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Yang C, Lv F, Yang J, Ding D, Cui L, Han Y. Surveillance and management of hepatocellular carcinoma after treatment of hepatitis C with direct-acting antiviral drugs. Ann Hepatol 2024; 30:101582. [PMID: 39276980 DOI: 10.1016/j.aohep.2024.101582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 08/11/2024] [Accepted: 08/15/2024] [Indexed: 09/17/2024]
Abstract
Hepatitis C virus (HCV) belongs to the Flaviviridae family, and is a single-stranded RNA virus with positive polarity. It is the primary cause of hepatocellular carcinoma (HCC) worldwide. The treatment of HCV has entered a new era with the advent of direct-acting antiviral drugs (DAAs) and is associated with cure rates of more than 95 %, making HCV the only curable viral disease. The successful treatment of chronic hepatitis C has greatly reduced, but not eliminated, the risk of HCC. Certain individuals, especially those with cirrhosis already present, remain vulnerable to HCC after achieving a sustained virological response (SVR). This article systematically reviews the recent studies on the risk and mechanisms of HCC development after HCV viral cure, the screening and predictive value of biological markers, and patient surveillance. Factors such as older age, diabetes, hepatic fat accumulation, alcohol use, and lack of fibrosis reversal are linked to increased HCC risk after HCV cure. The mechanism of HCC development after DAAs treatment remains unclear, but the possible mechanisms include immune cell dysfunction during HCV infection, cytokine network imbalance, epigenetic alterations, and host factors. Several biological markers and risk prediction models have been used to monitor the risk of HCC in CHC patients who have achieved SVR, but most still require validation and standardization. The implementation of risk-stratified surveillance programs is becoming urgent from a cost-effective point of view, but the availability of validated biomarkers to predict HCC in cured patients remains an unmet clinical need. Additionally, managing CHC patients who achieve SVR is becoming a growing challenge as an increasing number of HCV patients are cured.
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Affiliation(s)
- Caiyun Yang
- Xi'an Medical University, Xi'an 710021, Shannxi, PR China; National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, PR China
| | - Fengxiang Lv
- Xi'an Medical University, Xi'an 710021, Shannxi, PR China; National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, PR China
| | - Jiaqi Yang
- National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, PR China
| | - Dawei Ding
- National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, PR China
| | - Lina Cui
- National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, PR China.
| | - Ying Han
- National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Xijing Hospital, Air Force Military Medical University, Xi'an 710032, PR China.
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Ríos J, Sapena V, Mariño Z, Bruix J, Forns X, Morros R, Reig M, Torres F, Pontes C. Incidence of Liver and Non-liver Cancers After Hepatitis C Virus Eradication: A Population-Based Cohort Study. Drugs Real World Outcomes 2024; 11:389-401. [PMID: 38874848 PMCID: PMC11365915 DOI: 10.1007/s40801-024-00437-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/28/2024] [Indexed: 06/15/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Direct-acting antivirals (DAAs) offer a high rate of hepatitis C virus (HCV) eradication. However, concerns on the risk of cancer after HCV eradication remain. Our study aimed at quantifying the incidence of cancer in patients treated with anti-HCV therapies in Catalonia (Spain) and their matched controls. METHODS This was a population-based study using real-world data from the public healthcare system of Catalonia between 2012 and 2016. Propensity score matching was performed in patients with HCV infection treated with interferon-based therapy (IFN), sequential IFN and DAA (IFN+DAA), and DAA only (DAA) with concurrent controls. We estimated the annual incidence of overall cancer, hepatocellular carcinoma, and non-liver cancer of HCV-treated patients and their corresponding rate ratios. RESULTS The study included 11,656 HCV-treated patients and 49,545 controls. We found statistically significant increases in the rate of overall cancer for IFN+DAA-treated (rate ratio [RR] 1.77, 95% confidence interval [CI] 1.27-2.46) and DAA-treated patients (RR 1.90, 95% CI 1.66-2.19) and in the rate of HCC for IFN-treated (RR 1.50, 95% CI 1.02-2.22), IFN+DAA-treated (RR 3.89, 95% CI 2.26-6.69), and DAA-treated patients (RR 6.45, 95% CI 4.90-8.49) compared with their corresponding controls. Moreover, DAA-treated patients with cirrhosis showed an increased rate of overall cancer versus those without cirrhosis (RR 1.92, 95% CI 1.51-2.44). CONCLUSIONS Results showed that overall cancer and hepatocellular carcinoma incidence in Catalonia was significantly higher among HCV-treated patients compared with matched non-HCV-infected controls, and risks were higher in patients with cirrhosis. An increased awareness of the potential occurrence of uncommon malignant events and monitoring after HCV eradication therapy may benefit patients.
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Affiliation(s)
- José Ríos
- Department of Clinical Pharmacology, Hospital Clinic and Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Biostatistics Unit, Medical School, Universitat Autònoma de Barcelona, Campus, Cerdanyola, 08193, Barcelona, Spain
| | - Víctor Sapena
- Department of Clinical Pharmacology, Hospital Clinic and Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Barcelona Clinic Liver Cancer (BCLC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
| | - Rosa Morros
- Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain
- Department of Clinical Pharmacology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain
| | - María Reig
- Barcelona Clinic Liver Cancer (BCLC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
- Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
| | - Ferran Torres
- Biostatistics Unit, Medical School, Universitat Autònoma de Barcelona, Campus, Cerdanyola, 08193, Barcelona, Spain.
| | - Caridad Pontes
- Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain
- Department of Clinical Pharmacology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain
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Wasuwanich P, Rajborirug S, Egerman RS, Wen TS, Karnsakul W. Hepatitis C Prevalence and Birth Outcomes among Pregnant Women in the United States: A 2010-2020 Population Study. Pathogens 2024; 13:321. [PMID: 38668276 PMCID: PMC11054203 DOI: 10.3390/pathogens13040321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 04/01/2024] [Accepted: 04/12/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND The rates of hepatitis C virus (HCV) infection have increased in the pregnant population. We aim to describe the age-stratified clinical outcomes and trends for inpatient pregnant women with HCV in the U.S. METHODS We utilized hospitalization data from the 2010-2020 National Inpatient Sample. Pregnancy and HCV were identified according to their ICD-9/ICD-10 codes. Demographic and clinical data including cirrhosis, mortality, preterm birth, and stillbirth were extracted. The age groups were defined as ≤18, 19-25, 26-34, and ≥35 years. RESULTS We identified 195,852 inpatient pregnant women with HCV, among whom 0.7% were ≤18, 26.7% were 19-25, 57.9% were 26-34, and 14.8% were ≥35 years of age. The hospitalization rates of pregnant women with HCV increased overall between 2010 and 2020, with the highest velocity in the 26-34 age group. The 26-34 age group had the highest HCV burden, with an age-standardized hospitalization rate of 660 per 100,000 in 2020. The rates of mortality and cirrhosis were significantly higher in the HCV cohort and increased further with age (p < 0.05). Among the HCV pregnant cohort, 151,017 (77.1%) delivered during hospitalization. Preterm births and stillbirths were significantly higher in the HCV pregnant cohort compared to the controls across multiple age groups (p < 0.05). Minority race/ethnicity was associated with increased mortality, cirrhosis, preterm birth, and stillbirth (p < 0.001). HIV co-infection, hepatitis B co-infection, and diabetes increased the odds of cirrhosis (p < 0.001). CONCLUSIONS Hospitalizations of pregnant women with HCV are escalating, and these women are at increased risk of mortality, cirrhosis, preterm birth, and stillbirth with modifying factors, exacerbating risks further.
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Affiliation(s)
- Paul Wasuwanich
- University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Songyos Rajborirug
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | - Robert S. Egerman
- Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Tony S. Wen
- Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Milosevic I, Todorovic N, Filipovic A, Simic J, Markovic M, Stevanovic O, Malinic J, Katanic N, Mitrovic N, Nikolic N. HCV and HCC Tango-Deciphering the Intricate Dance of Disease: A Review Article. Int J Mol Sci 2023; 24:16048. [PMID: 38003240 PMCID: PMC10671156 DOI: 10.3390/ijms242216048] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 10/12/2023] [Accepted: 10/25/2023] [Indexed: 11/26/2023] Open
Abstract
Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) accounting for around one-third of all HCC cases. Prolonged inflammation in chronic hepatitis C (CHC), maintained through a variety of pro- and anti-inflammatory mediators, is one of the aspects of carcinogenesis, followed by mitochondrial dysfunction and oxidative stress. Immune response dysfunction including the innate and adaptive immunity also plays a role in the development, as well as in the recurrence of HCC after treatment. Some of the tumor suppressor genes inhibited by the HCV proteins are p53, p73, and retinoblastoma 1. Mutations in the telomerase reverse transcriptase promoter and the oncogene catenin beta 1 are two more important carcinogenic signaling pathways in HCC associated with HCV. Furthermore, in HCV-related HCC, numerous tumor suppressor and seven oncogenic genes are dysregulated by epigenetic changes. Epigenetic regulation of gene expression is considered as a lasting "epigenetic memory", suggesting that HCV-induced changes persist and are associated with liver carcinogenesis even after cure. Epigenetic changes and immune response dysfunction are recognized targets for potential therapy of HCC.
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Affiliation(s)
- Ivana Milosevic
- Faculty of Medicine, Department for Infectious Diseases, University of Belgrade, 11000 Belgrade, Serbia; (I.M.); (M.M.); (O.S.); (J.M.); (N.M.)
- University Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia; (N.T.); (A.F.); (J.S.); (N.K.)
| | - Nevena Todorovic
- University Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia; (N.T.); (A.F.); (J.S.); (N.K.)
| | - Ana Filipovic
- University Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia; (N.T.); (A.F.); (J.S.); (N.K.)
| | - Jelena Simic
- University Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia; (N.T.); (A.F.); (J.S.); (N.K.)
| | - Marko Markovic
- Faculty of Medicine, Department for Infectious Diseases, University of Belgrade, 11000 Belgrade, Serbia; (I.M.); (M.M.); (O.S.); (J.M.); (N.M.)
- University Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia; (N.T.); (A.F.); (J.S.); (N.K.)
| | - Olja Stevanovic
- Faculty of Medicine, Department for Infectious Diseases, University of Belgrade, 11000 Belgrade, Serbia; (I.M.); (M.M.); (O.S.); (J.M.); (N.M.)
- University Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia; (N.T.); (A.F.); (J.S.); (N.K.)
| | - Jovan Malinic
- Faculty of Medicine, Department for Infectious Diseases, University of Belgrade, 11000 Belgrade, Serbia; (I.M.); (M.M.); (O.S.); (J.M.); (N.M.)
- University Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia; (N.T.); (A.F.); (J.S.); (N.K.)
| | - Natasa Katanic
- University Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia; (N.T.); (A.F.); (J.S.); (N.K.)
- Faculty of Medicine, University of Pristina Situated in Kosovska Mitrovica, 28000 Kosovska Mitrovica, Serbia
| | - Nikola Mitrovic
- Faculty of Medicine, Department for Infectious Diseases, University of Belgrade, 11000 Belgrade, Serbia; (I.M.); (M.M.); (O.S.); (J.M.); (N.M.)
- University Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia; (N.T.); (A.F.); (J.S.); (N.K.)
| | - Natasa Nikolic
- Faculty of Medicine, Department for Infectious Diseases, University of Belgrade, 11000 Belgrade, Serbia; (I.M.); (M.M.); (O.S.); (J.M.); (N.M.)
- University Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia; (N.T.); (A.F.); (J.S.); (N.K.)
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Przybyszewski EM, Chung RT. Unmet Needs in the Post-Direct-Acting Antiviral Era: Hepatocarcinogenesis After Hepatitis C Virus Eradication. J Infect Dis 2023; 228:S226-S231. [PMID: 37703341 PMCID: PMC10499186 DOI: 10.1093/infdis/jiac447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2023] Open
Abstract
Infection with chronic hepatitis C virus (HCV) is an important risk factor for hepatocellular carcinoma (HCC). Direct-acting antiviral therapy has transformed care for patients with HCV and reduces the risk of HCC. Despite HCV cure, a residual HCC risk remains in patients with advanced fibrosis and cirrhosis, with multiple mechanisms underlying subsequent hepatocarcinogenesis. Transcriptomic and proteomic signatures demonstrate the capacity for HCC risk stratification, and chemoprevention strategies are emerging. For now, pending more precise stratification, HCC surveillance of patients with cured HCV and advanced fibrosis or cirrhosis should continue.
