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Suwała S, Białczyk A, Koperska K, Rajewska A, Krintus M, Junik R. Prevalence and Crucial Parameters in Diabesity-Related Liver Fibrosis: A Preliminary Study. J Clin Med 2023; 12:7760. [PMID: 38137829 PMCID: PMC10744287 DOI: 10.3390/jcm12247760] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 11/28/2023] [Accepted: 12/16/2023] [Indexed: 12/24/2023] Open
Abstract
Diabetes and obesity have been recognized as confirmed risk factors for the occurrence of liver fibrosis. Despite the long-standing acknowledgment of "diabesity", the simultaneous existence of diabetes and obesity, scholarly literature has shown limited attention to this topic. The aim of this pilot study was to assess the prevalence of liver fibrosis among individuals with diabetes (specifically those who are obese) in order to identify the key factors associated with hepatofibrosis and determine the most important associations and differences between patients with and without liver fibrosis. The research included a total of 164 participants (48.17% had comorbid obesity). Liver elastography (Fibroscan) was performed on these individuals in addition to laboratory tests. Liver fibrosis was found in 34.76% of type 2 diabetes patients; male gender almost doubled the risk of hepatofibrosis (RR 1.81) and diabesity nearly tripled this risk (RR 2.81; however, in degree III of obesity, the risk was elevated to 3.65 times higher). Anisocytosis, thrombocytopenia, or elevated liver enzymes raised the incidence of liver fibrosis by 1.78 to 2.47 times. In these individuals, liver stiffness was negatively correlated with MCV, platelet count, and albumin concentration; GGTP activity and HbA1c percentage were positively correlated. The regression analysis results suggest that the concentration of albumin and the activity of GGTP are likely to have a substantial influence on the future management of liver fibrosis in patients with diabesity. The findings of this study can serve as the basis for subsequent investigations and actions focused on identifying potential therapeutic and diagnostic avenues.
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Affiliation(s)
- Szymon Suwała
- Department of Endocrinology and Diabetology, Nicolaus Copernicus University, Collegium Medicum, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland;
| | - Aleksandra Białczyk
- Evidence-Based Medicine Students Scientific Club of Department of Endocrinology and Diabetology, Nicolaus Copernicus University, Collegium Medicum, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland; (A.B.); (K.K.); (A.R.)
| | - Kinga Koperska
- Evidence-Based Medicine Students Scientific Club of Department of Endocrinology and Diabetology, Nicolaus Copernicus University, Collegium Medicum, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland; (A.B.); (K.K.); (A.R.)
| | - Alicja Rajewska
- Evidence-Based Medicine Students Scientific Club of Department of Endocrinology and Diabetology, Nicolaus Copernicus University, Collegium Medicum, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland; (A.B.); (K.K.); (A.R.)
| | - Magdalena Krintus
- Department of Laboratory Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland;
| | - Roman Junik
- Department of Endocrinology and Diabetology, Nicolaus Copernicus University, Collegium Medicum, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland;
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Zhao H, Huang M, Jiang L. Potential Roles and Future Perspectives of Chitinase 3-like 1 in Macrophage Polarization and the Development of Diseases. Int J Mol Sci 2023; 24:16149. [PMID: 38003338 PMCID: PMC10671302 DOI: 10.3390/ijms242216149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/03/2023] [Accepted: 11/05/2023] [Indexed: 11/26/2023] Open
Abstract
Chitinase-3-like protein 1 (CHI3L1), a chitinase-like protein family member, is a secreted glycoprotein that mediates macrophage polarization, inflammation, apoptosis, angiogenesis, and carcinogenesis. Abnormal CHI3L1 expression has been associated with multiple metabolic and neurological disorders, including diabetes, atherosclerosis, and Alzheimer's disease. Aberrant CHI3L1 expression is also reportedly associated with tumor migration and metastasis, as well as contributions to immune escape, playing important roles in tumor progression. However, the physiological and pathophysiological roles of CHI3L1 in the development of metabolic and neurodegenerative diseases and cancer remain unclear. Understanding the polarization relationship between CHI3L1 and macrophages is crucial for disease progression. Recent research has uncovered the complex mechanisms of CHI3L1 in different diseases, highlighting its close association with macrophage functional polarization. In this article, we review recent findings regarding the various disease types and summarize the relationship between macrophages and CHI3L1. Furthermore, this article also provides a brief overview of the various mechanisms and inhibitors employed to inhibit CHI3L1 and disrupt its interaction with receptors. These endeavors highlight the pivotal roles of CHI3L1 and suggest therapeutic approaches targeting CHI3L1 in the development of metabolic diseases, neurodegenerative diseases, and cancers.
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Affiliation(s)
| | - Mingdong Huang
- College of Chemistry, Fuzhou University, Fuzhou 350116, China;
| | - Longguang Jiang
- College of Chemistry, Fuzhou University, Fuzhou 350116, China;
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3
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Sonsuz A, Bakkaloglu OK. Biomarkers in Liver Disease. Biomark Med 2022. [DOI: 10.2174/9789815040463122010020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Symptoms and signs of liver diseases are highly variable depending on the
etiology, disease stage, and type of liver involvement. There are different types of liver
diseases; causes of liver diseases may be viral, toxic, metabolic, or autoimmune.
However, in some cases, liver disease can develop as a result of diseases of other
organs or systems. It is almost impossible to differentiate all of these solely on the basis
of clinical symptoms and findings. Furthermore, the early stages of liver disease may
be completely asymptomatic, or in some cases, the disease may progress with only
subtle and non-specific symptoms. Therefore, biomarkers have a critical role in
screening, diagnosis, staging, and evaluation of therapeutic response to treatment in
liver diseases.
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Affiliation(s)
- Abdullah Sonsuz
- Department of Internal Medicine-Gastroenterology, Cerrahpasa Medical Faculty, Istanbul
University – Cerrahpasa, Istanbul, Turkey
| | - Oguz Kagan Bakkaloglu
- Department of Internal Medicine-Gastroenterology, Cerrahpasa Medical Faculty, Istanbul
University – Cerrahpasa, Istanbul, Turkey
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Kaur N, Goyal G, Garg R, Tapasvi C, Chawla S, Kaur R. Potential role of noninvasive biomarkers during liver fibrosis. World J Hepatol 2021; 13:1919-1935. [DOI: 10.4254/wjh.v13.i12.1919 kaur n, goyal g, garg r, tapasvi c, chawla s, kaur r. potential role of noninvasive biomarkers during liver fibrosis. world j hepatol 2021; 13(12): 1919-1935 [pmid: 35069998 doi: 10.4254/wjh.v13.i12.1919]] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/06/2024] Open
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Kaur N, Goyal G, Garg R, Tapasvi C, Chawla S, Kaur R. Potential role of noninvasive biomarkers during liver fibrosis. World J Hepatol 2021; 13:1919-1935. [PMID: 35069998 PMCID: PMC8727215 DOI: 10.4254/wjh.v13.i12.1919] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 06/18/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
Various types of liver disease exist, such as hepatitis and alcoholic liver disease. These liver diseases can result in scarring of liver tissue, cirrhosis, and finally liver failure. During liver fibrosis, there is an excess and disorganized accumulation of extracellular matrix (ECM) components which cause the loss of normal liver cell functions. For patients with chronic liver disease, fibrosis prediction is an essential part of the assessment and management. To diagnose liver fibrosis, several invasive and noninvasive markers have been proposed. However, the adoption of invasive markers remains limited due to their inherent characteristics and poor patient acceptance rate. In contrast, noninvasive markers can expedite the clinical decision through informed judgment about disease stage and prognosis. These noninvasive markers are classified into two types: Imaging techniques and serum biomarkers. However, the diagnostic values of biomarkers associated with liver fibrosis have also been analyzed. For example, the serum levels of ECM proteins can react to either matrix accumulation or degradation. During virus-host interactions, several regulatory steps take place to control gene expression, such as the change in cellular microRNA expression profiles. MicroRNAs are a class of non-coding RNAs (18-20 long nucleotides) that function by post-transcriptional regulation of gene expression. Although various noninvasive markers have been suggested in recent years, certain limitations have restricted their clinical applications. Understanding the potential of non-invasive biomarkers as a therapeutic option to treat liver fibrosis is still in progress.
