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Establishment of the Dual Humanized TK-NOG Mouse Model for HIV-associated Liver Pathogenesis
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Hepatitis delta and HIV infection.

Vincent Soriano1, Kenneth E Sherman, Pablo Barreiro

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Hepatitis delta virus (HDV) infection in HIV-positive individuals poses a significant risk for liver disease. New therapies targeting HDV replication show promise for treatment and potential cure.

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Area of Science:

  • Hepatology
  • Virology
  • Infectious Diseases

Background:

  • Viral liver diseases are common in HIV-positive individuals, contributing to mortality.
  • Hepatitis C and B are manageable, but hepatitis delta virus (HDV) infection lacks effective treatments, increasing cirrhosis and liver cancer risk.
  • Sexual contact is the primary HDV transmission route in Europe and North America.

Purpose of the Study:

  • To review the current landscape of HDV treatment in HIV-coinfected patients.
  • To highlight emerging therapeutic strategies and their potential for HDV suppression and cure.
  • To discuss the implications of new cell entry receptor discoveries for HDV therapy.

Main Methods:

  • Review of current literature on HDV and HIV coinfection treatments.
  • Analysis of emerging therapeutic agents targeting HDV replication and cell entry.
  • Discussion of treatment goals, including viral suppression and potential cure.

Main Results:

  • Pegylated interferon-alfa (PegIFNα) has limited efficacy (<25% sustained clearance).
  • New therapies, including sodium taurocholate cotransporting polypeptide inhibitors (e.g., Myrcludex-B), prenylation inhibitors (e.g., lonafarnib), and nucleic acid polymers, show promise.
  • Sustained HDV replication suppression leads to improved liver enzymes and histology.

Conclusions:

  • Emerging HDV therapies offer new hope for managing liver disease in coinfected patients.
  • Co-administration with anti-HBV agents is crucial to prevent HBV rebound.
  • The potential for HDV cure exists, possibly without eradicating HBV cccDNA, by achieving viral suppression and HBsAg clearance.