Adrian M Di Bisceglie

Adrian M Di Bisceglie
Saint Louis University | SLU · Department of Internal Medicine

M.D.

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541
Publications
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Publications

Publications (541)
Article
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Anellovirus (AV) is a ubiquitous and diverse virus in the human population. An individual can be infected with multiple AV genera and species that form a heterogeneous repertoire, called the anellome. Due to its exceptional genetic diversity, efficient evaluation of anellome complexity remains a methodological challenge. In the current study, AV ge...
Article
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Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid), versus pla...
Article
Hepatitis B e antigen (HBeAg) is a soluble viral protein in plasma of patients with hepatitis B virus infection. HBeAg loss is an important first stage of viral antigen clearance. We determined the rate and predictors of HBeAg loss in a North American cohort with chronic hepatitis B viral infection (CHB). Among children and adults with CHB and with...
Article
Background and aims: Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable. Approach and results: We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs fo...
Article
Background Bacterial translocation plays a pivotal role in the natural course of cirrhosis and its complications. Serum-derived bovine immunoglobulin (SBI) is an oral medical food that has been shown to both reduce inflammation in the intestines and neutralize bacteria. It represents a unique intervention that has not been studied in this populatio...
Article
Background and Aims The long‐term impact of hepatitis C virus (HCV) therapy with all‐oral direct‐acting antivirals (DAAs) on patient‐reported outcomes (PROs) has not been well‐described. We characterized changes in PROs from pre‐treatment to 12 months post‐treatment in a real‐world cohort. Methods PROP UP was a multi‐center observational cohort st...
Article
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This study describes the design of the TARGET‐hepatocellular carcinoma (HCC) cohort and descriptive characteristics of the patient population at diagnosis among those who were enrolled in the cohort across academic and community clinical centers. TARGET‐HCC is a 5‐year, longitudinal, observational cohort of patients with HCC receiving care in usual...
Preprint
Full-text available
Background & Aims: Non-alcoholic steatohepatitis (NASH) is frequently associated with obesity and diabetes and may lead to progressive liver disease although current treatment options are limited. Berberine ursodeoxycholate is an ionic salt of berberine and ursodeoxycholic acid, representing a new molecular entity that offers the possibility of com...
Article
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Background Reduction in elevated serum cholesterol concentrations is important in the management of individuals at risk of atherosclerotic cardiovascular disease (ASCVD), such as myocardial infarction and thrombotic stroke. Although HMGCoA reductase inhibitors (“statins”) are frequently used for this purpose, a significant proportion of patients re...
Article
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With the widespread development of new drugs to treat chronic liver diseases (CLDs), including viral hepatitis and nonalcoholic steatohepatitis (NASH), more patients are entering trials with abnormal baseline liver tests and with advanced liver injury, including cirrhosis. The current regulatory guidelines addressing the monitoring, diagnosis, and...
Article
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Objective: Owing to the overwhelming dominance of human and commensal microbe sequences, low efficiency is a major concern in clinical viral sequencing using next-generation sequencing. DNA composed of 7-deaza-2'-deoxyguanosine 5'-triphosphate (c7dGTP), an analog of deoxyguanosine triphosphate (dGTP), is resistant to selective restriction enzymes....
Article
Background and aims: Outcomes of persons with chronic HBV infection in the era of antiviral therapy are not well characterized. We determined the incidence and factors associated with clinical outcomes in a multiethnic, North American cohort of adults with chronic HBV infection, who were not on antiviral therapy at enrollment. Methods: Adults wi...
Article
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Background: Viral relapse is a major concern in hepatitis C virus (HCV) antiviral therapy. Currently, there are no satisfactory methods to predict viral relapse, especially in the era of direct acting antivirals in which the virus often quickly becomes undetectable using PCR-based approaches that focus on a small viral region. Next-generation sequ...
