Dataset Information

Efficacy of antiviral therapy and host-virus interactions visualised using serial liver sampling with fine-needle aspirates.

ABSTRACT:

Background & aims

Novel therapies for chronic hepatitis B (CHB), such as RNA interference, target all viral RNAs for degradation, whereas nucleoside analogues are thought to block reverse transcription with minimal impact on viral transcripts. However, limitations in technology and sampling frequency have been obstacles to measuring actual changes in HBV transcription in the liver of patients starting therapy.

Methods

We used elective liver sampling with fine-needle aspirates (FNAs) to investigate the impact of treatment on viral replication in patients with CHB. Liver FNAs were collected from patients with CHB at baseline and 12 and 24 weeks after starting tenofovir alafenamide treatment. Liver FNAs were subjected to single-cell RNA sequencing and analysed using the Viral-Track method.

Results

HBV was the only viral genome detected and was enriched within hepatocytes. The 5' sequencing technology identified protein-specific HBV transcripts and showed that tenofovir alafenamide therapy specifically reduced pre-genomic RNA transcripts with little impact on HBsAg or HBx transcripts. Infected hepatocytes displayed unique gene signatures associated with an immunological response to viral infection.

Conclusions

Longitudinal liver sampling, combined with single-cell RNA sequencing, captured the dynamic impact of antiviral therapy on the replication status of HBV and revealed host-pathogen interactions at the transcriptional level in infected hepatocytes. This sequencing-based approach is applicable to early-stage clinical studies, enabling mechanistic studies of immunopathology and the effect of novel therapeutic interventions.

Impact and implications

Infection-dependent transcriptional changes and the impact of antiviral therapy on viral replication can be measured in longitudinal human liver biopsies using single-cell RNA sequencing data.

SUBMITTER: Kim SC

PROVIDER: S-EPMC10432215 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Efficacy of antiviral therapy and host-virus interactions visualised using serial liver sampling with fine-needle aspirates.

Kim Samuel C SC Wallin Jeffrey J JJ Ghosheh Yanal Y Zahoor Muhammad Atif MA Sanchez Vasquez Juan Diego JD Nkongolo Shirin S Fung Scott S Mendez Patricia P Feld Jordan J JJ Janssen Harry L A HLA Gehring Adam J AJ

JHEP reports : innovation in hepatology 20230619 9

<h4>Background & aims</h4>Novel therapies for chronic hepatitis B (CHB), such as RNA interference, target all viral RNAs for degradation, whereas nucleoside analogues are thought to block reverse transcription with minimal impact on viral transcripts. However, limitations in technology and sampling frequency have been obstacles to measuring actual changes in HBV transcription in the liver of patients starting therapy.<h4>Methods</h4>We used elective liver sampling with fine-needle aspirates (FNA ...[more]

PMID: 37600958

Similar Datasets

Project description:Background & aimsFinite duration of treatment associated with HBsAg loss is the current goal for improved therapeutic approaches against chronic HBV infection, as it indicates elimination or durable inactivation of intrahepatic covalently closed circular DNA (cccDNA). To assist drug development, the definition of early predictive markers of HBsAg loss by assessing their value in reflecting intrahepatic cccDNA levels and transcriptional activity is essential. Fine needle aspirates (FNAs) have recently emerged as a less invasive alternative to core liver biopsy (CLB) and showed to be useful for investigating intrahepatic immune responses. The aim of this study was to optimise and validate the use of FNA vs. CLB to evaluate the intrahepatic viral reservoir.MethodsPaired FNA/CLB samples were obtained from patients with HBeAg+ chronic hepatitis (n = 4), HBeAg- chronic hepatitis (n = 4), and HBeAg- chronic infection (n = 1). One HBeAg+ patient was undergoing tenofovir treatment. HBV 3.5-kb RNA and cccDNA were quantified by droplet digital PCR.ResultscccDNA was quantifiable in all but one FNA/CLB pair, showing the highest levels in untreated HBeAg+ patients, except for the tenofovir-treated patient. Similarly, 3.5-kb RNA was detectable in all but one FNA sample and showed higher levels in HBeAg+ patients. When comparing cccDNA and 3.5-kb RNA quantification in FNA vs. CLB samples, no statistically significant differences were identified.ConclusionsThese results demonstrate the possibility to quantify cccDNA and assess its transcriptional activity in patients with chronic hepatitis B by combining FNA and droplet digital PCR. This supports the use of FNA in clinical trials to evaluate the intrahepatic viral reservoir during the development of new antivirals and immunomodulatory agents.Impact and implicationsChronic hepatitis B infection is characterised by a complex interplay between immune responses and viral replication in the liver, which determines the long-term outcome of the disease. In this study, we show that fine needle aspiration of the liver, a less-invasive alternative to core biopsies, allows the assessment of the hepatic viral reservoir.

Dataset Information

Efficacy of antiviral therapy and host-virus interactions visualised using serial liver sampling with fine-needle aspirates.

Background & aims

Methods

Results

Conclusions

Impact and implications

Publications

Efficacy of antiviral therapy and host-virus interactions visualised using serial liver sampling with fine-needle aspirates.

Similar Datasets

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