Treatment with direct-acting antivirals improves peripheral insulin sensitivity in non-diabetic, lean chronic hepatitis C patients
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| Název: | Treatment with direct-acting antivirals improves peripheral insulin sensitivity in non-diabetic, lean chronic hepatitis C patients |
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| Autoři: | Gastaldi, Giacomo Gianni Giuseppe, Rocha Gomes, Diana Bianca, Schneiter, Philippe, Montet, Xavier Cédric Rodolphe, Tappy, Luc, Clement, Sophie, Negro, Francesco |
| Zdroj: | PLoS One PLoS ONE, Vol 14, Iss 6, p e0217751 (2019) PLOS ONE, Vol. 14, No 6 (2019) P. e0217751 PloS one, vol. 14, no. 6, pp. e0217751 |
| Informace o vydavateli: | Public Library of Science (PLoS), 2019. |
| Rok vydání: | 2019 |
| Témata: | Adult, Male, 0301 basic medicine, Adenine Nucleotides/pharmacology, Swine, Science, ddc:616.07, 616.07, Lymphocyte Activation, ddc:616.0757, Antiviral Agents, Young Adult, 03 medical and health sciences, Lymphocytes/immunology/metabolism, Thinness, Diabetes Mellitus, Animals, Cyclic AMP/metabolism, Humans, Antiviral Agents/therapeutic use, Cytokines/blood, Diabetes Mellitus/pathology, Female, Glucose/metabolism, Hepatitis C, Chronic/blood, Hepatitis C, Chronic/drug therapy, Insulin Resistance, Middle Aged, Thinness/complications, Cyclooxygenase Inhibitors, Uridine/metabolism, ddc:616, 0303 health sciences, 616.0757, Biological Transport/drug effects, Hepatitis C, Chronic, Phytohemagglutinins/pharmacology, 3. Good health, Glucose, Medicine, Cytokines, Prostaglandins E/metabolism, Research Article |
| Popis: | Hepatitis C virus (HCV) infection is associated with insulin resistance, which may lead to type 2 diabetes and its complications. Although HCV infects mainly hepatocytes, it may impair insulin sensitivity at the level of uninfected extrahepatic tissues (muscles and adipose tissue). The aim of this study was to assess whether an interferon-free, antiviral therapy may improve HCV-associated hepatic vs. peripheral insulin sensitivity.In a single-arm exploratory trial, 17 non-diabetic, lean chronic hepatitis C patients without significant fibrosis were enrolled, and 12 completed the study. Patients were treated with a combination of sofosbuvir/ledipasvir and ribavirin for 12 weeks, and were submitted to a 2-step euglycemic hyperinsulinemic clamp with tracers, together with indirect calorimetry measurement, to measure insulin sensitivity before and after 6 weeks of antivirals. A panel of 27 metabolically active cytokines was analyzed at baseline and after therapy-induced viral suppression.Clamp analysis performed in 12 patients who achieved complete viral suppression after 6 weeks of therapy showed a significant improvement of the peripheral insulin sensitivity (13.1% [4.6-36.7], p = 0.003), whereas no difference was observed neither in the endogenous glucose production, in lipolysis suppression nor in substrate oxidation. A distinct subset of hepatokines, potentially involved in liver-to-periphery crosstalk, was modified by the antiviral therapy.Pharmacological inhibition of HCV improves peripheral (but not hepatic) insulin sensitivity in non-diabetic, lean individuals with chronic hepatitis C without significant fibrosis. |
| Druh dokumentu: | Article Other literature type |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0217751 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/31170218 https://doaj.org/article/9ecc0c982bd745d5b7802daf85bccf11 https://ui.adsabs.harvard.edu/abs/2019PLoSO..1417751G/abstract https://archive-ouverte.unige.ch/unige:123540 https://archive-ouverte.unige.ch/unige:123540/ATTACHMENT01 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553748 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553748 https://www.ncbi.nlm.nih.gov/pubmed/31170218 https://archive-ouverte.unige.ch/unige:123540 https://serval.unil.ch/notice/serval:BIB_B58EBE032B57 https://serval.unil.ch/resource/serval:BIB_B58EBE032B57.P001/REF.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_B58EBE032B578 |
| Rights: | CC BY |
| Přístupové číslo: | edsair.doi.dedup.....a407c62b8f3a34827e4bf95b5c3edf0b |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Hepatitis C virus (HCV) infection is associated with insulin resistance, which may lead to type 2 diabetes and its complications. Although HCV infects mainly hepatocytes, it may impair insulin sensitivity at the level of uninfected extrahepatic tissues (muscles and adipose tissue). The aim of this study was to assess whether an interferon-free, antiviral therapy may improve HCV-associated hepatic vs. peripheral insulin sensitivity.In a single-arm exploratory trial, 17 non-diabetic, lean chronic hepatitis C patients without significant fibrosis were enrolled, and 12 completed the study. Patients were treated with a combination of sofosbuvir/ledipasvir and ribavirin for 12 weeks, and were submitted to a 2-step euglycemic hyperinsulinemic clamp with tracers, together with indirect calorimetry measurement, to measure insulin sensitivity before and after 6 weeks of antivirals. A panel of 27 metabolically active cytokines was analyzed at baseline and after therapy-induced viral suppression.Clamp analysis performed in 12 patients who achieved complete viral suppression after 6 weeks of therapy showed a significant improvement of the peripheral insulin sensitivity (13.1% [4.6-36.7], p = 0.003), whereas no difference was observed neither in the endogenous glucose production, in lipolysis suppression nor in substrate oxidation. A distinct subset of hepatokines, potentially involved in liver-to-periphery crosstalk, was modified by the antiviral therapy.Pharmacological inhibition of HCV improves peripheral (but not hepatic) insulin sensitivity in non-diabetic, lean individuals with chronic hepatitis C without significant fibrosis. |
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| ISSN: | 19326203 |
| DOI: | 10.1371/journal.pone.0217751 |