Article
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Immune checkpoint inhibitors (ICIs) have shown significant efficacy in patients with various malignancies, however, they are associated with a wide range of immune-related toxicities affecting many organs, including the liver. Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) is a distinctive form of drug induced liver injury (DI...
Article
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Background and Aims Direct-acting antiviral (DAA) HCV therapy is used in decompensated cirrhosis with the expectation of improvement in hepatic function. Little is known about the long-term benefit of successful treatment. Methods Patients with advanced/decompensated cirrhosis (MELD ≥10) in HCV-TARGET who initiated NS5A-containing DAA therapy prio...
Article
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In clinical virome research, whole-genome/transcriptome amplification is required when starting material is limited. An improved method, named “template-dependent multiple displacement amplification” (tdMDA), has recently been developed in our lab (Wang et al. in BioTechniques 63:21–25. https://doi.org/10.2144/000114566, 2017). In combination with...
Article
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Background The prevalence and risk factors for non-adherence to direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) in clinical practice settings are under-studied. Objectives (1) To quantify DAA non-adherence in the total cohort and among subgroups with and without mental health conditions, alcohol use, and substance use, and (2)...
Article
Introduction: Patients with hepatitis B early antigen (HBeAg)-negative chronic hepatitis B (CHB) and low-level viremia are a heterogeneous group. Identifying those at risk of developing active CHB requiring antiviral therapy is important. In this study, we prospectively characterize incidence rates and predictors of transitioning from inactive to...
Article
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Recent studies have suggested a negative impact of hepatocellular carcinoma (HCC) on sustained virologic response (SVR) to hepatitis C virus (HCV) direct acting antivirals (DAAs). We compared the effectiveness of DAAs in patients with cirrhosis, with and without HCC, and in those with HCC partially treated or untreated (PT/UT‐HCC) versus completely...
Article
Objective: Define chronic HBV phenotypes in a large, cohort of US and Canadian children utilizing recently published population-based upper limit of normal alanine aminotransferase levels (ULN ALT), compared to local laboratory ULN; identify relationships with host and viral factors. Background: Chronic hepatitis B virus (HBV) infection has been...
Article
Alpha‐1 antitrypsin deficiency (AATD) resulting from mutations in the SERPINA1 gene is associated with decreased circulating level of alpha‐1 antitrypsin, and homozygosity for the Z allele is well‐known to result in both lung disease (in the form of emphysema) and liver disease (1). Historically, the liver disease has been described as being differ...
Article
Background & aims: A comprehensive analysis of changes in symptoms and functioning during and after direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has not been conducted for patients treated in real-world clinical settings. Therefore, we evaluated patient-reported outcomes (PROs) in a diverse cohort of patients...
Article
Hepatocellular carcinoma (HCC) is a common cancer with unmet needs and limited effective therapeutic options. The management strategy for diagnosed HCC is based on Barcelona Clinic Liver Cancer (BCLC) staging. Advanced HCC is treated with systemic therapy comprising oral tyrosine kinase inhibitors (TKIs) and intravenous immune checkpoint inhibitors...
Article
Hepatitis B e antigen (HBeAg) is an important serological marker of hepatitis B virus (HBV) infection and is associated with higher levels of viremia, increased risk of infectivity to others and increased risk of hepatocellular carcinoma. We analyzed HBeAg status in a large cohort of adults and children enrolled in Cohort Studies of the Hepatitis B...
Article
Background & aims: The incidence and outcomes of alanine aminotransferase (ALT) flares during the natural history of chronic HBV infection has not been determined in a large, racially heterogeneous group of patients in North America. Methods: We collected data from the Hepatitis B Research Network-an observational cohort study of untreated adult...
Article
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Controversies exist regarding the classification of the different clinical phases of chronic hepatitis B (CHB) because hepatitis B virus (HBV) DNA and alanine aminotransferase levels fluctuate over time.1,2 To improve the distinction of clinical phases and the associated spectrum of clinical outcome,3,4 hepatitis B surface antigen (HBsAg) levels ma...