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Affiliation(s)
- Navneet Kaur
- Department of Biochemistry, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
| | - Gitanjali Goyal
- Department of Biochemistry, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
| | - Ravinder Garg
- Department of Medicine, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
| | - Chaitanya Tapasvi
- Department of Radiodiagnosis, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
| | - Sonia Chawla
- Department of Biochemistry, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
| | - Rajneet Kaur
- Department of Biochemistry, Guru Gobind Singh Medical College and Hospital, Baba Farid University of Health Sciences, Faridkot 151203, Punjab, India
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Kolesova O, Vanaga I, Laivacuma S, Derovs A, Kolesovs A, Radzina M, Platkajis A, Eglite J, Hagina E, Arutjunana S, Putrins DS, Storozenko J, Rozentale B, Viksna L. Intriguing findings of liver fibrosis following COVID-19. BMC Gastroenterol 2021; 21:370. [PMID: 34635073 PMCID: PMC8503733 DOI: 10.1186/s12876-021-01939-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 09/22/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Studies on a new coronavirus disease (COVID-19) show the elevation of liver enzymes and liver fibrosis index (FIB-4) independently on pre-existing liver diseases. It points to increased liver fibrogenesis during acute COVID-19 with possible long-term consequences. This study aimed to assess liver fibrosis in COVID-19 patients by serum hyaluronic acid (HA) and FIB-4. METHODS The study included the acute COVID-19 group (66 patients, 50% females, mean age 58.3 ± 14.6), the post-COVID group (58 patients in 3-6 months after the recovery, 47% females, mean age 41.2 ± 13.4), and a control group (17 people, 47% females, mean age 42.8 ± 11.0). Ultrasound elastography was performed in the post-COVID and control groups. RESULTS Sixty-five percent of the acute COVID-19 group had increased FIB-4 (> 1.45), and 38% of patients had FIB-4 ≥ 3.25. After matching by demographics, 52% of acute COVID-19 and 5% of the post-COVID group had FIB-4 > 1.45, and 29% and 2% of patients had FIB-4 ≥ 3.25, respectively. Increased serum HA (≥ 75 ng/ml) was observed in 54% of the acute COVID-19 and 15% of the post-COVID group. In the acute COVID-19 group, HA positively correlated with FIB-4, AST, ALT, LDH, IL-6, and ferritin and negatively with blood oxygen saturation. In the post-COVID group, HA did not correlate with FIB-4, but it was positively associated with higher liver stiffness and ALT. CONCLUSION More than half of acute COVID-19 patients had increased serum HA and FIB-4 related to liver function tests, inflammatory markers, and blood oxygen saturation. It provides evidence for the induction of liver fibrosis by multiple factors during acute COVID-19. Findings also indicate possible liver fibrosis in about 5% of the post-COVID group.
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Affiliation(s)
- Oksana Kolesova
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia.
- Institute of Microbiology and Virology, Joint Laboratory of Immunology and Immunogenetics, Rīga Stradiņš University, 5 Ratsupites Street, Riga, 1067, Latvia.
| | - Ieva Vanaga
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia
- Institute of Microbiology and Virology, Joint Laboratory of Immunology and Immunogenetics, Rīga Stradiņš University, 5 Ratsupites Street, Riga, 1067, Latvia
- Riga East Clinical University Hospital, Riga, Latvia
| | - Sniedze Laivacuma
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia
- Riga East Clinical University Hospital, Riga, Latvia
| | - Aleksejs Derovs
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia
| | - Aleksandrs Kolesovs
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia
- Faculty of Education, Psychology, and Art, University of Latvia, Riga, Latvia
| | - Maija Radzina
- Faculty of Medicine, University of Latvia, Riga, Latvia
- Radiology Research Laboratory, Rīga Stradiņš University, Riga, Latvia
- Diagnostic Radiology Institute, Paula Stradina Clinical University Hospital, Riga, Latvia
| | - Ardis Platkajis
- Department of Radiology, Rīga Stradiņš University, Riga, Latvia
| | - Jelena Eglite
- Institute of Microbiology and Virology, Joint Laboratory of Immunology and Immunogenetics, Rīga Stradiņš University, 5 Ratsupites Street, Riga, 1067, Latvia
| | - Elvira Hagina
- Institute of Microbiology and Virology, Joint Laboratory of Immunology and Immunogenetics, Rīga Stradiņš University, 5 Ratsupites Street, Riga, 1067, Latvia
| | | | - Davis Simanis Putrins
- Diagnostic Radiology Institute, Paula Stradina Clinical University Hospital, Riga, Latvia
| | - Jelena Storozenko
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia
- Central Laboratory Ltd., Riga, Latvia
| | - Baiba Rozentale
- Riga East Clinical University Hospital, Riga, Latvia
- Department of Public Health and Epidemiology, Rīga Stradiņš University, Riga, Latvia
| | - Ludmila Viksna
- Departments of Infectology, Rīga Stradiņš University, Riga, Latvia
- Riga East Clinical University Hospital, Riga, Latvia
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7
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Rodart IF, Pares MM, Mendes A, Accardo CM, Martins JRM, Silva CB, Carvalho FO, Barreto JA, Reis MG, Tersariol ILS, Nader HB. Diagnostic Accuracy of Serum Hyaluronan for Detecting HCV Infection and Liver Fibrosis in Asymptomatic Blood Donors. Molecules 2021; 26:molecules26133892. [PMID: 34202190 PMCID: PMC8270308 DOI: 10.3390/molecules26133892] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/18/2021] [Accepted: 06/22/2021] [Indexed: 01/04/2023] Open
Abstract
Background: The disease caused by hepatitis C virus (HCV) is asymptomatic, silent, and progressive liver disease. In HCV-infected patients the increase in serum HA is associated with the development of hepatic fibrosis and disease progression. Methods: HCV-RNA detection was performed in all serological samples of blood donors that tested positive using HCV Ultra ELISA. Determination of hyaluronan (HA) was performed in positive HCV samples using ELISA-like fluorometric method. The HA content was compared to HCV viral load, genotype of the virus, liver fibrosis as well as ALT and GGT liver biomarkers. Results: Persistently normal ALT (<40 U/L) and GGT (<50 U/L) serum levels were detected in 75% and 69% of the HCV-Infected blood donors, respectively. Based on ROC analysis, the HA value < 34.2 ng/mL is an optimal cut-off point to exclude HCV viremia (specificity = 91%, NPV = 99%). Applying HA value ≥34.2 ng/mL significant liver fibrosis (≥F2) can be estimated in 46% of the HCV-infected blood donors. HA serum level (≥34.2 ng/mL) associated with a high ALT level (>40 U/mL) can correctly identify HCV infection and probable liver fibrosis (sensitivity = 96% and specificity = 90%) in asymptomatic blood donors. Conclusions: A high level of HA (≥34.2 ng/mL) in association with ALT (≥40 U/L) in serum can provide a good clinical opportunity to detect HCV-infected asymptomatic persons that potentially require a liver biopsy confirmation and antiviral treatment to prevent the development of advanced liver fibrosis or cirrhosis.
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Affiliation(s)
- Itatiana F. Rodart
- Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo 04021-001, Brazil; (I.F.R.); (A.M.); (C.M.A.); (J.R.M.M.)
| | - Madalena M. Pares
- Associação Beneficente de Coleta de Sangue (COLSAN), São Paulo 04038-000, Brazil; (M.M.P.); (C.B.S.); (F.O.C.); (J.A.B.)
| | - Aline Mendes
- Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo 04021-001, Brazil; (I.F.R.); (A.M.); (C.M.A.); (J.R.M.M.)
| | - Camila M. Accardo
- Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo 04021-001, Brazil; (I.F.R.); (A.M.); (C.M.A.); (J.R.M.M.)
| | - João R. M. Martins
- Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo 04021-001, Brazil; (I.F.R.); (A.M.); (C.M.A.); (J.R.M.M.)
| | - Cleidenice B. Silva
- Associação Beneficente de Coleta de Sangue (COLSAN), São Paulo 04038-000, Brazil; (M.M.P.); (C.B.S.); (F.O.C.); (J.A.B.)
| | - Fabrício O. Carvalho
- Associação Beneficente de Coleta de Sangue (COLSAN), São Paulo 04038-000, Brazil; (M.M.P.); (C.B.S.); (F.O.C.); (J.A.B.)
| | - José A. Barreto
- Associação Beneficente de Coleta de Sangue (COLSAN), São Paulo 04038-000, Brazil; (M.M.P.); (C.B.S.); (F.O.C.); (J.A.B.)
| | - Mitermayer G. Reis
- Laboratório de Hepatites Virais, Centro de Pesquisas Gonçalo Muniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil;
| | - Ivarne L. S. Tersariol
- Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo 04021-001, Brazil; (I.F.R.); (A.M.); (C.M.A.); (J.R.M.M.)
- Correspondence: (I.L.S.T.); (H.B.N.); Tel.: +55-11-5579-3175 (I.L.S.T.); +55-11-5549-4629 (H.B.N.)
| | - Helena B. Nader
- Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo 04021-001, Brazil; (I.F.R.); (A.M.); (C.M.A.); (J.R.M.M.)
