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Davis J, Umeh U, Saba R. Treatment of SARS-CoV-2 (COVID-19): A safety perspective. World J Pharmacol 2021; 10:1-32. [DOI: 10.5497/wjp.v10.i1.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 08/22/2021] [Accepted: 09/17/2021] [Indexed: 02/06/2023] Open
Abstract
The goal of this review is to report a balanced perspective of current evidence for efficacy of treatments for coronavirus disease 2019 (COVID-19) against the historical safety of these treatments as of May 2021. We preselected therapies of interest for COVID-19 based on national guidelines and modified over time. We searched PubMed and Medline for these specific COVID-19 treatments and data related to their efficacy. We also searched for prior randomized controlled trials of each therapy to assess adverse effects, and we obtained the Food and Drug Administration Approval label for this information. Several drugs have been approved for the treatment of COVID-19, and many more are under study. This includes dexamethasone, remdesivir, hydroxychloroquine/chloroquine, lopinvir/ritonavir, interferon or interleukin inhibitors, convalescent plasma and several vitamins and minerals. The strongest evidence for benefit is mortality benefit with dexamethasone in patients with COVID-19 and hypoxemia, although there is a signal of harm if this is started too early. There are several other promising therapies, like interleukin inhibitors and ivermectin. Hydroxychloroquine/chloroquine, lopinvir/ritonavir, and convalescent plasma do not have enough evidence of benefit to outweigh the known risks of these drugs.
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Affiliation(s)
- Joshua Davis
- Department of Emergency Medicine, Vituity, Wichita, KS 67214, United States
| | - Ugochukwu Umeh
- College of Medicine, Medical University of Lublin, Lublin 20-093, Poland
| | - Rand Saba
- Department of Surgery, Ascension Providence Hospital, Southfield, MI 48075, United States
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Parlati L, Hollande C, Pol S. Treatment of hepatitis C virus infection. Clin Res Hepatol Gastroenterol 2021; 45:101578. [PMID: 33272891 DOI: 10.1016/j.clinre.2020.11.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 11/06/2020] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus infection affects 71 million people worldwide. It is at the origin of a multi-organ disease associating hepatic manifestations, cryoglobulinemic vasculitis and general manifestations linked to chronic inflammation (diabetes, cardio-, reno- or cerebrovascular manifestations, extra-hepatic cancers including non-Hodgkin's lymphoma). The significant morbidity and mortality linked to the hepatitis C virus therefore justify its screening and access to treatments which have increased considerably over the past two decades. Understanding the replicative cycle of the hepatitis C virus has enabled the development of direct HCV-specific antivirals targeting viral proteins (NS3/4A protease, NS5B polymerase and the multifunctional NS5A replication complex). The combination of two to three specific inhibitors often co-formulated in a capsule, without pegylated interferon and most often without ribavirin, allows high antiviral efficacy (more than 97% cure) for a treatment duration of 8-12 weeks with satisfactory tolerance. HCV infection is the only chronic viral infection that can be cured and the hepatic or extrahepatic manifestations are mainly reversible. This underlines the importance of strengthening screening and access to care policies in order to achieve the elimination of viral infection C in the short term, in 2030, as expected from the program of the World Health Organization. If this elimination is possible in some countries (Iceland, France, Germany …), it seems compromised in others where prevention (USA), screening and/or access to care are still insufficient (Sub-Saharan Africa, Russia…).
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Affiliation(s)
- Lucia Parlati
- Département d'Hépatologie, APHP, Hôpital Cochin, Paris, France
| | - Clémence Hollande
- Département d'Hépatologie, APHP, Hôpital Cochin, Paris, France; Université de Paris, Inserm U-1223 et Immunité des Cellules Dendritiques, Institut Pasteur, Paris, France
| | - Stanislas Pol
- Département d'Hépatologie, APHP, Hôpital Cochin, Paris, France; Université de Paris, Inserm U-1223 et Immunité des Cellules Dendritiques, Institut Pasteur, Paris, France.
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Pol S, Lagaye S. The remarkable history of the hepatitis C virus. Microbes Infect 2019; 21:263-270. [PMID: 31295571 DOI: 10.1016/j.micinf.2019.06.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 03/25/2019] [Accepted: 04/01/2019] [Indexed: 12/23/2022]
Abstract
The infection with the hepatitis C virus (HCV) is an example of the translational research success. The reciprocal interactions between clinicians and scientists have allowed in 30 years the initiation of empirical treatments by interferon, the discovery of the virus, the development of serological and virological tools for diagnosis but also for prognosis (the non-invasive biochemical or morphological fibrosis tests, the predictors of the specific immune response including genetic IL28B polymorphisms). Finally, well-tolerated and effective treatments with oral antivirals inhibiting HCV non-structural viral proteins involved in viral replication have been marketed this last decade, allowing the cure of all infected subjects. HCV chronic infection, which is a public health issue, is a hepatic disease which may lead to a cirrhosis and an hepatocellular carcinoma (HCC) but also a systemic disease with extra-hepatic manifestations either associated with a cryoglobulinemic vasculitis or chronic inflammation. The HCV infection is the only chronic viral infection which may be cured: the so-called sustained virologic response, defined by undetectable HCV RNA 12 weeks after the end of the treatment, significantly reduces the risk of morbidity and mortality associated with hepatic and extra-hepatic manifestations which are mainly reversible. The history of HCV ends with the pangenotypic efficacy of the multiple combinations, easy to use for 8-12 weeks with one to three pills per day and little problems of tolerance. This explains the short 30 years from the virus discovery to the viral hepatitis elimination policy proposed by the World Health Organization (WHO) in 2016.
