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Ferreira J, Sheflin-Findling S. Update on Pediatric Hepatitis C Infection. Curr Gastroenterol Rep 2025; 27:18. [PMID: 40019674 PMCID: PMC11870864 DOI: 10.1007/s11894-024-00955-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/03/2024] [Indexed: 03/01/2025]
Abstract
PURPOSEOF REVIEW Hepatitis C virus (HCV) infections continue to steadily increase in the United States and remain a major public health challenge. This review aims to provide a comprehensive overview of HCV infection in children, focusing on recent advancements in screening, diagnosis, and treatment. RECENT FINDINGS Effective screening strategies, including universal screening of pregnant women and nucleic acid testing for all perinatally exposed infants at 2 to 6 months of age, have been implemented to identify infected individuals early. Direct-acting antiviral agents have revolutionized treatment, offering high cure rates for children of all ages. Despite significant progress, challenges remain in achieving HCV elimination. These include the need for improved access to testing and treatment, as well as ongoing efforts to develop a preventive vaccine. Continued research and implementation of effective strategies are essential to reduce the burden of HCV infection.
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Affiliation(s)
- Johanna Ferreira
- Division of Pediatric Gastroenterology, Liver Disease and Nutrition, Cohen Children's Medical Center/Northwell, The Zucker School of Medicine at Hofstra, 1991 Marcus Avenue, Suite M100 , Lake Success, NY, 11042, USA.
| | - Shari Sheflin-Findling
- Division of Pediatric Gastroenterology, Liver Disease and Nutrition, Cohen Children's Medical Center/Northwell, The Zucker School of Medicine at Hofstra, 1991 Marcus Avenue, Suite M100 , Lake Success, NY, 11042, USA
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Weigand K, Peschel G, Grimm J, Höring M, Krautbauer S, Liebisch G, Müller M, Buechler C. Serum Phosphatidylcholine Species 32:0 as a Biomarker for Liver Cirrhosis Pre- and Post-Hepatitis C Virus Clearance. Int J Mol Sci 2024; 25:8161. [PMID: 39125730 PMCID: PMC11311844 DOI: 10.3390/ijms25158161] [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: 06/04/2024] [Revised: 07/23/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
Phosphatidylcholine (PC) is an essential lipid for liver health and lipoprotein metabolism, but its circulating levels have rarely been studied in patients with cirrhosis. Chronic hepatitis C virus (HCV) infection causes lipid abnormalities and is a major cause of cirrhosis. Effective HCV elimination with direct-acting antivirals (DAAs) is associated with the normalization of serum low-density lipoprotein cholesterol levels. Since PC is abundant in all lipoprotein particles, this study analyzed the association between serum PC species levels and liver cirrhosis before and after HCV eradication. Therefore, 27 PC species were measured by Fourier Transform Mass Spectrometry in the serum of 178 patients with chronic HCV infection at baseline and in 176 of these patients at the end of therapy. The PC species did not correlate with viral load, and the levels of 13 PC species were reduced in patients infected with genotype 3a compared to those affected with genotype 1. Four PC species were slightly elevated 12 weeks after DAA initiation, and genotype-related changes were largely normalized. Patients with HCV and cirrhosis had higher serum levels of PC 30:0 and 32:0 before and at the end of therapy. PC species containing polyunsaturated fatty acids were mostly decreased in cirrhosis. The levels of polyunsaturated, but not saturated, PC species were inversely correlated with the model of the end-stage liver disease score. A receiver operating characteristic curve analysis showed area under the curve values of 0.814 and 0.826 for PC 32:0 and 0.917 and 0.914 for % PC 32:0 (relative to the total PC levels) for the classification of cirrhosis at baseline and at the end of therapy, respectively. In conclusion, the specific upregulation of PC 32:0 in cirrhosis before and after therapy may be of diagnostic value in HCV-related cirrhosis.
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Affiliation(s)
- Kilian Weigand
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (K.W.); (G.P.); (J.G.); (M.M.)
- Department of Gastroenterology, Gemeinschaftsklinikum Mittelrhein, 56073 Koblenz, Germany
| | - Georg Peschel
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (K.W.); (G.P.); (J.G.); (M.M.)
- Department of Internal Medicine, Klinikum Fürstenfeldbruck, 82256 Fürstenfeldbruck, Germany
| | - Jonathan Grimm
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (K.W.); (G.P.); (J.G.); (M.M.)
| | - Marcus Höring
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany; (M.H.); (S.K.); (G.L.)
| | - Sabrina Krautbauer
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany; (M.H.); (S.K.); (G.L.)
| | - Gerhard Liebisch
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany; (M.H.); (S.K.); (G.L.)
| | - Martina Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (K.W.); (G.P.); (J.G.); (M.M.)
| | - Christa Buechler
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (K.W.); (G.P.); (J.G.); (M.M.)
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Jarasvaraparn C, Hartley C, Karnsakul W. Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children. Pathogens 2024; 13:180. [PMID: 38392918 PMCID: PMC10891648 DOI: 10.3390/pathogens13020180] [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: 12/15/2023] [Revised: 01/30/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children.
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Affiliation(s)
- Chaowapong Jarasvaraparn
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, IN 46201, USA
| | - Christopher Hartley
- Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, MD 21287, USA;
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
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Peschel G, Krautbauer S, Weigand K, Grimm J, Höring M, Liebisch G, Müller M, Buechler C. Rising Lysophosphatidylcholine Levels Post-Hepatitis C Clearance. Int J Mol Sci 2024; 25:1198. [PMID: 38256273 PMCID: PMC10816147 DOI: 10.3390/ijms25021198] [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: 11/28/2023] [Revised: 01/17/2024] [Accepted: 01/17/2024] [Indexed: 01/24/2024] Open
Abstract
Hepatitis C virus (HCV) infection alters lysophosphatidylcholine (LPC) metabolism, enhancing viral infectivity and replication. Direct-acting antivirals (DAAs) effectively treat HCV and rapidly normalize serum cholesterol. In serum, LPC species are primarily albumin-bound but are also present in lipoprotein particles. This study aims to assess the impact of HCV eradication on serum LPC species levels in patients infected with HCV. Therefore, 12 different LPC species were measured by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the sera of 178 patients with chronic HCV infections at baseline, and in 176 of these patients after therapy with DAAs. All LPC species increased at 4 and 12 weeks post-initiation of DAA therapy. The serum profiles of the LPC species were similar before and after the viral cure. Patients with HCV and liver cirrhosis exhibited lower serum levels of all LPC species, except LPC 16:1, both before and after DAA treatment. Percentages of LPC 18:1 (relative to the total LPC level) were higher, and % LPC 22:5 and 22:6 were lower in cirrhotic compared to non-cirrhotic patients at baseline and at the end of therapy. LPC species levels inversely correlated with the model of end-stage liver disease score and directly with baseline and post-therapy albumin levels. Receiver operating characteristic curve analysis indicated an area under the curve of 0.773 and 0.720 for % LPC 18:1 (relative to total LPC levels) for classifying fibrosis at baseline and post-therapy, respectively. In summary, HCV elimination was found to increase all LPC species and elevated LPC 18:1 relative to total LPC levels may have pathological significance in HCV-related liver cirrhosis.
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Affiliation(s)
- Georg Peschel
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (G.P.); (K.W.); (J.G.); (M.M.)
- Department of Internal Medicine, Klinikum Fürstenfeldbruck, 82256 Fürstenfeldbruck, Germany
| | - Sabrina Krautbauer
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany; (S.K.); (M.H.); (G.L.)
| | - Kilian Weigand
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (G.P.); (K.W.); (J.G.); (M.M.)
- Department of Gastroenterology, Gemeinschaftsklinikum Mittelrhein, 56073 Koblenz, Germany
| | - Jonathan Grimm
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (G.P.); (K.W.); (J.G.); (M.M.)
| | - Marcus Höring
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany; (S.K.); (M.H.); (G.L.)
| | - Gerhard Liebisch
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany; (S.K.); (M.H.); (G.L.)
| | - Martina Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (G.P.); (K.W.); (J.G.); (M.M.)
| | - Christa Buechler
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (G.P.); (K.W.); (J.G.); (M.M.)
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Venkatesh V, Seetharaman K, Anushree N. Treatment of hepatitis C in children and adolescents: how far have we reached? World J Pediatr 2023; 19:107-119. [PMID: 36129634 DOI: 10.1007/s12519-022-00612-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 08/18/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a global public health problem and also generates a significant case load in children and adolescents. With the introduction of directly acting antivirals (DAA), the treatment and care of HCV-infected patients have progressed significantly. The available treatment options in children are limited, and this review aims to provide an overview of treatment of HCV infection in children and adolescents with the current available DAA regimens. DATA SOURCES This comprehensive review was undertaken after searching the PubMed/Medline and Embase databases for the available up-to-date literature on pediatric HCV infection and treatment using hepatitis C virus infection/HCV, directly acting antivirals/DAA, natural history, treatment, pediatrics, children, and adolescents as keywords. RESULTS Combination therapies with highly effective DAA regimes, such as sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, sofosbuvir/daclatasvir, sofosbuvir/ribavirin and others, are available for use in children. Most of the DAA regimens have either received or are pending to receive regulatory approval by different medical/drug agencies for use in children and adolescents. Pan-genotypic regimens are also available in children and adolescents, and these regimens can be used while skipping genotype testing. CONCLUSION The literature on different DAA regimens for use in children shows that these regimens have higher cure rates with minimal side effects and shorter duration of therapy.
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Affiliation(s)
- Vybhav Venkatesh
- Department of Gastroenterology and Hepatobiliary Sciences, IMS and SUM Hospital, SOA University, Bhubaneswar, India
| | - Keerthivasan Seetharaman
- Department of Pediatrics, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
| | - Neha Anushree
- Department of Pediatrics, Command Hospital-Southern Command, Pune, 411040, India.
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Foster MA, Moorman AC, Teshale EH. Hepatitis C Virus. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2023:1156-1160.e3. [DOI: 10.1016/b978-0-323-75608-2.00220-2] [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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Weigand K, Peschel G, Grimm J, Müller M, Höring M, Krautbauer S, Liebisch G, Buechler C. HCV Infection and Liver Cirrhosis Are Associated with a Less-Favorable Serum Cholesteryl Ester Profile Which Improves through the Successful Treatment of HCV. Biomedicines 2022; 10:biomedicines10123152. [PMID: 36551908 PMCID: PMC9775323 DOI: 10.3390/biomedicines10123152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/28/2022] [Accepted: 12/03/2022] [Indexed: 12/12/2022] Open
Abstract
Background: Infection with hepatitis C virus (HCV) lowers serum cholesterol levels, which rapidly recover during therapy with direct-acting antivirals (DAAs). Serum cholesterol is also reduced in patients with liver cirrhosis. Studies investigating serum cholesterol in patients with chronic liver diseases are generally based on enzymatic assays providing total cholesterol levels. Hence, these studies do not account for the individual cholesteryl ester (CE) species, which have different properties according to acyl chain length and desaturation. Methods: Free cholesterol (FC) and 15 CE species were quantified by flow injection analysis high-resolution Fourier Transform mass spectrometry (FIA-FTMS) in the serum of 178 patients with chronic HCV before therapy and during treatment with DAAs. Results: Serum CEs were low in HCV patients with liver cirrhosis and, compared to patients without cirrhosis, proportions of CE 16:0 and 16:1 were higher whereas % CE 20:4 and 20:5 were reduced. FC levels were unchanged, and the CE/FC ratio was consequently low in cirrhosis. FC and CEs did not correlate with viral load. Four CE species were reduced in genotype 3 compared to genotype 1-infected patients. During DAA therapy, 9 of the 15 measured CE species, and the CE/FC ratio, increased. Relative to total CE levels, % CE 16:0 declined and % CE 18:3 was higher at therapy end. At this time, % CE 14:0, 16:0 and 16:1 were higher and % CE 20:4 and 22:6 were lower in the cirrhosis than the non-cirrhosis patients. Viral genotype associated changes of CEs disappeared at therapy end. Conclusions: The serum CE composition differs between patients with and without liver cirrhosis, and changes through the efficient elimination of HCV. Overall, HCV infection and cirrhosis are associated with a higher proportion of CE species with a lower number of carbon atoms and double bonds, reflecting a less-favorable CE profile.