- Correspondence: (I.L.S.T.); (H.B.N.); Tel.: +55-11-5579-3175 (I.L.S.T.); +55-11-5549-4629 (H.B.N.)
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Guerra-Ruiz AR, Casals G, Iruzubieta P, Lalana M, Leis A, López RM, Crespo J, Morales-Ruiz M. Valoración bioquímica en la enfermedad hepática grasa asociada a la disfunción metabólica. ADVANCES IN LABORATORY MEDICINE 2021; 2:209-219. [PMCID: PMC10197419 DOI: 10.1515/almed-2020-0062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 10/18/2020] [Indexed: 11/15/2022]
Abstract
La enfermedad hepática grasa asociada a la disfunción metabólica (MAFLD) se define por el acúmulo de grasa en el hígado en presencia de alteraciones metabólicas. Suele cursar de forma asintomática y puede progresar a formas graves de enfermedad hepática, ligadas a la aparición de inflamación y/o fibrosis. Su prevalencia es muy elevada (26%), resultando en un alto número de pacientes con riesgo de presentar una enfermedad hepática avanzada. El presente documento describe los marcadores serológicos más relevantes en la caracterización y diagnóstico de la MAFLD, y se propone un ejemplo de su integración en un algoritmo diagnóstico en práctica clínica habitual. En la actualidad se dispone de índices serológicos útiles en el manejo de los pacientes con MAFLD, especialmente en la estratificación del riesgo de la presencia fibrosis. Una gran parte de la población está en riesgo de desarrollar enfermedad hepática grave. La integración de los marcadores serológicos no invasivos en la estratificación del riesgo de fibrosis hepática puede contribuir a un mejor control y manejo de los pacientes con MAFLD.
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Affiliation(s)
- Armando R. Guerra-Ruiz
- Grupo de trabajo de valoración bioquímica de la enfermedad hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML), Barcelona, España
- Servicio de Análisis Clínicos, Hospital Universitario Marqués de Valdecilla, Santander, España
| | - Gregori Casals
- Grupo de trabajo de valoración bioquímica de la enfermedad hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML), Barcelona, España
- Servicio de Bioquímica y Genética Molecular, CDB, Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD, Barcelona, España
| | - Paula Iruzubieta
- Sociedad Española de Patología Digestiva (SEPD), Madrid, España
- Servicio Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, IDIVAL, Santander, España
| | - Marta Lalana
- Grupo de trabajo de valoración bioquímica de la enfermedad hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML), Barcelona, España
- Servicio de Análisis Clínicos, Hospital de Barbastro, Huesca, España
| | - Alba Leis
- Grupo de trabajo de valoración bioquímica de la enfermedad hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML), Barcelona, España
- Servicio de Análisis Clínicos y Bioquímica, Laboratori Clínic Metropolitana Nord, Hospital Universitari Germans Trias i Pujol, Badalona, España
| | - Rosa María López
- Grupo de trabajo de valoración bioquímica de la enfermedad hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML), Barcelona, España
- Unidad de Patología hepática, Departamentos de Bioquímica y Microbiología, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, España
| | - Javier Crespo
- Sociedad Española de Patología Digestiva (SEPD), Madrid, España
- Servicio Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, IDIVAL, Santander, España
| | - Manuel Morales-Ruiz
- Grupo de trabajo de valoración bioquímica de la enfermedad hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML), Barcelona, España
- Servicio de Bioquímica y Genética Molecular-Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Departamento de Biomedicina de la Facultad de Medicina y Ciencias de la Salud-Universidad de Barcelona, Barcelona, España
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9
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Guerra-Ruiz AR, Casals G, Iruzubieta P, Lalana M, Leis A, López RM, Crespo J, Morales-Ruiz M. Biochemical assessment of metabolic associated fatty liver disease. ADVANCES IN LABORATORY MEDICINE 2021; 2:199-219. [PMID: 37363330 PMCID: PMC10197265 DOI: 10.1515/almed-2021-0009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 10/18/2020] [Indexed: 01/05/2023]
Abstract
Metabolic-associated fatty liver disease (MAFLD) is defined as fat accumulation in the liver in the presence of metabolic alterations. This disorder is generally asymptomatic and may progress to severe liver disease, which are linked to inflammation and/or fibrosis. MAFLD has a high prevalence (26%) and therefore a considerable number of patients are at high risk of having advanced liver disease. This document provides an overview of the most relevant serological markers in the characterization and diagnosis of MAFLD. An example is provided of a routine diagnostic algorithm that incorporates serological testing. A range of useful serological scores are currently available for the management of MAFLD patients, especially for the stratification of patients at risk of fibrosis. A large proportion of the population is at risk of developing severe liver disease. The integration of non-invasive serological markers in the stratification of patients at risk for liver fibrosis may contribute to improve the control and management of MAFLD patients.
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Affiliation(s)
- Armando R. Guerra-Ruiz
- Commission on Biochemistry of Liver Disease, Spanish Society of Laboratory Medicine (SEQC-ML), Barcelona, Spain
- Service of Clinical Analysis, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Gregori Casals
- Commission on Biochemistry of Liver Disease, Spanish Society of Laboratory Medicine (SEQC-ML), Barcelona, Spain
- Service of Biochemistry and Molecular Genetics, CDB, Hospital Clinic de Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain
| | - Paula Iruzubieta
- Spanish Society of Digestive Pathology (SEPD), Madrid, Spain
- Service of Digestive System, Hospital Universitario Marqués de Valdecilla, Clinical and Traslational Research Group on Digestive Disorders, IDIVAL, Santander, Spain
| | - Marta Lalana
- Commission on Biochemistry of Liver Disease, Spanish Society of Laboratory Medicine (SEQC-ML), Barcelona, Spain
- Service of Clinical Analysis, Hospital de Barbastro, Huesca, Spain
| | - Alba Leis
- Commission on Biochemistry of Liver Disease, Spanish Society of Laboratory Medicine (SEQC-ML), Barcelona, Spain
- Service of Clinical Analysis and Biochemistry, Laboratori Clínic Metropolitana Nord, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Rosa María López
- Commission on Biochemistry of Liver Disease, Spanish Society of Laboratory Medicine (SEQC-ML), Barcelona, Spain
- Departments of Biochemistry and Microbiology, Unit of Liver Disease, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Javier Crespo
- Spanish Society of Digestive Pathology (SEPD), Madrid, Spain
- Service of Digestive System, Hospital Universitario Marqués de Valdecilla, Clinical and Traslational Research Group on Digestive Disorders, IDIVAL, Santander, Spain
| | - Manuel Morales-Ruiz
- Commission on Biochemistry of Liver Disease, Spanish Society of Laboratory Medicine (SEQC-ML), Barcelona, Spain
- Department of Biomedicine of the Faculty of Medicine and Health Sciences, Service of Biochemistry and Molecular Genetics, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
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10
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Chitinase 3-like 1 is a profibrogenic factor overexpressed in the aging liver and in patients with liver cirrhosis. Proc Natl Acad Sci U S A 2021; 118:2019633118. [PMID: 33888584 DOI: 10.1073/pnas.2019633118] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Older age at the time of infection with hepatitis viruses is associated with an increased risk of liver fibrosis progression. We hypothesized that the pace of fibrosis progression may reflect changes in gene expression within the aging liver. We compared gene expression in liver specimens from 54 adult donors without evidence of fibrosis, including 36 over 40 y old and 18 between 18 and 40 y old. Chitinase 3-like 1 (CHI3L1), which encodes chitinase-like protein YKL-40/CHI3L1, was identified as the gene with the greatest age-dependent increase in expression in liver tissue. We investigated the cellular source of CHI3L1 in the liver and its function using liver tissue specimens and in vitro models. CHI3L1 expression was significantly higher in livers of patients with cirrhosis of diverse etiologies compared with controls represented by patients who underwent liver resection for hemangioma. The highest intrahepatic CHI3L1 expression was observed in cirrhosis due to hepatitis D virus, followed by hepatitis C virus, hepatitis B virus, and alcohol-induced cirrhosis. In situ hybridization of CHI3L1 messenger RNA (mRNA) identified hepatocytes as the major producers of CHI3L1 in normal liver and in cirrhotic tissue, wherein hepatocytes adjacent to fibrous septa showed higher CHI3L1 expression than did those in more distal areas. In vitro studies showed that recombinant CHI3L1 promotes proliferation and activation of primary human hepatic stellate cells (HSCs), the major drivers of liver fibrosis. These findings collectively demonstrate that CHI3L1 promotes liver fibrogenesis through a direct effect on HSCs and support a role for CHI3L1 in the increased susceptibility of aging livers to fibrosis progression.