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Affiliation(s)
- Stanislas Pol
- Université Paris Descartes, Paris, France; Département d'Hépatologie, Hôpital Cochin, APHP, Paris, France; INSERM UMS-20, Institut Pasteur, Paris, France; Immunobiologie des Cellules Dendritiques, Institut Pasteur, Paris, France; INSERM U1223, Institut Pasteur, Paris, France.
| | - Sylvie Lagaye
- Immunobiologie des Cellules Dendritiques, Institut Pasteur, Paris, France; INSERM U1223, Institut Pasteur, Paris, France.
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Pol S, Lagaye S. The remarkable history of the hepatitis C virus. Genes Immun 2019; 20:436-446. [PMID: 31019253 DOI: 10.1038/s41435-019-0066-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 03/25/2019] [Accepted: 04/01/2019] [Indexed: 02/06/2023]
Abstract
The infection with the hepatitis C virus (HCV) is an example of the translational research success. The reciprocal interactions between clinicians and scientists have allowed in 30 years the initiation of empirical treatments by interferon, the discovery of the virus, the development of serological and virological tools for diagnosis but also for prognosis (the non-invasive biochemical or morphological fibrosis tests, the predictors of the specific immune response including genetic IL28B polymorphisms). Finally, well-tolerated and effective treatments with oral antivirals inhibiting HCV non-structural viral proteins involved in viral replication have been marketed this last decade, allowing the cure of all infected subjects. HCV chronic infection, which is a public health issue, is a hepatic disease, which may lead to a cirrhosis and an hepatocellular carcinoma (HCC) but also a systemic disease with extra-hepatic manifestations either associated with a cryoglobulinemic vasculitis or chronic inflammation. The HCV infection is the only chronic viral infection, which may be cured: the so-called sustained virologic response, defined by undetectable HCV RNA 12 weeks after the end of the treatment, significantly reduces the risk of morbidity and mortality associated with hepatic and extra-hepatic manifestations, which are mainly reversible. The history of HCV ends with the pangenotypic efficacy of the multiple combinations, easy to use for 8-12 weeks with one to three pills per day and little problems of tolerance. This explains the short 30 years from the virus discovery to the viral hepatitis elimination policy proposed by the World Health Organization (WHO) in 2016.
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Affiliation(s)
- Stanislas Pol
- Université Paris Descartes, Paris, France. .,Département d'Hépatologie, Hôpital Cochin, APHP, Paris, France. .,INSERM UMS-20, Institut Pasteur, Paris, France. .,Immunobiologie des Cellules Dendritiques, Institut Pasteur, Paris, France. .,INSERM U1223, Institut Pasteur, Paris, France.
| | - Sylvie Lagaye
- Immunobiologie des Cellules Dendritiques, Institut Pasteur, Paris, France. .,INSERM U1223, Institut Pasteur, Paris, France.
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Carrat F, Fontaine H, Dorival C, Simony M, Diallo A, Hezode C, De Ledinghen V, Larrey D, Haour G, Bronowicki JP, Zoulim F, Asselah T, Marcellin P, Thabut D, Leroy V, Tran A, Habersetzer F, Samuel D, Guyader D, Chazouilleres O, Mathurin P, Metivier S, Alric L, Riachi G, Gournay J, Abergel A, Cales P, Ganne N, Loustaud-Ratti V, D'Alteroche L, Causse X, Geist C, Minello A, Rosa I, Gelu-Simeon M, Portal I, Raffi F, Bourliere M, Pol S. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study. Lancet 2019; 393:1453-1464. [PMID: 30765123 DOI: 10.1016/s0140-6736(18)32111-1] [Citation(s) in RCA: 458] [Impact Index Per Article: 76.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 08/12/2018] [Accepted: 08/28/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort. METHODS We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458. FINDINGS Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0-40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2·77, 95% CI 2·07-3·71) and decompensated cirrhosis (3·83, 2·29-6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33-0·70) and hepatocellular carcinoma (0·66, 0·46-0·93), and was not associated with decompensated cirrhosis (1·14, 0·57-2·27). INTERPRETATION Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection. FUNDING INSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche.
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Affiliation(s)
- Fabrice Carrat
- Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Unité de Santé Publique, Paris, France.