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Affiliation(s)
- Kilian Weigand
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
- Department of Gastroenterology, Gemeinschaftsklinikum Mittelrhein, 56073 Koblenz, Germany
| | - Georg Peschel
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
- Department of Internal Medicine, Klinikum Fürstenfeldbruck, 82256 Fürstenfeldbruck, Germany
| | - Jonathan Grimm
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Martina Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Marcus Höring
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Sabrina Krautbauer
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Gerhard Liebisch
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Christa Buechler
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
- Correspondence: ; Tel.: +49-941-944-7009
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Mari PC, Gulati R, Fragassi P. Adolescent Hepatitis C: Prevalence, Impact, and Management Challenges. ADOLESCENT HEALTH MEDICINE AND THERAPEUTICS 2021; 12:45-53. [PMID: 33994820 PMCID: PMC8112853 DOI: 10.2147/ahmt.s263864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 04/21/2021] [Indexed: 12/09/2022]
Abstract
The prevalence of Hepatitis C virus infection (HCV), a leading cause of chronic liver disease worldwide, is rising in the United States (US) and other high-income countries, especially among youth and young adults. This surge in cases is closely associated with the opioid crisis and intravenous drug use (IVDU). However, its prevalence and impact on the adolescent population have not been thoroughly studied and therefore is poorly understood. The pediatric population tends to have milder liver disease and progression when compared to adults; however, there is a risk of developing liver cirrhosis, in addition to facing decreased quality of life and stigmatization from the disease. The recent approval of direct-acting antiviral (DAA) regimens for all HCV genotypes and age greater than 3 years has revolutionized its management. Therapy has shifted from the prolonged interferon-based regimens, to shorter duration, once daily oral pills that are highly effective, curative and with fewer side effects. Therapy is now indicated for all adolescents with hepatitis C virus infection, regardless of stage of liver disease, recent IVDU, or coinfection with HIV, therefore eliminating a lifetime risk of chronic liver disease, cirrhosis and hepatocarcinoma. Nonetheless, adolescents are rarely tested or treated for hepatitis C infection, and very few adolescents complete therapy. Implementation of point of care (POC) testing of high-risk youth at drug treatment centers or other juvenile facilities may be a good strategy to increase testing, diagnosis and therapy. This review article aims to educate pediatricians and other primary care providers to help decrease the existing knowledge gap on the subject.
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Affiliation(s)
- Paula Chaves Mari
- Department of Pediatrics, MetroHealth Medical Center, Cleveland, OH, USA
| | - Reema Gulati
- Department of Pediatrics, MetroHealth Medical Center, Cleveland, OH, USA
| | - Philip Fragassi
- Department of Pediatrics, MetroHealth Medical Center, Cleveland, OH, USA
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Grimm J, Peschel G, Müller M, Schacherer D, Wiest R, Weigand K, Buechler C. Rapid Decline of Serum Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) in Non-Cirrhotic Patients with Chronic Hepatitis C Infection Receiving Direct-Acting Antiviral Therapy. J Clin Med 2021; 10:1621. [PMID: 33920491 PMCID: PMC8069657 DOI: 10.3390/jcm10081621] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 03/30/2021] [Accepted: 04/06/2021] [Indexed: 02/06/2023] Open
Abstract
Direct-acting antivirals (DAAs) efficiently eradicate the hepatitis C virus (HCV). Low-density lipoprotein (LDL) levels increase rapidly upon DAA treatment. Proprotein convertase subtilisin/kexin 9 (PCSK9) induces degradation of the hepatic LDL receptor and thereby elevates serum LDL. The aim of this study was to determine serum PCSK9 concentrations during and after DAA therapy to identify associations with LDL levels. Serum PCSK9 was increased in 82 chronic HCV-infected patients compared to 55 patients not infected with HCV. Serum PCSK9 was low in HCV patients with liver cirrhosis, but patients with HCV-induced liver cirrhosis still exhibited higher serum PCSK9 than patients with non-viral liver cirrhosis. Serum PCSK9 correlated with measures of liver injury and inflammation in cirrhotic HCV patients. In patients without liver cirrhosis, a positive association of serum PCSK9 with viral load existed. Serum PCSK9 was not different between viral genotypes. Serum PCSK9 did not correlate with LDL levels in HCV patients irrespective of cirrhotic status. Serum PCSK9 was reduced, and LDL was increased at four weeks after DAA therapy start in non-cirrhotic HCV patients. Serum PCSK9 and LDL did not change upon DAA treatment in the cirrhotic group. The rapid decline of PCSK9 after the start of DAA therapy in conjunction with raised LDL levels in non-cirrhotic HCV patients shows that these changes are not functionally related.
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Affiliation(s)
- Jonathan Grimm
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (J.G.); (G.P.); (M.M.); (D.S.); (K.W.)
| | - Georg Peschel
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (J.G.); (G.P.); (M.M.); (D.S.); (K.W.)
| | - Martina Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (J.G.); (G.P.); (M.M.); (D.S.); (K.W.)
| | - Doris Schacherer
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (J.G.); (G.P.); (M.M.); (D.S.); (K.W.)
| | - Reiner Wiest
- Department of Visceral Surgery and Medicine, University Inselspital, 3010 Bern, Switzerland;
| | - Kilian Weigand
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (J.G.); (G.P.); (M.M.); (D.S.); (K.W.)
| | - Christa Buechler
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (J.G.); (G.P.); (M.M.); (D.S.); (K.W.)
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Peschel G, Grimm J, Gülow K, Müller M, Buechler C, Weigand K. Chemerin Is a Valuable Biomarker in Patients with HCV Infection and Correlates with Liver Injury. Diagnostics (Basel) 2020; 10:diagnostics10110974. [PMID: 33228201 PMCID: PMC7699464 DOI: 10.3390/diagnostics10110974] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 11/18/2020] [Accepted: 11/18/2020] [Indexed: 02/08/2023] Open
Abstract
Hepatitis C virus (HCV)-induced inflammation contributes to progressive liver disease. The chemoattractant protein chemerin is associated with systemic inflammation. We hypothesized that chemerin is a biomarker that predicts the severity of liver disease in HCV patients. Furthermore, we investigated whether serum chemerin levels change during the course of HCV treatment using direct-acting antivirals (DAAs). Therefore, we measured serum concentration of chemerin in a cohort of 82 HCV-infected patients undergoing DAA treatment. Serum chemerin was positively associated with leukocyte count and negatively with markers of hepatic function and the model of end-stage liver disease (MELD) score. Low circulating chemerin levels significantly correlated with advanced liver fibrosis and cirrhosis as measured by the fibrosis-4 (FIB-4) score, the aminotransferase/platelet (AST/PLT) ratio index (APRI) score and the non-alcoholic fatty liver disease (NAFLD) score. Chemerin did not correlate with viral load or viral genotype. Treatment with DAAs did not improve MELD score and leukocyte count within the observation period, up to three months after the end of DAA treatment. Accordingly, chemerin levels remained unchanged during the treatment period. We conclude that low circulating chemerin is a noninvasive biomarker for hepatic dysfunction and advanced liver fibrosis and cirrhosis in HCV infection.
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Hepatitis C in 2020: A North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper. J Pediatr Gastroenterol Nutr 2020; 71:407-417. [PMID: 32826718 DOI: 10.1097/mpg.0000000000002814] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In 1989, a collaboration between the Centers for Disease Control (CDC) and a California biotechnology company identified the hepatitis C virus (HCV, formerly known as non-A, non-B hepatitis virus) as the causative agent in the epidemic of silent posttransfusion hepatitis resulting in cirrhosis. We now know that, the HCV genome is a 9.6 kb positive, single-stranded RNA. A single open reading frame encodes a 3011 amino acid residue polyprotein that undergoes proteolysis to yield 10 individual gene products, consisting of 3 structural proteins (core and envelope glycoproteins E1 and E2) and 7 nonstructural (NS) proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B), which participate in posttranslational proteolytic processing and replication of HCV genetic material. Less than 25 years later, a new class of medications, known as direct-acting antivirals (DAAs) which target these proteins, were introduced to treat HCV infection. These highly effective antiviral agents are now approved for use in children as young as 3 years of age and have demonstrated sustained virologic responses exceeding 90% in most genotypes. Although tremendous scientific progress has been made, the incidence of acute HCV infections has increased by 4-fold since 2005, compounded in the last decade by a surge in opioid and intravenous drug use. Unfortunately, awareness of this deadly hepatotropic virus among members of the lay public remains limited. Patient education, advocacy, and counseling must, therefore, complement the availability of curative treatments against HCV infection if this virus is to be eradicated.
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Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71:686-721. [PMID: 31816111 PMCID: PMC9710295 DOI: 10.1002/hep.31060] [Citation(s) in RCA: 523] [Impact Index Per Article: 104.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 11/21/2019] [Indexed: 02/06/2023]
Affiliation(s)
| | - Timothy R. Morgan
- Chief of Hepatology Veterans Affairs Long Beach Healthcare System Long Beach CA
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13
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Greenaway E, Biondi MJ, Feld JJ, Ling SC. Hepatitis C virus infection in mothers and children. CANADIAN LIVER JOURNAL 2019; 2:210-224. [DOI: 10.3138/canlivj.2019-0009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Accepted: 03/28/2019] [Indexed: 12/22/2022]
Abstract
Many unique challenges are associated with hepatitis C infection in mothers and children. The preconception, antenatal, and postnatal phases each offer opportunities to reduce transmission of the virus from mother to infant or to identify the need for treatment. Management of children and youth with hepatitis C is now entering the era of direct-acting antivirals. Improvements are needed in the identification of infected mothers and children and their linkage to appropriate expert care.
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Affiliation(s)
- Emma Greenaway
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Mia J Biondi
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Arthur Labatt Family School of Nursing, Western University, London, Ontario, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada
| | - Simon C Ling
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
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14
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Molecular surveillance of hepatitis C virus genotypes identifies the emergence of a genotype 4d lineage among men in Quebec, 2001-2017. ACTA ACUST UNITED AC 2019; 45:230-237. [PMID: 31650986 DOI: 10.14745/ccdr.v45i09a02] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Background Molecular phylogenetics are generally used to confirm hepatitis C virus (HCV) transmission events. In addition, the Laboratoire de santé publique du Québec (LSPQ) has been using molecular phylogenetics for surveillance of HCV genotyping since November 2001. Objectives To describe the emergence of a specific lineage of HCV genotype 4d (G4d) and its characteristics using molecular phylogenetics as a surveillance tool for identifying HCV strain clustering. Methods The LSPQ prospectively applied Sanger sequencing and phylogenetic analysis to determine the HCV genotype on samples collected from November 2001 to December 2017. When a major G4d cluster was identified, demographic information, HIV-infection status and syphilis test results were analyzed. Results Phylogenetic analyses performed on approximately 22,000 cases identified 122 G4d cases. One major G4d cluster composed of 37 cases was singled out. Two cases were identified in 2010, 10 from 2011-2014 and 25 from 2015-2017. Cases in the cluster were concentrated in two urban health regions. Compared to the other G4d cases, cluster cases were all male (p<0.001) and more likely to be HIV-positive (adjusted risk ratio: 4.4; 95% confidence interval: 2.5-7.9). A positive syphilis test result was observed for 27 (73%) of the cluster cases. The sequences in this cluster and of four outlier cases were located on the same monophyletic lineage as G4d sequences reported in HIV-positive men who have sex with men (MSM) in Europe. Conclusion Molecular phylogenetics enabled the identification and surveillance of ongoing transmission of a specific HCV G4d lineage in HIV-positive and HIV-negative men in Quebec and its cross-continental spread. This information can orient intervention strategies to avoid transmission of HCV in MSM.