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11
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Sarmento-Castro R, Méndez J, Horta A, Gonçalves C, Vasconcelos O, Seabra J, Abreu M, Gonçalves MJ, Santos MJ, Tavares AP. Hepatitis C treatment outcome in former or current intravenous drug users coinfected with HIV, with or without directly observed therapy. Infect Dis (Lond) 2020; 53:9-18. [PMID: 32820689 DOI: 10.1080/23744235.2020.1806352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
BACKGROUND Intravenous drug users (IDUs) with hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfection are recognised as a high-risk, vulnerable group. METHODS Between February 2015 and April 2018, a single-centre, non-interventional cohort study was conducted in an outpatient setting, to evaluate the sustained virologic response (SVR12) and assess treatment uptake models. The study included 385 former or recent IDUs divided into two groups: A-without use of opioid substitution treatment (OST) and B-patients taking opioid substitution; patients in group B received OST and self-administered therapy (B1) or OST and therapy under DOT (B2). Patients were characterised by demographic and clinical features and compared for treatment response. Correlations between SVR12 and independent variables were determined by logistic regression. RESULTS Patients were mostly males (88.3%) with a mean age of 46 ± 5 years and HCV genotype 1a (63.7%). Approximately 28% were treatment-experienced and 84.9% received sofosbuvir/ledipasvir. The mean CD4+T count was 649 cells/mm3, and most individuals were on antiretroviral therapy with undetectable viral loads (97.4%). SVR12 was achieved in 94.8%, and only eight patients relapsed. No significant differences were found in treatment effect between individuals taking opioid substitutes under different treatment models. Correlations were found between HCV viral response and both HIV suppression and albumin levels. CONCLUSIONS IDU with HCV/HIV coinfection, including individuals on self-administration of HCV therapy and opioid substitution treatments or in DOT programmes, are no longer considered a difficult-to-treat group, as they achieve high rates of SVR12.
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Affiliation(s)
- R Sarmento-Castro
- Serviço de Doenças Infeciosas, Centro Hospitalar Universitário do Porto - Largo Prof. Abel Salazar, Porto, Portugal
| | - J Méndez
- Serviço de Doenças Infeciosas, Centro Hospitalar Universitário do Porto - Largo Prof. Abel Salazar, Porto, Portugal
| | - A Horta
- Serviço de Doenças Infeciosas, Centro Hospitalar Universitário do Porto - Largo Prof. Abel Salazar, Porto, Portugal
| | - C Gonçalves
- Serviço de Doenças Infeciosas, Centro Hospitalar Universitário do Porto - Largo Prof. Abel Salazar, Porto, Portugal
| | - O Vasconcelos
- Serviço de Doenças Infeciosas, Centro Hospitalar Universitário do Porto - Largo Prof. Abel Salazar, Porto, Portugal
| | - J Seabra
- Serviço de Doenças Infeciosas, Centro Hospitalar Universitário do Porto - Largo Prof. Abel Salazar, Porto, Portugal
| | - M Abreu
- Serviço de Doenças Infeciosas, Centro Hospitalar Universitário do Porto - Largo Prof. Abel Salazar, Porto, Portugal
| | - M J Gonçalves
- Serviço de Doenças Infeciosas, Centro Hospitalar Universitário do Porto - Largo Prof. Abel Salazar, Porto, Portugal
| | - M J Santos
- Serviço de Doenças Infeciosas, Centro Hospitalar Universitário do Porto - Largo Prof. Abel Salazar, Porto, Portugal.,ARSN - Administração Regional De Saúde Do Norte I.P, Porto, Portugal
| | - A P Tavares
- Serviço de Doenças Infeciosas, Centro Hospitalar Universitário do Porto - Largo Prof. Abel Salazar, Porto, Portugal
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12
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Gharibvand MM, Asare M, Motamedfar A, Alavinejad P, Momeni M. Ultrasound shear wave elastography and liver biopsy to determine liver fibrosis in adult patients. J Family Med Prim Care 2020; 9:943-949. [PMID: 32318450 PMCID: PMC7113977 DOI: 10.4103/jfmpc.jfmpc_828_19] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 12/27/2019] [Accepted: 01/08/2020] [Indexed: 02/06/2023] Open
Abstract
Introduction: Liver biopsy is considered as the gold standard for diagnosis of chronic liver disease, yet liver biopsy is an invasive method that may be associated with complications. Therefore, non-invasive methods are needed to diagnose fibrosis. This study was conducted to compare liver stiffness measured by Shear-wave Elastography (SWE) to fibrosis in liver biopsy. Method and Materials: In this prospective study, 176 adult patients with chronic liver disease of different etiologies were included. All patients were evaluated using SWE and a liver biopsy. The diagnostic accuracy of SWE was evaluated using receiver operating characteristics (ROC) plots based on the degree of fibrosis (METAVIR score). SPSS software version 19 was used for statistical analysis and P < 0.05 considered significant. Results: There was a significant correlation between liver stiffness and fibrosis stage (ρ=0.939; P < 0.0001). The ROC curve AUC were 0.871, 0.895 and 0.937 for fibrosis stages F2, F3 and F4 respectively. The cutoff values were 8.6 kPa for F2, 10.7 kPa for F3, and 13.8 kPa for F4, with sensitivity and specificity of 81.76% and 77.01%, 90.20% and 78.40%, 89.53% and 94.38% respectively. Conclusion: The results of this study showed that liver SWE is an effective non-invasive method for assessing liver fibrosis in patients with chronic liver disease of different etiologies.
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Affiliation(s)
- Mohammad M Gharibvand
- Department of Radiology, Golestan Hospital, Ahvaz Jundishapur University of Medicine, Ahvaz, Iran
| | - Mohammad Asare
- Department of Radiology, Golestan Hospital, Ahvaz Jundishapur University of Medicine, Ahvaz, Iran
| | - Azim Motamedfar
- Department of Radiology, Golestan Hospital, Ahvaz Jundishapur University of Medicine, Ahvaz, Iran
| | - Pezhman Alavinejad
- Department of Internal Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Momeni
- Department of Radiology, Golestan Hospital, Ahvaz Jundishapur University of Medicine, Ahvaz, Iran
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13
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Shiha G, Mousa N. Noninvasive Biomarkers for Liver Fibrosis. LIVER DISEASES 2020:427-441. [DOI: 10.1007/978-3-030-24432-3_36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
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14
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Wu Z, Dong X, Wang G, Zhao H. Clinical noninvasive markers for antiviral therapy decision in chronic hepatitis B with alanine aminotransferase less than two times upper limit of normal. J Viral Hepat 2019; 26:287-296. [PMID: 30380162 DOI: 10.1111/jvh.13030] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 10/01/2018] [Accepted: 10/04/2018] [Indexed: 12/12/2022]
Abstract
Liver biopsy is the reference method for antiviral therapy decision-making in chronic hepatitis B (CHB) when alanine aminotransferase (ALT) is less than two times of upper limit of normal (<2ULN). Our aim was to explore noninvasive markers for antiviral therapy decision in CHB with ALT <2ULN. A total of 452 treatment-naïve CHB patients with ALT < 2ULN who had undergone liver biopsy were analysed in this prospective multi-centre study. If liver biopsy showed moderate or severe inflammation (histology activity index ≥ 5) or significant fibrosis (Ishak fibrosis score ≥ 3), antiviral treatment was recommended. We analysed data using univariate and multivariate analyses and receiver operating characteristic curves (ROC). Two hundred and sixty-nine (59.5%) of 452 cases with ALT < 2ULN had moderate, severe or significant inflammation. Aspartate aminotransferase (AST) (P = 0.03), anti-hepatitis B virus core antibody (anti-HBc) (P = 0.003) and liver stiffness measurement (LSM) (P = 0.000) were independent variables for antiviral therapy decision-making, with area under the ROC curve (AUROC) of 0.718, 0.703 and 0.819, respectively. Our novel AAF index, which combined AST, anti-HBc and LSM, showed better performance with AUROC of 0.876, 0.877 and 0.876 in estimation, validation and total set. Finally, 247 (54.6%) of 452 patients could avoid liver biopsy based on AAF index. Furthermore, performances of 23 noninvasive models were unsatisfactory for antiviral therapy decision with AUROC < 0.800, which were inferior to AAF index. In conclusion, AST, anti-HBc and LSM were related to antiviral therapy decision-making among CHB patients with ALT < 2ULN. Thus, the novel AAF index was a more reliable noninvasive model for antiviral therapy decision-making.
