Evidence map›Paper›PMID 36972796›Full record

ArticleJournal of hepatology2024

Single-cell atlas of the liver myeloid compartment before and after cure of chronic viral hepatitis.

Ang Cui, Bo Li, Michael S Wallace, Anna L K Gonye, Christopher Oetheimer, Hailey Patel, Pierre Tonnerre, Jacinta A Holmes, David Lieb, Brianna S Yao and 21 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02476617 (An Exploratory Study to Evaluate Immune Restoration Following Removal of Viral Antigen in Treatment-Naïve and Treatment-Experienced Adults With Genotype), which is not on this map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
8.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02476617 phase3completednot on this map

An Exploratory Study to Evaluate Immune Restoration Following Removal of Viral Antigen in Treatment-Naïve and Treatment-Experienced Adults With Genotype (GT) 1a Chronic Hepatitis C Virus (HCV) Infection Administered Ombitasvir/ ABT-450/Ritonavir With Dasabuvir and Ribavirin (RBV) for 12 Weeks

TypeinterventionalSponsorAbbVieRan2015 to 2016Enrolled25ConditionsChronic Hepatitis C, Hepatitis C (HCV), Hepatitis C Genotype 1aArmsombitasvir/paritaprevir/ritonavir, dasabuvir, ribavirin
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025
    Review
  8. Navigating the Hepatic Immune Landscape With Fine Needle Aspiration of the Liver-An Emerging Technique.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  9. Article
  10. Advances in Single-Cell Sequencing for Infectious Diseases: Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. After the Storm: Persistent Molecular Alterations Following HCV Cure.International journal of molecular sciences · 2024
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors at 3 institutions in 3 countries.

Ang CuiBroad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: ang_cui@g.harvard.edu.
Bo LiBroad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard University Virology Program, Harvard Medical School, Boston, MA, USA.
Michael S WallaceDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Anna L K GonyeBroad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Christopher OetheimerDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Hailey PatelDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Pierre TonnerreDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Institut de Recherche Saint-Louis, Université Paris Cité, Inserm U976 (HIPI), Team ATIP-Avenir, Paris, France.
Jacinta A HolmesDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, VIC, Australia.
David LiebBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Brianna S YaoBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Aileen MaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Kela RobertsBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Marcos DamasioDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Jonathan H ChenBroad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Daphnee PiouDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Charles Carlton-SmithDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Joelle BrownDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Ravi MylvaganamDepartment of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Jeremy Man Hon FungDepartment of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Moshe Sade-FeldmanBroad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Jasneet AnejaDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Jenna GustafsonDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Eliana T EpsteinDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Shadi SalloumDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Cynthia BrisacDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Ashraf ThabetDepartment of Interventional Radiology, Massachusetts General Hospital, Boston, MA, USA.
Arthur Y KimDivision of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Georg M LauerDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Nir HacohenBroad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: nhacohen@mgh.harvard.edu.
Raymond T ChungDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: chung.raymond@mgh.harvard.edu.
Nadia AlatrakchiDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: nalatrakchi@mgh.harvard.edu.
Harvard University · USBroad Institute · USMassachusetts General Hospital · US

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ARTHUR Y KIM · 2004 to 2026
$94.4M
Virology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI GEORG Michael LAUER · 2009 to 2026
$48.1M
HIV-Hepatitis C Virus Cooperative Interactions and Liver Disease ProgressionR01DK098079 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHUNG, RAYMOND T · 2013 to 2016
$2.7M
HIV-Associated Macrophage Alterations and Progressive Liver DiseaseR01DK108370 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHUNG, RAYMOND T · 2015 to 2019
$1.6M
HIV-induced monocyte and macrophage perturbations driving liver fibrogenesisR56DK134251 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI ALATRAKCHI, NADIA, CHUNG, RAYMOND T · 2022 to 2022
$651k
Influx Flow CytometerS10OD016372 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2013 to 2013
$600k
ImageStream X Analyzer 2011S10OD012027 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2012 to 2012
$595k
Translational Immunology Core's FACSAria Cell SorterS10RR023440 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2008 to 2008
$500k
DEPARTMENT OF PATHOLOGY LSR2 CYTOMETER: TRANSPLANTATIONS10RR020936 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2005 to 2005
$389k
NCRR NIH HHS S10 RR020936NCRR NIH HHS S10 RR023440NIAID NIH HHS P30 AI060354NIAID NIH HHS U19 AI082630NIDDK NIH HHS R01 DK098079NIDDK NIH HHS R01 DK108370NIDDK NIH HHS R56 DK134251NIH HHS S10 OD012027NIH HHS S10 OD016372
6 · The paper itself

Abstract

BACKGROUND &

aimsChronic viral infections present serious public health challenges; however, direct-acting antivirals (DAAs) are now able to cure nearly all patients infected with hepatitis C virus (HCV), representing the only cure of a human chronic viral infection to date. DAAs provide a valuable opportunity to study immune pathways in the reversal of chronic immune failures in an in vivo human system.

methodsTo leverage this opportunity, we used plate-based single-cell RNA-seq to deeply profile myeloid cells from liver fine needle aspirates in patients with HCV before and after DAA treatment. We comprehensively characterised liver neutrophils, eosinophils, mast cells, conventional dendritic cells, plasmacytoid dendritic cells, classical monocytes, non-classical monocytes, and macrophages, and defined fine-grained subpopulations of several cell types.

resultsWe discovered cell type-specific changes post-cure, including an increase in MCM7+STMN1+ proliferating CD1C+ conventional dendritic cells, which may support restoration from chronic exhaustion. We observed an expected downregulation of interferon-stimulated genes (ISGs) post-cure as well as an unexpected inverse relationship between pre-treatment viral load and post-cure ISG expression in each cell type, revealing a link between viral loads and sustained modifications of the host's immune system. We found an upregulation of PD-L1/L2 gene expression in ISG-high neutrophils and IDO1 expression in eosinophils, pinpointing cell subpopulations crucial for immune regulation. We identified three recurring gene programmes shared by multiple cell types, distilling core functions of the myeloid compartment.

conclusionsThis comprehensive single-cell RNA-seq atlas of human liver myeloid cells in response to cure of chronic viral infections reveals principles of liver immunity and provides immunotherapeutic insights. CLINICAL

trial registrationThis study is registered at ClinicalTrials.gov (NCT02476617). IMPACT AND IMPLICATIONS: Chronic viral liver infections continue to be a major public health problem. Single-cell characterisation of liver immune cells during hepatitis C and post-cure provides unique insights into the architecture of liver immunity contributing to the resolution of the first curable chronic viral infection of humans. Multiple layers of innate immune regulation during chronic infections and persistent immune modifications after cure are revealed. Researchers and clinicians may leverage these findings to develop methods to optimise the post-cure environment for HCV and develop novel therapeutic approaches for other chronic viral infections.

Indexed as

Hepatitis CHepatitis C, ChronicAntiviral AgentsHepacivirusHumansPersistent InfectionAntiviral AgentsChronic infectionsDirect-acting antiviralEosinophilsFine needle aspirationHepatitis C virusImmune cellsInnate immunityLiverMyeloid cellsNeutrophilsPD-L1Single-cell RNA-sequencingViral infections

Identifiers

PMID36972796
PMCPMC11651724
OpenAlexW4360955686

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.