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15
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Karnsakul W, Schwarz KB. Management of Hepatitis C Infection in children in the era of Direct-acting Antiviral Agents. J Viral Hepat 2019; 26:1034-1039. [PMID: 30980688 DOI: 10.1111/jvh.13113] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 03/22/2019] [Accepted: 03/26/2019] [Indexed: 12/12/2022]
Abstract
Chronic hepatitis C certainly is a global health burden in children as well as in adults. Spontaneous viral clearance can occur in early childhood but is uncommon thereafter. Although the majority of cases are asymptomatic during childhood and young adulthood, without an effective treatment, children who acquire HCV via vertical transmission can develop chronic liver disease and other complications including end-stage liver disease and hepatocellular carcinoma in adulthood. Efforts from worldwide health organizations, the pharmaceutical industry, and clinical and research institutions have resulted in very effective interferon-free therapy with direct-acting antiviral agents (DAAs) for HCV-infected children. In this manuscript, we will briefly review the epidemiology of HCV in children, historic treatment, current published data on DAAs in children and conclude with suggestions for management of the child with HCV in the era of DAAs.
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Affiliation(s)
- Wikrom Karnsakul
- Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kathleen B Schwarz
- Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Maryland
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16
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Abd-Elgawad MM, Baddour NM, Salem MA. Chronic hepatitis C in children: Clinical spectrum and histopathological study. ALEXANDRIA JOURNAL OF MEDICINE 2019. [DOI: 10.1016/j.ajme.2013.03.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
| | - Nahed M. Baddour
- Pathology Department, Faculty of Medicine , Alexandria University , Egypt
| | - Mona A.E. Salem
- Pathology Department, Faculty of Medicine , Alexandria University , Egypt
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17
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Indolfi G, Easterbrook P, Dusheiko G, El-Sayed MH, Jonas MM, Thorne C, Bulterys M, Siberry G, Walsh N, Chang MH, Meyers T, Giaquinto C, Wirth S, Chan PL, Penazzato M. Hepatitis C virus infection in children and adolescents. Lancet Gastroenterol Hepatol 2019; 4:477-487. [PMID: 30982721 DOI: 10.1016/s2468-1253(19)30046-9] [Citation(s) in RCA: 103] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 01/20/2019] [Accepted: 01/22/2019] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated morbidity and mortality worldwide. Short-course, oral, curative, direct-acting antiviral regimens have transformed treatment for HCV infection. Since the 2016 launch of the first global strategy towards elimination of viral hepatitis as a public health threat by 2030, the predominant focus of the global response has been on the treatment of adults, who bear the greatest burden of morbidity and mortality of HCV-related chronic liver disease. Compared with adults, there has been little attention paid to addressing the response to HCV in children and adolescents, in part because of the scarcity of data to inform specific paediatric management practices and policy. In this Series paper, we summarise knowledge on the epidemiology, natural history, and treatment of chronic HCV infection in adolescents and children, and we highlight key differences from infection acquired in adulthood. The estimated global prevalence and burden of HCV infection in children aged 1-19 years is 0·15%, corresponding to 3·5 million people (95% CI 3·1-3·9 million). HCV infection is usually asymptomatic during childhood, and cirrhosis and hepatocellular carcinoma are rare. Sofosbuvir with ledipasvir and sofosbuvir with ribavirin have received regulatory approval and guidelines recommend their use in adolescents aged 12 years and older with HCV infection. In April, 2019, glecaprevir with pibrentasvir also received regulatory approval for adolescents aged 12-17 years. Key actions to address the current policy gaps and achieve treatment scale-up that is comparable to that in adults include: establishment of a campaign on access to testing and treatment that is targeted at children and adolescents; fast-track evaluation of pan-genotypic regimens; and accelerated approval of paediatric formulations. Research gaps that need to be addressed include: age-specific prevalence studies of HCV viraemia in priority countries; further validation of non-invasive tests for staging of liver disease in children; and establishment of paediatric treatment registries and international consortia to promote collaborative research agendas.
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Affiliation(s)
- Giuseppe Indolfi
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Florence, Italy
| | - Philippa Easterbrook
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland.
| | - Geoffrey Dusheiko
- King's College Hospital, London, UK; University College London Medical School, London, UK
| | - Manal H El-Sayed
- Department of Paediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA
| | - Claire Thorne
- UCL Great Ormond Street Institute of Child Health, University College London, NIHR GOSH BRC, London, UK
| | - Marc Bulterys
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland
| | - George Siberry
- Office of the US Global AIDS Coordinator, US Department of State, Washington, DC, USA
| | - Nick Walsh
- Pan American Health Organization, World Health Organization Regional Office for the Americas, Washington, DC, USA
| | - Mei-Hwei Chang
- Department of Paediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Tammy Meyers
- Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Carlo Giaquinto
- Department of Women and Child Health, University of Padova, Padova, Italy
| | - Stefan Wirth
- Department of Paediatrics, Helios Medical Centre Wuppertal, Witten-Herdecke University, Witten, Germany
| | - Po-Lin Chan
- World Health Organization Regional Office for the Western Pacific, Manila, Philippines
| | - Martina Penazzato
- Global Hepatitis Programme and HIV Department, World Health Organization, Geneva, Switzerland
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18
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Morishita A, Yoneyama H, Iwama H, Fujita K, Watanabe M, Hirose K, Tadokoro T, Oura K, Sakamoto T, Mimura S, Nomura T, Oryu M, Himoto T, Shimotohno K, Masaki T. Circulating microRNA-636 is associated with the elimination of hepatitis C virus by ombitasvir/paritaprevir/ritonavir. Oncotarget 2018; 9:32054-32062. [PMID: 30174796 PMCID: PMC6112829 DOI: 10.18632/oncotarget.25889] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 07/13/2018] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) infection causes sustained inflammation and fibrosis. Several oral direct-acting antivirals (DAAs) including ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) were recently developed for HCV elimination. The combination of DAAs brought a higher sustained viral response (SVR) rate to anti-HCV therapy compared to interferon (IFN)-based regimens. However, 5% of hepatitis C patients who undergo DAA therapy still suffer from a sustained HCV infection. MicroRNA (miRNA) is essentially interfering, endogenous noncoding RNA that has been investigated as a new biomarker for the response to DAA in hepatitis C patients. Here we used a miRNA array and real-time polymerase chain reaction (PCR) to determine the targetable miRNA before and 12 weeks after OBV/PTV/r treatment for refractory hepatitis C. We used replicon cells, in which genotype 1b type HCV is stably transfected in Huh7 cells, to determine whether miRNA can inhibit HCV replication. Among 2,555 miRNAs, three were significantly up-regulated and eight miRNAs were down-regulated in serum 12 weeks after OBV/PTV/r treatment. An unsupervised hierarchical clustering analysis, using Pearson's correlation, showed that the miRNA profiles between before and 12 weeks after OBV/PTV/r treatment were clustered separately. At 12 weeks after OBV/PTV, miR-636 was targeted among the eight down-regulated miRNAs, and the expression level of circulating miR-636 was significantly diminished. The amount of HCV-RNA was significantly diminished 48 hours after miR-636 inhibitor transfection in HCV replicon cells. In conclusion, miR-636 might be one of the essential targetable molecules in HCV patients who undergo DAA therapy and still suffer from a sustained HCV infection.
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Affiliation(s)
- Asahiro Morishita
- Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
| | - Hirohito Yoneyama
- Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
| | - Hisakazu Iwama
- Life Science Research Center, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
| | - Miwako Watanabe
- Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
| | - Kayo Hirose
- Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
| | - Kyoko Oura
- Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
| | - Teppei Sakamoto
- Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
| | - Shima Mimura
- Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
| | - Takako Nomura
- Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
| | - Makoto Oryu
- Department of Internal Medicine, Kagawa Saiseikai Hospital, Tahikamimachi, Takamatsu, Kagawa 761-8076, Japan
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Hara, Mure-cho, Takamatsu, Kagawa 761-0123, Japan
| | - Kunitada Shimotohno
- Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Kohnodai, Ichikawa, Chiba 272-8516, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan
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19
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Garvey P, Murphy N, Flanagan P, Brennan A, Courtney G, Crosbie O, Crowe J, Hegarty J, Lee J, McIver M, McNulty C, Murray F, Nolan N, O'Farrelly C, Stewart S, Tait M, Norris S, Thornton L. Disease outcomes in a cohort of women in Ireland infected by hepatitis C-contaminated anti-D immunoglobulin during 1970s. J Hepatol 2017; 67:1140-1147. [PMID: 28843656 DOI: 10.1016/j.jhep.2017.07.034] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 06/21/2017] [Accepted: 07/15/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIM In the mid-1990s, a group of Rh negative women was diagnosed with hepatitis C virus (HCV) genotype 1b infection, following administration of contaminated anti-D immunoglobulin in 1977-79. We aimed to describe their disease history and estimate the effect of selected host and treatment factors on disease progression. METHODS We conducted a cohort study on the women infected with HCV. Information was collected from records at seven HCV treatment centres on demographics, treatment and health outcomes up to the 31st December 2013. We calculated cumulative incidence, case fatality, and sub hazard ratios (SHR) for disease progression using competing risks regression. RESULTS Six hundred and eighty-two patients were included in the study. Among the chronically infected patients (n=374), 35% completed interferon-based antiviral treatment; 42% of whom had a sustained virological response. At the end of 2013, 19%, 1.9%, and 4.9% of chronically infected patients had developed cirrhosis, hepatocellular carcinoma, and liver-related death, respectively, compared with 10%, 0.8%, and 2.4% at the end of 2008. At the end of 2013, 321 (86%) of the chronically infected patients remained alive, 247 (77%) of whom were still chronically infected. Factors associated with increased cirrhosis rates included high alcohol intake (aSHR=4.9 [2.5-9.5]) and diabetes mellitus (aSHR=5.0 [2.9-8.8]). CONCLUSIONS Development of liver-related outcomes accelerated with time, with the risk of cirrhosis, hepatocellular carcinoma, and liver-related death doubling in the last five years of follow-up, particularly in women with high alcohol consumption and diabetes mellitus. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of alcohol, and that data be collected on this cohort after a further five years to analyse the effect of subsequent antiviral treatment during this rapidly evolving period in HCV treatment history. LAY SUMMARY In the mid-1990s, a group of women were diagnosed with chronic hepatitis C virus (HCV) infection following receipt of contaminated anti-D immunoglobulin between 1977 and 1979 in Ireland. Seventy-two (19%) developed cirrhosis and 18 had died from liver-related causes (5%) after 36years of infection. Disease progression accelerated in the last five years of follow-up, particularly in women with diabetes mellitus and high alcohol consumption. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of high alcohol consumption.