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Affiliation(s)
- Eric M Przybyszewski
- Liver Center and Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Raymond T Chung
- Liver Center and Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
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6
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Lara-Aguilar V, Crespo-Bermejo C, Llamas-Adán M, Grande-García S, Cortijo-Alfonso ME, Martín-Carbonero L, Domínguez L, Ryan P, de Los Santos I, Bartolomé-Sanchez S, Valle-Millares D, Jiménez-Sousa MÁ, Briz V, Fernández-Rodríguez A. HCV spontaneous clearers showed low senescence profile in people living with HIV under long ART. J Med Virol 2023; 95:e28955. [PMID: 37465865 DOI: 10.1002/jmv.28955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 05/30/2023] [Accepted: 06/29/2023] [Indexed: 07/20/2023]
Abstract
Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls. Oxidative stress biomarkers were analyzed at lipid, DNA, protein, and nitrates levels, as well as antioxidant capacity and glutathione reductase enzyme. Replicative senescence was evaluated by relative telomere length (RTL) measurement. Additionally, 26 markers of Senescence-Associated Secretory Phenotype (SASP) were analyzed by multiplex immunoassays (Luminex xMAP technology). Differences were evaluated by generalized linear model (GLMs) adjusted by most significant covariates. The SC group had a senescence signature similar to the HIV control group and slightly lower SASP levels. However, significant differences were observed with respect to the CHC group, where an increase in the nitrate concentration [adjusted arithmetic mean ratio, aAMR = 1.73 (1.27-2.35), p < 0.001, q = 0.009] and the secretion of 13 SASP-associated factors [granulocyte macrophage colony-stimulating factor (GM-CSF), interferon-β, interleukin (IL)-1β, IL-2, IL-8, IL-13, tumor necrosis factor (TNF)-α, IL-1α, IL-1RA, IL-7, IL-15, C-X-C motif chemokine ligand 10 (IP-10), stem cell factor (SCF); q < 0.1)] was detected. The CHC group also showed higher values of IL-1α, IP-10, and placental growth factor 1 (PIGF-1) than HIV controls. The SC group showed a slightly lower senescence profile than the HIV group, which could indicate a more efficient control of viral-induced senescence due to their immune strengths. Chronic HCV infection in PLWHIV led to an increase in nitrate and elevated SASP biomarkers favoring the establishment of viral persistence.
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Affiliation(s)
- Violeta Lara-Aguilar
- Viral Hepatitis Reference and Research Laboratory, National Center of Microbiology, Institute of Health Carlos III, Madrid, Majadahonda, Spain
| | - Celia Crespo-Bermejo
- Viral Hepatitis Reference and Research Laboratory, National Center of Microbiology, Institute of Health Carlos III, Madrid, Majadahonda, Spain
| | - Manuel Llamas-Adán
- Viral Hepatitis Reference and Research Laboratory, National Center of Microbiology, Institute of Health Carlos III, Madrid, Majadahonda, Spain
| | - Sergio Grande-García
- Viral Hepatitis Reference and Research Laboratory, National Center of Microbiology, Institute of Health Carlos III, Madrid, Majadahonda, Spain
| | - María Engracia Cortijo-Alfonso
- Viral Hepatitis Reference and Research Laboratory, National Center of Microbiology, Institute of Health Carlos III, Madrid, Majadahonda, Spain
| | | | - Lourdes Domínguez
- VIH Unit, Internal Medicine Service, Doce de Octubre Hospital Biomedical Research Institute (imas12), Madrid, Spain
- King's College London University, London, UK
| | - Pablo Ryan
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Institute of Health Carlos III, Madrid, Spain
- Department of Infectious Diseases, HIV/Hepatitis Internal Medicine Service, Infanta Leonor University Hospital, Madrid, España
| | - Ignacio de Los Santos
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Institute of Health Carlos III, Madrid, Spain
- Internal Medicine-Infectious Diseases Service, La Princesa University Hospital, Madrid, España
| | - Sofía Bartolomé-Sanchez
- Viral Hepatitis Reference and Research Laboratory, National Center of Microbiology, Institute of Health Carlos III, Madrid, Majadahonda, Spain
| | - Daniel Valle-Millares
- Viral Hepatitis Reference and Research Laboratory, National Center of Microbiology, Institute of Health Carlos III, Madrid, Majadahonda, Spain
| | - María Ángeles Jiménez-Sousa
- Viral Hepatitis Reference and Research Laboratory, National Center of Microbiology, Institute of Health Carlos III, Madrid, Majadahonda, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Institute of Health Carlos III, Madrid, Spain
| | - Verónica Briz
- Viral Hepatitis Reference and Research Laboratory, National Center of Microbiology, Institute of Health Carlos III, Madrid, Majadahonda, Spain
| | - Amanda Fernández-Rodríguez
- Viral Hepatitis Reference and Research Laboratory, National Center of Microbiology, Institute of Health Carlos III, Madrid, Majadahonda, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Institute of Health Carlos III, Madrid, Spain
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Omar H, Waked I, Elakel W, Salama R, Abdel-Razik W, Elmakhzangy H, Abdel-Rahman YO, Saeed R, Elshafaey A, Ziada DH, Ismail SA, Dabbous HM, Esmat G. Evolution of liver fibrosis after interferon-based anti-hepatitis C virus therapy failure in 3,049 chronic hepatitis C patients without cirrhosis. Arab J Gastroenterol 2023; 24:65-72. [PMID: 36725374 DOI: 10.1016/j.ajg.2023.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 11/11/2022] [Accepted: 01/03/2023] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND STUDY AIMS Liver fibrosis is the underlying causeof hepatitis C virus (HCV)-related disease progression to endpoints such as cirrhosis, liver failure, and hepatocellular carcinoma. The aim of our study was to assess changes in hepatic fibrosis in patients with chronic HCV who had a fibrosis evaluation at two time points at least six months apart. PATIENTS AND METHODS This was a retrospective cohort study that included patients who had failed interferon therapy and received HCV retreatment with direct-acting antivirals (DAAs) at least six months later. Patients were evaluated previously for fibrosis according to liver biopsy and fibrosis biomarkers were evaluated before pegylated interferon and ribavirin (PEG/RBV) therapy. Fibrosis was re-evaluated with fibrosis-4 (FIB-4) scores before starting DAAs. RESULTS A total of 3,049 patients were included [age 43.47 ± 9.07 years, 55.20 % males] and baseline histopathology showed F1, F2, and F3 in 16.86 %, 46.21 %, and 36.93 %, respectively. The mean time interval between the last dose of previously failed IFN-therapy to the first dose of DAAs was 2.38 (±1.07) years. Overall, there was a significant increase in FIB-4 scores at retreatment times (from 11.71 ± 1.13 to 22.26 ± 1.68, p < 0.001). Patients with baseline FIB-4 < 1.45 (n = 1,569) and between 1.45 and 3.25 (n = 1,237) had significant increases in their FIB-4 at the retreatment time point [median difference; 0.41 (0.91) and 0.24 (1.5), p < 0.001, respectively], whereas patients with FIB-4 > 3.25 had significant reduction of their FIB-4 score at a retreatment timepoint [-0.98 (2.93), p ≤ 0.001]. CONCLUSION Fibrosis progressed in most patients, even within six months for some patients, and this indicates retreatment of non-system vascular resistance patients even if they do not have significant fibrosis.
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Affiliation(s)
- Heba Omar
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Egypt.
| | - Imam Waked
- Hepatology Department, National Liver Institute, Menoufiya University, Shebeen El Kom, Egypt
| | - Wafaa Elakel
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Egypt
| | - Rabab Salama
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Egypt
| | - Wael Abdel-Razik
- Hepatology Department, National Liver Institute, Menoufiya University, Shebeen El Kom, Egypt
| | - Hesham Elmakhzangy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Egypt
| | | | | | - Arwa Elshafaey
- Public Health and Community Medicine, Cairo University, Cairo, Egypt
| | - Dina H Ziada
- Tropical Medicine and Infectious Disease, Tanta University, Egypt
| | | | - Hany M Dabbous
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Egypt
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8
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Abdelhamed W, El-Kassas M. Hepatocellular carcinoma and hepatitis C virus treatments: The bold and the beautiful. J Viral Hepat 2023; 30:148-159. [PMID: 36461645 DOI: 10.1111/jvh.13778] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 10/07/2022] [Accepted: 11/26/2022] [Indexed: 12/04/2022]
Abstract
The occurrence of hepatocellular carcinoma (HCC) is one of the most serious complications of hepatitis C virus (HCV) infection. Recently, effective antiviral medications have made sustained viral response (SVR) or cure a realistic therapeutic goal for most chronic HCV patients. Given HCV's tumorigenic propensity, it is not surprising that achieving SVR is helpful in preventing HCC. This review briefly summarizes and discusses the existing evidence on the relationship between hepatic carcinogenesis and viral eradication by antivirals, which is mainly divided into interferon-based and direct-acting antivirals (DAAs) based therapy. DAAs have changed the treatment landscape of chronic HCV, reaching high rates of SVR even in patients with advanced cirrhosis, with few contraindications and little side effects. Although some early reports suggested that DAA treatment increased the chance of HCC occurrence, more subsequent observational studies have refuted this theory. The probability of HCC recurrence after HCV eradication appears to be decreasing over time following SVR. Despite virological suppression/cure, individuals with liver cirrhosis are still at risk of HCC and should be monitored. There is a considerable need for markers/scores to predict the long-term risk of HCC in patients with HCV-related liver disease who attain SVR with direct-acting antivirals.
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Affiliation(s)
- Walaa Abdelhamed
- Endemic Medicine Department, Faculty of Medicine, Sohag University, Sohag, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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Biomarkers for the Detection and Management of Hepatocellular Carcinoma in Patients Treated with Direct-Acting Antivirals. Cancers (Basel) 2022; 14:cancers14112700. [PMID: 35681679 PMCID: PMC9179595 DOI: 10.3390/cancers14112700] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 05/24/2022] [Accepted: 05/25/2022] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Chronic Hepatitis C virus (HCV) represents the main etiological factor for hepatocellular carcinoma (HCC) in developed countries. The introduction of direct-acting antivirals (DAAs) improved the eradication of the hepatitis C virus (HCV) but not the reduction in the incidence of HCV-associated HCC. Some patients still develop HCC, even after reaching a sustained virological response (SVR). This review is a summary of pre-clinical studies that investigated predictive biomarkers for HCC occurrence and recurrence in HCV-infected patients treated with DAAs. The presented biomarkers are found dysregulated in serum or tissue at specific time points (before, during, after DAA treatment or post SVR) and correlated with HCC-predisposing conditions. Thus, this review aims to improve the management of patients developing HCV-induced HCC. Abstract Hepatocellular carcinoma (HCC) is the sixth-most common type of cancer worldwide and chronic Hepatitis C virus (HCV) represents the main etiological factor in developed countries. HCV promotes hepatocarcinogenesis through persistent liver inflammation and dysregulation of cell signaling pathways. The introduction of direct-acting antivirals (DAAs) resulted in a significant improvement in the eradication of the virus, with an expected reduction of HCC incidence. However, the risk of HCC development can persist after DAA treatment. Recent studies have investigated the potential use of molecular biomarkers that predict HCC occurrence or recurrence helping the stratification of patients under surveillance. This review aimed to summarize all pre-clinical exploration of predictive biomarkers to identify DAA-treated patients at risk for HCC development. Dysregulated microRNAs, lncRNAs, histone modifications, cytokines, proteins, and sphingolipids represent various classes of HCC risk predictors identified in two different biological sources (tissue and serum). The non-invasive serum markers can provide a more accessible means to perform clinical monitoring and predict the risk of HCC. In addition, conditions like cirrhosis, predisposing to HCC, strongly correlate with most of the molecular predictors identified, supporting the value of these molecules as possible biomarkers of HCC in DAA-treated patients.