| | | | - Céline Dorival
- Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
| | - Mélanie Simony
- ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), Unit for Basic and Clinical Research on Viral Hepatitis, Paris, France
| | - Alpha Diallo
- Clinical Trial Safety and Public Health, Paris, France
| | - Christophe Hezode
- Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France
| | - Victor De Ledinghen
- Hepatology Unit Hôpital Haut-Lévêque, Pessac, and INSERM U1053, Université Bordeaux Segalen, Bordeaux, France
| | - Dominique Larrey
- Liver Unit, Institute for Regenerative Medicine and Biotherapy-INSERM 1183, Hôpital Saint Eloi, Montpellier, France
| | - Georges Haour
- Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
| | - Jean-Pierre Bronowicki
- INSERM U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Fabien Zoulim
- Department of Hepatology, Hospices Civils de Lyon, INSERM U1052, Université de Lyon, Lyon, France
| | - Tarik Asselah
- INSERM, Hepatology, Hospital Beaujon, Centre de Recherche sur l'Inflammation (CRI), University Paris Diderot, Clichy, France
| | - Patrick Marcellin
- INSERM, Hepatology, Hospital Beaujon, Centre de Recherche sur l'Inflammation (CRI), University Paris Diderot, Clichy, France
| | - Dominique Thabut
- Sorbonne Université, Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié-Salpétrière, AP-HP, INSERM Unité Mixte de Recherche (UMR)-S938, Paris, France
| | - Vincent Leroy
- Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire (CHU), INSERM U1209, Université Grenoble Alpes, Grenoble, France
| | - Albert Tran
- Digestive Centre, CHU de Nice, INSERM U1065-8, Nice, France
| | - François Habersetzer
- Centre d'Investigation Clinique (CIC), INSERM 1110, and Pôle Hépato-digestif des Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Université Paris-Sud, UMR-S1193, Université Paris-Saclay, and Hepatinov, Villejuif, France
| | - Dominique Guyader
- CHU de Rennes, Service d'Hépatologie, University Rennes 1, L'Institut National de la Recherche Agronomique (INRA), INSERM, Institut NUMECAN (Nutrition, Métabolismes et Cancer), UMR-A1341, and UMR-S1241, Rennes, France
| | - Olivier Chazouilleres
- Department of Hepatology, Hôpital Saint-Antoine, AP-HP, Sorbonne Université, Paris, France
| | - Philippe Mathurin
- Service des Maladies de l'Appareil Digestif, Université Lille 2, and INSERM U795, Lille, France
| | - Sophie Metivier
- Department of Hepatology and Gastroenterology, CHU Purpan, Toulouse, France
| | - Laurent Alric
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, Toulouse, France; UMR 152 PHARMA-DEV (Pharmacochimie et Biologie pour le Développement), Institut de Recherche pour le Développement (IRD)-Université Toulouse 3, Toulouse, France
| | - Ghassan Riachi
- Department of Hepatology and Gastroenterology, CHU Charles Nicolle, Rouen, France
| | - Jérôme Gournay
- Gastroenterology and Hepatology Department, Institut des Maladies de l'Appareil Digestif, University Hospital Nantes, Nantes, France
| | - Armand Abergel
- Department of Digestive and Hepatobiliary Diseases, Estaing University Hospital, and UMR Auvergne University, Centre National de la Recherche Scientifique (CNRS) 6284 ISIT (Image Sciences for Innovations Techniques), Clermont-Ferrand, France
| | - Paul Cales
- Hepatology Department, University Hospital, Angers, France; Hémodynamique, Interaction Fibrose et Invasivité Tumorales Hépatiques (HIFIH) Laboratory, Bretagne Loire University, Angers, France
| | - Nathalie Ganne
- Department of Hepatology, Hôpitaux Universitaires Paris Seine-Saint-Denis, site Jean Verdier, AP-HP, Bondy, France; Université Paris 13, Sorbonne Paris Cité et INSERM UMR 1162, Paris, France
| | - Véronique Loustaud-Ratti
- Department of Hepatology and Gastroenterology, CHU Limoges, INSERM U1248, Université de Limoges, Limoges, France
| | - Louis D'Alteroche
- Unit of Hepatology, Hépatogastroentérologie, CHU Trousseau, Tours, France
| | - Xavier Causse
- Department of Hepatology and Gastroenterology, Centre Hospitalier Régional (CHR), Orléans, France
| | - Claire Geist
- Department of Hepatology and Gastroenterology, CHR, Metz, France
| | - Anne Minello
- Department of Hepatology and Gastroenterology, University Hospital Dijon, INSERM UMR 1231, Dijon, France
| | - Isabelle Rosa
- Department of Hepatology and Gastroenterology, Centre Hospitalier Intercommunal, Créteil, France
| | - Moana Gelu-Simeon
- Service d'Hépato-Gastroentérologie, CHU de Pointe-à-Pitre, and Faculté de Médecine, Université des Antilles, Pointe-à-Pitre, Guadeloupe, France; INSERM, UMR-S1085, Institut de Recherche en Santé, Environnement et Travail (IRSET), Rennes, France
| | - Isabelle Portal
- Service d'Hépato-Gastroentérologie, Hôpital de la Timone, Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France
| | - François Raffi
- Department of Infectious Diseases, Hotel-Dieu Hospital, INSERM CIC 1413, Nantes University Hospital, Nantes, France
| | - Marc Bourliere
- Department of Hepatology and Gastroenterology, Hôpital Saint Joseph, Marseille, France
| | - Stanislas Pol
- AP-HP, Hôpital Cochin, Unité d'Hépatologie, Paris, France; Université Paris Descartes, INSERM U1223 and USM-20, Institut Pasteur, Paris, France
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Parlati L, Sirmai L, Dupuy CA, Glotz D, Pol S. Evidence of HCV recovery after therapy of hepatitis C virus infection by direct acting antivirals. Clin Res Hepatol Gastroenterol 2019; 43:e18-e19. [PMID: 30293896 DOI: 10.1016/j.clinre.2018.09.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 09/05/2018] [Indexed: 02/04/2023]
Affiliation(s)
- Lucia Parlati
- Université Paris Descartes, 75006 Paris, France; Hepatology Department, 75014 Paris, France; Cochin hospital, AP-HP, UPMC, 75014 Paris, France.
