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Hepatitis01:25

Hepatitis

Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...
Viral Hepatitis I: Introduction01:28

Viral Hepatitis I: Introduction

Viral hepatitis is an inflammatory condition of the liver caused by infection with hepatotropic viruses, most commonly hepatitis A, B, C, D, and E. Despite variations in structure and transmission, all viruses mentioned infect hepatocytes and provoke immune responses that can hinder liver function. Additionally, some non-hepatotropic viruses can also lead to hepatic inflammation.Hepatitis A VirusHepatitis A virus (HAV) is transmitted through the fecal–oral route, typically by ingestion of food...

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Updated: Jun 25, 2026

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Differential Intrahepatic Integrated HBV DNA Patterns Between HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B.

Daryl T-Y Lau, Elena S Kim, Zhili Wang

    Medrxiv : the Preprint Server for Health Sciences
    |March 17, 2025
    PubMed
    Summary

    Integrated HBV DNA (iDNA) is a significant source of HBsAg in HBeAg(-) chronic hepatitis B (CHB) patients. This study highlights iDNA

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    Area of Science:

    • Hepatology
    • Virology
    • Molecular Biology

    Background:

    • Hepatitis B surface antigen (HBsAg) can originate from intrahepatic covalently closed circular DNA (cccDNA) and integrated HBV DNA (iDNA).
    • Understanding the relative contributions of cccDNA and iDNA to HBsAg production is crucial for chronic hepatitis B (CHB) management.

    Purpose of the Study:

    • To investigate the role of intrahepatic HBV DNA forms, specifically cccDNA and iDNA, in HBsAg production in treatment-naive CHB patients.
    • To compare the characteristics of iDNA and cccDNA in HBeAg-positive (HBeAg+) and HBeAg-negative (HBeAg-) CHB participants.

    Main Methods:

    • Analysis of liver tissues from 24 HBeAg(+) and 32 HBeAg(-) treatment-naive CHB participants.
    • Quantification of intrahepatic cccDNA using qPCR after selective digestion.
    • Detection and characterization of intrahepatic iDNA using HBV hybridization-targeted next-generation sequencing (HBV-NGS) and ChimericSeq for junction analysis.

    Main Results:

    • HBeAg(+) participants showed higher levels of intrahepatic cccDNA, serum HBV DNA, HBV RNA, HBcrAg, and qHBsAg compared to HBeAg(-) participants.
    • HBsAg staining was prevalent in over 85% of livers in both HBeAg(+) and HBeAg(-) groups.
    • HBeAg(-) participants predominantly had iDNA (>50% of total HBV DNA), while HBeAg(+) participants had a more balanced or cccDNA-dominant profile; iDNA integration patterns differed between groups, with clustering at DR2-DR1 in HBeAg(-) livers.

    Conclusions:

    • Serum HBV RNA and HBcrAg levels correlate with intrahepatic cccDNA concentrations.
    • In HBeAg(-) CHB patients, high levels of intrahepatic iDNA and HBsAg, despite lower cccDNA, suggest iDNA is the primary source of HBsAg.
    • The distinct integration patterns of iDNA may reflect different mechanisms of HBV DNA integration in HBeAg(+) versus HBeAg(-) CHB.