Efficacy of antiviral therapy and host–virus interactions visualised using serial liver sampling with fine-needle aspirates
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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
|
| Series: | JHEP Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555923001489 |
| _version_ | 1797732886990815232 |
|---|---|
| author | Samuel C. Kim Jeffrey J. Wallin Yanal Ghosheh Muhammad Atif Zahoor Juan Diego Sanchez Vasquez Shirin Nkongolo Scott Fung Patricia Mendez Jordan J. Feld Harry L.A. Janssen Adam J. Gehring |
| author_facet | Samuel C. Kim Jeffrey J. Wallin Yanal Ghosheh Muhammad Atif Zahoor Juan Diego Sanchez Vasquez Shirin Nkongolo Scott Fung Patricia Mendez Jordan J. Feld Harry L.A. Janssen Adam J. Gehring |
| author_sort | Samuel C. Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T12:20:00Z |
| format | Article |
| id | doaj.art-c7aebf2062a9451e8b6acf89ff2a9203 |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-03-12T12:20:00Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-c7aebf2062a9451e8b6acf89ff2a92032023-08-30T05:54:41ZengElsevierJHEP Reports2589-55592023-09-0159100817Efficacy of antiviral therapy and host–virus interactions visualised using serial liver sampling with fine-needle aspiratesSamuel C. Kim0Jeffrey J. Wallin1Yanal Ghosheh2Muhammad Atif Zahoor3Juan Diego Sanchez Vasquez4Shirin Nkongolo5Scott Fung6Patricia Mendez7Jordan J. Feld8Harry L.A. Janssen9Adam J. Gehring10Gilead Sciences, Inc., Foster City, CA, USAGilead Sciences, Inc., Foster City, CA, USAToronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaToronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaToronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, CanadaToronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Department of Internal Medicine IV (Gastroenterology, Hepatology, Infectious Diseases), University Hospital Heidelberg, Heidelberg, GermanyToronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaGilead Sciences, Inc., Foster City, CA, USAToronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaToronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Erasmus Medical Center, Division of Gastroenterology and Hepatology, Rotterdam, The NetherlandsToronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada; Corresponding author. Address: PMCRT 10-356, 101 College St, Toronto, ON, M5G 1L7, Canada. Tel.: +1-(416)-634-7095.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.http://www.sciencedirect.com/science/article/pii/S2589555923001489Hepatitis BHepatocyteViral-TrackFNAFine needle aspirateLiver |
| spellingShingle | Samuel C. Kim Jeffrey J. Wallin Yanal Ghosheh Muhammad Atif Zahoor Juan Diego Sanchez Vasquez Shirin Nkongolo Scott Fung Patricia Mendez Jordan J. Feld Harry L.A. Janssen Adam J. Gehring Efficacy of antiviral therapy and host–virus interactions visualised using serial liver sampling with fine-needle aspirates JHEP Reports Hepatitis B Hepatocyte Viral-Track FNA Fine needle aspirate Liver |
| title | Efficacy of antiviral therapy and host–virus interactions visualised using serial liver sampling with fine-needle aspirates |
| title_full | Efficacy of antiviral therapy and host–virus interactions visualised using serial liver sampling with fine-needle aspirates |
| title_fullStr | Efficacy of antiviral therapy and host–virus interactions visualised using serial liver sampling with fine-needle aspirates |
| title_full_unstemmed | Efficacy of antiviral therapy and host–virus interactions visualised using serial liver sampling with fine-needle aspirates |
| title_short | Efficacy of antiviral therapy and host–virus interactions visualised using serial liver sampling with fine-needle aspirates |
| title_sort | efficacy of antiviral therapy and host virus interactions visualised using serial liver sampling with fine needle aspirates |
| topic | Hepatitis B Hepatocyte Viral-Track FNA Fine needle aspirate Liver |
| url | http://www.sciencedirect.com/science/article/pii/S2589555923001489 |
| work_keys_str_mv | AT samuelckim efficacyofantiviraltherapyandhostvirusinteractionsvisualisedusingserialliversamplingwithfineneedleaspirates AT jeffreyjwallin efficacyofantiviraltherapyandhostvirusinteractionsvisualisedusingserialliversamplingwithfineneedleaspirates AT yanalghosheh efficacyofantiviraltherapyandhostvirusinteractionsvisualisedusingserialliversamplingwithfineneedleaspirates AT muhammadatifzahoor efficacyofantiviraltherapyandhostvirusinteractionsvisualisedusingserialliversamplingwithfineneedleaspirates AT juandiegosanchezvasquez efficacyofantiviraltherapyandhostvirusinteractionsvisualisedusingserialliversamplingwithfineneedleaspirates AT shirinnkongolo efficacyofantiviraltherapyandhostvirusinteractionsvisualisedusingserialliversamplingwithfineneedleaspirates AT scottfung efficacyofantiviraltherapyandhostvirusinteractionsvisualisedusingserialliversamplingwithfineneedleaspirates AT patriciamendez efficacyofantiviraltherapyandhostvirusinteractionsvisualisedusingserialliversamplingwithfineneedleaspirates AT jordanjfeld efficacyofantiviraltherapyandhostvirusinteractionsvisualisedusingserialliversamplingwithfineneedleaspirates AT harrylajanssen efficacyofantiviraltherapyandhostvirusinteractionsvisualisedusingserialliversamplingwithfineneedleaspirates AT adamjgehring efficacyofantiviraltherapyandhostvirusinteractionsvisualisedusingserialliversamplingwithfineneedleaspirates |