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Affiliation(s)
- Zhao Wu
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Xiaoqin Dong
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Guiqiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.,The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, China.,Peking University International Hospital, Beijing, China
| | - Hong Zhao
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.,Peking University International Hospital, Beijing, China
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15
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Dong XQ, Wu Z, Zhao H, Wang GQ. Evaluation and comparison of thirty noninvasive models for diagnosing liver fibrosis in chinese hepatitis B patients. J Viral Hepat 2019; 26:297-307. [PMID: 30380170 DOI: 10.1111/jvh.13031] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 10/07/2018] [Accepted: 10/09/2018] [Indexed: 12/15/2022]
Abstract
The limitations of liver biopsy have led to the development of indirect noninvasive models for liver fibrosis assessment. We aimed to evaluate and compare the performance of 30 noninvasive models to predict fibrosis stage in treatment-naïve and treated chronic hepatitis B (CHB) patients. A total of 576 Chinese treatment-naïve CHB patients and 236 treated CHB patients who had undergone percutaneous liver biopsy were included in the analysis. Histological grading and staging was assessed by the Ishak scoring system. The diagnostic accuracies of 30 noninvasive models were assessed by area under the receiver operating characteristic curves (AUROCs). In treatment-naïve CHB patients, the AUROCs of the 30 noninvasive models for discriminating significant fibrosis (SF) were less than 0.800, and only the AUROC of the PP score for diagnosing advanced fibrosis (AF) was more than 0.800, while the AUROCs of FIB-4, FibroQ, HB-F, Lok index, PHP score and PP score for predicting cirrhosis were greater than 0.800. In treated CHB patients, only the AUROCs of APRI, GUCI, King's score and Wang I for identifying cirrhosis were more than 0.800. The Spearman correlation analysis identified that only the changes in FCI and Virahep-C model values were weakly correlated with changes in Ishak fibrosis scores before and after treatment (r = 0.206, p = 0.008; r = 0.187, p = 0.016, respectively). In conclusion, in Chinese CHB patients, the 30 existing noninvasive models were not suitable for assessing each stage of fibrosis except cirrhosis before and after antiviral therapy, especially in gauging progression and regression of liver fibrosis following therapy.
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Affiliation(s)
- Xiao-Qin Dong
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Zhao Wu
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Hong Zhao
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.,Peking University International Hospital, Beijing, China
| | - Gui-Qiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.,Peking University International Hospital, Beijing, China.,The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, China
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16
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Prospects in non-invasive assessment of liver fibrosis: Liquid biopsy as the future gold standard? Biochim Biophys Acta Mol Basis Dis 2018; 1864:1024-1036. [PMID: 29329986 DOI: 10.1016/j.bbadis.2018.01.009] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 01/04/2018] [Accepted: 01/07/2018] [Indexed: 12/11/2022]
Abstract
Liver fibrosis is the result of persistent liver injury, and is characterized by sustained scar formation and disruption of the normal liver architecture. The extent of fibrosis is considered as an important prognostic factor for the patient outcome, as an absence of (early) treatment can lead to the development of liver cirrhosis and hepatocellular carcinoma. Till date, the most sensitive and specific way for the diagnosis and staging of liver fibrosis remains liver biopsy, an invasive diagnostic tool, which is associated with high costs and discomfort for the patient. Over time, non-invasive scoring systems have been developed, of which the measurements of serum markers and liver stiffness are validated for use in the clinic. These tools lack however the sensitivity and specificity to detect small changes in the progression or regression of both early and late stages of fibrosis. Novel non-invasive diagnostic markers with the potential to overcome these limitations have been developed, but often lack validation in large patient cohorts. In this review, we will summarize novel trends in non-invasive markers of liver fibrosis development and will discuss their (dis-)advantages for use in the clinic.
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17
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Abstract
Patients with HIV have a proclivity to develop liver fibrosis, especially when associated with other conditions such as HCV, HBV, and NAFLD. Identifying HIV-infected patients with significant fibrosis or cirrhosis plays an important role in clinical and therapeutic decision-making. Liver biopsy is currently considered as the gold standard for fibrosis assessment but carries many shortcomings (cost, invasiveness, complications, false negative rate of 20 %). Multiple non-invasive methods of liver fibrosis assessment have been developed, but not all have been studied in HIV-infected individuals. Non-invasive liver fibrosis tools include both serologic-based testing scores (rely on direct and/or indirect markers) such as APRI, FIB4, FibroTest, FibroSpect II, HepaScore, or imaging-based methods such as vibration controlled liver elastography. There is validated data to support the use of non-invasive modalities of fibrosis assessment in HIV-HCV co-infected individuals for the exclusion of cirrhosis, but may be poorly reliable or not enough data exists for the assessment of other co-morbid disease processes.
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18
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Keating SM, Dodge JL, Norris PJ, Heitman J, Gange SJ, French AL, Glesby MJ, Edlin BR, Latham PS, Villacres MC, Greenblatt RM, Peters MG. The effect of HIV infection and HCV viremia on inflammatory mediators and hepatic injury-The Women's Interagency HIV Study. PLoS One 2017; 12:e0181004. [PMID: 28902848 PMCID: PMC5597129 DOI: 10.1371/journal.pone.0181004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 05/22/2017] [Indexed: 12/21/2022] Open
Abstract
Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = 18), ART-treated HIV-controlled (ARTc, n = 20), uncontrolled on anti-retroviral therapy (ARTuc, n = 21) and elite HIV controllers (Elite, n = 20). All were HCV seroreactive and had either resolved (HCV RNA-; <50IU/mL) or had chronic HCV infection (HCV RNA+). In HCV and HIV groups, aspartate aminotransferase to platelet ratio (APRI) was measured and compared to serum cytokines, chemokines, growth factors and cell adhesion molecules. APRI correlated with sVCAM, sICAM, IL-10, and IP-10 levels and inversely correlated with EGF, IL-17, TGF-α and MMP-9 levels. Collectively, all HCV RNA+ subjects had higher sVCAM, sICAM and IP-10 compared to HCV RNA-. In the ART-treated HCV RNA+ groups, TNF-α, GRO, IP-10, MCP-1 and MDC were higher than HIV-, Elite or both. In ARTuc, FGF-2, MPO, soluble E-selectin, MMP-9, IL-17, GM-CSF and TGF-α are lower than HIV-, Elite or both. Differential expression of soluble markers may reveal mechanisms of pathogenesis or possibly reduction of fibrosis in HCV/HIV co-infection.
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Affiliation(s)
- Sheila M. Keating
- Blood Systems Research Institute, San Francisco, California, United States of America
- Department of Laboratory Medicine, University of California San Francisco, California, United States of America
- * E-mail:
| | - Jennifer L. Dodge
- Department of Surgery, UCSF, San Francisco, California, United States of America
| | - Philip J. Norris
- Blood Systems Research Institute, San Francisco, California, United States of America
- Department of Laboratory Medicine, University of California San Francisco, California, United States of America
- Department of Medicine, UCSF, San Francisco, California, United States of America
| | - John Heitman
- Blood Systems Research Institute, San Francisco, California, United States of America
| | - Stephen J. Gange
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America
| | - Audrey L. French
- CORE Center, Stroger Hospital of Cook County, Chicago, Illinois, United States of America
| | - Marshall J. Glesby
- Department of Medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York, New York, United States of America
| | - Brian R. Edlin
- Department of Medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York, New York, United States of America
- Department of Medicine, SUNY Downstate, Brooklyn, New York, United States of America
| | - Patricia S. Latham
- Department of Pathology and Medicine, George Washington University Medical Center, Washington DC, United States of America
| | - Maria C. Villacres
- Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Ruth M. Greenblatt
- Department of Pharmacology, UCSF, San Francisco, California, United States of America
| | - Marion G. Peters
- Department of Medicine, UCSF, San Francisco, California, United States of America
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19
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Liver Fibrosis and Hepatitis B Coinfection among ART Naïve HIV-Infected Patients at a Tertiary Level Hospital in Northwestern Tanzania: A Cross-Sectional Study. J Trop Med 2017; 2017:5629130. [PMID: 28828009 PMCID: PMC5554579 DOI: 10.1155/2017/5629130] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Revised: 06/11/2017] [Accepted: 06/22/2017] [Indexed: 12/16/2022] Open
Abstract
Background Liver fibrosis which is a common complication of chronic hepatitis B infection is rarely diagnosed in low-resource countries due to limited capacity to perform biopsy studies. Data on the utilization of noninvasive techniques which are feasible for diagnosis of liver fibrosis in these settings among HIV-infected patients is scarce. The objective of this study was to establish the magnitude of liver fibrosis by using both aspartate-aminotransferase-to-platelets ratio and fibrosis-4 scores with associated hepatitis B coinfection among antiretroviral therapy naïve HIV-infected patients. Methods We reviewed data of 743 adult patients attending HIV clinic with available hepatitis B surface antigen test results. Baseline clinical information was recorded and aspartate-aminotransferase-to-platelet ratio and fibrosis-4 scores were calculated. The cut-off values of 1.5 and 3.25 were used for diagnosis of significant fibrosis by aspartate-aminotransferase-to-platelets ratio and fibrosis-4 scores, respectively. Results The prevalence of liver fibrosis was 3.5% when aspartate-aminotransferase-to-platelet score was used and 4.6% with fibrosis-4 score and they were both significantly higher among patients with hepatitis B coinfection. Younger patients with HIV advanced disease and elevated liver transaminases had increased risk of having hepatitis B coinfection. Conclusion A remarkable number of HIV-infected patients present with liver fibrosis, predominantly those with hepatitis B infection.
