Persistence of hepatitis C virus during and after otherwise clinically successful treatment of chronic hepatitis C with standard pegylated interferon α-2b and ribavirin therapy

Resolution of chronic hepatitis C is considered when serum HCV RNA becomes repeatedly undetectable and liver enzymes normalize. However, long-term persistence of HCV following therapy with pegylated interferon-α/ribavirin (PegIFN/R) was reported when more sensitive assays and testing of serial plasm...

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Published in:PloS one 2013-11, Vol.8 (11), p.e80078
Main Authors: Chen, Annie Y, Zeremski, Marija, Chauhan, Ranjit, Jacobson, Ira M, Talal, Andrew H, Michalak, Tomasz I
Format: Article
Language:English
Subjects:
Antiviral Agents - administration & dosage
Antiviral Agents - therapeutic use
Biopsy
Female
Gastroenterology
Gene sequencing
Genomes
Health sciences
Hepacivirus - genetics
Hepacivirus - isolation & purification
Hepacivirus - physiology
Hepatitis
Hepatitis C
Hepatitis C, Chronic - drug therapy
Hepatitis C, Chronic - virology
Hepatology
Humans
Infections
Interferon
Interferon-alpha - administration & dosage
Interferon-alpha - therapeutic use
Limit of Detection
Liver
Lymphoid cells
Male
Medicine
Mutation
Patients
Peripheral blood mononuclear cells
Polyethylene Glycols - administration & dosage
Polyethylene Glycols - therapeutic use
Recombinant Proteins - administration & dosage
Recombinant Proteins - therapeutic use
Replication
Ribavirin
Ribavirin - administration & dosage
Ribavirin - therapeutic use
Ribonucleic acid
RNA
RNA viruses
RNA, Viral - blood
Therapy
Virology
Virus Replication
Viruses
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Chauhan, Ranjit
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Michalak, Tomasz I
description Resolution of chronic hepatitis C is considered when serum HCV RNA becomes repeatedly undetectable and liver enzymes normalize. However, long-term persistence of HCV following therapy with pegylated interferon-α/ribavirin (PegIFN/R) was reported when more sensitive assays and testing of serial plasma, lymphoid cells (PBMC) and/or liver biopsies was applied. Our aim was to reassess plasma and PBMCs collected during and after standard PegIFN/R therapy from individuals who became HCV RNA nonreactive by clinical testing. Of particular interest was to determine if HCV genome and its replication remain detectable during ongoing treatment with PegIFN/R when evaluated by more sensitive detection approaches. Plasma acquired before (n = 11), during (n = 25) and up to 12-88 weeks post-treatment (n = 20) from 9 patients and PBMC (n = 23) from 3 of them were reanalyzed for HCV RNA with sensitivity
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However, long-term persistence of HCV following therapy with pegylated interferon-α/ribavirin (PegIFN/R) was reported when more sensitive assays and testing of serial plasma, lymphoid cells (PBMC) and/or liver biopsies was applied. Our aim was to reassess plasma and PBMCs collected during and after standard PegIFN/R therapy from individuals who became HCV RNA nonreactive by clinical testing. Of particular interest was to determine if HCV genome and its replication remain detectable during ongoing treatment with PegIFN/R when evaluated by more sensitive detection approaches. Plasma acquired before (n = 11), during (n = 25) and up to 12-88 weeks post-treatment (n = 20) from 9 patients and PBMC (n = 23) from 3 of them were reanalyzed for HCV RNA with sensitivity &lt;2 IU/mL. Clone sequencing of the HCV 5'-untranslated region from plasma and PBMCs was done in 2 patients. 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However, long-term persistence of HCV following therapy with pegylated interferon-α/ribavirin (PegIFN/R) was reported when more sensitive assays and testing of serial plasma, lymphoid cells (PBMC) and/or liver biopsies was applied. Our aim was to reassess plasma and PBMCs collected during and after standard PegIFN/R therapy from individuals who became HCV RNA nonreactive by clinical testing. Of particular interest was to determine if HCV genome and its replication remain detectable during ongoing treatment with PegIFN/R when evaluated by more sensitive detection approaches. Plasma acquired before (n = 11), during (n = 25) and up to 12-88 weeks post-treatment (n = 20) from 9 patients and PBMC (n = 23) from 3 of them were reanalyzed for HCV RNA with sensitivity &lt;2 IU/mL. Clone sequencing of the HCV 5'-untranslated region from plasma and PBMCs was done in 2 patients. HCV RNA was detected in 17/25 (68%) plasma and 8/10 (80%) PBMC samples collected from 8 of 9 patients during therapy, although only 5.4% plasma samples were positive by clinical assays. Among post-treatment HCV RNA-negative plasma samples, 9 of 20 (45.3%) were HCV reactive for up to 59 weeks post-treatment. Molecularly evident replication was found in 6/12 (50%) among PBMC reactive for virus RNA positive strand collected during or after treatment. Pre-treatment point mutations persisted in plasma and/or PBMC throughout therapy and follow-up. Therefore, HCV is not completely cleared during ongoing administration of PegIFN/R otherwise capable of ceasing progression of CHC and virus commonly persists at levels not detectable by the current clinical testing. The findings suggest the need for continued evaluation even after patients achieve undetectable HCV RNA post-treatment.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24278242</pmid><doi>10.1371/journal.pone.0080078</doi><oa>free_for_read</oa></addata></record>
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1932-6203
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source Open Access: PubMed Central; Publicly Available Content Database (Proquest) (PQ_SDU_P3)
subjects Antiviral Agents - administration & dosage
Antiviral Agents - therapeutic use
Biopsy
Female
Gastroenterology
Gene sequencing
Genomes
Health sciences
Hepacivirus - genetics
Hepacivirus - isolation & purification
Hepacivirus - physiology
Hepatitis
Hepatitis C
Hepatitis C, Chronic - drug therapy
Hepatitis C, Chronic - virology
Hepatology
Humans
Infections
Interferon
Interferon-alpha - administration & dosage
Interferon-alpha - therapeutic use
Limit of Detection
Liver
Lymphoid cells
Male
Medicine
Mutation
Patients
Peripheral blood mononuclear cells
Polyethylene Glycols - administration & dosage
Polyethylene Glycols - therapeutic use
Recombinant Proteins - administration & dosage
Recombinant Proteins - therapeutic use
Replication
Ribavirin
Ribavirin - administration & dosage
Ribavirin - therapeutic use
Ribonucleic acid
RNA
RNA viruses
RNA, Viral - blood
Therapy
Virology
Virus Replication
Viruses
title Persistence of hepatitis C virus during and after otherwise clinically successful treatment of chronic hepatitis C with standard pegylated interferon α-2b and ribavirin therapy
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