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Affiliation(s)
- Patricia Garvey
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland; European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control, Stockholm, Sweden.
| | - Niamh Murphy
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | - Paula Flanagan
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | - Aline Brennan
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | | | | | - John Crowe
- Mater Misericordiae University Hospital, Dublin, Ireland
| | - John Hegarty
- St Vincent's University Hospital, Dublin, Ireland
| | - John Lee
- University College Hospital, Galway, Ireland
| | - Margaret McIver
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | | | | | - Niamh Nolan
- St Vincent's University Hospital, Dublin, Ireland
| | | | | | - Michele Tait
- Health Service Executive, Dr. Steevens Hospital, Dublin, Ireland
| | | | - Lelia Thornton
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
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20
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Abstract
Chronic viral hepatitis is a global health threat and financial burden. Hepatitis B and C viruses (HBV and HCV) are the most common causes of chronic viral hepatitis in the United States. Most cases are asymptomatic before adulthood. Research has resulted in effective therapy for HCV and the promise of effective therapies for HBV. For HCV, therapy is pegylated interferon and ribavirin. Clinical trials with effective direct-acting antiviral agents are underway in pediatrics. For HBV, approved agents are alpha-interferon, lamivudine, adefovir, tenofovir, and entecavir. However, treatment seldom results in functional cure and more effective therapies are urgently needed.
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Affiliation(s)
- Wikrom Karnsakul
- Pediatric Liver Center, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 2-117, Baltimore, MD 21287, USA.
| | - Kathleen B Schwarz
- Professor, Pediatric Liver Center, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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21
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Endo D, Satoh K, Shimada N, Hokari A, Aizawa Y. Impact of interferon-free antivirus therapy on lipid profiles in patients with chronic hepatitis C genotype 1b. World J Gastroenterol 2017; 23:2355-2364. [PMID: 28428715 PMCID: PMC5385402 DOI: 10.3748/wjg.v23.i13.2355] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Revised: 02/20/2017] [Accepted: 03/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the influence of interferon-free antivirus therapy on lipid profiles in chronic hepatitis C virus genotype 1b (HCV1b) infection. METHODS Interferon-free antiviral agents were used to treat 276 patients with chronic HCV1b infection, and changes in serum lipids of those who achieved sustained virologic response (SVR) were examined. The treatment regimen included 24 wk of daclatasvir plus asunaprevir (DCV + ASV) or 12 wk of sofosbuvir plus ledipasvir (SOF + LDV). SVR was achieved in 121 (85.8%) of 141 patients treated with DCV + ASV and 132 (97.8%) of 135 patients treated with SOF + LDV. In the two patient groups (DCV + ASV-SVR and SOF + LDV-SVR), serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides were measured at baseline during treatment and at 4 and 12 wk after treatment. Then, longitudinal changes in lipid profiles were analyzed. RESULTS Serum levels of TC, LDL-C, and HDL-C were significantly increased throughout the observation period in both the DCV + ASV-SVR and SOF + LDV-SVR groups. During antivirus treatment, the increases in TC and LDL-C were significantly greater in the SOF + LDV-SVR group than in the DCV + ASV-SVR group (P < 0.001). At 4 and 12 wk after the therapy, serum levels of TC and LDL-C were similar between the two groups and were significantly greater than those at baseline. Approximately 75%-80% of the increase in TC was derived from an increased LDL-C. In multiple regression analysis, the difference in therapy protocol (DCA + ASV or SOF + LDV) was an independent predictor that was significantly associated with the increase in TC and LDL-C at 4 wk of therapy. CONCLUSION Serum cholesterol significantly increased during SOF + LDV treatment. After treatment, HCV elimination was associated with a similar increase in cholesterol regardless of the therapy protocol.
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22
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Squires JE, Balistreri WF. Hepatitis C virus infection in children and adolescents. Hepatol Commun 2017; 1:87-98. [PMID: 29404447 PMCID: PMC5721428 DOI: 10.1002/hep4.1028] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 02/17/2017] [Accepted: 02/22/2017] [Indexed: 12/11/2022] Open
Affiliation(s)
- James E Squires
- Division of Gastroenterology, Hepatology, and Nutrition Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center Pittsburgh PA
| | - William F Balistreri
- Division of Gastroenterology Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine Cincinnati OH
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23
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Abstract
Hepatitis is defined as inflammation of the liver. This inflammation can be acute and self-limited, chronic (leading to cirrhosis and an increased risk for hepatocellular carcinoma), or fulminant (requiring lifesaving liver transplantation). Although there are many causes of hepatitis, this article focuses on the main childhood viral hepatidities: types A, B, C, D, and E. This review discusses the main characteristics of each virus, including salient epidemiology, clinical characteristics, diagnosis, treatment, and prevention strategies. [Pediatr Ann. 2016;45(12):e420-e426.].
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24
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Pan YF, Zheng Y, Qin T, Feng L, Zhang Q, Ping XG, Pan YT, Wang XP, Bai L, Li HH. Disease progression in Chinese patients with hepatitis C virus RNA-positive infection via blood transfusion. Exp Ther Med 2016; 12:3476-3484. [PMID: 27882182 DOI: 10.3892/etm.2016.3792] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 08/23/2016] [Indexed: 12/14/2022] Open
Abstract
The majority of patients with hepatitis C virus (HCV) in China were infected via blood transfusion prior to the year 1996. In this systematic retrospective cohort study, disease progression in 804 consecutive patients with transfusion-acquired HCV is investigated. In addition, the occurrence of compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma (HCC) is analyzed among these patients, along with the risk factors for disease progression. Patients with cirrhosis or HCC were classified as the serious development group (SD group) and the remaining patients with chronic hepatitis were classified as the hepatitis group (H group). Significant differences were found between the two groups in age at the time of infection, duration of infection and age at the time of observation. SD group patients were significantly older at the time of transfusion (33.73 vs. 23.56 years; P<0.001), with a significantly longer mean duration of HCV infection (21.88 vs. 21.15 years; P=0.029) compared with that in the H group. Male gender and age at the time of transfusion were significant risk factors for HCC (OR=2.48, P=0.031 and OR=1.07, P=0.002, respectively). Age was a significant risk factor for disease progression in older Chinese patients with transfusion-acquired HCV, and there were significant differences in the prevalence of compensated cirrhosis, decompensated cirrhosis and HCC between the age groups (P<0.001), suggesting that more patients with HCV may develop cirrhosis or HCC in their third and fourth decades of infection. Results of the present study will be helpful for predicting disease progression in Chinese patients with HCV infected via blood transfusion.
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Affiliation(s)
- Yan-Feng Pan
- Department of Infection, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Yan Zheng
- Department of Infection, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Tao Qin
- Department of Hepatobiliary Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China
| | - Lei Feng
- Department of Infection, The First Hospital Affiliated to Henan University, Kaifeng, Henan 475000, P.R. China
| | - Qian Zhang
- Department of Infection, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Xiao-Gong Ping
- Department of Infection, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Yan-Ting Pan
- Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Xiao-Ping Wang
- Department of Infection, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Li Bai
- Department of Infection, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Hua-Hua Li
- Department of Infection, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
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25
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Senatore S, Galli C, Conti A, Faccini M, Cantoni S, Ciconali G, Mainardi G, Lamberti A, Dighera R, Radice Trolli F, Oggioni C, Angelini Sironi L, Cozzolino M, Zanetti AR, Romanò L. Hepatitis C virus outbreak in a haemodialysis unit: learning from failures. J Hosp Infect 2016; 94:249-252. [PMID: 27613441 DOI: 10.1016/j.jhin.2016.07.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Accepted: 07/29/2016] [Indexed: 10/21/2022]
Abstract
The investigation of an outbreak of hepatitis C virus in an Italian haemodialysis (HD) centre showed that three patients acquired infection with the same strain, affecting a chronically hepatitis C virus (HCV)-infected patient receiving HD in the same room and during the same shifts. Through our observational analysis many possible modes of transmission were identified, but none could be definitively identified as the route of HCV spread in this small cluster. This outbreak confirms that repeated opportunities for nosocomial HCV transmission may occur among HD patients due to several breaches in the standard precautions for bloodborne infections by healthcare staff.
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Affiliation(s)
- S Senatore
- Dipartimento di Prevenzione Medico, ATS Milano, Milano, Italy
| | - C Galli
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milano, Italy
| | - A Conti
- Dipartimento di Prevenzione Medico, ATS Milano, Milano, Italy
| | - M Faccini
- Dipartimento di Prevenzione Medico, ATS Milano, Milano, Italy
| | - S Cantoni
- Dipartimento di Prevenzione Medico, ATS Milano, Milano, Italy
| | - G Ciconali
- Dipartimento di Prevenzione Medico, ATS Milano, Milano, Italy
| | - G Mainardi
- Dipartimento di Prevenzione Medico, ATS Milano, Milano, Italy
| | - A Lamberti
- Dipartimento di Prevenzione Medico, ATS Milano, Milano, Italy
| | - R Dighera
- Dipartimento di Prevenzione Medico, ATS Milano, Milano, Italy
| | - F Radice Trolli
- Dipartimento di Prevenzione Medico, ATS Milano, Milano, Italy
| | - C Oggioni
- Direzione Medica Ospedaliera, ASST Santi Paolo e Carlo, Presidio S Paolo, Milano, Italy
| | - L Angelini Sironi
- Unità di Nefrologia e Dialisi, ASST Santi Paolo e Carlo, Presidio S Paolo, Milano, Italy
| | - M Cozzolino
- Unità di Nefrologia e Dialisi, ASST Santi Paolo e Carlo, Presidio S Paolo, Milano, Italy; Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy
| | - A R Zanetti
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milano, Italy
| | - L Romanò
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milano, Italy.
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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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Satoh K, Nagano T, Seki N, Tomita Y, Aida Y, Sugita T, Itagaki M, Sutoh S, Abe H, Aizawa Y. High level of serum cholesteryl ester transfer protein in active hepatitis C virus infection. World J Hepatol 2016; 8:291-300. [PMID: 26925203 PMCID: PMC4757652 DOI: 10.4254/wjh.v8.i5.291] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 12/30/2015] [Accepted: 01/27/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the significance of cholesteryl ester transfer protein (CETP) in lipoprotein abnormalities in chronic hepatitis C virus (HCV) infection. METHODS We evaluated the significance of the serum concentration of CETP in 110 Japanese patients with chronic HCV infection. Fifty-five patients had active HCV infection, and HCV eradication had been achieved in 55. The role of CETP in serum lipoprotein abnormalities, specifically, in triglyceride (TG) concentrations in the four major classes of lipoproteins, was investigated using Pearson correlations in conjunction with multiple regression analysis and compared them between those with active HCV infection and those in whom eradication had been achieved. RESULTS The serum CETP levels of patients with active HCV infection were significantly higher than those of patients in whom HCV eradication was achieved (mean ± SD, 2.84 ± 0.69 μg/mL vs 2.40 ± 1.00 μg/mL, P = 0.008). In multiple regression analysis, HCV infection status (active or eradicated) was an independent factor significantly associated with the serum CETP level. TG concentrations in low-density lipoprotein (mean ± SD, 36.25 ± 15.28 μg/mL vs 28.14 ± 9.94 μg/mL, P = 0.001) and high-density lipoprotein (HDL) (mean ± SD, 25.9 ± 7.34 μg/mL vs 17.17 ± 4.82 μg/mL, P < 0.001) were significantly higher in patients with active HCV infection than in those in whom HCV eradication was achieved. The CETP level was strongly correlated with HDL-TG in patients with active HCV infection (R = 0.557, P < 0.001), whereas CETP was not correlated with HDL-TG in patients in whom HCV eradication was achieved (R = -0.079, P = 0.56). CONCLUSION Our results indicate that CETP plays a role in abnormalities of lipoprotein metabolism in patients with chronic HCV infection.