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20
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Moqueet N, Kanagaratham C, Gill MJ, Hull M, Walmsley S, Radzioch D, Saeed S, Platt RW, Klein MB. A prognostic model for development of significant liver fibrosis in HIV-hepatitis C co-infection. PLoS One 2017; 12:e0176282. [PMID: 28467457 PMCID: PMC5415136 DOI: 10.1371/journal.pone.0176282] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 04/07/2017] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Liver fibrosis progresses rapidly in HIV-Hepatitis C virus (HCV) co-infected individuals partially due to heightened inflammation. Immune markers targeting stages of fibrogenesis could aid in prognosis of fibrosis. METHODS A case-cohort study was nested in the prospective Canadian Co-infection Cohort (n = 1119). HCV RNA positive individuals without fibrosis, end-stage liver disease or chronic Hepatitis B at baseline (n = 679) were eligible. A random subcohort (n = 236) was selected from those eligible. Pro-fibrogenic markers and Interferon Lambda (IFNL) rs8099917 genotype were measured from first available sample in all fibrosis cases (APRI ≥ 1.5 during follow-up) and the subcohort. We used Cox proportional hazards and compared Model 1 (selected clinical predictors only) to Model 2 (Model 1 plus selected markers) for predicting 3-year risk of liver fibrosis using weighted Harrell's C and Net Reclassification Improvement indices. RESULTS 113 individuals developed significant liver fibrosis over 1300 person-years (8.63 per 100 person-years 95% CI: 7.08, 10.60). Model 1 (age, sex, current alcohol use, HIV RNA, baseline APRI, HCV genotype) was nested in model 2, which also included IFNL genotype and IL-8, sICAM-1, RANTES, hsCRP, and sCD14. The C indexes (95% CI) for model 1 vs. model 2 were 0.720 (0.649, 0.791) and 0.756 (0.688, 0.825), respectively. Model 2 classified risk more appropriately (overall net reclassification improvement, p<0.05). CONCLUSIONS Including IFNL genotype and inflammatory markers IL-8, sICAM-1, RANTES, hs-CRP, and sCD14 enabled better prediction of the 3-year risk of significant liver fibrosis over clinical predictors alone. Whether this modest improvement in prediction justifies their additional cost requires further cost-benefit analyses.
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Affiliation(s)
- Nasheed Moqueet
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada
| | - Cynthia Kanagaratham
- Department of Medicine and Department of Human Genetics, McGill University, Montreal, QC, Canada
| | - M. John Gill
- Southern Alberta HIV Clinic, Calgary, Alberta, Canada
| | - Mark Hull
- BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, BC, Canada
| | - Sharon Walmsley
- Toronto General Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Danuta Radzioch
- Department of Medicine and Department of Human Genetics, McGill University, Montreal, QC, Canada
| | - Sahar Saeed
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada
| | - Robert W. Platt
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada
| | - Marina B. Klein
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada
- Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada
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21
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Lutterkort GL, Wranke A, Yurdaydin C, Budde E, Westphal M, Lichtinghagen R, Stift J, Bremer B, Hardtke S, Keskin O, Idilman R, Koch A, Manns MP, Dienes HP, Wedemeyer H, Heidrich B. Non-invasive fibrosis score for hepatitis delta. Liver Int 2017; 37:196-204. [PMID: 27428078 DOI: 10.1111/liv.13205] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 07/14/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Identifying advanced fibrosis in chronic hepatitis delta patients and thus in need of urgent treatment is crucial. To avoid liver biopsy, non-invasive fibrosis scores may be helpful but have not been evaluated for chronic hepatitis delta yet. METHODS We evaluated eight non-invasive fibrosis scores in 100 HDV RNA-positive patients with available central histological reading. New cut-off values were calculated by using Receiver Operating Characteristics and Youden indexes. Predictors for the presence of ISHAK F3-6 were revealed by t-tests or Mann-Whitney tests. RESULTS None of the tested scores had an area under the curve (AUROC) > 0.8 and performed according to our predefined requirements of a sensitivity of >80% and a positive predictive value (PPV) >90% - even after adaption. However, the ELF score was able to identify advanced fibrosis with a high sensitivity (93%) and PPV (81%), but relies on expensive extracellular matrix markers with bad availability in many endemic regions of HDV. Thus, we developed a novel non-invasive approach and identified low cholinesterase (P=.002), low albumin (P=.041), higher gamma glutamyl transferase, as well as older age (P<.001) as predictors of fibrosis resulting in the Delta Fibrosis Score (DFS). The DFS performed with a sensitivity of 85% and PPV of 93% with an AUROC of 0.87. CONCLUSIONS Existing non-invasive fibrosis scores are either impracticable or do not perform well in chronic hepatitis delta patients. However, the new Delta Fibrosis Score is the first non-invasive fibrosis score specifically developed for chronic hepatitis delta and requires only standard parameters.
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Affiliation(s)
- Gunnar L Lutterkort
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Anika Wranke
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Cihan Yurdaydin
- Department of Gastroenterology, Ankara University Medical Faculty, Ankara, Turkey
| | - Eva Budde
- Institute for Biostatistics, Hannover Medical School, Hannover, Germany
| | - Max Westphal
- Institute for Biostatistics, Hannover Medical School, Hannover, Germany
| | - Ralf Lichtinghagen
- Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
| | - Judith Stift
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Birgit Bremer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Svenja Hardtke
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infectious Disease Research (DZIF), Partner Site Hannover-Braunschweig, HepNet Study-House, Hannover, Germany
| | - Onur Keskin
- Department of Gastroenterology, Ankara University Medical Faculty, Ankara, Turkey
| | - Ramazan Idilman
- Department of Gastroenterology, Ankara University Medical Faculty, Ankara, Turkey
| | - Armin Koch
- Institute for Biostatistics, Hannover Medical School, Hannover, Germany
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infectious Disease Research (DZIF), Partner Site Hannover-Braunschweig, HepNet Study-House, Hannover, Germany
| | - Hans P Dienes
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infectious Disease Research (DZIF), Partner Site Hannover-Braunschweig, HepNet Study-House, Hannover, Germany
| | - Benjamin Heidrich
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infectious Disease Research (DZIF), Partner Site Hannover-Braunschweig, HepNet Study-House, Hannover, Germany
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Wilson EM, Rosenthal ES, Kattakuzhy S, Tang L, Kottilil S. Clinical Laboratory Testing in the Era of Directly Acting Antiviral Therapies for Hepatitis C. Clin Microbiol Rev 2017; 30:23-42. [PMID: 27795306 PMCID: PMC5217793 DOI: 10.1128/cmr.00037-16] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Directly acting antiviral (DAA) combination therapies for chronic hepatitis C virus (HCV) infection are highly effective, but treatment decisions remain complex. Laboratory testing is important to evaluate a range of viral, host, and pharmacological factors when considering HCV treatment, and patients must be monitored during and after therapy for safety and to assess the viral response. In this review, we discuss the laboratory tests relevant for the treatment of HCV infection in the era of DAA therapy, grouped according to viral and host factors.
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Affiliation(s)
- Eleanor M Wilson
- Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland, USA
- Critical Care Medicine Department of the NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
| | - Elana S Rosenthal
- Critical Care Medicine Department of the NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
| | - Sarah Kattakuzhy
- Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland, USA
- Critical Care Medicine Department of the NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
| | - Lydia Tang
- Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland, USA
| | - Shyam Kottilil
- Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland, USA
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Incidence and Predictors of Advanced Liver Fibrosis by a Validated Serum Biomarker in Liver Transplant Recipients. Can J Gastroenterol Hepatol 2017; 2017:4381864. [PMID: 28409147 PMCID: PMC5376470 DOI: 10.1155/2017/4381864] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Accepted: 06/13/2015] [Indexed: 12/29/2022] Open
Abstract
Background and Aims. Serum fibrosis biomarkers have shown good accuracy in the liver transplant (LT) population. We employed a simple serum biomarker to elucidate incidence and predictors of advanced fibrosis after LT over a long follow-up period. Methods. We included 440 consecutive patients who underwent LT between 1991 and 2013. Advanced liver fibrosis was defined as FIB-4 > 3.25 beyond 12 months after LT. Results. Over 2030.5 person-years (PY) of follow-up, 189 (43%) developed FIB-4 > 3.25, accounting for an incidence of 9.3/100 PY (95% confidence interval [CI], 8.1-10.7). Advanced fibrosis was predicted by chronic HCV infection (adjusted hazard ratio (aHR) = 3.96, 95% CI 2.92-5.36, p < 0.001), hypoalbuminemia (aHR = 2.31, 95% CI 1.72-3.09; p < 0.001), and hyponatremia (aHR = 1.48, 95% CI 1.09-2.01; p = 0.01). LT recipients with more than 1 predictor had a higher incidence of advanced fibrosis, the highest being when all 3 predictors coexisted (log-rank: p < 0.001). Conclusions. Chronic HCV infection, hypoalbuminemia, and hyponatremia predict progression to advanced liver fibrosis following LT. Patients with these risk factors should be serially monitored using noninvasive fibrosis biomarkers and prioritized for interventions.