| | - Laura Sirmai
- Université Paris Descartes, 75006 Paris, France; Hepatology Department, 75014 Paris, France; Cochin hospital, AP-HP, UPMC, 75014 Paris, France
| | - Claire-Antoinette Dupuy
- Nephrology Department, 75010 Paris, France; Saint-Louis hospital, AP-HP, Inserm U1660, 75010 Paris, France
| | - Denis Glotz
- Nephrology Department, 75010 Paris, France; Saint-Louis hospital, AP-HP, Inserm U1660, 75010 Paris, France
| | - Stanislas Pol
- Université Paris Descartes, 75006 Paris, France; Hepatology Department, 75014 Paris, France; Cochin hospital, AP-HP, UPMC, 75014 Paris, France; UMS-20, Institut Pasteur, 75015 Paris, France; Center for Translational Science, Institut Pasteur, 75015 Paris, France
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Abstract
Interferon-free regimens combine different second-wave direct-acting antiviral agents (DAAs), which target the main viral proteins involved in the replication cycle of hepatitis C virus (HCV): NS3/4A protease inhibitors (simeprevir or paritaprevir boosted by ritonavir), NS5B nucleos(t)idic (sofosbuvir) and nonnucleos(t)idic (dasabuvir) polymerase inhibitors, NS5A replication complex inhibitors (daclatasvir, ledipasvir, elbasvir, velpatasvir). Combinations of two or three DAAs, given for 8-24 weeks reach sustained virology response (SVR) rates greater than 90% with good tolerance. SVR rates and safety are similar in clinical trials and in real life, usually higher than 95% in the per-protocol analysis. Next-generation DAAs are now expected. To be competitive, these new combinations need to prove their added value regarding the pill burden, the reduced duration of treatment, the drug-drug interaction profile and safety. Zepatier is a fixed-dose combination product coformulating MK-5172 [grazoprevir (GZR), 100 mg QD] and MK-8742 [elbasvir or (EBR) 50 mg QD]: it combines highly potent inhibitors of the HCV NS3/4A protease and NS5A replication complex, respectively. This review provides a summary of the main evidence available for the use of GZR/EBR and highlights the strength of this combination.
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Affiliation(s)
- Anaïs Vallet-Pichard
- Université Paris Descartes, Hepatology Department Cochin Hospital, APHP, INSERM U1213 and USM-20 Institut Pasteur, Paris, France
| | - Stanislas Pol
- Département d’Hépatologie, Hôpital Cochin, AP-HP, 27 rue du faubourg Saint-Jacques, 75679 Paris Cedex 14, France
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Pol S, Corouge M. Treatment of hepatitis C: perspectives. Med Mal Infect 2014; 44:449-54. [PMID: 25174659 DOI: 10.1016/j.medmal.2014.07.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Revised: 07/15/2014] [Accepted: 07/22/2014] [Indexed: 12/20/2022]
Abstract
The treatment of hepatitis C virus (HCV) infection has significantly improved in the last 2 decades. The association of pegylated interferon alfa and ribavirin (PR) has allowed a sustained virologic response (SVR) for nearly 15 years i.e. a viral cure of the infection for 45% of genotype 1-, 65% of genotype 4-, 70% of genotype 3- and around 85% of genotype 2-infected patients. A better understanding of the HCV life cycle has led to the development of direct-acting antiviral drugs (DAAs) targeted against viral proteins (NS3/4A protease, NS5B polymerase with nucleotide and non-nucleotide inhibitors, NS5A viral replication complex). The combination of first-generation protease inhibitors with PR demonstrated a high antiviral effectiveness (75% of SVR but restricted to genotypes 1) with substantial adverse effects for the first-generation protease inhibitors, which obtained market approval in 2011 (telaprevir and boceprevir), recommendations for use in HCV monoinfected patients in 2012, and in HCV/HIV coinfected in 2013. Then, the combination of second-generation protease inhibitors with PR increased SVR rates from 75 to 90%, while reducing treatment duration, adverse effects, and the number of pills. The next step will be using an interferon and ribavirin-free combination of DAAs; it should become the standard of care in 2015. These excellent results in "easy-to-treat" patients and in small populations in the first studies were confirmed in phase III studies and in "difficult-to-treat" patients (treatment-- especially protease inhibitors--previously treated patients, cirrhotic patients, liver and renal transplant patients, HIV coinfected patients, and multi-drug treated patients, at increased risk of drug interaction). The high antiviral potency of these new combinations has changed the definition of "difficult-to-treat patients". These unique achievements in drug history make any previous publication on hepatitis C treatment obsolete.
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Affiliation(s)
- S Pol
- Université Paris Descartes, AP-HP, Unité d'Hépatologie, Hôpital Cochin, INSERM U-1016, Institut Cochin, Paris, France.
| | - M Corouge
- Université Paris Descartes, AP-HP, Unité d'Hépatologie, Hôpital Cochin, INSERM U-1016, Institut Cochin, Paris, France
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Kong Y, Wang X, Shang Y, Schroder PM, Liang W, Ling X, Guo Z, He X. Efficacy and tolerability of telaprevir for chronic hepatitis virus C genotype 1 infection: a meta-analysis. PLoS One 2012; 7:e52158. [PMID: 23284915 PMCID: PMC3527389 DOI: 10.1371/journal.pone.0052158] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2011] [Accepted: 11/15/2012] [Indexed: 01/22/2023] Open
Abstract
Background Chronic hepatitis C virus (HCV) infection is one of the leading causes of hepatic cirrhosis and hepatocellular carcinoma, and HCV genotype 1 is the most prevalent genotype and is resistant to current standard therapy. We performed this meta-analysis to evaluate the efficacy and safety of telaprevir-based therapy for chronic HCV genotype 1 infection. Methods We included randomized controlled trials with no year or language restriction. All data were analyzed using a random-effects model by Review Manager v5.0. The primary outcome was the proportion of patients achieving sustained virologic response (SVR), and the secondary outcomes were HCV relapse rate, incidence of severe adverse events (SAEs), and discontinuation due to adverse events. Results The proportion of achieving SVR was significantly higher in the telaprevir group (odds ratio [OR] = 3.40 [1.92, 6.00], P<0.0001; I2 = 87%) regardless of a patients’ previous treatment status. It was also significantly higher in the 24-week and 48-week treatment groups (OR = 4.52 [2.08, 9.81], P<0.001; I2 = 85%, and OR = 4.05 [1.56, 10.56], P = 0.004; I2 = 92%, respectively), while it was comparable in the 12-week treatment group (OR = 1.32 [0.63, 2.75], P = 0.46; I2 = 35%). In addition, the HCV relapse rate was significantly reduced in the telaprevir group (OR = 0.28 [0.16, 0.49], P<0.001; I2 = 76%). However, the incidence of SAE (OR = 1.56 [1.15, 2.10], P = 0.004; I2 = 0%) and study discontinuation due to adverse events (OR = 2.24 [1.43, 3.50], P<0.001; I2 = 37%) were significantly higher in the telaprevir group. Conclusion Despite its higher incidence of SAEs and discontinuation due to adverse events, telaprevir-based therapy can increase the proportion of achieving SVR in both previously treated and untreated chronic HCV-1 infected patients.