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Affiliation(s)
- Kenichi Satoh
- Kenichi Satoh, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Yuta Aida, Tomonori Sugita, Munenori Itagaki, Satoshi Sutoh, Hiroshi Abe, Yoshio Aizawa, Department of Gastroenterology and Hepatology, Internal Medicine of Jikei University Katsushika Medical Center, Katsushikaku, Tokyo 125-8506, Japan
| | - Tomohisa Nagano
- Kenichi Satoh, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Yuta Aida, Tomonori Sugita, Munenori Itagaki, Satoshi Sutoh, Hiroshi Abe, Yoshio Aizawa, Department of Gastroenterology and Hepatology, Internal Medicine of Jikei University Katsushika Medical Center, Katsushikaku, Tokyo 125-8506, Japan
| | - Nobuyoshi Seki
- Kenichi Satoh, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Yuta Aida, Tomonori Sugita, Munenori Itagaki, Satoshi Sutoh, Hiroshi Abe, Yoshio Aizawa, Department of Gastroenterology and Hepatology, Internal Medicine of Jikei University Katsushika Medical Center, Katsushikaku, Tokyo 125-8506, Japan
| | - Yoichi Tomita
- Kenichi Satoh, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Yuta Aida, Tomonori Sugita, Munenori Itagaki, Satoshi Sutoh, Hiroshi Abe, Yoshio Aizawa, Department of Gastroenterology and Hepatology, Internal Medicine of Jikei University Katsushika Medical Center, Katsushikaku, Tokyo 125-8506, Japan
| | - Yuta Aida
- Kenichi Satoh, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Yuta Aida, Tomonori Sugita, Munenori Itagaki, Satoshi Sutoh, Hiroshi Abe, Yoshio Aizawa, Department of Gastroenterology and Hepatology, Internal Medicine of Jikei University Katsushika Medical Center, Katsushikaku, Tokyo 125-8506, Japan
| | - Tomonori Sugita
- Kenichi Satoh, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Yuta Aida, Tomonori Sugita, Munenori Itagaki, Satoshi Sutoh, Hiroshi Abe, Yoshio Aizawa, Department of Gastroenterology and Hepatology, Internal Medicine of Jikei University Katsushika Medical Center, Katsushikaku, Tokyo 125-8506, Japan
| | - Munenori Itagaki
- Kenichi Satoh, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Yuta Aida, Tomonori Sugita, Munenori Itagaki, Satoshi Sutoh, Hiroshi Abe, Yoshio Aizawa, Department of Gastroenterology and Hepatology, Internal Medicine of Jikei University Katsushika Medical Center, Katsushikaku, Tokyo 125-8506, Japan
| | - Satoshi Sutoh
- Kenichi Satoh, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Yuta Aida, Tomonori Sugita, Munenori Itagaki, Satoshi Sutoh, Hiroshi Abe, Yoshio Aizawa, Department of Gastroenterology and Hepatology, Internal Medicine of Jikei University Katsushika Medical Center, Katsushikaku, Tokyo 125-8506, Japan
| | - Hiroshi Abe
- Kenichi Satoh, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Yuta Aida, Tomonori Sugita, Munenori Itagaki, Satoshi Sutoh, Hiroshi Abe, Yoshio Aizawa, Department of Gastroenterology and Hepatology, Internal Medicine of Jikei University Katsushika Medical Center, Katsushikaku, Tokyo 125-8506, Japan
| | - Yoshio Aizawa
- Kenichi Satoh, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Yuta Aida, Tomonori Sugita, Munenori Itagaki, Satoshi Sutoh, Hiroshi Abe, Yoshio Aizawa, Department of Gastroenterology and Hepatology, Internal Medicine of Jikei University Katsushika Medical Center, Katsushikaku, Tokyo 125-8506, Japan
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Abstract
Hepatitis C infection is a global health problem. Most infected children have not been identified. Perinatal transmission is the most common mode of acquisition. Liver disease owing to chronic hepatitis C virus (HCV) infection progresses slowly in individuals infected early in life. Serious complications rarely affect patients during childhood. Successful treatment of HCV in adults has improved and recommendations have changed. Treatment in children should be deferred until direct-acting antivirals and interferon-free regimens are available to this population. If treatment cannot be deferred, regimens including peginterferon and ribavirin can be given to children with compensated liver disease.
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Affiliation(s)
- Christine K Lee
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
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Mohamad B, Hanouneh IA, Zein NN, Lopez R, Matloob A, Alkhouri N. Liver Transplant in Young Adults with Chronic Hepatitis C Virus: An Argument for Hepatitis C Treatment in Childhood. EXP CLIN TRANSPLANT 2015; 14:201-6. [PMID: 26476199 DOI: 10.6002/ect.2015.0092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES We sought to assess the characteristics of hepatitis C virus-positive young adults who received a liver transplant and to evaluate posttransplant outcomes. MATERIALS AND METHODS United Network for Organ Sharing database was conducted from 1989 to 2012, and retrospective analysis was performed on all hepatitis C virus-positive young adult patients (aged, 8-35 y) who underwent a liver transplant in the United States. RESULTS A total of 506 hepatitis C virus subjects were included. Average age at time of transplant was 30.1 ± 4.8 years. Median follow-up after first liver transplant was 46.1 months (13, 89.3 mo). During this time, 217 patients (42.8%) died at a mean age at the time of death of 34 ± 6.7 years including 176/ 506 (34.8%) after the first liver transplant, 34/71 (48.6%) after the second liver transplant, and 7/8 (87.5%) after the third liver transplant. The majority (65.7%) of retransplants were performed for hepatitis C virus recurrence. A mean of 1.15 liver transplants were performed per patient. Overall, 262 subjects were transplanted in the pre-Model for End-stage Liver Disease era, and 244 were transplanted post-MELD. Younger age, higher bilirubin, higher creatinine, hepatitis C carcinoma, shorter wait time, shorter cold ischemia time, nonwhite donor race, and the use of mycophenolate mofetil were significantly more common in the post-Model for End-stage Liver Disease era (all with P < .05). Importantly, 5-year patient and graft survival were not different between the pre- and post-Model for End-stage Liver Disease era. CONCLUSIONS Liver transplant in young adults for hepatitis C virus acquired during childhood has poor outcomes that did not improve in the post-Model for End-stage Liver Disease era. These findings should prompt more aggressive evaluation and treatment for hepatitis C virus in children.
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Affiliation(s)
- Bashar Mohamad
- From the Department of Gastroenterology and Hepatology and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
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30
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Indolfi G, Guido M, Azzari C, Resti M. Histopathology of hepatitis C in children, a systematic review: implications for treatment. Expert Rev Anti Infect Ther 2015. [PMID: 26202832 DOI: 10.1586/14787210.2015.1070668] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Chronic hepatitis C in children is usually considered a clinically mild and slowly progressive disease. Few pediatric studies focused on histopathology of children with hepatitis C are available. Those available show, overall, a wide spectrum of findings ranging from normal liver to cirrhosis and hepatocellular carcinoma. The present systematic review provides a comprehensive overview of the studies that explored histopathology in children with hepatitis C. Factors affecting the presence and the degree of necroinflammation, fibrosis and steatosis and the risk of progression to advanced liver disease were extensively evaluated. Insights on the possible role of histopathology findings in the decision-making process of whether or not to treat children with hepatitis C are provided.
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Affiliation(s)
- Giuseppe Indolfi
- a 1 Paediatric and Liver Unit Meyer Children's University Hospital of Florence, Viale Pieraccini 34, I-50139 Firenze, Italy
| | - Maria Guido
- b 2 Department of Medicine-DIMED, Surgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy
| | - Chiara Azzari
- c 3 Immunology Unit and Laboratory at Meyer Children's University Hospital of Florence and Department of Health Sciences, University of Florence, Viale Pieraccini 34, I-50139 Firenze, Italy
| | - Massimo Resti
- a 1 Paediatric and Liver Unit Meyer Children's University Hospital of Florence, Viale Pieraccini 34, I-50139 Firenze, Italy
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31
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Lee CK, Jonas MM. Treating HCV infection in children. Clin Liver Dis (Hoboken) 2015; 5:14-16. [PMID: 31312437 PMCID: PMC6490444 DOI: 10.1002/cld.439] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2014] [Revised: 10/09/2014] [Accepted: 10/16/2014] [Indexed: 02/04/2023] Open
Affiliation(s)
- Christine K. Lee
- Division of Gastroenterology, Hepatology and NutritionBoston Children's HospitalBostonMA
| | - Maureen M. Jonas
- Division of Gastroenterology, Hepatology and NutritionBoston Children's HospitalBostonMA
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You H, Liu S, Xie Y, Cong R, Sun Y, Ren J, Wei K, Jin X, Shi Y, Zhang H, Li J, Wei L, Zhuang H, Cheng M, Jia J. Novel host genetic variations associated with spontaneous clearance of a single-source outbreak of HCV1b infections. BMJ Open Gastroenterol 2015; 1:e000010. [PMID: 26462265 PMCID: PMC4533326 DOI: 10.1136/bmjgast-2014-000010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Revised: 08/24/2014] [Accepted: 08/29/2014] [Indexed: 12/13/2022] Open
Abstract
Background and aims A total of 105 patients were identified as accidentally infected with hepatitis C virus genotype 1b (HCV1b) through blood transfusion from a single blood donor. This group provides a unique patient population to study host factors involved in the spontaneous clearance of HCV and disease progression. Methods Clinical markers, HCV RNA and eight single nucleotide polymorphisms (SNPs) of interleukin-28B (IL-28B) were detected. Exome capture and sequencing were analysed for association with HCV clearance. Results Among the 85 patients with the positive HCV antibody, 27 cases (31.8%) were HCV RNA negative over a period of 9–12 years. Of the 58 patients with positive HCV RNA, 22.4% developed chronic hepatitis, and 5.2% developed cirrhosis. Age was found to be associated with HCV1b clearance. IL-28 rs10853728 CC showed the trend. By exon sequencing, 39 SNPs were found to be significantly different in spontaneous clearance patients (p<0.001). Two SNPs in the tenascin receptor (TNR), five in the transmembrane protease serine 11A (TMPRSS11A), and one in the serine peptidase inhibitor kunitz type 2 (SPINT2) showed the closest associations (p<10−5). Conclusions Host genetic analyses on the unique, single source HCV1b-infected patient population has suggested that age and mutations in TNR, TMPRSS11A and SPINT2 genes may be factors associated with HCV clearance.