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Wirth S. Chronic Viral Hepatitis B and C. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:833-842. [DOI: 10.1007/978-3-030-80068-0_63] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Piselli P, Serraino D, Fusco M, Girardi E, Pirozzi A, Toffolutti F, Cimaglia C, Taborelli M. Hepatitis C virus infection and risk of liver-related and non-liver-related deaths: a population-based cohort study in Naples, southern Italy. BMC Infect Dis 2021; 21:667. [PMID: 34238231 PMCID: PMC8268172 DOI: 10.1186/s12879-021-06336-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 06/17/2021] [Indexed: 12/16/2022] Open
Abstract
Background Hepatitis C virus (HCV) infection represents a global health issue with severe implications on morbidity and mortality. This study aimed to evaluate the impact of HCV infection on all-cause, liver-related, and non-liver-related mortality in a population living in an area with a high prevalence of HCV infection before the advent of Direct-Acting Antiviral (DAA) therapies, and to identify factors associated with cause-specific mortality among HCV-infected individuals. Methods We conducted a cohort study on 4492 individuals enrolled between 2003 and 2006 in a population-based seroprevalence survey on viral hepatitis infections in the province of Naples, southern Italy. Study participants provided serum for antibodies to HCV (anti-HCV) and HCV RNA testing. Information on vital status to December 2017 and cause of death were retrieved through record-linkage with the mortality database. Hazard ratios (HRs) for cause-specific mortality and 95% confidence intervals (CIs) were estimated using Fine-Grey regression models. Results Out of 626 deceased people, 20 (3.2%) died from non-natural causes, 56 (8.9%) from liver-related conditions, 550 (87.9%) from non-liver-related causes. Anti-HCV positive people were at higher risk of death from all causes (HR = 1.38, 95% CI: 1.12–1.70) and liver-related causes (HR = 5.90, 95% CI: 3.00–11.59) than anti-HCV negative ones. Individuals with chronic HCV infection reported an elevated risk of death due to liver-related conditions (HR = 6.61, 95% CI: 3.29–13.27) and to any cause (HR = 1.51, 95% CI: 1.18–1.94). The death risk of anti-HCV seropositive people with negative HCV RNA was similar to that of anti-HCV seronegative ones. Among anti-HCV positive people, liver-related mortality was associated with a high FIB-4 index score (HR = 39.96, 95% CI: 4.73–337.54). Conclusions These findings show the detrimental impact of HCV infection on all-cause mortality and, particularly, liver-related mortality. This effect emerged among individuals with chronic infection while those with cleared infection had the same risk of uninfected ones. These results underline the need to identify through screening all people with chronic HCV infection notably in areas with a high prevalence of HCV infection, and promptly provide them with DAAs treatment to achieve progressive HCV elimination and reduce HCV-related mortality. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06336-9.
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Affiliation(s)
- Pierluca Piselli
- Department of Epidemiology and Pre-Clinical Research, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy
| | - Diego Serraino
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini 2, 33081, Aviano, PN, Italy
| | - Mario Fusco
- Registro Tumori, ASL Napoli-3 Sud, Brusciano, Naples, Italy
| | - Enrico Girardi
- Department of Epidemiology and Pre-Clinical Research, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy
| | - Angelo Pirozzi
- Registro Tumori, ASL Napoli-3 Sud, Brusciano, Naples, Italy
| | - Federica Toffolutti
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini 2, 33081, Aviano, PN, Italy
| | - Claudia Cimaglia
- Department of Epidemiology and Pre-Clinical Research, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy
| | - Martina Taborelli
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini 2, 33081, Aviano, PN, Italy.
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12
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Chang CH, Liu CY, Chen SJ, Tsai HC. Hepatitis C virus and hepatitis B virus in patients with schizophrenia. Medicine (Baltimore) 2021; 100:e26218. [PMID: 34087899 PMCID: PMC8183751 DOI: 10.1097/md.0000000000026218] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 05/17/2021] [Indexed: 01/04/2023] Open
Abstract
This study evaluated the severe hepatic outcome (SHO) in patients with schizophrenia and viral hepatitis who received antipsychotics.Using the nationwide Taiwan National Health Insurance Research Database, patients first diagnosed with schizophrenia between 2002 and 2013 were identified. Patients diagnosed with schizophrenia who had viral hepatitis, including hepatitis B virus (HBV) or hepatitis C virus (HCV), were designated as the viral hepatitis group. A control group without viral hepatitis was matched for age, sex, and index year in a 2:1 ratio. Patients with severe hepatic outcomes before enrollment were excluded. The 2 cohorts were observed until December 31, 2013. The primary endpoint was occurrence of a SHO, including liver cancer, liver failure, liver decompensation, or transplantation.Among the 16,365 patients newly diagnosed with schizophrenia between January 2002 and December 2013, we identified 614 patients with viral hepatitis and 1228 matched patients without viral hepatitis. Of these 1842 patients, 41 (2.22%) developed SHOs, including 26 (4.23%) in the viral hepatitis group and 15 (1.22%) in the control group, during the mean follow-up period of 3.71 ± 2.49 years. Cox proportional hazard analysis indicated that the SHO risk increased by 3.58 (95% confidence interval [CI]: 1.859-6.754; P < .001) in patients with schizophrenia and viral hepatitis. Moreover, patients with schizophrenia having HCV had a higher SHO risk than those without viral hepatitis (hazard ratio: 5.07, 95% CI: 1.612-15.956; P < .0001). Patients having both schizophrenia and viral hepatitis, especially HCV, had a higher risk of SHOs.
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Affiliation(s)
- Chun-Hung Chang
- Institute of Clinical Medical Science, China Medical University
- Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung
- An Nan Hospital, China Medical University, Tainan
| | - Chieh-Yu Liu
- Biostatistical Consulting Lab, Department of Speech Language Pathology and Audiology, National Taipei University of Nursing and Health Sciences, Taipei
| | - Shaw-Ji Chen
- Department of Psychiatry, Taitung MacKay Memorial Hospital, Taitung
- Department of Medicine, Mackay Medical College, New Taipei
| | - Hsin-Chi Tsai
- Department of Psychiatry, Tzu-Chi General Hospital, Hualien City
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, R.O.C
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Facente SN, Patel S, Hecht J, Wilson E, McFarland W, Page K, Vickerman P, Fraser H, Burk K, Morris MD. Hepatitis C Care Cascades for 3 Populations at High Risk: Low-income Trans Women, Young People Who Inject Drugs, and Men Who Have Sex With Men and Inject Drugs. Clin Infect Dis 2021; 73:e1290-e1295. [PMID: 33768236 PMCID: PMC8442786 DOI: 10.1093/cid/ciab261] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND To achieve elimination of hepatitis C virus (HCV) infection, limited resources can be best allocated through estimation of "care cascades" among groups disproportionately affected. In San Francisco and elsewhere, these groups include young (age ≤ 30 years) people who inject drugs (YPWID), men who have sex with men who inject drugs (MSM-IDU), and low-income trans women. METHODS We developed cross-sectional HCV care cascades for YPWID, MSM-IDU, and trans women using diverse data sources. Population sizes were estimated using an inverse variance-weighted average of estimates from the peer-reviewed literature between 2013 and 2019. Proportions of past/current HCV infection, diagnosed infection, treatment initiation, and evidence of cure (sustained virologic response at 12 weeks posttreatment) were estimated from the literature using data from 7 programs and studies in San Francisco between 2015 and 2020. RESULTS The estimated number of YPWID in San Francisco was 3748; 58.4% had past/current HCV infection, of whom 66.4% were diagnosed with current infection, 9.1% had initiated treatment, and 50% had confirmed cure. The corresponding figures for the 8135 estimated MSM-IDU were: 29.4% with past/current HCV infection, 70.3% diagnosed with current infection, 28.4% initiated treatment, and 38.9% with confirmed cure. For the estimated 951 low-income trans women, 24.8% had past/current HCV infection, 68.9% were diagnosed with current infection, 56.5% initiated treatment, and 75.5% had confirmed cure. CONCLUSIONS In all 3 populations, diagnosis rates were relatively high; however, attention is needed to urgently increase treatment initiation in all groups, with a particular unmet need among YPWID.
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Affiliation(s)
- Shelley N Facente
- School of Public Health, Division of Epidemiology and Biostatistics, University of California Berkeley, Berkeley, California, USA,Facente Consulting, Richmond, California, USA
| | - Sheena Patel
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
| | - Jennifer Hecht
- San Francisco AIDS Foundation, San Francisco, California, USA
| | - Erin Wilson
- San Francisco Department of Public Health, San Francisco, California, USA
| | - Willi McFarland
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA,San Francisco Department of Public Health, San Francisco, California, USA
| | - Kimberly Page
- University of New Mexico, Albuquerque, New Mexico, USA
| | - Peter Vickerman
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Hannah Fraser
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Katie Burk
- San Francisco Department of Public Health, San Francisco, California, USA
| | - Meghan D Morris
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA,Correspondence: M. D. Morris, 550 16th St, Box 124, San Francisco, CA 94153, USA ()
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Goetsch MR, Tamhane A, Overton ET, Towns GC, Franco RA. Direct Acting Antivirals in Hepatitis C-Infected Kidney Transplant Recipients: Associations with Long-term Graft Failure and Patient Mortality. Pathog Immun 2020; 5:275-290. [PMID: 33089036 PMCID: PMC7556425 DOI: 10.20411/pai.v5i1.369] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 03/21/2020] [Indexed: 02/06/2023] Open
Abstract
Background Direct-acting antiviral (DAA) therapy among hepatitis C virus (HCV)-infected kidney transplant recipients is associated with short-term improvement in protein/creatinine (P/C) ratios, but how HCV cure affects long-term graft outcomes remains unknown. Methods This is a retrospective follow-up study of 59 HCV-infected patients who underwent kidney transplant at the University of Alabama at Birmingham between 2007-2015 who were followed until the end of 2017. We examined the association of DAA-induced HCV cure with graft failure or death by survival analyses (Kaplan-Meier, Cox regression). Results Mean age was 55 years, 73% were African American, and 68% were male. Median baseline creatinine was 1.4 mg/dL, P/C ratio was 0.5, and estimated glomerular filtration rate (eGFR) was 59 mL/min. Of those who received DAA, 24 (83%) achieved cure. The remaining 5 DAA patients (17%) did not have documented evidence of sustained virologic response (SVR). Overall, 19 (32%) patients experienced graft failure or death; with lower incidence in treated patients than untreated (4 vs 15 events; 2.6 vs 10.3 per 100 person-years [cHR 0.19, 95% CI: 0.06-0.66]). When adjusted for age, sex, race, and proteinuria, the association remained strong and invariant across time-varying (aHR 0.30, 95% CI: 0.08-1.10), time-averaged (aHR 0.28, 95% CI: 0.07-1.07), and time-varying-cumulative (aHR 0.32, 95% CI: 0.08-1.21) proteinuria metrics. Conclusions DAAs therapy was associated with improved graft survival and reduced mortality. While not statistically significant, the association was strong, and these single-center findings warrant larger studies to demonstrate the benefits of HCV treatment in this population.
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Affiliation(s)
| | - Ashutosh Tamhane
- Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama
| | - Edgar T Overton
- Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama
| | - Graham C Towns
- Department of Medicine, Division of Nephrology, University of Alabama School of Medicine, Birmingham, Alabama
| | - Ricardo A Franco
- Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama
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Kim NG, Kullar R, Khalil H, Saab S. Meeting the WHO hepatitis C virus elimination goal: Review of treatment in paediatrics. J Viral Hepat 2020; 27:762-769. [PMID: 32386099 DOI: 10.1111/jvh.13317] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/06/2020] [Accepted: 04/13/2020] [Indexed: 12/12/2022]
Abstract
Over 3 million paediatric patients globally and ~50 000 in the United States are estimated to be infected with HCV. Eradicating HCV in children helps prevent liver fibrosis, cirrhosis and hepatocellular carcinoma; reduces extra-hepatic manifestations of HCV; improves quality of life; and increases survival. The 2019 American Association for the Study of Liver Diseases-Infectious Diseases Society of America (AASLD-IDSA) guidelines now recommend direct-acting antiviral (DAA) treatment with an approved regimen for all children and adolescents with HCV infection aged ≥3 years. We conducted a descriptive review of the new DAA treatments for HCV infection in the paediatric population. Ledipasvir/sofosbuvir (LDV/SOF) and sofosbuvir with ribavirin (SOF/RBV) are now approved for those ≥3 years old under specific clinical scenarios; sofosbuvir/velpatasvir (SOF/VEL) is the only pangenotypic agent approved for those ≥6 years or ≥17 kg, and glecaprevir/pibrentasvir (GLE/PIB) is approved for adolescents ≥12 years old or ≥45 kg. These DAA regimens are well-tolerated and have comparable sustained virologic response rates at 12 weeks post-treatment compared to those reported in adults (close to 100%). The introduction of DAAs has significantly changed the landscape of HCV treatment in adults and children with HCV infection and has increased confidence that the 2030 World Health Organization elimination goal may be attainable. Further studies are warranted to determine the optimal treatment for children with HCV infection, including timing, regimen and duration. Additionally, with the recent paediatric approvals, long-term safety data are needed.
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Affiliation(s)
- Nathan G Kim
- Department of Medicine, University of California at Los Angeles, Los Angeles, California
| | | | - Haydar Khalil
- Department of Medicine, University of California at Los Angeles, Los Angeles, California
| | - Sammy Saab
- Department of Medicine, University of California at Los Angeles, Los Angeles, California
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Laursen TL, Sandahl TD, Kazankov K, George J, Grønbæk H. Liver-related effects of chronic hepatitis C antiviral treatment. World J Gastroenterol 2020; 26:2931-2947. [PMID: 32587440 PMCID: PMC7304101 DOI: 10.3748/wjg.v26.i22.2931] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 03/26/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
More than five years ago, the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral (DAA) drugs. They proved highly efficient in curing patients with chronic hepatitis C (CHC), including patients with cirrhosis. The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis, but the exact cause of the expected benefit was unclear. Further, little was known about how the underlying liver disease would be affected during and after viral clearance. In this review, we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects, such as macrophage activation, and the time-dependent effects of therapy, with specific emphasis on inflammation, structural liver changes, and liver function, as these factors are all related to morbidity and mortality in CHC patients. It seems clear that antiviral therapy, especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis. There seems to be a time-dependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions. These improvements lead to favorable effects on liver function, followed by an improvement in cognitive dysfunction and portal hypertension. Overall, the data provide knowledge on the several beneficial effects of DAA therapy on liver-related parameters in CHC patients suggesting short- and long-term improvements in the underlying disease with the promise of an improved long-term prognosis.