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Njei B, McCarty TR, Luk J, Ewelukwa O, Ditah I, Lim JK. Use of transient elastography in patients with HIV-HCV coinfection: A systematic review and meta-analysis. J Gastroenterol Hepatol 2016; 31:1684-1693. [PMID: 26952020 PMCID: PMC5014713 DOI: 10.1111/jgh.13337] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Revised: 02/23/2016] [Accepted: 02/28/2016] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIM Patients with HIV-hepatitis C virus (HCV) coinfection progress towards liver fibrosis and cirrhosis more rapidly compared with HCV mono-infected individuals. This necessitates an accurate assessment of liver stiffness with transient elastography to guide treatment. METHODS Searches of PubMed, EMBASE, Web of Science, and the Cochrane Library databases were performed through January 2016 to assess the diagnostic accuracy of transient elastography for liver stiffness in the HIV-HCV population. Included studies were analyzed according to the Cochrane DTA Working Group methodology. Bivariate and hierarchical models were used to compute pooled sensitivity and specificity. Positive and negative likelihood ratios were also determined. A Fagan nomogram was constructed. Meta-regression analysis was performed with assessment of publication bias using Deeks' funnel plot asymmetry testing. RESULTS A total of six studies (n = 756) met the inclusion criteria. The diagnostic accuracy of elastography for the diagnosis of moderate (≥F2) fibrosis was 88% (95% confidence interval [CI], 0.85-0.90). The pooled sensitivity and specificity of moderate fibrosis was 97% (95% CI, 0.82-0.91) and 64% (95% CI, 0.45-0.79), respectively. The diagnostic accuracy of elastography for the assessment of cirrhosis was 94% (95% CI, 0.91-0.95). The pooled sensitivity and specificity for cirrhosis was 90% (95% CI, 0.74-0.97) and 87% (95% CI, 0.80-0.92), respectively. Meta-regression analysis demonstrated that CD4 cell count did not impact diagnostic accuracy of elastography. CONCLUSIONS Transient elastography is a noninvasive imaging modality with excellent ability to assess for cirrhosis in patients with HIV-HCV coinfection.
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Affiliation(s)
- Basile Njei
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.
- Investigative Medicine Program, Yale Center of Clinical Investigation, New Haven, CT, USA.
| | - Thomas R McCarty
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Jeffrey Luk
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Oforbuike Ewelukwa
- Gastroenterology and Hepatology, University of Florida, Gainesville, FL, USA
| | - Ivo Ditah
- Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Joseph K Lim
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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25
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Naglot S, Aggarwal P, Dey S, Dalal K. Estimation of Serum YKL-40 by Real-Time Surface Plasmon Resonance Technology in North-Indian Asthma Patients. J Clin Lab Anal 2016; 31. [PMID: 27616735 DOI: 10.1002/jcla.22028] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2014] [Accepted: 06/16/2016] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Many studies reported for estimating serum YKL-40 using ELISA or RIA methods. This study introduces the plausible utilization of real-time surface plasmon resonance (SPR) technology in investigating the expression of serum YKL-40 protein levels and ELISA method for serum IgE in bronchial asthma. METHODS A commercially available BIAcore 2000 instrument, based on SPR technology, was utilized for assessing serum YKL-40 levels in a control sample size of 45 and active sample size of 97. Antibody immobilization was optimized to obtain the best sensor performance and a sensitive analytic detection. A commercially available ELISA kit was utilized for detecting serum IgE to estimate allergic condition-associated asthma. RESULTS The results of SPR technology could distinctly classify with highly statistical significance, the asthma severities by estimating the elevated levels of YKL-40 in blood sera of minute quantities (up to 0.33 ng/ml), and thus differentiates superior utility in comparison with ELISA method. No statistically significant correlation of YKL-40 and IgE was observed. CONCLUSIONS Serum YKL-40 may be used as a protein marker in classifying asthma severity by applying SPR technology as a reliable, label-free, highly sensitive, and cost-effective tool.
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Affiliation(s)
- Sarla Naglot
- Department of Biophysics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Praveen Aggarwal
- Department of Emergency Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Sharmistha Dey
- Department of Biophysics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Krishna Dalal
- Department of Biophysics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
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Chin JL, Pavlides M, Moolla A, Ryan JD. Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy? Front Pharmacol 2016; 7:159. [PMID: 27378924 PMCID: PMC4913110 DOI: 10.3389/fphar.2016.00159] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Accepted: 05/31/2016] [Indexed: 12/13/2022] Open
Abstract
Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care.
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Affiliation(s)
- Jun L Chin
- School of Medicine and Medical Science, University College Dublin Dublin, Ireland
| | - Michael Pavlides
- Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford Oxford, UK
| | - Ahmad Moolla
- Radcliffe Department of Medicine, University of Oxford Oxford, UK
| | - John D Ryan
- Translational Gastroenterology Unit, University of Oxford Oxford, UK
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27
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Babaei Z, Parsian H. Hyaluronic acid algorithm-based models for assessment of liver fibrosis: translation from basic science to clinical application. Hepatobiliary Pancreat Dis Int 2016; 15:131-40. [PMID: 27020628 DOI: 10.1016/s1499-3872(16)60062-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND The estimation of liver fibrosis is usually dependent on liver biopsy evaluation. Because of its disadvantages and side effects, researchers try to find non-invasive methods for the assessment of liver injuries. Hyaluronic acid has been proposed as an index for scoring the severity of fibrosis, alone or in algorithm models. The algorithm model in which hyaluronic acid was used as a major constituent was more reliable and accurate in diagnosis than hyaluronic acid alone. This review described various hyaluronic acid algorithm-based models for assessing liver fibrosis. DATA SOURCE A PubMed database search was performed to identify the articles relevant to hyaluronic acid algorithm-based models for estimating liver fibrosis. RESULT The use of hyaluronic acid in an algorithm model is an extra and valuable tool for assessing liver fibrosis. CONCLUSIONS Although hyaluronic acid algorithm-based models have good diagnostic power in liver fibrosis assessment, they cannot render the need for liver biopsy obsolete and it is better to use them in parallel with liver biopsy. They can be used when frequent liver biopsy is not possible in situations such as highlighting the efficacy of treatment protocol for liver fibrosis.
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Affiliation(s)
- Zeinab Babaei
- Student Research Committee & Department of Biochemistry and Biophysics, and Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
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Enhanced liver fibrosis marker as a noninvasive predictor of mortality in HIV/hepatitis C virus-coinfected women from a multicenter study of women with or at risk for HIV. AIDS 2016; 30:723-9. [PMID: 26595542 DOI: 10.1097/qad.0000000000000975] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Coinfection with hepatitis C virus (HCV) is a major cause of morbidity and mortality among individuals with HIV. Our objective was to assess the prognostic performance of noninvasive measures of liver fibrosis in predicting all-cause mortality in women with HIV/HCV coinfection. DESIGN We studied HCV/HIV coinfected women enrolled in the prospective, multicenter Women's Interagency HIV Study. Aspartate aminotransferase to platelet ratio and FIB-4 were used to identify women without fibrosis at all visits and women who progressed to severe fibrosis. METHODS Enhanced liver fibrosis (ELF), which utilizes direct measures of fibrosis, hyaluronic acid, procollagen III aminoterminal peptide and tissue inhibitor of matrix metalloproteinase was performed. RESULTS Included were 381 women with 2296 ELF measurements, with mean follow-up 8.3 ± 3.3 years. There were 134 deaths (60% with severe liver fibrosis). Receiver operator characteristic curves at fixed time windows prior to death or at end of follow-up showed that ELF was best at predicting mortality when tested within a year of death (area under the curve for ELF 0.85 vs. APRI 0.69, P < 0.0001 and vs. FIB-4 0.75, P = 0.0036); and 1-3 years prior (ELF 0.71 vs. APRI 0.61, P = 0.005 and vs. FIB-4 0.65, P = 0.06). Use of all three measures did not improve on ELF alone. In multivariate logistic regression models controlling for CD4 cell count, HIV viral load, antiretroviral use and age, ELF continued to perform better than APRI and FIB-4. CONCLUSION ELF predicted all-cause mortality and was superior to APRI and FIB-4 in HIV/HCV coinfected women.