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Affiliation(s)
- Yuan Kong
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoping Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yushu Shang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Paul M. Schroder
- Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, Ohio, United States of America
| | - Wenhua Liang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoting Ling
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhiyong Guo
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- * E-mail: (ZG); (XH)
| | - Xiaoshun He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- * E-mail: (ZG); (XH)
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Kelly DA, Haber B, González-Peralta RP, Murray KF, Jonas MM, Molleston JP, Narkewicz MR, Sinatra FR, Lang T, Lachaux A, Wirth S, Shelton M, Te HS, Pollack H, Deng W, Noviello S, Albrecht JK. Durability of sustained response shown in paediatric patients with chronic hepatitis C who were treated with interferon alfa-2b plus ribavirin. J Viral Hepat 2012; 19:263-70. [PMID: 22404724 DOI: 10.1111/j.1365-2893.2011.01544.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Long-term studies in adults indicate that sustained virologic response (SVR) after combination treatment for chronic hepatitis C (CHC) predicts long-term clearance. Although peginterferon plus ribavirin is now standard care for children with CHC, long-term follow-up studies are not yet available. This study evaluated durability of virologic response over 5 years in children previously treated with interferon alfa-2b plus ribavirin (IFN/R). Ninety-seven of 147 children with CHC, who were treated with IFN/R and completed the 6-month follow-up in two previous clinical trials, participated in this long-term follow-up study. All were assessed annually for up to 5 years; patients with SVR were assessed for durability of virologic response. Children with SVR (n = 56) and those with detectable hepatitis C virus (HCV) RNA 24-week post-treatment (n = 41) were followed for a median of 284 weeks. Overall, 70% (68/97) of patients completed the 5-year follow-up. One patient with genotype 1a CHC had SVR and relapsed at year 1 of follow-up with the same genotype. Kaplan-Meier estimate for sustained response at 5 years was 98% (95% CI: 95%, 100%). Six patients with low-positive HCV RNA levels (n = 4) or missing HCV RNA at the 24-week follow-up visit (n = 2) in the initial treatment studies had virologic response during this long-term follow-up study. Linear growth rate was impaired during treatment with rapid increases in the immediate 6 months post-treatment. Mean height percentile at the end of the 5-year follow-up was slightly less than the mean pretreatment height percentile. Five patients experienced serious adverse events; none related to study drug exposure. SVR after IFN/R predicts long-term clearance of HCV in paediatric patients; growth normalized in the majority of children during the long-term follow-up. Similar long-term results could be expected after peginterferon alfa-2b plus ribavirin treatment.
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Affiliation(s)
- D A Kelly
- Liver Unit, Birmingham Children's Hospital, Birmingham, UK.
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13
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Pol S, Fontaine H. Traitements personnalisés du virus de l’hépatite C. Presse Med 2012; 41:146-52. [DOI: 10.1016/j.lpm.2011.07.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2011] [Accepted: 07/27/2011] [Indexed: 10/14/2022] Open
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14
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Corouge M, Pol S. New treatments for chronic hepatitis C virus infection. Med Mal Infect 2011; 41:579-87. [PMID: 21764234 DOI: 10.1016/j.medmal.2011.04.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2011] [Accepted: 04/06/2011] [Indexed: 01/27/2023]
Abstract
The treatment of hepatitis C virus infection (HCV) by a combination of pegylated interferon and ribavirin, according to early viral kinetics, leads to a sustained virological response (SVR) in more than 50% of patients with chronic infection. This SVR is a complete recovery of the infection but more than 50% of genotype 1-infected patients do not achieve SVR. A better understanding of the viral cycle, and the characterization of viral enzymes which are potential targets, resulted in the development of new molecules, direct acting antivirals (DAA) targeted against HCV, either specific of genotype 1 (protease inhibitors NS3/NS4A and polymerase inhibitors NS5B) or with a wider spectrum (NS5A or entry inhibitors), and non-specific antivirals (new interferons, cyclophilin inhibitors). We describe the results of phase II and III trials which clearly demonstrated a 20 to 30% increase in the SVR rate of genotype 1-infected patients, either naïve or treatment experienced. These new drugs should be approved by the end of 2011, after a temporary approval for compassionate use in cirrhotic patients with previous relapse or partial response to the combination therapy. In the future, the main limitations of triple therapy will be safety (cutaneous rash or anemia which may be controlled), cost, compliance, viral resistance, and drug interactions that must be avoided by educating patients and physicians.
