Methods: We examined the seroprevalence of ZIKV in HIV/HBV co-infected persons in Ghana from sera samples collected from 2012 to 2014 using ELISA assays and plaque reduction neutralization tests (PRNT).

Results: Overall, ZIKV antibody was detected in 12.

Hepatitis D diagnostics:Utilization and testing in the United States.

Hepatitis D virus (HDV) infection may accompany acute or chronic hepatitis B virus infection. While HDV infection in the United States is thought to be uncommon, there are limited data regarding frequency of testing, and prevalence of HDV antibody and HDV RNA. We evaluated the use of HDV antibody testing using electronic medical record (EMR) data.

Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in HCV/HIV Coinfected Patients.

Background And Aims: The prevalence of naturally occurring HCV-NS5A resistance-associated substitutions (RAS) to DAA drugs might affect the response to treatment in HCV/HIV coinfected subjects. There are limited data on the frequency of HCV-NS5A naturally occurring drug-RAS at baseline in HCV/HIV coinfected patients when ultra-deep sequencing methodologies are applied.

Methods: HCV-NS5A-RAS were evaluated among 25 subjects in each group.

Characterization of HCV NS3 Protease Variants in HCV/HIV-Coinfected Patients by Ultra-Deep Sequence Analysis: Relationship with Hepatic Fibrosis.

Background: Treatment of HCV/HIV coinfection is now largely based on utilization of direct acting agents. Pretreatment viral resistant-associated variants (RAVs) and host liver condition may affect the sustained virological response. In this study, we explored relative prevalence of protease resistance-associated mutations, the evolution of those RAVs after 12 weeks of pegylated interferon alfa exposure, and the role hepatic fibrosis might have on RAV display.

Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients.

The IL28B gene is associated with spontaneous or treatment-induced HCV viral clearance. However, the mechanism by which the IL28B single nucleotide polymorphism (SNP) affects the extra-hepatic HCV immune responses and its relationship to HCV pathogenesis have not been thoroughly investigated. To examine the mechanism by which IL28B affects HCV clearance.

Prevalence of Diagnosed and Undiagnosed Hepatitis C in a Midwestern Urban Emergency Department.

Background: Targeted hepatitis C virus (HCV) screening is recommended. Implementation of screening in emergency department (ED) settings is challenging and controversial. Understanding HCV epidemiology in EDs could motivate and guide screening efforts.

Evaluating the Role of Cellular Immune Responses in the Emergence of HCV NS3 Resistance Mutations During Protease Inhibitor Therapy.

The efficacy of protease inhibitor drugs in hepatitis C virus (HCV) treatment is limited by the selection and expansion of drug-resistant mutations. HCV replication is error-prone and genetic variability within the dominant epitopes ensures its persistence. The aims of this study are to evaluate the role of cellular immune response in the emergence of HCV protease resistance mutations and its effects on treatment outcome.

Modulation of HCV replication after combination antiretroviral therapy in HCV/HIV co-infected patients.

The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients co-infected with HIV. Co-infection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth.

HIV variability in the liver and evidence of possible compartmentalization.

There is growing evidence to suggest that HIV may interact with several hepatic cell types; however, evaluation of HIV variability in liver tissue has not been addressed to date. Among 16 HIV-positive individuals examined, nine (56%) had detectable HIV RNA in the liver. The mean CD4 cell count for these nine individuals was 337 cells/mm(3) (range: 0-601), while their mean plasma HIV RNA level was 106,974 copies/ml (range: 1200-320,740).