Detection and characterization of Hepatitis B virus double-stranded linear DNA-derived covalently closed circular DNA in chronic hepatitis B patients.

Background And Aims: Hepatitis B virus (HBV) generates a double-stranded linear DNA (dslDNA) byproduct during replication. This dslDNA can undergo intermolecular and intramolecular nonhomologous end-joining (NHEJ) recombination, resulting in viral integration and dslDNA derived covalently closed circular DNAs (dsl-cccDNAs), respectively. The insertions and deletions (INDELs) at the end-joining site around the direct repeat (DR) 1 motif have been used to differentiate dsl-cccDNA from the authentic cccDNA.

A Rare Case of Recurrent Intrahepatic Cholestasis of Pregnancy With Prolonged Postpartum Hepatic Inflammation Despite Normalization of Bile Acid Levels.

Intrahepatic cholestasis of pregnancy is one of the most common liver diseases during the second and third trimesters of pregnancy, but its pathogenesis remains unclear. Intrahepatic cholestasis of pregnancy is associated with elevations of maternal bile acids, serum aminotransferases, and adverse fetal outcomes. Besides direct cytotoxic liver injury by bile acids, it has been suggested that bile acid-induced oxidative stress and mitochondrial injury lead to a cascade of inflammatory responses.

Case of cryoglobulinaemia associated with chronic hepatitis B.

We present a case of a woman in her 50s with chronic hepatitis B (CHB) who had a longstanding history of arthralgia and swollen joints associated with severe fatigue. Investigations were consistent with a diagnosis of hepatitis B virus (HBV)-related cryoglobulinaemia. Two months after treatment with tenofovir alafenamide, an antiviral therapy for HBV, there was a significant improvement of her symptoms and undetectable serum cryoglobulins.

Treatment Algorithm for Managing Chronic Hepatitis B Virus Infection in the United States: 2021 Update.

Background & Aims: Chronic hepatitis B (CHB) infection remains the most frequent etiology of hepatocellular carcinoma globally as well as a major cause of cirrhosis. Despite vaccination, substantial numbers of persons have already been infected with hepatitis B virus and remain at risk of progressive liver disease.

Methods: In 2004, a CHB management algorithm was developed by a panel of North American hepatologists, which was subsequently updated in 2006, 2008, and 2015.

Highly multiplexed 2-dimensional imaging mass cytometry analysis of HBV-infected liver.

Studies of human hepatitis B virus (HBV) immune pathogenesis are hampered by limited access to liver tissues and technologies for detailed analyses. Here, utilizing imaging mass cytometry (IMC) to simultaneously detect 30 immune, viral, and structural markers in liver biopsies from patients with hepatitis B e antigen+ (HBeAg+) chronic hepatitis B, we provide potentially novel comprehensive visualization, quantitation, and phenotypic characterizations of hepatic adaptive and innate immune subsets that correlated with hepatocellular injury, histological fibrosis, and age. We further show marked correlations between adaptive and innate immune cell frequencies and phenotype, highlighting complex immune interactions within the hepatic microenvironment with relevance to HBV pathogenesis.

Liver Cancer-Specific Serine Protease Inhibitor Kazal Is a Potentially Novel Biomarker for the Early Detection of Hepatocellular Carcinoma.

Introduction: Liver cancer-secreted serine protease inhibitor Kazal (LC-SPIK) is a protein that is specifically elevated in cases of hepatocellular carcinoma (HCC). We assessed the performance of LC-SPIK in detecting HCC, including its early stages, in patients with cirrhosis, hepatitis B virus (HBV), and hepatitis C virus (HCV).

Methods: We enrolled 488 patients, including 164 HCC patients (81 early HCC) and 324 controls in a blinded, prospective, case-control study.

Hepatic IFN-Induced Protein with Tetratricopeptide Repeats Regulation of HCV Infection.

Interferons (IFNs) suppress viral infection through the induction of >400 interferon-stimulated genes (ISGs). Among ISGs, IFN-induced protein with tetratricopeptide repeats (IFITs) is one of the most potent and well-characterized ISGs. IFIT family consists of 4 cluster genes.

Correction: Application of the Doylestown algorithm for the early detection of hepatocellular carcinoma.

[This corrects the article DOI: 10.1371/journal.pone.

Application of the Doylestown algorithm for the early detection of hepatocellular carcinoma.

Background: We previously developed a logistic regression algorithm that uses AFP, age, gender, ALK and ALT levels to improve the detection of hepatocellular carcinoma (HCC). In 3,158 patients from 5 independent sites, this algorithm, referred to as the "Doylestown" algorithm, increased the AUROC of AFP 4% to 12% and had equal benefit regardless of tumor size or the etiology of liver disease.

Aims: Analysis of the Doylestown algorithm using samples from individuals taken before their diagnosis of HCC.

Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE2RD) for diagnostics.

Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients' homes.

A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: 2015 Update.

Chronic hepatitis B (CHB) continues to be an important public health problem worldwide, including in the United States. An algorithm for managing CHB was developed by a panel of United States hepatologists in 2004 and subsequently updated in 2006 and 2008. Since 2008, additional data on long-term safety and efficacy of licensed therapies have become available and have better defined therapeutic options for CHB.

Recent advances in micro/nanotechnologies for global control of hepatitis B infection.