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Affiliation(s)
- Tea L Laursen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Thomas D Sandahl
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Konstantin Kazankov
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, Sydney NSW 2145, Australia
- University of Sydney, Sydney NSW 2145, Australia
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
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Brochado-Kith Ó, Gómez Sanz A, Real LM, Crespo García J, Ryan Murúa P, Macías J, Cabezas González J, Troya J, Pineda JA, Arias Loste MT, Díez Viñas V, Jiménez-Sousa MÁ, Medrano de Dios LM, Cuesta De la Plaza I, Monzón Fernández S, Resino García S, Fernández-Rodríguez A. MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection. J Clin Med 2019; 8:jcm8060849. [PMID: 31207946 PMCID: PMC6617112 DOI: 10.3390/jcm8060849] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 06/03/2019] [Accepted: 06/11/2019] [Indexed: 12/12/2022] Open
Abstract
Factors involved in the spontaneous cleareance of a hepatitis C (HCV) infection are related to both HCV and the interaction with the host immune system, but little is known about the consequences after a spontaneous resolution. The main HCV extrahepatic reservoir is the peripheral blood mononuclear cells (PBMCs), and their transcriptional profile provides us information of innate and adaptive immune responses against an HCV infection. MicroRNAs regulate the innate and adaptive immune responses, and they are actively involved in the HCV cycle. High Throughput sequencing was used to analyze the miRNA profiles from PBMCs of HCV chronic naïve patients (CHC), individuals that spontaneously clarified HCV (SC), and healthy controls (HC). We did not find any differentially expressed miRNAs between SC and CHC. However, both groups showed similar expression differences (21 miRNAs) with respect to HC. This miRNA signature correctly classifies HCV-exposed (CHC and SC) vs. HC, with the has-miR-21-3p showing the best performance. The potentially targeted molecular pathways by these 21 miRNAs mainly belong to fatty acids pathways, although hippo signaling, extracellular matrix (ECM) interaction, proteoglycans-related, and steroid biosynthesis pathways were also altered. These miRNAs target host genes involved in an HCV infection. Thus, an HCV infection promotes molecular alterations in PBMCs that can be detected after an HCV spontaneous resolution, and the 21-miRNA signature is able to identify HCV-exposed patients (either CHC or SC).
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Affiliation(s)
- Óscar Brochado-Kith
- Unit of Viral Infection and Immunity, National Center for Microbiology, Institute of Health Carlos III, Majadahonda, 28220 Madrid, Spain.
| | - Alicia Gómez Sanz
- Unit of Viral Infection and Immunity, National Center for Microbiology, Institute of Health Carlos III, Majadahonda, 28220 Madrid, Spain.
| | - Luis Miguel Real
- Unidad Clínica de Enfermedades Infecciosas, Hospital Universitario de Valme, 41014 Sevilla, Spain.
| | - Javier Crespo García
- Gastroenterology and Hepatology Department, Hospital Universitario Marques de Valdecilla, 39008 Santander, Spain.
- Institute Valdecilla (IDIVAL), School of Medicine, University of Cantabria, 39005 Santander, Spain.
| | - Pablo Ryan Murúa
- Internal Medicine Service, University Hospital Infanta Leonor, School of Medicine, Complutense University of Madrid, Gregorio Marañón Health Research Institute, 28009 Madrid, Spain.
| | - Juan Macías
- Unidad Clínica de Enfermedades Infecciosas, Hospital Universitario de Valme, 41014 Sevilla, Spain.
| | - Joaquín Cabezas González
- Gastroenterology and Hepatology Department, Hospital Universitario Marques de Valdecilla, 39008 Santander, Spain.
- Institute Valdecilla (IDIVAL), School of Medicine, University of Cantabria, 39005 Santander, Spain.
| | - Jesús Troya
- Internal Medicine Service, University Hospital Infanta Leonor, School of Medicine, Complutense University of Madrid, Gregorio Marañón Health Research Institute, 28009 Madrid, Spain.
| | - Juan Antonio Pineda
- Unidad Clínica de Enfermedades Infecciosas, Hospital Universitario de Valme, 41014 Sevilla, Spain.
| | - María Teresa Arias Loste
- Gastroenterology and Hepatology Department, Hospital Universitario Marques de Valdecilla, 39008 Santander, Spain.
- Institute Valdecilla (IDIVAL), School of Medicine, University of Cantabria, 39005 Santander, Spain.
| | - Victorino Díez Viñas
- Internal Medicine Service, University Hospital Infanta Leonor, School of Medicine, Complutense University of Madrid, Gregorio Marañón Health Research Institute, 28009 Madrid, Spain.
| | - María Ángeles Jiménez-Sousa
- Unit of Viral Infection and Immunity, National Center for Microbiology, Institute of Health Carlos III, Majadahonda, 28220 Madrid, Spain.
| | - Luz María Medrano de Dios
- Unit of Viral Infection and Immunity, National Center for Microbiology, Institute of Health Carlos III, Majadahonda, 28220 Madrid, Spain.
| | - Isabel Cuesta De la Plaza
- Bioinformatics Unit, Unidades Comunes Científico Técnicas, Institute of Health Carlos III, Majadahonda, 28220 Madrid, Spain.
| | - Sara Monzón Fernández
- Bioinformatics Unit, Unidades Comunes Científico Técnicas, Institute of Health Carlos III, Majadahonda, 28220 Madrid, Spain.
| | - Salvador Resino García
- Unit of Viral Infection and Immunity, National Center for Microbiology, Institute of Health Carlos III, Majadahonda, 28220 Madrid, Spain.
| | - Amanda Fernández-Rodríguez
- Unit of Viral Infection and Immunity, National Center for Microbiology, Institute of Health Carlos III, Majadahonda, 28220 Madrid, Spain.
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Cost Effectiveness of Universal Screening for Hepatitis C Virus Infection in the Era of Direct-Acting, Pangenotypic Treatment Regimens. Clin Gastroenterol Hepatol 2019; 17:930-939.e9. [PMID: 30201597 DOI: 10.1016/j.cgh.2018.08.080] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 08/24/2018] [Accepted: 08/31/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Most persons infected with hepatitis C virus (HCV) in the United States were born from 1945 through 1965; testing is recommended for this cohort. However, HCV incidence is increasing among younger persons in many parts of the country and treatment is recommended for all adults with HCV infection. We aimed to estimate the cost effectiveness of universal 1-time screening for HCV infection in all adults living in the United States and to determine the prevalence of HCV antibody above which HCV testing is cost effective. METHODS We developed a Markov state transition model to estimate the effects of universal 1-time screening of adults 18 years or older in the United States, compared with the current guideline-based strategy of screening adults born from 1945 through 1965. We compared potential outcomes of 1-time universal screening of adults or birth cohort screening followed by antiviral treatment of those with HCV infection vs no screening. We measured effectiveness with quality-adjusted life-years (QALY), and costs with 2017 US dollars. RESULTS Based on our model, universal 1-time screening of US residents with a general population prevalence of HCV antibody greater than 0.07% cost less than $50,000/QALY compared with a strategy of no screening. Compared with 1-time birth cohort screening, universal 1-time screening and treatment cost $11,378/QALY gained. Universal screening was cost effective compared with birth cohort screening when the prevalence of HCV antibody positivity was greater than 0.07% among adults not in the cohort born from 1945 through 1965. CONCLUSIONS Using a Markov state transition model, we found a strategy of universal 1-time screening for chronic HCV infection to be cost effective compared with either no screening or birth cohort-based screening alone.
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Darvishian M, Janjua NZ, Chong M, Cook D, Samji H, Butt ZA, Yu A, Alvarez M, Yoshida E, Ramji A, Wong J, Woods R, Tyndall M, Krajden M. Estimating the impact of early hepatitis C virus clearance on hepatocellular carcinoma risk. J Viral Hepat 2018; 25:1481-1492. [PMID: 30047609 DOI: 10.1111/jvh.12977] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 06/04/2018] [Accepted: 07/03/2018] [Indexed: 12/15/2022]
Abstract
Although achieving sustained virological response (SVR) through antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) attributable to hepatitis C virus (HCV) infection, the impact of early viral clearance on HCC is not well defined. In this study, we compared the risk of HCC among individuals who spontaneously cleared HCV (SC), the referent population, with the risk in untreated chronic HCV (UCHC), those achieved SVR, and those who failed interferon-based treatment (TF). The BC Hepatitis Testers Cohort (BC-HTC) includes individuals tested for HCV between 1990-2013, integrated with medical visits, hospitalizations, cancers, prescription drugs and mortality data. This analysis included all HCV-positive patients with at least one valid HCV RNA by PCR on or after HCV diagnosis. Of 46 666 HCV-infected individuals, there were 12 527 (26.8%) SC; 24 794 (53.1%) UCHC; 5355 (11.5%) SVR and 3990 (8.5%) TF. HCC incidence was lowest (0.3/1000 person-years (PY)) in the SC group and highest in the TF group (7.7/1000 PY). In a multivariable model, compared to SC, TF had the highest HCC risk (hazard ratio (HR):14.52, 95% confidence interval (CI): 9.83-21.47), followed by UCHC (HR: 5.85; 95% CI: 4.07-8.41). Earlier treatment-based viral clearance similar to SC could decrease HCC incidence by 69.4% (95% CI: 57.5-78.0), 30% (95% CI: 10.8-45.1) and 77.5% (95% CI: 69.4-83.5) among UCHC, SVR and TF patients, respectively. In conclusion, using SC as a real-world comparator group, it showed that substantial reduction in HCC risk could be achieved with earlier treatment initiation. These analyses should be replicated in patients who have been treated with direct acting antiviral therapies.
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Affiliation(s)
- Maryam Darvishian
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Naveed Z Janjua
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mei Chong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Darrel Cook
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Hasina Samji
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Zahid A Butt
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Amanda Yu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Maria Alvarez
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Eric Yoshida
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Alnoor Ramji
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.,GI Research Institute, Vancouver, British Columbia, Canada
| | - Jason Wong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Ryan Woods
- British Columbia Cancer Agency, Vancouver, British Columbia, Canada
| | - Mark Tyndall
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mel Krajden
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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20
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Yang CHT, Goel A, Ahmed A. Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C. ADOLESCENT HEALTH MEDICINE AND THERAPEUTICS 2018; 9:103-110. [PMID: 30104913 PMCID: PMC6071628 DOI: 10.2147/ahmt.s147896] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Chronic infection with hepatitis C virus (HCV) affects an estimated 0.1%–2% of the pediatric population in the United States. While the clinical course in young children is indolent, adolescents who contract HCV have a disease course similar to adults, with a 26-fold increased risk of chronic liver disease-associated mortality, hepatocellular carcinoma, and need for curative liver transplantation. Furthermore, adolescent patients are entering childbearing age and carry a risk of passing HCV to their offspring via vertical transmission. Pegylated-interferon (PEG-IFN) with ribavirin was previously the only treatment option for pediatric patients with chronic hepatitis C (CHC), but the high likelihood of adverse reactions and subcutaneous route of administration limited its use and efficacy. Recently, the direct-acting antivirals (DAAs) ledipasvir (LDV) and sofosbuvir (SOF) were approved for adolescents with CHC. This review discusses the natural history of CHC in pediatric patients, data supporting LDV/SOF in adolescents, and ongoing studies evaluating DAAs in pediatric patients.
