Improvement in Hepatic Fibrosis Biomarkers Associated With Chemokine Receptor Inactivation Through Mutation or Therapeutic Blockade

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
Kenneth E ShermanShyam Kottilil

Abstract

The C-C chemokine receptor Type 5 (CCR5) is a key receptor for human immunodeficiency virus type 1 (HIV-1) entry into T-cells and a variant allele, CCR5 delta-32, is associated with decreased viral replication and disease progression. Active HIV-1 replication is highly associated with accelerated rates of hepatic fibrosis. We postulated that CCR5 plays a role in the development of hepatic fibrosis and evaluated the longitudinal effect of natural or drug-induced CCR5 mutation and blockade on biomarkers of liver fibrosis in HIV-1 patients. To accomplish this goal, we examined 2 distinct cohorts. First, we evaluated fibrosis markers in the Multicenter Hemophilia Cohort Studies (MHCS), which included subjects with HIV and hepatitis C virus (HCV) coinfection with the CCR5 delta-32 allele. We also evaluated an HIV-1 infected cohort that was treated with a dual CCR5/CCR2 antagonist, cenicriviroc. The enhanced liver fibrosis (ELF) index was validated against liver histology obtained from HCV/HIV and HCV patients and demonstrated strong correlation with fibrosis stage. In both the MHCS patients and patients treated with cenicriviroc, CCR5 mutation or blockade was associated with a significant decrease in the ELF index. Among the patient...Continue Reading

References

Nov 14, 1997·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·T L KatzensteinJ Gerstoft
Sep 25, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y BenhamouT Poynard
Aug 2, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y BenhamouUNKNOWN MultivirC Group
Nov 6, 2001·Annals of Internal Medicine·J P IoannidisUNKNOWN International Meta-Analysis of HIV Host Genetics
Dec 3, 2003·Proceedings of the National Academy of Sciences of the United States of America·Alison P Galvani, Montgomery Slatkin
Oct 27, 2005·PLoS Biology·Pardis C SabetiEric S Lander
Nov 22, 2005·Cytokine & Growth Factor Reviews·Christoph BeckerMarkus F Neurath
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Gordon K Smyth
May 23, 2006·BMC Bioinformatics·Matthew E RitchieGordon K Smyth
Nov 23, 2006·Nature Medicine·Jason M BrenchleyDaniel C Douek
Sep 11, 2010·BMC Gastroenterology·Mireen Friedrich-RustChristoph Sarrazin
Jan 21, 2011·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jason T BlackardKenneth E Sherman
May 10, 2011·TheScientificWorldJournal·Gero Hütter, Susanne Ganepola
Jan 20, 2012·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·J MacíasUNKNOWN FIBROCEL study group
Feb 22, 2012·Journal of Acquired Immune Deficiency Syndromes : JAIDS·William J TownerMichael J Silverberg
Oct 16, 2012·Cellular Signalling·Rohan SamarakoonPaul J Higgins
Dec 12, 2012·PloS One·Florence AbravanelUNKNOWN ANRS CO13 HEPAVIH Study Group
May 3, 2013·The Journal of Clinical Investigation·Detlef Schuppan, Yong Ook Kim
Apr 10, 2014·Journal of Clinical Gastroenterology·Flavia F FernandesRenata M Perez
Aug 8, 2014·Science Translational Medicine·Kenneth E ShermanAlan S Perelson
Aug 22, 2014·Journal of Clinical Gastroenterology·Flavia F FernandesMaria L Ferraz
Nov 14, 2014·Journal of the International AIDS Society·Enrique Ortega GonzalezGiovanna Llerena
Sep 5, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kenneth E ShermanDavid Thomas
Dec 20, 2015·Medicine·Raphael MohrJürgen Kurt Rockstroh
Mar 6, 2016·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Jennifer C PriceChloe L Thio
Mar 19, 2016·Journal of Acquired Immune Deficiency Syndromes : JAIDS·H Nina KimMari M Kitahata
Oct 22, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jana C MossanenFrank Tacke
Aug 18, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shadi SalloumRaymond T Chung
Aug 24, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Scott L FriedmanEric Lefebvre
Sep 25, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Oliver KrenkelFrank Tacke
Jan 18, 2018·Journal of Cellular Physiology·Nicola CoppolaAntonio De Luca
May 29, 2018·Journal of Hepatology·Maria Eugenia GuicciardiGregory J Gores

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Citations

Feb 14, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Giovanni GuaraldiUNKNOWN SHIVER Network
May 28, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Enass A Abdel-HameedKenneth E Sherman
Nov 28, 2020·The Journal of Infectious Diseases·Andre J Jeyarajan, Raymond T Chung
Nov 17, 2020·Current Opinion in Physiology·Ruoshui Li, Nikolaos G Frangogiannis

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