The control of hepatitis B virus (HBV) infection is a challenging task, specifically in developing countries there is limited access to diagnostics and antiviral treatment mainly due to high costs and insufficient healthcare infrastructure. Although the current diagnostic technologies can reliably detect HBV, they are relatively laborious, impractical and require expensive resources that are not suitable for resource-limited settings. Advances in micro/nanotechnology are pioneering the development of new generation methodologies in diagnosis and screening of HBV.

Next-generation sequencing reveals large connected networks of intra-host HCV variants.

Background: Next-generation sequencing (NGS) allows for sampling numerous viral variants from infected patients. This provides a novel opportunity to represent and study the mutational landscape of Hepatitis C Virus (HCV) within a single host.

Results: Intra-host variants of the HCV E1/E2 region were extensively sampled from 58 chronically infected patients.

Characteristics of adults in the hepatitis B research network in North America reflect their country of origin and hepatitis B virus genotype.

Background & Aims: Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the United States and Canada might be affected disproportionately. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network.

Innate immune tolerance and the role of kupffer cells in differential responses to interferon therapy among patients with HCV genotype 1 infection.

Background & Aims: In patients with hepatitis C virus (HCV) infection, interferon alfa (IFN-α) alters expression of IFN-stimulated genes (ISGs), but little is understood about factors that determine outcomes of therapy. We used a systems biology approach to evaluate the acute response of patients with chronic hepatitis C to IFN-α therapy.

Methods: We collected liver biopsy samples from 8 treatment-naïve patients with chronic HCV genotype 1 infection at baseline and 24 hours after treatment with IFN-α-2a (10 MU subcutaneously).

IFITM1 is a tight junction protein that inhibits hepatitis C virus entry.

Unlabelled: Type 1 interferon (IFN) continues to be the foundation for the current standard of care combination therapy for chronic hepatitis C virus (HCV) infection, yet the component interferon-stimulated genes (ISGs) that mediate the antiviral actions of IFN are not fully defined. Interferon-induced transmembrane protein 1 (IFITM1) is an ISG product that suppresses early stage infection by a number of viruses through an unknown mechanism of action. Moreover, the actions of IFITM1 on HCV infection are not fully elucidated.

Current Concepts of HBV/HCV Coinfection: Coexistence, but Not Necessarily in Harmony.

Hepatitis B and hepatitis C are important causes of chronic liver disease globally. Although HBV/HCV coinfection is not uncommon, its epidemiology is poorly defined. Numerous studies provided evidence that coinfection accelerates liver disease progression and increases the risk of hepatocellular carcinoma.

Current status of antiviral therapy for hepatitis B.

Chronic hepatitis B (CHB) is a major public health problem affecting up to 400 million people globally. Complications of CHB including liver failure and hepatocellular carcinoma result in 1.2 million deaths per year, making CHB the 10th leading cause of mortality worldwide.

Interferon regulatory factor-3 activation, hepatic interferon-stimulated gene expression, and immune cell infiltration in hepatitis C virus patients.

Unlabelled: Interferon regulatory factor-3 (IRF-3) activation directs alpha/beta interferon production and interferon-stimulated gene (ISG) expression, which limits virus infection. Here, we examined the distribution of hepatitis C virus (HCV) nonstructural 3 protein, the status of IRF-3 activation, and expression of IRF-3 target genes and ISGs during asynchronous HCV infection in vitro and in liver biopsies from patients with chronic HCV infection, using confocal microscopy and functional genomics approaches. In general, asynchronous infection with HCV stimulated a low-frequency and transient IRF-3 activation within responsive cells in vitro that was associated with cell-to-cell virus spread.

A pilot study of extended duration peginterferon alfa-2a for patients with hepatitis B e antigen-negative chronic hepatitis B.

Objectives: Forty-eight weeks of peginterferon alfa-2a is the approved regimen for chronic hepatitis B (CHB). Standard interferon is more effective for hepatitis B e antigen (HBeAg)-negative CHB when given for longer than 1 yr. This study evaluated peginterferon alfa-2a for 60 wk, alone or in combination with lamivudine.

The APRI may be enhanced by the use of the FIBROSpect II in the estimation of fibrosis in chronic hepatitis C.

Background: Multiple serum markers to estimate hepatic fibrosis in chronic liver disease have been proposed. The AST/Platelet Ratio Index (APRI) is a simple biochemical index that has been shown to be useful and accurate in about 50% of patients with chronic hepatitis C. We determined if the combination of the APRI and the FIBROSpect II, a commercially available hepatic fibrosis marker that measures 3 components of the extracellular hepatic matrix, would further help distinguish mild from significant fibrosis in a group of patients with chronic hepatitis C.

Hepatitis B: the pathway to recovery through treatment.

Hepatitis B is a major public health problem in the world today. Since 1985, the number of reported cases has declined as a direct result of universal immunization of neonates, vaccination of at-risk populations, lifestyle or behavioral changes in high-risk groups, refinements in the screening of blood donors, and the use of virally inactivated or genetically engineered products in patients with bleeding disorders. New and potent antiviral agents being developed and evaluated provide hope and optimism for those who are chronically infected with hepatitis B virus.

APRI: an easy and validated predictor of hepatic fibrosis in chronic hepatitis C.

Goals: To evaluate the aspartate aminotransferase/platelet ratio index (APRI) as a predictor of the presence or absence of significant fibrosis on liver biopsy of patients with chronic hepatitis C (HCV).

Background: The decision to treat HCV is often made on the basis of the presence or absence of significant fibrosis on the liver biopsy. Because liver biopsy is expensive and invasive a noninvasive marker to evaluate hepatic fibrosis would be useful.