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Affiliation(s)
- Christine Hong Ting Yang
- Division of Pediatric Gastroenterology, Stanford University School of Medicine, Stanford, CA, USA
| | - Aparna Goel
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA,
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA,
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21
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Pietsch V, Deterding K, Attia D, Ringe KI, Heidrich B, Cornberg M, Gebel M, Manns MP, Wedemeyer H, Potthoff A. Long-term changes in liver elasticity in hepatitis C virus-infected patients with sustained virologic response after treatment with direct-acting antivirals. United European Gastroenterol J 2018; 6:1188-1198. [PMID: 30288281 DOI: 10.1177/2050640618786067] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 06/08/2018] [Indexed: 12/12/2022] Open
Abstract
Background The use of interferon-free direct-acting antiviral agents (DAAs) is associated with a rapid short-term decrease in liver stiffness in chronic hepatitis C-infected patients with sustained virologic response (SVR). Objective The objective of this article is to evaluate long-term changes in liver elasticity in hepatitis C patients with SVR using transient elastography (TE), FIB-4 and APRI. Methods A total of 143 patients were treated with DAAs and reached SVR. Patients received TE measurement (median (range)) at treatment start (baseline), follow-up week 24 (FU24) and follow-up week 96 (FU96). Laboratory data were examined at each date and FIB-4 and APRI were calculated. Results Liver elasticity showed a significant decrease from baseline to FU24 (13.1 (3.1-75) kPa to 9.3 (2.9-69.1) kPa; p < 0.0001) and declined further until FU96 (7.9 (2.4-59.3) kPa; p < 0.0001). Liver inflammation and liver function parameters normalised during long-term follow-up. Progression of liver stiffness between FU24 to FU96 despite viral clearance was observed in 24 patients (17%). Long-term liver stiffness progression was associated with aspartate aminotransferase levels and TE change from baseline to FU24. Conclusion During long-term follow-up, the majority of patients with SVR had further improved liver stiffness values. Still, a significant proportion of patients may show long-term liver stiffness progression and thus continued TE follow-up is recommended.
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Affiliation(s)
- Veronika Pietsch
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Katja Deterding
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Department of Gastroenterology and Hepatology, University of Essen, Essen, Germany
| | - Dina Attia
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Kristina Imeen Ringe
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - Benjamin Heidrich
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Michael Gebel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Michael Peter Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Department of Gastroenterology and Hepatology, University of Essen, Essen, Germany
| | - Andrej Potthoff
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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22
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Axley P, Ahmed Z, Ravi S, Singal AK. Hepatitis C Virus and Hepatocellular Carcinoma: A Narrative Review. J Clin Transl Hepatol 2018; 6:79-84. [PMID: 29607308 PMCID: PMC5863002 DOI: 10.14218/jcth.2017.00067] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/14/2017] [Accepted: 11/20/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of liver-related death worldwide. Hepatitis C virus (HCV) infection is a major cause of advanced hepatic fibrosis and cirrhosis, with significantly increased risk for development of HCC. The morbidity and mortality of HCV-related HCC remains high, as rates of HCV cirrhosis continue to increase. The long-term goal of antiviral therapy for chronic HCV is to reduce complications from cirrhosis, including HCC. The advent of new direct-acting antivirals with high rates of virological clearance has revolutionized cure of HCV infection. While the development of HCC in HCV patients who achieve disease sustained virologic response is reduced, these patients remain at risk for HCC, particularly those patients with advanced fibrosis and cirrhosis. This review outlines the epidemiology of HCC in chronic HCV, various mechanisms, risk factors and pathophysiology that contribute to this disease process, screening recommendations, and the available data on the impact of new direct-acting antiviral treatment on the development on HCC.
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Affiliation(s)
- Page Axley
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Zunirah Ahmed
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sujan Ravi
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, AL, USA
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23
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El-Khayat HR, Kamal EM, El-Sayed MH, El-Shabrawi M, Ayoub H, RizK A, Maher M, El Sheemy RY, Fouad YM, Attia D. The effectiveness and safety of ledipasvir plus sofosbuvir in adolescents with chronic hepatitis C virus genotype 4 infection: a real-world experience. Aliment Pharmacol Ther 2018; 47:838-844. [PMID: 29349793 DOI: 10.1111/apt.14502] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Revised: 08/10/2017] [Accepted: 12/11/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND The combination of ledipasvir plus sofosbuvir was recently approved for treatment of adolescent (12-17 years) HCV genotype 1, 4, 5 & 6 patients. However, few clinical trials have been performed in genotype 1 patients. AIM To investigate the effectiveness and safety of ledipasvir plus sofosbuvir in chronic HCV adolescent patients with genotype 4 in the real world. METHODS This prospective multicentre (six centres) open-label study included 144 adolescent chronic HCV patients with genotype 4 (mean age 14 ± 2, 69% males). All patients received a combination tablet containing 400 mg sofosbuvir and 90 mg ledipasvir once daily for 12 weeks. Laboratory and virological markers were evaluated at baseline, week 4, week 8 and week 12 (EOT), and 12 weeks after end of treatment (SVR12). RESULTS SVR12 was observed in 142/144 patients (99%). The relapsers occurred in previous naïve patients (n = 2/128, 2%), while the experienced patients showed 100% SVR12. SVR12 was 98% in F0/F1 patients in comparison to 100% in F2 patients (P = 0.552). No serious side effects were observed, nor was treatment discontinuation or death. Headache was the most common side effect in all patients (20%). In experienced patients, pruritus (31%, P = 0.007), diarrhoea (44%, P < 0.001) and skin rash (19%, P = 0.002) were higher than in naïve patients. CONCLUSIONS A ledipasvir plus sofosbuvir regimen is well tolerated and effective, and can be used safely in treating adolescent patients with chronic hepatitis C genotype 4.
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Affiliation(s)
- H R El-Khayat
- Department of Gastroenterology, Hepatology and Endemic Medicine, Theodore Bilharz Research Institute, Cairo, Egypt
| | - E M Kamal
- Department of Gastroenterology, Hepatology and Endemic Medicine, Minia University Hospitals, Minia, Egypt
| | - M H El-Sayed
- Rheumatology Department, Cairo University Hospitals, Cairo, Egypt
| | - M El-Shabrawi
- Rheumatology Department, Cairo University Hospitals, Cairo, Egypt
| | - H Ayoub
- Department of Gastroenterology, Hepatology and Endemic Medicine, Ain Shams University Hospitals, Cairo, Egypt
| | - A RizK
- Rheumatology Department, Cairo University Hospitals, Cairo, Egypt
| | - M Maher
- Department of Gastroenterology, Hepatology and Endemic Medicine, Egyptian Military Academy, Cairo, Egypt
| | - R Y El Sheemy
- Department of Gastroenterology, Hepatology and Endemic Medicine, Minia University Hospitals, Minia, Egypt
| | - Y M Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Minia University Hospitals, Minia, Egypt
| | - D Attia
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Beni-suef University, Beni-suef, Egypt
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24
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Hallager S, Ladelund S, Christensen PB, Kjær M, Thorup Roege B, Grønbæk KE, Belard E, Barfod TS, Madsen LG, Gerstoft J, Tarp B, Krarup HB, Weis N. Liver-related morbidity and mortality in patients with chronic hepatitis C and cirrhosis with and without sustained virologic response. Clin Epidemiol 2017; 9:501-516. [PMID: 29123424 PMCID: PMC5661446 DOI: 10.2147/clep.s132072] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Chronic hepatitis C (CHC) causes liver cirrhosis in 5%-20% of patients, leading to increased morbidity and mortality. This study aimed to estimate liver-related morbidity and mortality among patients with CHC and cirrhosis in Denmark with and without antiviral treatment and sustained virologic response (SVR). Furthermore we aimed to estimate the rate of hepatocellular carcinoma (HCC) and decompensation associated with certain prognostic factors. MATERIALS AND METHODS Patients with CHC and cirrhosis registered in the Danish Database for Hepatitis B and C were eligible. Cirrhosis was based on liver biopsy, transient elastography, and clinical cirrhosis. Data were extracted from nationwide registries. The study period was from 2002 until 2013. RESULTS Of 1,038 patients included, 716 (69%) were male and the median age was 52 years. Median follow-up was 3.8 years, 360 patients died, and 233 of 519 treated patients achieved SVR. Alcohol overuse and hepatitis C virus genotype 3 were associated with an increased incidence rate (IR) of HCC, whereas diabetes and alcohol overuse were associated with increased IRs of decompensation. Achieving SVR reduced all-cause mortality (adjusted mortality rate ratio 0.68 [95% CI 0.43-1.09]) and liver-related mortality (mortality rate ratio 0.6 [95% CI 0.36-1]), as well as liver-related morbidity with adjusted IR ratios of 0.37 (95% CI 0.22-0.62) for HCC and 0.31 (95% CI 0.17-0.57) for decompensation. The IRs of HCC and decompensation remained elevated in patients with alcohol overuse after SVR. CONCLUSION Alcohol overuse, hepatitis C genotype 3, and diabetes were associated with liver-related morbidity in patients with CHC and cirrhosis. SVR markedly reduced liver-related morbidity and mortality; however, special attention to patients with alcohol overuse should continue after SVR.
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Affiliation(s)
- Sofie Hallager
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre
| | - Steen Ladelund
- Clinical Research Center, Copenhagen University Hospital, Hvidovre
| | - Peer Brehm Christensen
- Department of Infectious Diseases and Clinical Institute, Odense University Hospital, University of Southern Denmark, Odense
| | - Mette Kjær
- Department of Hepatology, Copenhagen University Hospital, Rigshospitalet
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen
| | | | | | - Erika Belard
- Department of Gastroenterology, Copenhagen University Hospital, Herlev
| | - Toke S Barfod
- Department of Internal Medicine, Zealand University Hospital, Roskilde
| | | | - Jan Gerstoft
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet
| | - Britta Tarp
- Diagnostic Centre, University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg
| | - Henrik Bygum Krarup
- Section of Molecular Diagnostics, Clinical Biochemistry and Department of Medical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Nina Weis
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen
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25
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Hepatitis C: Review of the Epidemiology, Clinical Care, and Continued Challenges in the Direct Acting Antiviral Era. CURR EPIDEMIOL REP 2017; 4:174-185. [PMID: 28785531 DOI: 10.1007/s40471-017-0108-x] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW This review highlights key studies and recently published data, policies, and recommendations related to hepatitis C virus (HCV) epidemiology, transmission, and treatment. RECENT FINDINGS HCV is a leading cause of liver-related deaths, cirrhosis, and hepatocellular carcinoma. Since 2011 and accelerating since 2013, new, safe, tolerable, and curative therapies have considerably altered clinical and public health frameworks related to the prevention, control and clinical management of HCV. Nevertheless, there are several populations in the United States that are important to consider because of disparities in HCV prevalence and transmission risk. Adults born during 1945-1965 have an estimated anti-HCV antibody prevalence of ~3%, which is six times higher than among other adults, are often unaware of their infections, and are at increased risk of having HCV-associated morbidity and mortality from decades of chronic infection. Since the early 2000s, increasing incidence of acute HCV infections among young, white, non-urban people who inject drugs have been reported. Despite promising therapeutic advances, significant challenges remain for reducing HCV-associated morbidity and mortality. SUMMARY The high burden of HCV and significant health consequences associated with chronic infection make HCV a critical public health priority. Advances in HCV treatment have created new opportunities for reducing HCV-associated morbidity and mortality. These treatments are safe, well-tolerated, and highly effective; however, benefits cannot be realized without a significant increase in the number of persons tested for HCV so that all chronically infected individuals can be aware of their diagnosis and linked to appropriate clinical care.
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26
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Chlibek R, Smetana J, Sosovickova R, Gal P, Dite P, Stepanova V, Pliskova L, Plisek S. Prevalence of hepatitis C virus in adult population in the Czech Republic - time for birth cohort screening. PLoS One 2017; 12:e0175525. [PMID: 28406947 PMCID: PMC5391198 DOI: 10.1371/journal.pone.0175525] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 03/27/2017] [Indexed: 12/15/2022] Open
Abstract
Chronic hepatitis C is curable disease. Low detection rate could be one of the reasons of poor treatment uptake. It is important to identify HCV prevalence and anti-hepatitis C virus (HCV) positive patients in population by effective screening strategy such as risk-based or birth cohort screening programs. There are no national population-based estimates of the HCV prevalence in the Czech Republic (CZ). The most recent seroprevalence survey determined a prevalence of positive anti-HCV antibodies of 0.2% (in 2001). The aim of the study was to determine the seroprevalence of HCV, HCV viraemia and HCV genotype in the CZ adult population. We also estimated the number of persons living with chronic hepatitis C in CZ. The examined group included 3000 adults, 18-90 years of age enrolled in 2015. All serum samples were examined to determined anti-HCV antibodies positivity, HCV-RNA positivity and genotypes. Of the 3000 samples, 50 were found to be anti-HCV-positive, for a seroprevalence of 1.67% (2.39% in males, 0.98% in females). The overall prevalence of positive HCV RNA was 0.93%: 1.5% in males, 0.39% in females. HCV genotype (GT) 1a was determined in 25%, GT 1b in 25% and GT 3a in 46%. Since 2001, the HCV seroprevalence has increased 8-fold. The highest HCV seroprevalence occurred in males aged 30-44 years. We can estimate that there are more than 140,000 people with HCV antibodies and more than 80,000 people with chronic hepatitis C living in the CZ. The introduction of birth cohort HCV screening could be beneficial for the country.