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Affiliation(s)
- M Corouge
- Unité d'hépatologie, hôpital Cochin, université Paris-Descartes, AP-HP, Inserm U-1016, 27, institut Cochin, rue du Faubourg-Saint-Jacques, 75679 Paris cedex, France
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15
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[ANRS HC 02 RIBAVIC: histo-pathological impact]. ACTA ACUST UNITED AC 2009; 33 Suppl 2:S106-9. [PMID: 19375037 DOI: 10.1016/s0399-8320(09)72449-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Anti-hepatitis C virus (HCV) therapy allows complete recovery of HCV infection (sustained virologic response). Reduction of necro-inflammation results usually in a stabilization then in a reduction of fibrosis and even of cirrhosis at least in patients with sustained virologic response. The randomised controlled RIBAVIC ANRS HC02 trial comparing the combination ribavirin-pegylated interferon-alpha2b versus ribavirine-standard interferon-alpha2b as first treatment in HIV-HCV co-infected patients allowed an analysis of 205 paired (pre- and post-treatment) biopsies using the Metavir and Ishak scores. A significant reduction was associated with sustained virologic response and non response with stabilization. There was no positive impact on fibrosis despite sustained virologic response and a deterioration in non responders. In multivariate analysis, didanosine and non response were significantly associated with fibrosis deterioration. The absence of fibrosis reversal in co-infected patients is related to virologic non response and probably to co-factors of fibrosis worsening, like the mitochondrial toxicity of antiretrovirals and especially of didanosine. In the RIBAVIC cohort (prospective followup of 383 co-infected HIV-HCV treated patients) with a median of 60 months, 21 patients (5 %) had a liver event: all were non responders and 20 had fibrosis score > or = F3. In multivariate analysis, factors associated with survival were virologic response to antiviral therapy, fibrosis score < F3 and baseline CD 4 count > 350/mL. These results emphasize the need of early therapeutic interventions to increase the rate of sustained virologic response and to decrease the rate of liver complications in the most severe patients.
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Mallet V, Gilgenkrantz H, Serpaggi J, Verkarre V, Vallet-Pichard A, Fontaine H, Pol S. Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med 2008; 149:399-403. [PMID: 18794559 DOI: 10.7326/0003-4819-149-6-200809160-00006] [Citation(s) in RCA: 223] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The effect of regression of cirrhosis in chronic hepatitis C is unknown. OBJECTIVE To evaluate the relation between regression of cirrhosis and clinical outcome in patients with chronic hepatitis C after antiviral therapy. DESIGN A cohort of patients with cirrhosis treated between 1988 and 2001. SETTING Hepatology unit of a tertiary care center in France. PATIENTS 96 patients with chronic hepatitis C and biopsy-proven cirrhosis (METAVIR score F4) who were treated with an interferon-based regimen and had at least 1 posttreatment liver biopsy. Patients were followed until November 2006. MEASUREMENTS Occurrence of a combined end point of liver-related events (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma, or liver transplantation) and death in patients with regression of cirrhosis (defined as a decrease from 4 to <or=2 METAVIR units on posttherapy liver biopsy). RESULTS The median follow-up was 118 months (interquartile range, 86 to 138 months). Eighteen patients had regression of cirrhosis. The incidence of the combined end point per 100 patient-years was 0 in patients with regression of cirrhosis and 4 in patients without regression of cirrhosis (P = 0.002, log-rank test). The transplantation-free survival rate at 10 years was 100% in patients with regression of cirrhosis and 74.2% in patients without regression of cirrhosis (P = 0.025). LIMITATIONS Selection of patients was retrospective; selection and survival biases may have influenced the estimates of the overall rate of regression of cirrhosis. The low number of patients who experienced regression of cirrhosis precludes analysis of factors that could predict regression of cirrhosis. CONCLUSION Regression of cirrhosis occurs after antiviral therapy in some patients with chronic hepatitis C. Regression is associated with decreased disease-related morbidity and improved survival.
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Affiliation(s)
- Vincent Mallet
- Université Paris Descartes; Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, INSERM U 567, Paris, France
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Cacoub P, Piroth L. Prise en charge des malades coinfectés VIH-VHC et VIH-VHB. ACTA ACUST UNITED AC 2007; 31:887-94. [DOI: 10.1016/s0399-8320(07)73986-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Pol S, Cacoub P, Pialoux G, Benhamou Y, Halfon P, Rosenthal E, Perronne C. Prise en charge des patients co-infectés VIH-VHC. ACTA ACUST UNITED AC 2007. [DOI: 10.1016/s0399-8320(07)92557-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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20
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Abstract
The estimated prevalence of hepatitis C virus (HCV) infection is 2%, representing 123 million infected individuals worldwide. HCV infection burdens public health in relation to hepatic (cirrhosis and its complications in 20% of patients) and extrahepatic (vasculitis) complications, and lessens quality of life. Major progress has been made in the last two decades for the diagnosis and treatment of HCV, including more appropriate screening strategies for HCV infection (improved sensitivity of serological and virological tests); a better evaluation of the impact of chronic HCV infection on the liver (semi-quantitative scoring systems of necro-inflammation and fibrosis on liver biopsy, non-invasive evaluation of fibrosis with biochemical markers and elastometry); and improved therapeutic regimens. This progress provides a better definition of who to treat (clinical impact or significant fibrosis); how to treat; tailoring therapies for doses and durations of the pegylated interferon plus ribavirin combination according to virological (mainly genotype and early viral kinetics, but also baseline viral load) and hosts factors (fibrosis, immune status, weight); and how to monitor efficacy and tolerance of therapy. The progress has now resulted in a 50% rate of complete HCV eradication, ranging 45 - 90% according to the genotype and especially in those patients with early viral response. New therapies, specifically HCV protease or polymerase inhibitors, in combination with pegylated interferon, or more potent and less toxic new formulations of interferons or ribavirin, will increase these encouraging results in the future.
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Affiliation(s)
- Stanislas Pol
- Hôpital Necker, APHP, Unité d'Hépatologie, 149 rue de Sèvres, 75015 Paris Cedex 15, France.