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Affiliation(s)
- Hong You
- Liver Research Center , Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University , Beijing , China
| | - Sandu Liu
- Department of Infectious Diseases , Qiannan People's Hospital , Guizhou , China
| | - Yong Xie
- Department of Infectious Diseases , Pingtang People's Hospital , Guizhou , China
| | - Rui Cong
- Liver Research Center , Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University , Beijing , China
| | - Yameng Sun
- Liver Research Center , Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University , Beijing , China
| | - Jingjing Ren
- Beijing Genomic Institute , Shenzhen, Guangdong , China
| | - Kangfei Wei
- Beijing Genomic Institute , Shenzhen, Guangdong , China
| | - Xin Jin
- Beijing Genomic Institute , Shenzhen, Guangdong , China
| | - Yujian Shi
- Beijing Genomic Institute , Shenzhen, Guangdong , China
| | - Haiying Zhang
- Hepatology Institute, Peking University People's Hospital , Beijing , China
| | - Jie Li
- Department of Microbiology , Peking University Health Science Center , Beijing , China
| | - Lai Wei
- Hepatology Institute, Peking University People's Hospital , Beijing , China
| | - Hui Zhuang
- Department of Microbiology , Peking University Health Science Center , Beijing , China
| | - Mingliang Cheng
- Department of Infectious Diseases , Guiyang Medical College , Guizhou , China
| | - Jidong Jia
- Liver Research Center , Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University , Beijing , China
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Zavaglia C, Silini E, Mangia A, Airoldi A, Piazzolla V, Vangeli M, Stigliano R, Foschi A, Mazzarelli C, Tinelli C. Prognostic factors of hepatic decompensation and hepatocellular carcinoma in patients with transfusion-acquired HCV infection. Liver Int 2014; 34:e308-16. [PMID: 24529078 DOI: 10.1111/liv.12502] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2013] [Accepted: 02/08/2014] [Indexed: 12/20/2022]
Abstract
AIMS Aim of this study was to assess if host (immunogenetic traits, age, sex), exogenous (alcohol) or viral factors (viral type, past HBV infection) might affect the progression of chronic hepatitis C to liver decompensation or the development of HCC in a cohort of patients exposed to a single blood transfusion prior to the introduction of anti-HCV screening. METHODS Two hundred and forty-eight patients with a history of a single exposure to blood or blood products prior to 1990 were retrospectively considered. Patients were devoid of other risk factors of liver disease or immunosuppression and naïve to antiviral therapies. Eight baseline variables were assessed: age at transfusion, sex, HBV core antibody, immunogenetic profile (DRB1*11, DRB1*1104, DRB1*07), HCV genotype and alcohol consumption. RESULTS The follow-up was 22 (SD: 11) years. Sixty-eight patients (27%) progressed to hepatic decompensation over a median period of 22.5 years (IQR: 14-30) and 41 patients (16%) developed HCC over a median period of 31 years (IQR: 24-38). The cumulative incidence of liver failure was 0.4% (95% CI: 0.1-3.1), 4.9% (95% CI: 2.6-9.3) and 16.2% (95% CI: 10.4-24.7) at 10, 20 and 30 years after blood transfusion respectively. By univariate analysis, only age at transfusion was correlated with the risk of decompensation. Stratifying the age of transfusion by tertiles, the incidence of hepatic decompensation was 0.7% per year in patients transfused at ≤24 years of age as compared to 1.2% and 1.9% per year in those transfused at 25-35 and >36 years of age respectively (HR: 5.5, 95% CI: 2.78-10.7, P<0.001). The risk of HCC development was correlated by univariate analysis with age at transfusion (as continuous variable, HR: 1.12, 95% CI: 1.08-1.16 per year of age, P<0.001, >36 compared to ≤24 years, HR: 10.3, 95% CI: 3.9-26.9, P<0.001) and male sex (HR: 4.2, 95% CI: 1.7-10, P=0.001). Multivariate analysis confirmed age at transfusion and male sex as independent predictors of HCC development [HR: 1.12 per year (95% CI: 1.08-1.16), P<0.001 and HR: 5.4 (95% CI: 2.2-13.2), P<0.001 respectively]. CONCLUSIONS In patients with transfusion-acquired HCV infection, age at transfusion affects the risk for hepatic decompensation. Age at transfusion and male sex are independent risk factors for HCC development.
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Affiliation(s)
- Claudio Zavaglia
- Struttura Complessa di Gastroenterologia ed Epatologia 'Crespi', Ospedale Niguarda, piazza Ospedale Maggiore 3, 20162, Milano, Italy
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Lee MH, Yang HI, Lu SN, Jen CL, You SL, Wang LY, L'Italien G, Chen CJ, Yuan Y. Hepatitis C virus genotype 1b increases cumulative lifetime risk of hepatocellular carcinoma. Int J Cancer 2014; 135:1119-26. [PMID: 24482200 DOI: 10.1002/ijc.28753] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Revised: 12/28/2013] [Accepted: 01/13/2014] [Indexed: 12/12/2022]
Abstract
The association between subtypes of hepatitis C virus (HCV) and risk of hepatocellular carcinoma (HCC) remained inconclusive and evaluated in both case-control and cohort studies. In the case-control study, 397 HCC cases from medical centers were compared with 410 community-based non-HCC controls. All of them were anti-HCV-seropositive, HBsAg-seronegative with serum HCV RNA levels ≥1,000 IU/mL. Logistic regression models were used to estimate the odds ratio (OR) with 95% confidence interval (95% CI) of HCV subtype after controlling for other HCC risk factors. In the cohort study, 866 anti-HCV-seropositive individuals were followed from 1991 to 2008 to assess the long-term HCC predictability of HCV subtypes. Newly developed HCC cases were ascertained by follow-up health examinations and computerized linkage with national databases. The percentage of HCV 1b subtype was higher among HCC cases than controls (64 vs. 55%, p < 0.001). Participant infected with HCV 1b had a higher mean serum HCV RNA level (2.0 × 10(6) IU/mL) than those infected with HCV non-1b (1.2 × 10(6) IU/mL, p < 0.001). The multivariate-adjusted OR (95% CI) of developing HCC for HCV 1b comparing to non-1b was 1.43 (1.02-2.02). After the long-term follow-up, the cumulative lifetime (30-80 years old) HCC risk was 19.2 and 29.7% for patients infected with HCV non-1b and 1b, respectively (p < 0.001). The multivariate-adjusted hazard ratio (95% CI) was 1.85 (1.06-3.22) for HCV 1b compared to non-1b. HCV subtype 1b, the most prevalent subtype in Taiwan, was associated with an increased HCC risk and a proactive clinical management is suggested for patients with HCV 1b.
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Affiliation(s)
- Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
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35
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Hardikar W, Schwarz KB. Treatment options for chronic hepatitis B and C infection in children. Expert Rev Anti Infect Ther 2014; 4:583-91. [PMID: 17009938 DOI: 10.1586/14787210.4.4.583] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
There has been a dramatic increase in treatment options for both chronic hepatitis B (CHB) and chronic hepatitis C (CHC) infection in adults over the past 5-10 years, resulting in standardized regimes for initial treatment, relapsers and even infection in the setting of recurrence post-liver transplantation. These regimes have resulted in the halting of the disease progression, reduction in the risk of hepatocellular carcinoma and removal of these infections as a contraindication for liver transplantation. However, treatment in children must be considered carefully in the context of the natural history of these infections and host factors, particularly the immunological mileu, which may affect response to therapy. The as yet unknown long-term effects of medications must also be balanced with the probability of significant life-long morbidity or mortality from chronic hepatitis and its complications. Furthermore, the development of drug resistance, particularly in the case of CHB, has significant implications for the pediatric patient who may exhaust effective therapeutic options at a relatively young age. For these reasons, initiation of therapy must be based on sound criteria. Based on the current data, we recommend that therapy should be offered to children with CHB who have an elevation in alanine aminotransferase (>2-3 x upper limit of normal) for more than 6 months. Therapy with interferon-alpha should be offered in the majority of cases with the aim of immune clearance as measured by early antigen seroconversion. By contrast, treatment indication for CHC in children remains controversial. If used, combination therapy with pegylated interferon and ribavirin is likely to produce the highest rates of sustained viral response.
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Affiliation(s)
- Winita Hardikar
- Royal Children's Hospital, Department of Gastroenterology and Nutrition, Melbourne, Australia.
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36
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Shah U. Infections of the Liver. DISEASES OF THE LIVER IN CHILDREN 2014. [PMCID: PMC7121352 DOI: 10.1007/978-1-4614-9005-0_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
The portal vein carries blood from the gastrointestinal tract to the liver and in so doing carries microbes as well. The liver may therefore be involved in infections with a myriad number of microbial organisms. While some of these infections most commonly occur in the immunocompromised host, others affect the immune competence. Hepatic infections may be primary in nature or secondary, as part of systemic or contagious disease. The purpose of this chapter is to provide a brief overview of the various infections of the liver in the pediatric patient.
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Mohan P, Barton BA, Narkewicz MR, Molleston JP, Gonzalez-Peralta RP, Rosenthal P, Murray KF, Haber B, Schwarz KB, Goodman ZD. Evaluating progression of liver disease from repeat liver biopsies in children with chronic hepatitis C: a retrospective study. Hepatology 2013; 58:1580-6. [PMID: 23703847 PMCID: PMC5493995 DOI: 10.1002/hep.26519] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2012] [Accepted: 05/01/2013] [Indexed: 12/13/2022]
Abstract
UNLABELLED Clinical and histologic progression of liver disease in untreated children with chronic hepatitis C virus (HCV) infection is poorly documented. The aim of this retrospective study was to characterize changes in liver histology over time in a cohort of HCV-infected children who had more than one liver biopsy separated by over 1 year. Forty-four untreated children without concurrent liver diseases, who had repeat liver biopsies at eight U.S.-based medical centers, were included. Biopsies were scored by a single pathologist for inflammation, fibrosis, and steatosis and were correlated with demographic data including age at biopsy, time from infection to biopsies, and laboratory values such as serum alanine aminotransferase (ALT). Mode of transmission was vertical in 25 (57%) and from transfusions in 17 children (39%). Genotype 1 was present in 30/35 (84%) children. The mean age at first and final biopsy was 8.6 and 14.5 years, respectively, and the mean interval between biopsies was 5.8 ± 3.5 years. Duration of infection to biopsy was 7.7 and 13.5 years, respectively. Laboratory values did not change significantly between the biopsies. Inflammation was minimal in about 50% at both timepoints. Fibrosis was absent in 16% in both biopsies, limited to portal/periportal in 73% in the first biopsy, and 64% in the final biopsy. Between the two biopsies, the proportion of patients with bridging fibrosis/cirrhosis increased from 11% to 20% (P = 0.005). CONCLUSION Although in aggregate this cohort did not show significant histologic progression of liver disease over 5 years, 29.5% (n = 13) of children showed an increase in severity of fibrosis. These findings may have long-term implications for the timing of follow-up biopsies and treatment decisions.