Article
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Background Symptom burden, medical comorbidities, and functional well-being of patients with chronic hepatitis C virus (HCV) initiating direct acting antiviral (DAA) therapy in real-world clinical settings are not known. We characterized these patient-reported outcomes (PROs) among HCV-infected patients and explored associations with sociodemograph...
Data
Full names of each subsite's local approving IRBs. (DOCX)
Data
Complete list of self-reported medical comorbidities. a Each participant only counted once in combined column. (DOCX)
Data
Complete list of MSAS symptoms. Symptom severity, frequency and distress are reported as percentages of those who endorsed the symptom presence. a Severity ranges from slight, moderate, severe, very severe; data shown is % reporting moderate, severe, very severe symptoms. b Frequency ranges from rarely, occasionally, frequently, almost constantly;...
Article
Background: To better understand symptoms experienced by patients infected with chronic hepatitis C virus (HCV), valid and reliable patient-reported outcome (PRO) measures are needed. Aim: To assess the reliability and validity of 10 patient-reported outcomes measurement information system (PROMIS) measures and the Headache Impact Test-6 (HIT-6)...
Article
Multiple displacement amplification (MDA) is widely used in whole-genome/transcriptome amplification. However, template-independent amplification (TIA) in MDA is a commonly observed phenomenon, particularly when using high concentrations of random hexamer primers and extended incubation times. Here, we demonstrate that the use of random pentamer pr...
Article
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Volume 91, no. 6, e02225-16, 2017, https://doi.org/10.1128/JVI.02225-16. Page 10, Fig. 8A: The STAT3 image was inadvertently omitted. Figure 8A should appear as shown below. This correction does not change the interpretation of data.
Article
Background: New highly efficacious direct-acting antiviral (DAA) therapies are available to treat chronic hepatitis C viral (HCV) infection. Real-world, patient-centered data on harms and benefits associated with these therapies are needed. Methods: PROP UP is a multi-center prospective observational study that plans to enroll 1600 patients star...
Article
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Importance: HCV associated liver fibrosis is a critical step for end stage liver disease progression. However, the molecular mechanisms for hepatic stellate cell activation by HCV-infected hepatocytes are underexplored. Here, we provide a role of miR-19a carried through the exosomes for intercellular communication between HCV-infected hepatocytes...
Article
The aim of this study was to assess the validity of categorization of chronic hepatitis B viral infection into stages or phases based upon measures of disease activity and viral load, assuming these phenotypes will be useful for prognostication and determining the need for antiviral therapy. We assessed the phenotype of hepatitis B of 1,390 adult p...
Article
Background: Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV-TARGET collects data in patients treated at tertiary academic and community centres. Aim: To assess efficacy of all-oral HCV therapy in advanced liver disease. Methods: Between December 2013 and October 2014, 240 patients wit...
Article
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African Americans (AA) have higher hepatocellular carcinoma (HCC) and mortality rates than Caucasians Americans (CA). Chronic hepatitis C virus (HCV) infection leads to cirrhosis and HCC. HCV infection is highly prevalent in AA population compared to other racial groups. African Americans are also less likely to naturally clear HCV, potentially con...
Article
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Acute liver failure (ALF) is a rare illness with a high mortality rate. The only favorable management is emergent liver transplantation. About 13% of ALF cases have no clear etiology. Epstein-Barr virus (EBV)-associated ALF accounts for less than 1% of all ALF cases, and is seen mostly in adults younger than 40 years. There are only a few cases of...
Article
Background & aims: The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determ...
Article
Hepatocellular carcinoma (HCC) is the world's third most common cancer and causes 600,000 deaths annually. Early detection is the key for improving the survival of HCC patients. Current diagnostic markers, such as alpha fetoprotein or fibroscan have their own limitations. Investigating serum microRNA as biomarkers for early diagnosis of cancer has...