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21
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Abdel-Salam OME. Antinociceptive and behavioral effects of ribavirin in mice. Pharmacol Biochem Behav 2006; 83:230-238. [PMID: 16563475 DOI: 10.1016/j.pbb.2006.01.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2005] [Revised: 01/16/2006] [Accepted: 01/31/2006] [Indexed: 12/28/2022]
Abstract
The antinociceptive effect of ribavirin, an antiviral drug, was studied after systemic injection using several pain tests in mice. In the hot-plate test of thermal pain, capsaicin-induced chemogenic pain, formalin test and abdominal stretching assay induced by the i.p. injection of 0.6% acetic acid, ribavirin produced a dose-related reduction in nociceptive responses. The visceral antinociceptive effect of ribavirin was unaffected by co-treatment with yohimbine, atropine or theophylline, but partially reversed by naloxone. Antinociception by ribavirin was augmented by treatment with prazosin, doxazosin, propranolol, guanethidine, glibenclamide, baclofen, indomethacin or cysteamine. Further, the ribavirin induced antinociception was enhanced by D2 receptor antagonists haloperidol, sulpiride, clozapine or domperidone and by the dopamine D2 receptor agonist bromocryptine. Ribavirin did not exhibit depression-like effect, nor it influenced the effect of amitriptyline in the forced swimming test. It did not impair cognitive performance in the Morris water Maze test. The present data demonstrate that ribavirin administered via systemic route possesses visceral and thermal anti-nociceptive properties. The ribavirin analgesic effect was partially reversed by naloxone, an opioid antagonist.
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Affiliation(s)
- Omar M E Abdel-Salam
- Department of Pharmacology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt.
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22
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Cacoub P, Pol S. [Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection: epidemiology, severity and recent therapeutic strategies]. Rev Med Interne 2005; 26:267-70. [PMID: 15820560 DOI: 10.1016/j.revmed.2004.12.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2004] [Accepted: 12/01/2004] [Indexed: 10/25/2022]
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Abstract
Modulation of the immune system can be addressed through a variety of specific and non-specific approaches. Many agents of synthetic and natural origin have stimulatory, suppressive or regulatory activity. There is growing evidence that drugs or biological agents capable of modulating single pathways or targets are of limited value as immune-related therapies. Systems biology approaches are now gaining more interest compared with monovalent approaches, which can be of limited benefits with complications. This has stimulated interest in the use of 'cocktails' of immunodrugs to restore immunostasis. Botanicals are chemically complex and diverse and could therefore provide appropriate combinations of synergistic moieties useful in drug discovery. Here, the importance of traditional medicine in natural product drug discovery related to immunodrugs is reviewed.
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Affiliation(s)
- Bhushan Patwardhan
- Bioprospecting Laboratory, Interdisciplinary School of Health Sciences, University of Pune, Pune - 411007, India.
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24
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Pol S, Lebray P, Vallet-Pichard A. HIV infection and hepatic enzyme abnormalities: intricacies of the pathogenic mechanisms. Clin Infect Dis 2004; 38 Suppl 2:S65-72. [PMID: 14986277 DOI: 10.1086/381499] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Liver enzyme elevations are common in human immunodeficiency virus (HIV)-infected patients, and their diagnosis or management may be difficult because of the intricacies of the pathogenic mechanisms involved. These include hepatotoxicity related to the highly active antiretroviral therapy (HAART) regimen, idiosyncratic or immunoallergic mechanisms, and direct cytotoxicity enhanced by an underlying liver disease. Liver enzyme abnormalities may also reflect hepatitis B (HBV) or hepatitis C (HCV) infection, which each have their own risks for chronic immune-mediated liver disease (including hepatitis flare after immune reconstitution) and of direct cytotoxicity. Finally, other factors may affect liver deterioration, including alcohol-related liver disease, nonalcoholic steatohepatitis associated with metabolic syndromes (e.g., hyperlipidemia, diabetes, or being overweight) that are potentially HAART related, and use of medication or illicit drugs (e.g., methamphetamine). A better understanding of these complex interactions, including adjustments of dosages of antiretroviral drugs, will probably help in the management of HIV-infected patients with liver enzyme abnormalities.
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Affiliation(s)
- Stanislas Pol
- Unité d'Hépatologie and INSERM U-370, Hôpital Necker, Paris, France.
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Pol S, Carnot F, Nalpas B, Lagneau JL, Fontaine H, Serpaggi J, Serfaty L, Bedossa P, Bréchot C. Reversibility of hepatitis C virus-related cirrhosis. Hum Pathol 2004; 35:107-12. [PMID: 14745732 DOI: 10.1016/j.humpath.2003.08.012] [Citation(s) in RCA: 92] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The aim of this retrospective study was to determine the potential reversibility of hepatitis C virus (HCV) cirrhosis with the combined antifibrotic effects of interferon-alpha and the increasing frequency of sustained virologic response. Sixty-four HCV-cirrhotic immunocompetent patients who underwent antiviral therapies (interferon-alpha with or without ribavirin) and pretreatment and posttreatment liver biopsies were included (group 1). Resolution of cirrhosis was defined as a decrease in the fibrosis score from 4 to 2 or less by the Metavir score after blinded analysis by 2 independent pathologists. An additional group of 4 HCV-infected dialysis patients (group 2) who had received antiviral treatment, among whom 3 underwent a combined renal and liver transplantation allowing the analysis of the whole liver, was also studied. In 5 (all stage Child A) of the 64 cirrhotic patients (7.8%), the final biopsy showed only F2 to portal and periportal fibrosis with rare fibrous septa without nodule formation. Four of these 5 were complete sustained responders (negative PCR and normal ALT), and 1 was a relapser. In group 2, reversibility of cirrhosis was observed in 3 of the 4 patients and was clearly shown in 2 patients by the analysis of the whole-liver examination at the time of the hepatectomy preceding the transplantation. In conclusion, long-lasting suppression of the necroinflammatory activity of liver disease and/or antifibrogenetic effects of interferon-alpha may allow regression of cirrhosis.