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Affiliation(s)
- Parvathi Mohan
- Children’s National Medical Center, The George Washington School of Medicine, Washington DC
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38
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Einberg AP, Lindh G, Hökeberg I, Papadogiannakis N, Fischler B. Neonatal blood transfusion as transmission route in chronic hepatitis C. Transfusion 2013; 54:1366-70. [DOI: 10.1111/trf.12462] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2012] [Revised: 09/09/2013] [Accepted: 09/09/2013] [Indexed: 01/04/2023]
Affiliation(s)
- Afrodite Psaros Einberg
- Department of Pediatrics; Karolinska University Hospital; Sweden
- CLINTEC; Karolinska Institutet; Stockholm Sweden
| | - Gudrun Lindh
- Department of Infectious Diseases; Karolinska University Hospital; Sweden
| | - Ingegerd Hökeberg
- Department of Communicable Disease Control and Prevention; Stockholm Sweden
| | | | - Björn Fischler
- Department of Pediatrics; Karolinska University Hospital; Sweden
- CLINTEC; Karolinska Institutet; Stockholm Sweden
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Koretz RL, Pleguezuelo M, Arvaniti V, Barrera Baena P, Ciria R, Gurusamy KS, Davidson BR, Burroughs AK. Interferon for interferon nonresponding and relapsing patients with chronic hepatitis C. Cochrane Database Syst Rev 2013; 2013:CD003617. [PMID: 23440791 PMCID: PMC6599819 DOI: 10.1002/14651858.cd003617.pub2] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The widely-accepted treatment outcome for chronic hepatitis C is the sustained viral response (that is, no measurable viral RNA in blood six months after treatment). However, this surrogate outcome (as well as the previously employed biochemical and histologic ones) has never been validated. This situation exists because there are very few randomized clinical trials that have used clinical events (mortality or manifestations of decompensated cirrhosis) as outcomes, because those clinical events only occur after many years of infection. Patients in whom initial therapy fails to produce sustained viral responses do become potential candidates for retreatment; some of these individuals are not candidates for ribavirin or protease inhibitors and consideration could be given to retreatment with interferon alone. OBJECTIVES To assess the benefits and harms of interferon monotherapy retreatment in chronic hepatitis C patients and to validate the currently employed surrogate outcomes in this group of patients. SEARCH METHODS We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until 16 August 2012. SELECTION CRITERIA Randomized trials comparing interferon versus placebo or no treatment in chronic hepatitis C nonresponders and relapsers to previous interferon. DATA COLLECTION AND ANALYSIS The primary outcomes were mortality (all-cause and hepatic), quality of life, and adverse events. Secondary outcomes were liver-related morbidity, sustained viral responses, biochemical responses, histologic improvements, and costs. We used both fixed-effect and random-effects model meta-analyses, reporting only the former if no difference existed. MAIN RESULTS Seven trials were identified. Two of them were at low risk of bias (the HALT-C and EPIC3 trials) and included 1676 patients. Both of these trials addressed the role of long-term low-dose pegylated interferon therapy in patients with severe fibrosis (demonstrated on liver biopsy) and were designed to assess the clinical outcomes. The remaining five trials included 300 patients and were at high risk of bias. Based on all trials reporting the outcomes, no significant difference was observed in either all-cause mortality (78/843 (9.3%) versus 62/867 (7.2%); risk ratio (RR) 1.30, 95% confidence interval (CI) 0.95 to 1.79; 3 trials) or hepatic mortality (41/532 (7.7%) versus 40/552 (7.2%); RR 1.07, 95% CI 0.70 to 1.63; 2 trials); however, when only the two trials at low risk of bias were combined, all-cause mortality was significantly higher in the recipients of the pegylated interferon (78/828 (9.4%) versus 57/848 (6.7%); RR 1.41, 95% CI 1.02 to 1.96) although trial sequential analysis could not exclude the possibility of random error. There was less variceal bleeding in the recipients of the interferon (4/843 (0.5%) versus 18/867 (2.1%); RR 0.24, 95% CI 0.09 to 0.67; 3 trials), although again trial sequential analysis could not exclude the presence of a type I error and the effect could not be confirmed in a random-effects model meta-analysis. No significant differences were seen with regard to the development of ascites, encephalopathy, hepatocellular carcinoma, or the need for liver transplantation. One trial reported quality of life data; the pain score was significantly worse in the recipients of the pegylated interferon. Adverse effects tended to be more common in the interferon recipients; the ones that were significantly more common included hematologic complications, infections, flu-like symptoms, and rash. The recipients of interferon had significantly more sustained viral responses (20/557 (3.6%) versus 1/579 (0.2%); RR 15.38, 95% CI 2.93 to 80.71; 4 trials) and a type I error was excluded by trial sequential analysis. The METAVIR activity score also improved (36/55 (65%) versus 20/46 (43.5%); RR 1.49, 95% CI 1.02 to 2.18; 2 trials). No significant differences were seen with regard to histologic fibrosis assessments. AUTHORS' CONCLUSIONS The clinical data were limited to patients with histologic evidence of severe fibrosis who were retreated with pegylated interferon. In this scenario, retreatment with interferon did not appear to provide significant clinical benefit and, when only the trials at low risk of bias were considered, retreatment for several years may even have increased all-cause mortality. Such treatment also produced adverse events. On the other hand, the treatment did result in improvement in some surrogate outcomes, namely sustained viral responses and histologic evidence of inflammation. Interferon monotherapy retreatment cannot be recommended for these patients. No clinical data are available for patients with less severe fibrosis. The sustained viral response cannot be used as a surrogate marker for hepatitis C treatment in this clinical setting with low sustained viral response rates and needs to be validated in others in which higher sustained viral response rates are reported.
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Delgado-Borrego A, Smith L, Jonas MM, Hall CA, Negre B, Jordan SH, Ogrodowicz M, Raza R, Ludwig DA, Miller T, Lipshultz SE, Gonzalez-Peralta R, Chung RT. Expected and actual case ascertainment and treatment rates for children infected with hepatitis C in Florida and the United States: epidemiologic evidence from statewide and nationwide surveys. J Pediatr 2012; 161:915-21. [PMID: 22765955 DOI: 10.1016/j.jpeds.2012.05.002] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2011] [Revised: 03/26/2012] [Accepted: 05/02/2012] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the rate of pediatric hepatitis C virus (HCV) case ascertainment relative to the estimated number of actual cases. STUDY DESIGN Data from Florida and United States health departments were used to assess pediatric HCV case ascertainment rates in Florida and nationwide. The percentage of children infected with HCV from Miami-Dade County receiving medical care by a pediatric gastroenterologist was estimated based on data obtained from physician questionnaires. RESULTS From 2000 through 2009, 2007 children were identified as having positive HCV antibody tests in Florida, only 12% of the expected number (n = 12 155). An estimated 1.6% of the expected children with HCV who tested Ab-positive (37 of 1935) were actively followed by a pediatric gastroenterologist in Miami-Dade County, Florida. Across the United States, only 4.9% of the expected cases have been identified. CONCLUSIONS The identification of children infected with HCV in the nation as a whole is grossly inadequate. Only a small fraction of cases are identified. In Florida, less than 2% of children identified receive treatment. Lack of identification and lack of treatment of children infected with HCV constitute critical public health problems. Strategies to increase awareness of HCV infection and to screen at-risk individuals could substantially improve morbidity and mortality while reducing health care costs.
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Affiliation(s)
- Aymin Delgado-Borrego
- Department of Pediatrics, Batchelor Children's Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
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Reggiardo MV, Fay F, Tanno M, García-Camacho G, Bottaso O, Ferretti S, Godoy A, Guerrita C, Paez M, Tanno F, Ruffinengo O, Benetti S, García Borrás SE, Rossi MC, Vorobioff J, Bessone F, Tanno H. Natural history of hepatitis C virus infection in a cohort of asymptomatic post-transfused subjects. Ann Hepatol 2012; 11:658-666. [PMID: 22947526 DOI: 10.1016/s1665-2681(19)31439-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/21/2025]
Abstract
UNLABELLED BACKGROUND & AIMS. Studies about the natural history of hepatitis C virus (HCV) infection report variable progression to cirrhosis depending on study design. Retrospective cross-sectional liver clinic studies overestimate the rate of fibrosis progression due to inclusion of patients with more severe disease leaving mild and asymptomatic patients underrepresented. We evaluated fibrosis progression in a group of "healthy" asymptomatic subjects, attending to a voluntary campaign for the detection of HCV infection. MATERIAL AND METHODS A detection campaign was launched on subjects transfused before 1993. Of 1699 volunteers, 61(3.6%) had HCV infection. A liver biopsy was performed in 40 (65%). Assessed risk factors for liver fibrosis were: sex, body mass index, alcohol consumption (> 20 g/d - > 40g/d ), genotype, HLA-DRB1 alleles, present age, age at infection and duration of infection. RESULTS 25 (62.5%) were women with a median age of 52.5 years. The median duration of infection was 21.5 years with a median age at infection of 27 years. As regards fibrosis, 25 (62.5%) had a Low Stage (F0-F1), 8 patients, 20%, had severe fibrosis, one patient (2.5%) had cirrhosis. Alcohol consumption was the only risk factor associated with fibrosis progression. CONCLUSIONS The low progression to cirrhosis may be explained by the clinical characteristics of our population: asymptomatic middle-aged "healthy" subjects infected at young age. The progression to severe fibrosis was noticeable; hence a longer follow-up might demonstrate changes in this outcome. Significant alcohol consumption clearly worsens the natural history of HCV infection; this is no so evident for occasional or mild alcohol consumers.
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Affiliation(s)
- María Virginia Reggiardo
- Gastroenterology and Hepatology Department, Hospital Provincial del Centenario, School of Medicine, University of Rosario, Argentina.
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Örmeci N, Erdem H. Basic answers to complicated questions for the course of chronic hepatitis C treatment. Expert Rev Gastroenterol Hepatol 2012; 6:371-82. [PMID: 22646258 DOI: 10.1586/egh.12.16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Hepatitis C virus infection is a long-lasting disease, which causes chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, thus leading to liver-related death. Currently, the optimal treatment for chronic hepatitis C infection is the combination of pegylated interferon and ribavirin. The aim of this review is to assess the long-term clinical outcomes of interferons alone or in combination with ribavirin in the management of chronic hepatitis C.
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Affiliation(s)
- Necati Örmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
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NASPGHAN practice guidelines: Diagnosis and management of hepatitis C infection in infants, children, and adolescents. J Pediatr Gastroenterol Nutr 2012; 54:838-55. [PMID: 22487950 DOI: 10.1097/mpg.0b013e318258328d] [Citation(s) in RCA: 149] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Hepatitis C virus (HCV) is an RNA virus that affects >180 million individuals worldwide with a high propensity for chronic infection. Children with HCV infection differ from adults in several ways including some modes of transmission, rates of clearance, progression of fibrosis, and the duration of potential chronic infection when acquired at birth. Since the discovery of HCV in 1989, there have been significant advances in the understanding of the virology and natural history of chronic HCV infection in children. In addition, there are now several treatment options for children with chronic hepatitis C infection and many new therapies on the horizon. As a consequence, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition brought together experts in pediatric hepatology to review the available data in children and provide clinicians with approaches to the diagnosis, management, and prevention of HCV infection in children and adolescents. The guideline details the epidemiology and natural history of HCV infection in children, the diagnostic workup, monitoring and treatment of disease, and provides an update on future treatment options and areas of research.
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Robinson JL, Doucette K. The natural history of hepatitis C virus infection acquired during childhood. Liver Int 2012; 32:258-70. [PMID: 22098487 DOI: 10.1111/j.1478-3231.2011.02633.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2011] [Accepted: 08/02/2011] [Indexed: 12/23/2022]
Abstract
BACKGROUND The outcome of patients with hepatitis C virus (HCV) infection acquired during childhood in the absence of antiviral therapy is not clear. AIMS The purpose of this study was to review the outcome of untreated HCV acquired in childhood. Only population-based studies were included, as referred cases would be predicted to have more severe disease. METHODS A systematic review of the literature was completed up to October 2010 to identify studies where a population was screened for HCV infection that was presumably acquired during childhood. Demographical and clinical data were collected on infected patients who had not been treated with an antiviral. Primary outcome was development of a severe adverse outcome (cirrhosis, hepatoma, need for a liver transplant or liver-related death). RESULTS There were 25 studies reporting a total of 733 infected patients. Liver biopsy results were provided for 180 patients (25%), revealing cirrhosis in eight (1.0% of the total and 4.0% of those who had a biopsy). None of the other patients developed a severe adverse outcome. As a result of the small number of patients with a severe adverse outcome, risk factors for HCV progression could not be identified. CONCLUSION Although HCV can lead to liver transplantation and death during childhood, the vast majority of patients with disease acquired during childhood have slowly progressive disease. There is no clear indication for antiviral therapy in the majority of children with HCV infection.
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Affiliation(s)
- Joan L Robinson
- Department of Pediatrics, University of Alberta, Edmonton, Canada.