Article
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Objective Due to a high efficacy in clinical trials, sofosbuvir (SOF) and ribavirin (RBV) for 12 or 16 weeks is recommended for treatment of patients with HCV genotype (GT) 2 infection. We investigated safety and effectiveness of these regimens for GT2 in HCV-TARGET participants. Design HCV-TARGET, an international, prospective observational study...
Article
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CD55/DAF, one of the regulators of complement activation, is known to limit excess complement activation on the host cell surface by accelerating the decay of C3 convertase. We reported previously that hepatitis C virus (HCV) infection or virus core protein expression upregulates CD55 expression. CD55 associates with HCV particles, potentially prot...
Article
Background: Sofosbuvir (SOF) is active against all hepatitis C virus (HCV) genotypes and SOF-based therapies lead to high rates of sustained virological response (SVR). However, genotype 3 (G3) HCV remains a challenge with lower SVR rates reported, particularly in patients with cirrhosis. This study reports the effectiveness and safety of SOF-base...
Article
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Background Overt hepatic encephalopathy (OHE) is a frequent complication of decompensated cirrhosis. Aims A multicenter prospective observational study was performed to assess the most commonly recorded presenting manifestations of OHE and its associated health-care burden. Methods Qualifying patients must have experienced ≥1 OHE episode within 30...
Article
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GS-9857, an inhibitor of the hepatitis C virus (HCV) nonstructural protein (NS) 3/4A, demonstrates potent activity against HCV genotypes 1-6 and improved coverage against commonly encountered NS3 resistance-associated variants (RAVs). In this study, the safety, tolerability, antiviral activity and pharmacokinetics (PK) of GS-9857 were evaluated in...
Article
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Hepatocellular carcinoma (HCC) is one of the most aggressive cancers and is the third leading cause of all cancer-related death. Limited noninvasive biomarkers are available for HCC detection. Early detection is the key in improving the survival of HCC patients. In this study, we tested the hypothesis that serum miRNAs can be used as a potential bi...
Article
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Viral quasispecies (QS) has long been considered to affect the efficiency of hepatitis C virus (HCV) antiviral therapy. Yet a correlation between the QS diversity and treatment outcomes has not been established conclusively. We previously measured HCV QS diversity by genome-wide quantification of high-resolution mutation load in HCV 1a patients ach...
Article
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Background & aims: The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. Method...
Article
Recurrent infection with the hepatitis C virus (HCV) after liver transplantation (LT) is associated with decreased graft and patient survival. Achieving sustained virological response (SVR) with antiviral therapy improves survival. Because interferon (IFN)-based therapy has limited efficacy and is poorly tolerated, there has been rapid transition t...
Article
Importance: HCV infection may develop into HCC as an end stage liver disease. We focused to understand the mechanism for risk of HCC from chronic HCV infection and identify targets for treatment. HCV infected primary and transformed human hepatocytes (PHH or THH) generated CSC. HCV induced spheres were highly sensitive to cell death from sorafenib...
Article
In chronic hepatitis C virus (HCV) infection, combination therapy of peginterferon and ribavirin does not guarantee viral eradication. Among factors relevant to therapeutic efficacy, the role of humoral immunity has not been examined thoroughly. In the current study, HCV pseudoparticles (HCVpp) were first generated with 80 patient-derived full-leng...
Article
BackgroundHCV-TARGET is a longitudinal observational study of chronic hepatitis C virus (HCV) patients treated with direct-acting anti-viral agents (DAAs) in a US consortium of 90 academic and community medical centres.AimTo assess utilisation of response-guided therapy (RGT) and sustained virological response (SVR) of a large cohort of patients.Me...
Article
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Unlabelled: Hepatitis C virus (HCV) is a serious global health problem and establishes chronic infection in a significant number of infected humans worldwide. Interferon (IFN) and IFN-stimulated genes (ISGs) are amplified during HCV infection but fail to eliminate virus from the liver in a large number of infected patients, and the mechanism is no...