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Schulman S, Kinnman N, Lindmarker P, von Sydow M. A randomized study of alpha-interferon plus ribavirin for 6 months or 12 months for the treatment of chronic hepatitis C in patients with bleeding disorders. Haemophilia 2002; 8:129-35. [PMID: 11952848 DOI: 10.1046/j.1365-2516.2002.00629.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Little is known about the optimal treatment in patients with chronic hepatitis C virus (HCV) who were infected by pooled plasma products. The aim of our study was to compare the efficacy of 6 and 12 months of combination therapy with interferon alpha-2b and ribavirin in patients with bleeding disorders and chronic HCV. In a randomized open study, 61 patients with haemophilia or von Willebrand disease received treatment with a combination of interferon alpha-2b and ribavirin at standard dosage for 6 or 12 months. Follow-up was done with analysis of HCV RNA after an additional 6 months. The prevalence of HCV genotype 1 was 67%. Overall, sustained viral response was achieved in 41%; 13 of 30 patients (43%) treated for 6 months vs. 12 of 31 patients (39%) treated for 12 months. The rate of sustained response was 22% in those with HCV genotype 1 and 80% in other genotypes (100% in genotype 2), with no difference between the treatment durations. The number of early discontinuations due to side-effects was 3 and 9, respectively. The study was stopped prematurely due to introduction of a more effective regimen, and the numbers are not sufficient to state equality. We conclude that the efficacy and safety of combination therapy against chronic hepatitis C in patients infected by pooled plasma products is similar to that observed in other populations. Six months of therapy seems sufficient in the case of HCV genotype 2. For other genotypes, the decision regarding duration of therapy has to be based on the tolerance of the individual patient together with experiences from other studies.
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Affiliation(s)
- S Schulman
- Department of Hematology, Stockholm, Sweden.
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Kao JH, Chen DS. Recent updates in hepatitis vaccination and the prevention of hepatocellular carcinoma. Int J Cancer 2002; 97:269-71. [PMID: 11774275 DOI: 10.1002/ijc.1608] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Jia-Horng Kao
- Graduate Institute of Clinical Medicine, Hepatitis Research Center, National Taiwan University Hospital and College of Medicine,7 Chung-Shan South Road, Taipei 100, Taiwan
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Pol S, Vallet-Pichard A, Fontaine H. Hepatitis C and human immune deficiency coinfection at the era of highly active antiretroviral therapy. J Viral Hepat 2002; 9:1-8. [PMID: 11851897 DOI: 10.1046/j.1365-2893.2002.00326.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Interactions between human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have been widely studied before the introduction of highly active antiretroviral therapies (HAART). We reviewed the potential impact of HAART on hepatitis C as well as the interactions between HIV and HCV therapies. Physicians should be aware of the potential risk of: (i) symptomatic liver disease in HCV-HIV-coinfected patients at the era of triple antiretroviral therapy; (ii) potential liver deterioration paralleling immune restoration; (iii) lack of impact of triple antiretroviral therapy on HCV load; and (iv) potential drug-related hepatitis which may modify the natural history of HCV-related liver disease. Liver biopsies should be performed regularly in these patients in order to identify patients with severe liver disease who require early initiation of anti-HCV therapy under close monitoring of their immune status. Treatment is, to date, based on the combination of ribavirin and interferon with an expected sustained response rate around 25%. An important unresolved issue is to better delineate the temporal place of anti-HCV and anti-HIV antiviral therapies. At least in coinfected patients with significant liver disease, namely necro-inflammatory activity and/or fibrosis >or= 2, we believe that anti-HCV therapy is the priority since it lessens the risk of drug-induced hepatitis and of hepatitis due to immune restoration.
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Affiliation(s)
- S Pol
- Unité d'Hépatologie et INSERM U-370, Hôpital Necker, Paris, France.
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Alvarez-Muñoz MT, Vences-Aviles MA, Damacio L, Vázquez-Rosales G, Torres J, González-Bravo F, Muñoz O. Hepatitis C virus RNA (HCV-RNA) in blood donors and family members seropositive for anti-HCV antibodies. Arch Med Res 2001; 32:442-5. [PMID: 11578761 DOI: 10.1016/s0188-4409(01)00307-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Non-A, non-B virus is responsible for 75-90% of all cases of blood transfusion-related hepatitis. The aim of this work was to determine hepatitis C virus RNA (HCV-RNA) in a group of blood donors and their household contacts. Serotype and genotype of the isolates were also studied. METHODS HCV antibodies were investigated in 44,588 blood donors with a commercial immunoassay. Forty-four seropositive donors and 72 household members were further studied. Quantitative analysis of viral RNA was performed with Amplicor HCV 2.0 test, while genotype was determined by INNO-LiPA test and serotype with Murex HCV test. RESULTS Among the 44,588 donors studied, 333 (0.74%) were positive for anti-HCV. Viral RNA was found in 35 (80%) of the 44 seropositive cases studied. Among the 72 household members, HCV antibodies were detected in six (8.3%) and HCV-RNA in four of these individuals. Serotype 1 and genotype 1 were the most frequent types detected (48 and 64%, respectively). The genotype in the blood donor matched that of his seropositive family member in four of six cases. CONCLUSIONS Our results suggest that intrafamilial transmission of HCV may occur and we stress the need to study household members of seropositive blood donors, as they have a high risk of infection. In this community, genotype 1 is the most prevalent type in blood donors and family members.
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Affiliation(s)
- M T Alvarez-Muñoz
- Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Centro Médico Nacional Siglo XXI (CMN-SXXI), Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.
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