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Spontaneous clearance of hepatitis C virus in vertically infected children. Eur J Pediatr 2012; 171:253-8. [PMID: 21735055 DOI: 10.1007/s00431-011-1517-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2011] [Accepted: 06/09/2011] [Indexed: 02/08/2023]
Abstract
UNLABELLED Spontaneous viral clearance of hepatitis C virus (HCV) has been reported to occur in children with vertical HCV infection. However, factors which are associated with or predispose for clearance are largely unknown. In this case series we retrospectively analyzed laboratory parameters associated with spontaneous clearance of HCV in vertically infected children. The charts of six patients with documented spontaneous viral clearance by the age of 5 years were reviewed regarding clinical course, liver function tests (LFTs) and trend of HCV gene copy numbers. Spontaneous viral elimination was observed between the 25th and 52nd months of age. All patients had elevated LFTs, which peaked before 20 months of life. Peak LFT elevation was followed by normalization of LFTs and decline in viral load. These findings suggest that, in vertically HCV-infected children, a potent inflammatory response in the liver precedes viral clearance. Therefore, temporarily elevated LFTs, followed by a decline of viral load may be indicative of a near viral clearance in early childhood. CONCLUSION Further investigations regarding the development of optimal treatment algorithms should take into account factors, which are associated with possible spontaneous viral resolution, such as viral genotype, favourable host factors as well as direct and indirect parameters of antiviral immunity, and the individual course of viral replication.
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Marabita F, Aghemo A, De Nicola S, Rumi MG, Cheroni C, Scavelli R, Crimi M, Soffredini R, Abrignani S, De Francesco R, Colombo M. Genetic variation in the interleukin-28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection. Hepatology 2011; 54:1127-34. [PMID: 21721028 DOI: 10.1002/hep.24503] [Citation(s) in RCA: 107] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2011] [Accepted: 06/07/2011] [Indexed: 12/15/2022]
Abstract
UNLABELLED Polymorphisms in the interleukin-28B (IL28B) region are associated with spontaneous and treatment-induced viral clearance in hepatitis C virus (HCV) infection. Nevertheless, it is unknown whether genetic variation at the IL28B locus influences the natural history of chronic HCV infection. Thus, we asked whether an association between IL28B polymorphisms and liver fibrosis progression existed. We studied 247 consecutive patients with chronic HCV, an accurate estimate of the date of infection, and a liver biopsy performed before any treatment. No patient had a history of alcohol abuse or coinfection with other viruses. We assessed the role of rs8099917 and rs12979860 polymorphisms and the effect of host and environmental factors on fibrosis progression. Blood transfusion (75%) was the main modality of infection. Median age at infection was 21 years, and median interval between infection and liver biopsy was 25 years. One hundred twenty-nine patients (52%) were infected by HCV-1, 74 (30%) by HCV-2, 34 (14%) by HCV-3, and 10 (4%) by HCV-4. Bridging fibrosis/cirrhosis (Ishak ≥ 4) was detected in 24% of patients. Age at infection had a marked effect on fibrosis progression by both a linear model and Cox proportional-hazard regression (P < 2E-16). A 12.1% increase in the hazard of advanced fibrosis was estimated for each additional year at infection, suggesting that this was the major explanatory variable in this cohort. Male gender (P < 0.05), HCV genotype 3 (P < 0.001) and steatosis (P < 0.05) were also associated with faster fibrosis progression. Conversely, the two IL28B polymorphisms had no impact on fibrosis progression. CONCLUSION In HCV patients with a known date of infection, IL28B genotype was not associated with fibrosis progression rate or with the risk of developing advanced liver fibrosis.
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Abdel-Hady M, Bunn SK, Sira J, Brown RM, Brundler MA, Davies P, Kelly DA. Chronic hepatitis C in children--review of natural history at a National Centre. J Viral Hepat 2011; 18:e535-40. [PMID: 21914074 DOI: 10.1111/j.1365-2893.2011.01456.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The natural history of hepatitis C virus (HCV) infection in adults has been established, but less is known about outcome in children. We conducted a retrospective review of patients referred to Birmingham Children's Hospital Liver Unit, from 1991 till 2008, with the diagnosis of HCV was undertaken. Only children with documented positive HCV RNA and a minimum duration of follow-up of 6 months were included. One hundred and thirty-three children were identified. The route of transmission was transfusion acquired in 47%, vertically acquired in 49% and transplantation in 2%. Since 2000, most children were infected vertically. The overall rate of spontaneous viral clearance was 17.5% with higher clearance (27%) in the transfusion group compared to the vertically acquired group (9%). Seventy-six had a liver biopsy at diagnosis. There was no evidence of fibrosis in 46%, mild fibrosis in 50% and moderate to severe fibrosis in 4%. None had cirrhosis. There was a statistically significant relationship between fibrosis score and older age at the time of biopsy (P = 0.02) and longer duration of infection (P = 0.05). Eighty children received treatment for HCV. Sustained viral response (SVR) was influenced by viral genotypes, with significantly increased response rates in genotypes (G) 2 and 3 compared to G 1 and 4. Vertical infection is now the major route of HCV infection in children in the UK. Histological changes were mild at diagnosis, but the severity of fibrosis progressed with age. Consideration should be given to improve detection and diagnosis to refer children to specialist centres for management and antiviral therapy before developing fibrosis.
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Affiliation(s)
- M Abdel-Hady
- Liver Unit, Birmingham Children's Hospital, Birmingham, UK.
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Ochi H, Maekawa T, Abe H, Hayashida Y, Nakano R, Imamura M, Hiraga N, Kawakami Y, Aimitsu S, Kao JH, Kubo M, Tsunoda T, Kumada H, Nakamura Y, Hayes CN, Chayama K. IL-28B predicts response to chronic hepatitis C therapy--fine-mapping and replication study in Asian populations. J Gen Virol 2011; 92:1071-1081. [PMID: 21228123 DOI: 10.1099/vir.0.029124-0] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Type I interferon (IFN) is used for the treatment of chronic hepatitis C virus (HCV) infection. Despite advances in antiviral therapy, a large proportion of patients remain infected following current therapies. Through a genome-wide scan, we found two variants (rs8099917 and rs12979860) in the IL-28B locus that affect the outcome of PEG-IFN and ribavirin combination therapy, consistent with recent studies (P = 6.52×10(-8); odds ratio 2.46 and P = 8.63×10(-8), odds ratio 2.40, respectively). Significant associations were also observed in the case of IFN monotherapy for HCV genotypes 1b and 2a. With rs8099917, HCV genotype 1b patients had a significantly lower frequency of the favourable genotype (86.6 %) compared with healthy controls (91.7 %), and HCV genotype 2a patients had an intermediate frequency (89.9 %). Similar results were found for rs12979860. Fine-mapping analysis revealed that rs8099917 had the strongest association with treatment outcome and 14 others, including four novel single nucleotide polymorphisms, had comparable associations. Haplotype analysis revealed that none of the haplotypes showed stronger association than any single marker. Early non-responders who could not achieve 2 log viral decline during the first 12 weeks of treatment had higher odds ratios for these two variants. The favourable allele of rs8099917 is also associated with initial viral decline at 2 and 4 weeks following the start of therapy. Multivariate analysis of PEG-IFN and ribavirin-treated patients showed that rs8099917 genotype, viral load, fibrosis and age were significant predictors of response to therapy. Common variation at the IL-28B locus is predictive of various IFN-based therapies for HCV independent of regimen or HCV genotype.
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Affiliation(s)
- Hidenori Ochi
- Department of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
- Laboratory for Liver Diseases, the RIKEN Center for Genomic Medicine, Hiroshima, Japan
| | - Toshiro Maekawa
- Laboratory for Liver Diseases, the RIKEN Center for Genomic Medicine, Hiroshima, Japan
| | - Hiromi Abe
- Department of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
- Laboratory for Liver Diseases, the RIKEN Center for Genomic Medicine, Hiroshima, Japan
| | - Yasufumi Hayashida
- Department of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Rikita Nakano
- Pharmacology Research Laboratories, Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan
| | - Michio Imamura
- Department of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Nobuhiko Hiraga
- Department of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Yoshiiku Kawakami
- Clinical Research Center, Hiroshima University Hospital, Hiroshima, Japan
| | - Shiomi Aimitsu
- Department of Hepatology, Hiroshima Red Cross Hospital, Hiroshima, Japan
| | - Jia-Horng Kao
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Michiaki Kubo
- Laboratory for Genotyping Development, the RIKEN Center for Genomic Medicine, Yokohama, Japan
| | - Tatsuhiko Tsunoda
- Laboratory for Medical Informatics, the RIKEN Center for Genomic Medicine, Yokohama, Japan
| | | | - Yusuke Nakamura
- Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - C Nelson Hayes
- Department of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
- Laboratory for Liver Diseases, the RIKEN Center for Genomic Medicine, Hiroshima, Japan
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49
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Bailey J. An Assessment of the Use of Chimpanzees in Hepatitis C Research Past, Present and Future: 2. Alternative Replacement Methods. Altern Lab Anim 2010; 38:471-94. [DOI: 10.1177/026119291003800602] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The use of chimpanzees in hepatitis C virus (HCV) research was examined in the report associated with this paper ( 1: Validity of the Chimpanzee Model), in which it was concluded that claims of past necessity of chimpanzee use were exaggerated, and that claims of current and future indispensability were unjustifiable. Furthermore, given the serious scientific and ethical issues surrounding chimpanzee experimentation, it was proposed that it must now be considered redundant — particularly in light of the demonstrable contribution of alternative methods to past and current scientific progress, and the future promise that these methods hold. This paper builds on this evidence, by examining the development of alternative approaches to the investigation of HCV, and by reviewing examples of how these methods have contributed, and are continuing to contribute substantially, to progress in this field. It augments the argument against chimpanzee use by demonstrating the comprehensive nature of these methods and the valuable data they deliver. The entire life-cycle of HCV can now be investigated in a human (and much more relevant) context, without recourse to chimpanzee use. This also includes the testing of new therapies and vaccines. Consequently, there is no sound argument against the changes in public policy that propose a move away from chimpanzee use in US laboratories.
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Affiliation(s)
- Jarrod Bailey
- New England Anti-Vivisection Society, Boston, MA, USA
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50
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Cesaro S, Bortolotti F, Petris MG, Brugiolo A, Guido M, Carli M. An updated follow-up of chronic hepatitis C after three decades of observation in pediatric patients cured of malignancy. Pediatr Blood Cancer 2010; 55:108-12. [PMID: 20127849 DOI: 10.1002/pbc.22438] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The aim of the study was to evaluate the clinical characteristics and the long-term outcome of chronic hepatitis C in a cohort of Caucasian children cured of pediatric malignancy. PROCEDURE The study population included 83 consecutive patients, referred to our Center with a diagnosis of leukemia/lymphoma (50) or solid tumors (33) between 1977 and 1989 and infected with hepatitis C virus (HCV) during chemotherapy. RESULTS At enrollment 77 subjects were HCV-RNA positive. After a median follow-up of 21 years (range 13-36), a sustained virological response (SVR) was obtained in 3 of 29 patients (10%) treated with interferon (IFN), in 1 of 3 patients (33%) treated with IFN and ribavirin, and in 5 of 11 patients (42%) treated with pegylated-IFN and ribavirin (P = 0.03). Forty-two patients remained untreated and only one (2.5%) cleared viremia. Four of 77 patients (5%) developed cirrhosis while other 4 patients died of causes not related to liver. At last follow-up, 72% of HCV-RNA positive patients had abnormal ALT. CONCLUSIONS In patients cured of pediatric malignancy chronic hepatitis C tends to run an indolent course during childhood and adolescence but more than 70% of treated and more than 80% of untreated cases children maintained HCV viremia. Moreover, after 2-3 decades of observation, 60% of HCV-RNA positive patients had abnormal ALT and 5% had developed cirrhosis. Among treated patients, IFN or pegylated-IFN and ribavirin obtained the higher rate of HCV-RNA clearance.
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Affiliation(s)
- Simone Cesaro
- Pediatric Hematology Oncology, Department of Pediatrics, University of Padova, Padova, Italy.
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