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Affiliation(s)
- Roman Chlibek
- Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic
| | - Jan Smetana
- Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic
| | - Renata Sosovickova
- Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic
| | - Peter Gal
- Military Health Institute, Prague, Czech Republic
| | - Petr Dite
- Military Health Institute, Prague, Czech Republic
| | - Vlasta Stepanova
- Department of Clinical Microbiology, University Hospital Hradec Kralove, Czech Republic
| | - Lenka Pliskova
- Department of Clinical Chemistry and Diagnostics, University Hospital Hradec Kralove, Czech Republic
| | - Stanislav Plisek
- Department of Infectious Diseases, Charles University Medical Faculty and University Hospital Hradec Kralove, Czech Republic
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27
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Yang CHT, Yoo ER, Ahmed A. The Role of Direct-acting Antivirals in the Treatment of Children with Chronic Hepatitis C. J Clin Transl Hepatol 2017; 5:59-66. [PMID: 28507928 PMCID: PMC5411358 DOI: 10.14218/jcth.2016.00053] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 12/13/2016] [Accepted: 01/05/2017] [Indexed: 12/13/2022] Open
Abstract
In the United States, chronic infection with the hepatitis C virus (HCV) affects an estimated 0.1-2% of the pediatric population, who are consequently at risk for major complications, including cirrhosis, hepatocellular carcinoma, and death. The current standard of treatment for chronic hepatitis C (CHC) in children is pegylated-interferon-alpha (PEG-IFN) in combination with ribavirin. PEG-IFN/ribavirin therapy is approved for children ages 3 and older; however, it is often held from use until adulthood because of its extensive list of potential side effects and high likelihood of causing adverse symptoms. While CHC is usually indolent in children and adolescents, immediately treating and curbing the spread of HCV before adulthood is important, as there can be transmission to other individuals via sexual activity and infected females can later vertically transmit the infection during pregnancy, the latter representing the most common means of transmission for children in the United States. The recent development of direct-acting antivirals has shown promising results in clinical trials for use in children and has dramatically increased the rates of sustained virological response in adults while improving side effect profiles as compared to interferon-based treatments. Given the usually indolent course of CHC in children, significant side effects of the currently-approved PEG-IFN/ribavirin therapy, and likely availability of all-oral interferon-free regimens for children within a few years, deferring treatment in clinically-stable children with CHC in anticipation of upcoming superior treatment modalities may be justified.
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Affiliation(s)
- Christine Hong Ting Yang
- Division of Pediatric Gastroenterology, Stanford University School of Medicine, Stanford, CA, USA
| | - Eric R. Yoo
- Department of Medicine, University of Illinois College of Medicine, Chicago, IL, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
- *Correspondence to: Aijaz Ahmed, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 750 Welch Road, Suite #210, Stanford, CA 94304, USA. Tel: +1-650-498-5691, Fax: +1-650-498-5692, E-mail:
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28
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Ivanov AV, Valuev-Elliston VT, Tyurina DA, Ivanova ON, Kochetkov SN, Bartosch B, Isaguliants MG. Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis. Oncotarget 2017; 8:3895-3932. [PMID: 27965466 PMCID: PMC5354803 DOI: 10.18632/oncotarget.13904] [Citation(s) in RCA: 123] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Accepted: 12/05/2016] [Indexed: 12/11/2022] Open
Abstract
Virally induced liver cancer usually evolves over long periods of time in the context of a strongly oxidative microenvironment, characterized by chronic liver inflammation and regeneration processes. They ultimately lead to oncogenic mutations in many cellular signaling cascades that drive cell growth and proliferation. Oxidative stress, induced by hepatitis viruses, therefore is one of the factors that drives the neoplastic transformation process in the liver. This review summarizes current knowledge on oxidative stress and oxidative stress responses induced by human hepatitis B and C viruses. It focuses on the molecular mechanisms by which these viruses activate cellular enzymes/systems that generate or scavenge reactive oxygen species (ROS) and control cellular redox homeostasis. The impact of an altered cellular redox homeostasis on the initiation and establishment of chronic viral infection, as well as on the course and outcome of liver fibrosis and hepatocarcinogenesis will be discussed The review neither discusses reactive nitrogen species, although their metabolism is interferes with that of ROS, nor antioxidants as potential therapeutic remedies against viral infections, both subjects meriting an independent review.
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Affiliation(s)
- Alexander V. Ivanov
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
| | | | - Daria A. Tyurina
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
| | - Olga N. Ivanova
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
| | - Sergey N. Kochetkov
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
| | - Birke Bartosch
- Inserm U1052, Cancer Research Center Lyon, University of Lyon, Lyon, France
- DevWeCan Laboratories of Excellence Network, France
| | - Maria G. Isaguliants
- Riga Stradins University, Riga, Latvia
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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29
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Petruzziello A, Marigliano S, Loquercio G, Cacciapuoti C. Hepatitis C virus (HCV) genotypes distribution: an epidemiological up-date in Europe. Infect Agent Cancer 2016; 11:53. [PMID: 27752280 PMCID: PMC5062817 DOI: 10.1186/s13027-016-0099-0] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Accepted: 09/02/2016] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a major public health burden in Europe, causing an increasing level of liver-related morbidity and mortality, characterized by several regional variations in the genotypes distribution. A comprehensive review of the literature from 2000 to 2015 was used to gather country-specific data on prevalence and genotype distribution of HCV infection in 33 European countries (about 80 % of the European population), grouped in three geographical areas (Western, Eastern and Central Europe), as defined by the Global Burden of Diseases project (GBD). The estimated prevalence of HCV in Europe is 1.7 % showing a decrease than previously reported (− 0.6 %) and accounting over 13 million of estimated cases. The lowest prevalence (0.9 %) is reported from Western Europe (except for some rural areas of Southern Italy and Greece) and the highest (3.1 %) from Central Europe, especially Romania and Russia. The average HCV viraemic rate is 72.4 %, with a population of almost 10 million of HCV RNA positive patients. Genotype distribution does not show high variability among the three macro-areas studied, ranging between 70.0 % (Central Europe), 68.1 % (Eastern Europe) and 55.1 % (Western Europe) for genotype 1, 29.0 % (Western Europe), 26.6 % (Eastern Europe) and 21.0 % (Central Europe) for genotype 3. Genotype 2 seems, instead, to have a major prevalence in the Western Europe (8.9 %), if compared to Eastern (4.3 %) or Central (3.2 %), whereas genotype 4 is present especially in Central and Western area (4.9 % and 5.8 %, respectively). Despite the eradication of transmission by blood products, HCV infection continues to be one of the leading blood-borne infections in Europe. The aim of this review is, therefore, to provide an update on the epidemiology of HCV infection across Europe, and to foster the discussion about eventual potential strategies to eradicate it.
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Affiliation(s)
- Arnolfo Petruzziello
- Virology and Molecular Biology Unit "V. Tridente", Istituto Nazionale Tumori - Fondazione "G. Pascale", IRCCS Italia, Via Mariano Semmola, 80131 Naples, Italy
| | - Samantha Marigliano
- Virology and Molecular Biology Unit "V. Tridente", Istituto Nazionale Tumori - Fondazione "G. Pascale", IRCCS Italia, Via Mariano Semmola, 80131 Naples, Italy
| | - Giovanna Loquercio
- Virology and Molecular Biology Unit "V. Tridente", Istituto Nazionale Tumori - Fondazione "G. Pascale", IRCCS Italia, Via Mariano Semmola, 80131 Naples, Italy
| | - Carmela Cacciapuoti
- Virology and Molecular Biology Unit "V. Tridente", Istituto Nazionale Tumori - Fondazione "G. Pascale", IRCCS Italia, Via Mariano Semmola, 80131 Naples, Italy
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Kapol N, Lochid-Amnuay S, Teerawattananon Y. Economic evaluation of pegylated interferon plus ribavirin for treatment of chronic hepatitis C in Thailand: genotype 1 and 6. BMC Gastroenterol 2016; 16:91. [PMID: 27492396 PMCID: PMC4974770 DOI: 10.1186/s12876-016-0506-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 07/29/2016] [Indexed: 12/12/2022] Open
Abstract
Background Pegylated interferon alpha 2a, alpha 2b and ribavirin have been included to the National List of Essential Medicines (NLEM) for treatment of only chronic hepatitis C genotypes 2 and 3 in Thailand. This reimbursement policy has not covered for other genotypes of hepatitis C virus infection (HCV) especially for genotypes 1 and 6 that account for 30-50 % of all HCV infection in Thailand. Therefore, this research determined whether pegylated interferon alpha 2a or alpha 2b plus ribavirin is more cost-effective than a palliative care for treatment of HCV genotype 1 and 6 in Thailand. Methods A cost-utility analysis using a model-based economic evaluation was conducted based on a societal perspective. A Markov model was developed to estimate costs and quality-adjusted life years (QALYs) comparing between the combination of pegylated interferon alpha 2a or alpha 2b and ribavirin with a usual palliative care for genotype 1 and 6 HCV patients. Health-state transition probabilities, virological responses, and utility values were obtained from published literatures. Direct medical and direct non-medical costs were included and retrieved from published articles and Thai Standard Cost List for Health Technology Assessment. The incremental cost-effectiveness ratio (ICER) was presented as costs in Thai baht per QALY gained. Results HCV treatment with pegylated interferon alpha 2a or alpha 2b plus ribavirin was dominant or cost-saving in Thailand compared to a palliative care. The ICER value was negative with lower in total costs (peg 2a- 747,718vs. peg 2b- 819,921 vs. palliative care- 1,169,121 Thai baht) and more in QALYs (peg 2a- 13.44 vs. peg 2b- 13.14 vs. palliative care- 11.63 years) both in HCV genotypes 1 and 6. Conclusion As cost-saving results, the Subcommittee for Development of the NLEM decided to include both pegylated interferon alpha 2a and alpha 2b into the NLEM for treatment of HCV genotype 1 and 6 recently. Economic evaluation for these current drugs can be further applied to other novel medications for HCV treatment.
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Affiliation(s)
- Nattiya Kapol
- Department of Community Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand, 73000.
| | - Surasit Lochid-Amnuay
- Department of Community Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand, 73000
| | - Yot Teerawattananon
- Health Intervention and Technology Assessment Program (HITAP), Ministry of Public Health, Nonthaburi, Thailand
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Affiliation(s)
- Yen H Pham
- Texas Children's Hospital, Baylor College of Medicine, 18200 Katy Freeway, Suite 250, Houston, TX 77094, USA.
| | - Philip Rosenthal
- UCSF Benioff Children's Hospital, University of California San Francisco, 550 16th Street, 5th Floor, San Francisco, CA 94143, USA
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Mostafa A, Shimakawa Y, Medhat A, Mikhail NN, Chesnais CB, Arafa N, Bakr I, El Hoseiny M, El-Daly M, Esmat G, Abdel-Hamid M, Mohamed MK, Fontanet A. Excess mortality rate associated with hepatitis C virus infection: A community-based cohort study in rural Egypt. J Hepatol 2016; 64:1240-6. [PMID: 26921686 DOI: 10.1016/j.jhep.2016.02.033] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 02/12/2016] [Accepted: 02/16/2016] [Indexed: 12/28/2022]
Abstract
BACKGROUND & AIMS >80% of people chronically infected with hepatitis C virus (HCV) live in resource-limited countries, yet the excess mortality associated with HCV infection in these settings is poorly documented. METHODS Individuals were recruited from three villages in rural Egypt in 1997-2003 and their vital status was determined in 2008-2009. Mortality rates across the cohorts were compared according to HCV status: chronic HCV infection (anti-HCV antibody positive and HCV RNA positive), cleared HCV infection (anti-HCV antibody positive and HCV RNA negative) and never infected (anti-HCV antibody negative). Data related to cause of death was collected from a death registry in one village. RESULTS Among 18,111 survey participants enrolled in 1997-2003, 9.1% had chronic HCV infection, 5.5% had cleared HCV infection, and 85.4% had never been infected. After a mean time to follow-up of 8.6years, vital status was obtained for 16,282 (89.9%) participants. When compared to those who had never been infected with HCV in the same age groups, mortality rate ratios (MRR) of males with chronic HCV infection aged <35, 35-44, and 45-54years were 2.35 (95% CI 1.00-5.49), 2.87 (1.46-5.63), and 2.22 (1.29-3.81), respectively. No difference in mortality rate was seen in older males or in females. The all-cause mortality rate attributable to chronic HCV infection was 5.7% (95% CI: 1.0-10.1%), while liver-related mortality was 45.5% (11.3-66.4%). CONCLUSIONS Use of a highly potent new antiviral agent to treat all villagers with positive HCV RNA may reduce all-cause mortality rate by up to 5% and hepatic mortality by up to 40% in rural Egypt.
