Before Direct-Acting Antivirals for Hepatitis C Virus : Evaluation of Core Protein R70Q and L/C91M Substitutions in Chronically Infected Brazilian Patients Unresponsive to IFN and/or RBV
Although chronic hepatitis C has been effectively treated with direct-acting antivirals (DAAs), the use of conventional therapy with peg-interferon (Peg-IFN) or (predominantly) ribavirin (RBV), remains widespread. R70Q/H and L/C91M amino acid substitutions in the hepatitis C virus (HCV) core protein may modulate responses to IFN and/or RBV, and are associated with cirrhosis, hepatocellular carcinoma (HCC), insulin resistance, and liver steatosis. We evaluated the R70Q/H and L/C91M substitutions, clinical and epidemiological profiles, and risk factors of Brazilian patients chronically infected with HCV subgenotypes 1a and 1b (HCV-GT1a and HCV-GT1b) unresponsive to IFN and/or RBV therapy. Sequencing and pyrosequencing analyses and sociodemographic and clinical predictive variables were used to assess the relationship between R70Q/H and L/C91M substitutions. Leukocyte counts, ALT levels, and ALT/AST ratios were significantly reduced in treated individuals, but more of these patients had advanced fibrosis and cirrhosis. L91M was more prevalent (19.7%), occurring only in HCV-GT1b, followed by R70Q/P (11.5%) and R70P (1.4%). R70Q/P exhibited higher mean AST, ALT, and GGT values, whereas L91M showed higher mean GGT values. Pyrosequencing of the L91M position revealed mutant subpopulations in 43.75% of samples.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Viruses - 15(2023), 1 vom: 09. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Campos, Letícia Bomfim [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 26.01.2023 Date Revised 16.11.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/v15010187 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM351909419 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM351909419 | ||
| 003 | DE-627 | ||
| 005 | 20231226052522.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/v15010187 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1172.xml |
| 035 | |a (DE-627)NLM351909419 | ||
| 035 | |a (NLM)36680226 | ||
| 035 | |a (PII)187 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Campos, Letícia Bomfim |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Before Direct-Acting Antivirals for Hepatitis C Virus |b Evaluation of Core Protein R70Q and L/C91M Substitutions in Chronically Infected Brazilian Patients Unresponsive to IFN and/or RBV |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 26.01.2023 | ||
| 500 | |a Date Revised 16.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Although chronic hepatitis C has been effectively treated with direct-acting antivirals (DAAs), the use of conventional therapy with peg-interferon (Peg-IFN) or (predominantly) ribavirin (RBV), remains widespread. R70Q/H and L/C91M amino acid substitutions in the hepatitis C virus (HCV) core protein may modulate responses to IFN and/or RBV, and are associated with cirrhosis, hepatocellular carcinoma (HCC), insulin resistance, and liver steatosis. We evaluated the R70Q/H and L/C91M substitutions, clinical and epidemiological profiles, and risk factors of Brazilian patients chronically infected with HCV subgenotypes 1a and 1b (HCV-GT1a and HCV-GT1b) unresponsive to IFN and/or RBV therapy. Sequencing and pyrosequencing analyses and sociodemographic and clinical predictive variables were used to assess the relationship between R70Q/H and L/C91M substitutions. Leukocyte counts, ALT levels, and ALT/AST ratios were significantly reduced in treated individuals, but more of these patients had advanced fibrosis and cirrhosis. L91M was more prevalent (19.7%), occurring only in HCV-GT1b, followed by R70Q/P (11.5%) and R70P (1.4%). R70Q/P exhibited higher mean AST, ALT, and GGT values, whereas L91M showed higher mean GGT values. Pyrosequencing of the L91M position revealed mutant subpopulations in 43.75% of samples | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a amino acid substitutions R70Q/H and L/C91M | |
| 650 | 4 | |a chronic hepatitis C | |
| 650 | 4 | |a clinical and epidemiological profiles | |
| 650 | 4 | |a host risk factors | |
| 650 | 4 | |a non-sustained viral response | |
| 650 | 4 | |a pyrosequencing | |
| 650 | 4 | |a subpopulations | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Interferon-alpha |2 NLM | |
| 650 | 7 | |a Polyethylene Glycols |2 NLM | |
| 650 | 7 | |a 3WJQ0SDW1A |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a Ribavirin |2 NLM | |
| 650 | 7 | |a 49717AWG6K |2 NLM | |
| 700 | 1 | |a de Almeida, Nathália Alves Araújo |e verfasserin |4 aut | |
| 700 | 1 | |a de Santana, Catarina Góis |e verfasserin |4 aut | |
| 700 | 1 | |a Barbosa, Evorah Nascimento Pereira |e verfasserin |4 aut | |
| 700 | 1 | |a Horta, Marco Aurelio Pereira |e verfasserin |4 aut | |
| 700 | 1 | |a Amendola Pires, Márcia |e verfasserin |4 aut | |
| 700 | 1 | |a Brandão Mello, Carlos Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a de Paula, Vanessa Salete |e verfasserin |4 aut | |
| 700 | 1 | |a de Barros, José Júnior França |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Viruses |d 2009 |g 15(2023), 1 vom: 09. Jan. |w (DE-627)NLM192382764 |x 1999-4915 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2023 |g number:1 |g day:09 |g month:01 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/v15010187 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2023 |e 1 |b 09 |c 01 | ||