Single hepatocytes show persistence and transcriptional inactivity of hepatitis B

• DOI: 10.1172/jci.insight.140584
• Publication Date: 2020-10-01T15:01:40Z
• Authors: Ashwin Balagopal; Tanner Grudda; Ruy M. Ribeiro; Yasmeen S. Saad; Hyon S. Hwang; Jeffrey Quinn; Michael Murphy; Kathleen Ward; Richard K. Sterling; Yang Zhang; Alan S. Perelson; Mark S. Sulkowski; William O. Osburn; Chloe L. Thio
• Keywords: cccDNA; Laser capture microdissection

There is no cure for the more than 270 million people chronically infected with HBV. Nucleos(t)ide analogs (NUCs), mainstay of anti-HBV treatment, block HBV reverse transcription. NUCs do not eliminate intranuclear covalently closed circular DNA (cccDNA), from which viral RNAs, including pregenomic RNA (pgRNA), are transcribed. A key gap in designing a understanding how affect replication and transcription because serum markers yield an incomplete view intrahepatic We applied single-cell laser capture microdissection droplet digital PCR to paired liver biopsies collected 5 HBV/HIV-coinfected persons who took over 2-4 years. From biopsy 1 2, proportions HBV-infected hepatocytes declined adherence NUC treatment (P < 0.05); we extrapolated that eradication will take 10 decades these participants. In individual hepatocytes, pgRNA levels diminished 28- 73-fold during corresponding decreased tissue core antigen staining 0.01). 4 out participants, cccDNA but undetectable (transcriptionally inactive) were present, enriched 3 participants treatment. Further work unravel mechanisms transcriptional inactivation may lead therapies can achieve this all resulting functional cure.