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Affiliation(s)
- Aya Mostafa
- Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Yusuke Shimakawa
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France
| | - Ahmed Medhat
- Department of Gastroenterology & Tropical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Nabiel N Mikhail
- Department of Biostatistics and Cancer Epidemiology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Cédric B Chesnais
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France; UMI 233, Institut de Recherche pour le Développement (IRD), Montpellier, France
| | - Naglaa Arafa
- Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Iman Bakr
- Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mostafa El Hoseiny
- Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mai El-Daly
- Viral Hepatitis Research Laboratory, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Gamal Esmat
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Abdel-Hamid
- Viral Hepatitis Research Laboratory, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, Egypt
| | - Mostafa K Mohamed
- Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Arnaud Fontanet
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France; Département d'Infection et Épidémiologie, Conservatoire National des Arts et Métiers, Paris, France.
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Tholey DM, Ahn J. Impact of Hepatitis C Virus Infection on Hepatocellular Carcinoma. Gastroenterol Clin North Am 2015; 44:761-73. [PMID: 26600218 DOI: 10.1016/j.gtc.2015.07.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) incidence in the United States is increasing, partly because of risk factors such as diabetes, fatty liver, hepatitis B virus, and human immunodeficiency virus coinfection. Achieving sustained virologic response (SVR) is the most significant factor in reducing HCV-associated HCC incidence. Improved SVR with the next generation of direct-acting antivirals brings hope for decreased HCC mortality. Nevertheless, surveillance for HCC remains important because HCC can still occur despite SVR, especially in cirrhotics. Individualized risk stratification through increased understanding of HCC pathogenesis and improved surveillance holds the promise for future reduction of HCC incidence.
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Affiliation(s)
- Danielle M Tholey
- Gastroenterology & Hepatology, Oregon Health & Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA
| | - Joseph Ahn
- Division of Gastroenterology and Hepatology, Oregon Health & Sciences University, 3181 Southwest Sam Jackson Park Road, Mail Code L461, Portland, OR 97239, USA.
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van der Meer AJ. Value anti-hepatitis C virus therapy by its clinical efficacy. Hepatology 2015; 62:334-6. [PMID: 25892650 DOI: 10.1002/hep.27850] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 04/14/2015] [Indexed: 12/15/2022]
Affiliation(s)
- Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
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Hartwell D, Cooper K, Frampton GK, Baxter L, Loveman E. The clinical effectiveness and cost-effectiveness of peginterferon alfa and ribavirin for the treatment of chronic hepatitis C in children and young people: a systematic review and economic evaluation. Health Technol Assess 2015; 18:i-xxii, 1-202. [PMID: 25350588 DOI: 10.3310/hta18650] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Optimal therapy for children with chronic hepatitis C is unclear. Two treatment regimens are currently licensed in children. OBJECTIVES To assess the clinical effectiveness and cost-effectiveness of peginterferon alfa-2a (Pegasys®, Roche) and peginterferon alfa-2b [ViraferonPeg®, Merck Sharp & Dohme (MSD)] in combination with ribavirin (RBV), within their licensed indications, for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3-17 years. DATA SOURCES Twelve electronic bibliographic databases, including The Cochrane Library, MEDLINE and EMBASE, were searched from inception to November 2012. Bibliographies of retrieved papers, key hepatitis C websites and symposia and manufacturers' submissions to the National Institute for Health and Care Excellence were also searched, and clinical experts were contacted. REVIEW METHODS Systematic reviews of clinical effectiveness and cost-effectiveness were conducted, including studies of health-related quality of life (HRQoL), following standard guidelines to ensure methodological rigour. Clinical effectiveness studies were included if they were in children and young people aged 3-17 years with chronic compensated HCV of any severity, including those with human immunodeficiency virus co-infection and those who were treatment naive or had been previously treated. Eligible interventions were peginterferon alfa-2a or peginterferon alfa-2b, each in combination with RBV, compared against best supportive care (BSC) or against each other, and study designs were randomised controlled trials (RCTs) or non-RCTs, or uncontrolled cohort studies. Outcomes included sustained virological response (SVR) and adverse events. Previously published Markov state-transition economic models of chronic HCV in adults were adapted to estimate the cost-effectiveness of peginterferon alfa-2a and -2b (in combination with RBV), compared with BSC and with one another in children. The model extrapolated the impact of SVR on life expectancy, quality-adjusted life expectancy and lifetime costs. Uncertainty was explored through probabilistic and deterministic sensitivity analyses. RESULTS Seven studies [two peginterferon alfa-2a and RBV (Copegus®, Roche), and five peginterferon alfa-2b and RBV (Rebetol®, MSD)] were included in the review of clinical effectiveness. Six were single-arm cohort studies and one was a RCT for which only those data for a single arm met the inclusion criteria. Overall, the studies were relatively small and of generally poor quality. SVR rates ranged from 53% to 66% (peginterferon alfa-2a) and 29% to 75% (peginterferon alfa-2b) (49% to 65% if excluding two studies with very small sample sizes). Rates of non-response and relapse were variable and adverse events were generally mild. No studies of cost-effectiveness or HRQoL in children and young people met the inclusion criteria. HRQoL, utilities and costs of treatment were therefore taken from studies of adults with chronic HCV. From this model, peginterferon alfa (-2a or -2b) in combination with RBV was more effective and had lower lifetime costs than BSC. Peginterferon alfa-2a had slightly lower lifetime costs and higher quality-adjusted life-years than peginterferon alfa-2b; therefore, peginterferon alfa-2b was dominated by peginterferon alfa-2a. Results were robust to changes in the sensitivity analyses. LIMITATIONS There were few good quality studies and parameter data had to be taken from adult studies, which is a limitation of the work. CONCLUSIONS Treatment of children and young people with peginterferon (alfa-2a or -2b) and RBV may be an effective therapy. Results from the independent Markov model suggest that peginterferon (alfa-2a or -2b) in combination with RBV is cost-effective compared with BSC. However, the available evidence is of poor quality. Future research into the impact of these treatments on growth and quality of life in children and young people is recommended. STUDY REGISTRATION This study is registered as PROSPERO CRD42012002743. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Debbie Hartwell
- Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK
| | - Keith Cooper
- Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK
| | - Geoff K Frampton
- Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK
| | - Louise Baxter
- Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK
| | - Emma Loveman
- Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK
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Abstract
Hepatitis C virus infection is a leading cause of liver-related morbidity and mortality. In the paediatric population, HCV infection is underdiagnosed and undertreated in the absence of robust screening policies worldwide, and a lack of tolerable, effective treatment. The recent advances in HCV drug development allow for optimism, a change in outcomes for the millions of children infected with this virus and a unique opportunity for strategies aiming at HCV eradication. The rapid development of the new compounds has been followed by a welcome shift in the regulatory processes; however, strategies aiming at improving diagnosis, selecting the best combinations and addressing mother-to-child transmission issues are required for the new therapeutic agents to be introduced safely and effectively in the paediatric population and to contribute to the goal of virus eradication.
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Eradikation des Hepatitis-C-Virus und Verhinderung klinischer Endpunkte. GASTROENTEROLOGE 2015. [DOI: 10.1007/s11377-015-0995-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Gentile I, Borgia G. A pill a day keeps HCV away. THE LANCET. INFECTIOUS DISEASES 2015; 15:616-7. [PMID: 25863561 DOI: 10.1016/s1473-3099(15)70127-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples, Naples 80131, Italy.
| | - Guglielmo Borgia
- Department of Clinical Medicine and Surgery, University of Naples, Naples 80131, Italy
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Marinho RT, Duarte H, Gíria J, Nunes J, Ferreira A, Velosa J. The burden of alcoholism in fifteen years of cirrhosis hospital admissions in Portugal. Liver Int 2015; 35:746-55. [PMID: 24750642 DOI: 10.1111/liv.12569] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Accepted: 04/17/2014] [Indexed: 12/27/2022]
Abstract
BACKGROUND & AIMS Deploying a longitudinal perspective, we observe how cirrhosis caused mortality rates in Portugal are converging with the levels reported in the European Union (15 countries). However, we still lack analysis of the burden of alcoholic cirrhosis in terms of hospital admissions and associated mortality. As Portugal may be considered a paradigmatic case in Europe, our aim was to characterize the evolution of hospital admissions for alcoholic cirrhosis between 1993 and 2008 and draw conclusions for other countries. METHODS Retrospective analysis of the hepatic cirrhosis admissions in 97 Portuguese state hospitals was carried out based on the National Registry. RESULTS We report a convergence in terms of mortality rates resulting from cirrhosis between Portugal and European Union (a differential of 6.7 deaths per 100 000 habitants in 1994 to 0.4 in 2008). We accounted for 81 543 hospital admissions for cirrhosis: 84% for alcoholic cirrhosis and 16% for non-alcoholic cirrhosis. Hospital admissions have increased 29% in men and with no increase in women. In the male, alcoholic cirrhosis patient group aged between 40 and 54, the rise in hospital admissions was more pronounced with an increase of around 45%. These patients underwent longer lengths of stay and reported higher mortality rates and passing away 20 years earlier than the average national expectancy of life. CONCLUSIONS These data draw attention to the burden of alcohol consumption not only in Portugal but also in other countries and its impacts on hospital systems and on policy making.
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Affiliation(s)
- Rui T Marinho
- Department of Gastroenterology and Hepatology, University Hospital of Santa Maria, Medical School of Lisbon, Lisbon, Portugal
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Khaderi S, Shepherd R, Goss JA, Leung DH. Hepatitis C in the pediatric population: Transmission, natural history, treatment and liver transplantation. World J Gastroenterol 2014; 20:11281-11286. [PMID: 25170212 PMCID: PMC4145766 DOI: 10.3748/wjg.v20.i32.11281] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Accepted: 05/14/2014] [Indexed: 02/06/2023] Open
Abstract
The number of children affected by the hepatitis C virus (HCV) in the United States is estimated to be between 23000 to 46000. The projected medical cost for children with HCV in the United States is upwards of 200 million over the next decade. The implementation of routine screening of blood supply has virtually eliminated transmission via transfusion and vertical transmission is now the most common mode of infection in children. Infections acquired during infancy are more likely to spontaneously resolve and fibrosis of the liver tends to increase with age suggesting slow progressive histologic injury. Anti-viral treatment may be warranted in children with persistently elevated liver enzymes or with significant fibrosis on liver biopsy. Current standard of care includes weekly pegylated interferon and ribavirin twice daily. Predictors of high sustained viral response include genotype 2 and 3 and low viral load in children with genotype 1 (< 600000 IU/mL). Triple therapy is associated with a significantly higher rate of sustained virologic response (> 90%). Only 34 pediatric patients were transplanted with hepatitis C between January 2008 and April 2013. The majority of pediatric patients were born prior to universal screening of blood products and, as of June 2013, there are only two pediatric patients awaiting liver transplantation for end-stage liver disease secondary to hepatitis C. Pediatric survival rates post-transplant are excellent but graft survival is noticeably reduced compared to adults (73.73% for pediatric patients at one year compared to 87.69% in adult patients). New safe potent, and all-oral effective antiviral therapies for recurrent HCV should help increase graft survival.
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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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Fracture risk in hepatitis C virus infected persons: results from the DANVIR cohort study. J Hepatol 2014; 61:15-21. [PMID: 24650694 DOI: 10.1016/j.jhep.2014.03.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2013] [Revised: 03/06/2014] [Accepted: 03/07/2014] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS The association between Hepatitis C virus (HCV)-infection and fracture risk is not well characterized. We compared fracture risk between HCV-seropositive (HCV-exposed) patients and the general population and between patients with cleared and chronic HCV-infection. METHODS Outcome measures were time to first fracture at any site, time to first low-energy and first non-low-energy (other) fracture in 12,013 HCV-exposed patients from the DANVIR cohort compared with a general population control cohort (n=60,065) matched by sex and age. Within DANVIR, 4500 patients with chronic HCV-infection and 2656 patients with cleared HCV-infection were studied. RESULTS Compared with population controls, HCV-exposed patients had increased overall risk of fracture [adjusted incidence rate ratio (aIRR) 2.15, 95% Confidence Interval (CI) 2.03-2.28], increased risk of low-energy fracture (aIRR 2.13, 95% CI: 1.93-2.35) and of other fracture (aIRR 2.18, 95% CI: 2.02-2.34). Compared with cleared HCV-infection, chronic HCV-infection was not associated with increased risk of fracture at any site (aIRR 1.08, 95% CI: 0.97-1.20), or other fracture (aIRR 1.04, 95% CI: 0.91-1.19). The aIRR for low-energy fracture was 1.20 (95% CI: 0.99-1.44). CONCLUSIONS HCV-exposed patients had increased risk of all fracture types. In contrast, overall risk of fracture did not differ between patients with chronic vs. cleared HCV-infection, although chronic HCV-infection might be associated with a small excess risk of low-energy fractures. Our study suggests that fracture risk in HCV-infected patients is multi-factorial and mainly determined by lifestyle-related factors associated with HCV-exposure.
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Younossi ZM, Kanwal F, Saab S, Brown KA, El-Serag HB, Kim WR, Ahmed A, Kugelmas M, Gordon SC. The impact of hepatitis C burden: an evidence-based approach. Aliment Pharmacol Ther 2014; 39:518-31. [PMID: 24461160 DOI: 10.1111/apt.12625] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Revised: 10/11/2013] [Accepted: 12/30/2013] [Indexed: 12/08/2022]
Abstract
BACKGROUND Infection with the hepatitis C virus (HCV) has been considered a major cause of mortality, morbidity and resource utilisation in the US. In addition, HCV is the main cause of hepatocellular cancer (HCC) in the US. Recent developments in the diagnosis and treatment of HCV, including new recommendations pertaining to screening for HCV by the Centers for Disease Control and Prevention and newer treatment regimens with high efficacy, short duration and the potential for interferon-free therapies, have energised the health care practitioners regarding HCV management. AIM To assess the full impact of HCV burden on clinical, economic and patient-reported outcomes. METHODS An expert panel was convened to assess the full impact of HCV burden on a number of important outcomes using an evidence-based approach predicated on Grading of Recommendations Assessment, Development and Evaluation methodology. The literature was summarised, graded using an evidence-based approach and presented during the workshop. Workshop presentations were intended to review recent, relevant evidence-based literature and provide graded summary statements pertaining to HCV burden on topics including the relationships between HCV and the development of important outcomes. RESULTS The associations of HCV with cirrhosis, HCC, liver-related mortality, type 2 diabetes mellitus, rheumatological diseases and quality of life impairments are supported by strong evidence. Also, there is strong evidence that sustained viral eradication of HCV can improve important outcomes such as mortality and quality of life. CONCLUSIONS The current evidence suggests that HCV has been associated with tremendous clinical, economic and quality of life burden.
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Affiliation(s)
- Z M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA; Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, Falls Church, VA, USA
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van der Meer AJ, Wedemeyer H, Feld JJ, Hansen BE, Manns MP, Zeuzem S, Janssen HLA. Is there sufficient evidence to recommend antiviral therapy in hepatitis C? J Hepatol 2014; 60:191-6. [PMID: 23973931 DOI: 10.1016/j.jhep.2013.07.043] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 06/17/2013] [Accepted: 07/15/2013] [Indexed: 12/16/2022]
Abstract
While patients with chronic hepatitis C virus (HCV) infection are treated in order to prevent liver-related morbidity and mortality, we rely on sustained virological response (SVR) as a virological biomarker to evaluate treatment efficacy in both clinical practice as well as in drug development. However, conclusive evidence for the clinical benefit of antiviral therapy or validity of SVR as surrogate marker, as derived from trials randomizing patients to a treatment or control arm, is lacking. In fact, the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial recently showed an increased mortality rate among interferon-treated patients compared to untreated controls. Consequently, the recommendation to treat patients with chronic HCV infection was challenged. Here, we argue that the possible harmful effect of long-term low-dose pegylated interferon mono therapy, as was observed in the HALT-C trial cohort, cannot be extrapolated to potentially curative short-term treatment regimens. Furthermore, we discuss SVR as a surrogate biomarker, based on numerous studies which indicated an association between SVR and improvements in health-related quality of life, hepatic inflammation and fibrosis, and portal pressure as well as a reduced risk for hepatocellular carcinoma (HCC), liver failure and mortality.
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Affiliation(s)
- Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany
| | - Jordan J Feld
- Liver Centre, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
| | - Bettina E Hansen
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Michael P Manns
- Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany; Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
| | - S Zeuzem
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
| | - Harry L A Janssen
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Liver Centre, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
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Fuster D, Cheng DM, Quinn EK, Nunes D, Saitz R, Samet JH, Tsui JI. Chronic hepatitis C virus infection is associated with all-cause and liver-related mortality in a cohort of HIV-infected patients with alcohol problems. Addiction 2014; 109:62-70. [PMID: 24112091 PMCID: PMC3947001 DOI: 10.1111/add.12367] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Revised: 04/23/2013] [Accepted: 09/12/2013] [Indexed: 12/12/2022]
Abstract
AIMS To assess the association between hepatitis C virus (HCV) infection and overall and liver-related death in human immunodeficiency virus (HIV)-infected patients with alcohol problems. DESIGN We analyzed data from a cohort of HIV-infected adults with current or past alcohol problems enrolled between 2001 and 2003, searching for causes of death until 2010 using the National Death Index. SETTING AND PARTICIPANTS Participants were HIV-infected adults with current or past alcohol problems, recruited in Boston, MA from HIV clinics at two hospitals, homeless shelters, drug treatment programs, subject referrals, flyers and another cohort study with comparable recruitment sites. MEASUREMENTS The primary and secondary outcomes were all-cause and liver-related mortality, respectively. The main independent variable was hepatitis C virus (HCV) RNA status (positive versus negative). Mortality rates and Kaplan-Meier survival curves were calculated by HCV status for both overall and liver-related mortality. Cox proportional hazards models were used to assess the association between HCV infection and overall and liver-related death, adjusting for alcohol and drug use over time. FINDINGS A total of 397 adults (50% HCV-infected) were included. As of 31 December 2009, 83 cohort participants had died (60 HCV-infected, 23 HCV-uninfected; log-rank test P < 0.001), and 26 of those deaths were liver-related (21 HCV-infected, five HCV-uninfected; log-rank test P < 0.001). All-cause and liver-related mortality rates were 4.68 and 1.64 deaths per 100 person-years for HCV-infected patients and 1.65 and 0.36 per 100 person-years for those without HCV, respectively. In the fully adjusted Cox model, HCV infection was associated with both overall [hazard ratio (HR) = 2.55, 95% confidence interval (CI) = 1.50-4.33, P < 0.01], and liver-related mortality (HR = 3.24, 95% CI = 1.18-8.94, P = 0.02]. CONCLUSION Hepatitis C virus infection is associated independently with all-cause and liver-related mortality in human immunodeficiency virus-infected patients with alcohol problems, even when accounting for alcohol and other drug use.
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Affiliation(s)
- Daniel Fuster
- Clinical Addiction Research and Education (CARE) Unit, Section of General Internal Medicine, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, MA, USA
| | - Debbie M. Cheng
- Clinical Addiction Research and Education (CARE) Unit, Section of General Internal Medicine, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, MA, USA,Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
| | - Emily K. Quinn
- Data Coordinating Center, Boston University School of Public Health, Boston, MA, USA
| | - David Nunes
- Section of Gastroenterology, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, MA, USA
| | - Richard Saitz
- Clinical Addiction Research and Education (CARE) Unit, Section of General Internal Medicine, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, MA, USA,Department of Epidemiology, Boston University School of Public Health, Boston, MA
| | - Jeffrey H. Samet
- Clinical Addiction Research and Education (CARE) Unit, Section of General Internal Medicine, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, MA, USA,Department of Community Health Sciences, Boston University School of Public Health, Boston, MA
| | - Judith I. Tsui
- Clinical Addiction Research and Education (CARE) Unit, Section of General Internal Medicine, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, MA, USA
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Jepsen P, Vilstrup H, Lash TL. Development and validation of a comorbidity scoring system for patients with cirrhosis. Gastroenterology 2014; 146:147-56; quiz e15-6. [PMID: 24055278 DOI: 10.1053/j.gastro.2013.09.019] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Revised: 09/11/2013] [Accepted: 09/12/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS At least 40% of patients with cirrhosis have comorbidities that increase mortality. We developed a cirrhosis-specific comorbidity scoring system (CirCom) to help determine how these comorbidities affect mortality and compared it with the generic Charlson Comorbidity Index. METHODS We used data from nationwide health care registries to identify Danish citizens diagnosed with cirrhosis in 1999-2008 (n = 12,976). They were followed through 2010 and characterized by 34 comorbidities. We used Cox regression to assign severity weights to comorbidities with an adjusted mortality hazard ratio (HR) ≥ 1.20. Each patient's CirCom score was based on, at most, 2 of these comorbidities. Performance was measured with Harrell's C statistic and the Net Reclassification Index (NRI) and results were compared with those obtained using the Charlson Index (based on 17 comorbidities). Findings were validated in 2 separate cohorts of patients with alcohol-related cirrhosis or chronic hepatitis C. RESULTS The CirCom score included chronic obstructive pulmonary disease, acute myocardial infarction, peripheral arterial disease, epilepsy, substance abuse, heart failure, nonmetastatic cancer, metastatic cancer, and chronic kidney disease; 24.2% of patients had 1 or more of these, and mortality correlated with the CirCom score. Patients' CirCom score correlated with their Charlson Comorbidity Index (Kendall's τ = 0.57; P < .0001). Compared with the Charlson Index, the CirCom score increased Harrell's C statistic by 0.6% (95% confidence interval: 0.3%-0.8%). The NRI for the CirCom score was 5.2% (95% confidence interval: 3.7%-6.9%), and the NRI for the Charlson Index was 3.6% (95% confidence interval: 2.3%-5.0%). Similar results were obtained from the validation cohorts. CONCLUSIONS We developed a scoring system to predict mortality among patients with cirrhosis based on 9 comorbidities. This system had higher C statistic and NRI values than the Charlson Comorbidity Index, and is easier to use. It could therefore be a preferred method to predict death or survival of patients and for use in epidemiologic studies.
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Affiliation(s)
- Peter Jepsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Timothy L Lash
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
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A multidisciplinary support programme increases the efficiency of pegylated interferon alfa-2a and ribavirin in hepatitis C. J Hepatol 2013; 59:926-33. [PMID: 23811030 DOI: 10.1016/j.jhep.2013.06.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2013] [Revised: 06/18/2013] [Accepted: 06/19/2013] [Indexed: 12/30/2022]
Abstract
BACKGROUND & AIMS Adherence to antiviral treatment is important to achieve sustained virological response (SVR) in chronic hepatitis C (CHC). We evaluated the efficiency of a multidisciplinary support programme (MSP), based on published HIV treatment experience, to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC. METHODS 447 patients receiving antiviral treatment were distributed into 3 groups: control group (2003-2004, n=147), MSP group (2005-2006, n=131), and MSP-validation group (2007-2009, n=169). The MSP group included two hepatologists, two nurses, one pharmacist, one psychologist, one administrative assistant, and one psychiatrist. Cost-effectiveness analysis was performed using a Markov model. RESULTS Adherence and SVR rates were higher in the MSP (94.6% and 77.1%) and MSP-validation (91.7% and 74.6%) groups compared to controls (78.9% and 61.9%) (p<0.05 in all cases). SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls (67.7% vs. 48.9%, p=0.02) compared with genotypes 2 or 3 (87.7% vs. 81.4%, p=n.s.). The MSP was the main predictive factor of SVR in patients with genotype 1. The rate of adherence in patients with psychiatric disorders was higher in the MSP groups (n=95, 90.5%) compared to controls (n=28, 75.7%) (p=0.02). The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group. The MSP group achieved more quality-adjusted life years (QALYs) (16.317 QALYs) than controls (15.814 QALYs) and was dominant in all genotypes. CONCLUSIONS MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC, being cost-effective.
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Omland LH, Osler M, Jepsen P, Krarup H, Weis N, Christensen PB, Roed C, Sørensen HT, Obel N. Socioeconomic status in HCV infected patients - risk and prognosis. Clin Epidemiol 2013; 5:163-72. [PMID: 23766659 PMCID: PMC3678712 DOI: 10.2147/clep.s43926] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Background and aims It is unknown whether socioeconomic status (SES) is a risk factor for hepatitis C virus (HCV) infection or a prognostic factor following infection. Methods From Danish nationwide registries, we obtained information on three markers of SES: employment, income, and education. In a case control design, we examined HCV infected patients and controls; conditional logistic regression was employed to obtain odds ratios (ORs) for HCV infection for each of the three SES markers, adjusting for the other two SES markers, comorbidity, and substance abuse. In a cohort design, we used Cox regression analysis to compute mortality rate ratios (MRRs) for each of the three SES markers, adjusting for the other two SES markers, comorbidity level, age, substance abuse, and gender. Results When compared to employed persons, ORs for HCV infection were 2.71 (95% confidence interval [CI]: 2.24–3.26) for disability pensioners and 2.24 (95% CI: 1.83–2.72) for the unemployed. When compared to persons with a high income, ORs were 1.64 (95% CI: 1.34–2.01) for low income persons and 1.19 (95% CI: 1.02–1.40) for medium income persons. The OR was 1.35 (95% CI: 1.20–1.52) for low education (no more than basic schooling). When compared to employed patients, MRRs were 1.71 (95% CI: 1.22–2.40) for unemployed patients and 2.24 (95% CI: 1.63–3.08) for disability pensioners. When compared to high income patients, MRRs were 1.47 (95% CI: 1.05–2.05) for medium income patients and 1.64 (95% CI: 1.13–2.34) for low income patients. Educational status was not associated with mortality. Conclusion Low SES was associated with an increased risk of HCV infection and with poor prognosis in HCV infected patients.
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Affiliation(s)
- Lars Haukali Omland
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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