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Mohammed IA, Diab SM, Soliman DR, Shalaby WA. Study of serum YKL-40 in children with bronchial asthma. EGYPTIAN PEDIATRIC ASSOCIATION GAZETTE 2016. [DOI: 10.1016/j.epag.2015.11.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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Valva P, Ríos DA, De Matteo E, Preciado MV. Chronic hepatitis C virus infection: Serum biomarkers in predicting liver damage. World J Gastroenterol 2016; 22:1367-1381. [PMID: 26819506 PMCID: PMC4721972 DOI: 10.3748/wjg.v22.i4.1367] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 08/04/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
Currently, a major clinical challenge in the management of the increasing number of hepatitis C virus (HCV) infected patients is determining the best means for evaluating liver impairment. Prognosis and treatment of chronic hepatitis C (CHC) are partly dependent on the assessment of histological activity, namely cell necrosis and inflammation, and the degree of liver fibrosis. These parameters can be provided by liver biopsy; however, in addition to the risks related to an invasive procedure, liver biopsy has been associated with sampling error mostly due to suboptimal biopsy size. To avoid these pitfalls, several markers have been proposed as non-invasive alternatives for the diagnosis of liver damage. Distinct approaches among the currently available non-invasive methods are (1) the physical ones based on imaging techniques; and (2) the biological ones based on serum biomarkers. In this review, we discuss these approaches with special focus on currently available non-invasive serum markers. We will discuss: (1) class I serum biomarkers individually and as combined panels, particularly those that mirror the metabolism of liver extracellular matrix turnover and/or fibrogenic cell changes; (2) class II biomarkers that are indirect serum markers and are based on the evaluation of common functional alterations in the liver; and (3) biomarkers of liver cell death, since hepatocyte apoptosis plays a significant role in the pathogenesis of HCV infection. We highlight in this review the evidence behind the use of these markers and assess the diagnostic accuracy as well as advantages, limitations, and application in clinical practice of each test for predicting liver damage in CHC.
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ORASAN OLGAHILDA, CIULEI GEORGE, COZMA ANGELA, SAVA MADALINA, DUMITRASCU DANLUCIAN. Hyaluronic acid as a biomarker of fibrosis in chronic liver diseases of different etiologies. CLUJUL MEDICAL (1957) 2016; 89:24-31. [PMID: 27004022 PMCID: PMC4777465 DOI: 10.15386/cjmed-554] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 09/17/2015] [Indexed: 12/27/2022]
Abstract
Chronic liver diseases represent a significant public health problem worldwide. The degree of liver fibrosis secondary to these diseases is important, because it is the main predictor of their evolution and prognosis. Hyaluronic acid is studied as a non-invasive marker of liver fibrosis in chronic liver diseases, in an attempt to avoid the complications of liver puncture biopsy, considered the gold standard in the evaluation of fibrosis. We review the advantages and limitations of hyaluronc acid, a biomarker, used to manage patients with chronic viral hepatitis B or C infection, non-alcoholic fatty liver disease, HIV-HCV coinfection, alcoholic liver disease, primary biliary cirrhosis, biliary atresia, hereditary hemochromatosis and cystic fibrosis.
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Affiliation(s)
- OLGA HILDA ORASAN
- 4th Medical Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - GEORGE CIULEI
- 4th Medical Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - ANGELA COZMA
- 4th Medical Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - MADALINA SAVA
- 4th Medical Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - DAN LUCIAN DUMITRASCU
- 2nd Medical Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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AST/ALT ratio is not useful in predicting the degree of fibrosis in chronic viral hepatitis patients. Eur J Gastroenterol Hepatol 2015; 27:1361-6. [PMID: 26352130 DOI: 10.1097/meg.0000000000000468] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND AND AIM Noninvasive tests are primarily used for staging hepatic fibrosis in patients with chronic liver disease. In clinical practice, serum aminotransferase levels, coagulation parameters, and platelet count have been used to predict whether or not a patient has cirrhosis. In addition, several studies have evaluated the accuracy of combinations (or ratios) of these measures. The present study aimed to investigate the relationship between five noninvasive models [AST/ALT ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), Bonacini cirrhosis discriminant score (CDS), age-platelet index (APind), and King's score] and the degree of hepatic fibrosis as determined by biopsy in patients with chronic hepatitis B and C. PATIENTS AND METHODS A total of 380 patients with viral hepatitis (237 with chronic hepatitis B and 143 with chronic hepatitis C) who were seen at our clinic between January 2005 and January 2011 were retrospectively analyzed. The degree of fibrosis was determined using the Ishak score. Patients with a fibrosis score of 0-2 were considered to have low fibrosis and those with a score between 3 and 6 were considered to have high fibrosis. Five noninvasive models were compared between the groups with low and high fibrosis. RESULTS There were statistically significant differences between the hepatitis B and C patients with high and low fibrosis with respect to APind (4.49±2.35 vs. 2.41±1.84; P<0.001 in hepatitis B and 4.83±2.25 vs. 2.92±1.88; P<0.001 in hepatitis C), APRI (1.00±1.17 vs. 0.47±0.39; P<0.001 in hepatitis B and 1.01±1.01 vs. 0.41±0.29; P<0.001 in hepatitis C), CDS (4.53±1.90 vs. 3.58±1.30; P<0.001 in hepatitis B and 4.71±2.03 vs. 3.42±1.49; P<0.05 in hepatitis C), and King's score (24.31±3.14 vs. 7.65±6.70; P<0.001 in hepatitis B and 24.82±2.55 vs. 8.33±7.29; P<0.001 in hepatitis C). There were no significant differences in the AAR between the hepatitis B and C patients with high and low fibrosis (0.78±0.31 vs. 0.74±0.34; P=0.082 in hepatitis B and 0.91±0.40 vs. 0.85±0.27; P=0.25 in hepatitis C). The area under the receiver-operating characteristic curve of the APind, APRI, CDS, and King's score in the hepatitis B group were 0.767, 0.710, 0.646, and 0.770, respectively; these values were 0.732, 0.763, 0.677, and 0.783, respectively, in the hepatitis C group. CONCLUSION In conclusion, our data suggest that four of the five noninvasive methods evaluated in this study can be used to predict advanced fibrosis in patients with hepatitis B and C. However, there was no significant relationship between the degree of hepatic fibrosis and the AAR score, indicating that AAR is not useful in estimating the fibrosis stage in hepatitis B and C patients.
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EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015; 63:237-64. [PMID: 25911335 DOI: 10.1016/j.jhep.2015.04.006] [Citation(s) in RCA: 1316] [Impact Index Per Article: 131.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Accepted: 04/09/2015] [Indexed: 02/06/2023]
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Vinikoor MJ, Sinkala E, Mweemba A, Zanolini A, Mulenga L, Sikazwe I, Fried MW, Eron JJ, Wandeler G, Chi BH. Elevated AST-to-platelet ratio index is associated with increased all-cause mortality among HIV-infected adults in Zambia. Liver Int 2015; 35:1886-92. [PMID: 25581487 PMCID: PMC4478217 DOI: 10.1111/liv.12780] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2014] [Accepted: 01/04/2015] [Indexed: 12/27/2022]
Abstract
BACKGROUND & AIMS We investigated the association between significant liver fibrosis, determined by AST-to-platelet ratio index (APRI), and all-cause mortality among HIV-infected patients prescribed antiretroviral therapy (ART) in Zambia. METHODS Among HIV-infected adults who initiated ART, we categorized baseline APRI scores according to established thresholds for significant hepatic fibrosis (APRI ≥1.5) and cirrhosis (APRI ≥2.0). Using multivariable logistic regression we identified risk factors for elevated APRI including demographic characteristics, body mass index (BMI), HIV clinical and immunological status, and tuberculosis. In the subset tested for hepatitis B surface antigen (HBsAg), we investigated the association of hepatitis B virus co-infection with APRI score. Using Kaplan-Meier analysis and Cox proportional hazards regression we determined the association of elevated APRI with death during ART. RESULTS Among 20 308 adults in the analysis cohort, 1027 (5.1%) had significant liver fibrosis at ART initiation including 616 (3.0%) with cirrhosis. Risk factors for significant fibrosis or cirrhosis included male sex, BMI <18, WHO clinical stage 3 or 4, CD4(+) count <200 cells/mm(3) , and tuberculosis. Among the 237 (1.2%) who were tested, HBsAg-positive patients had four times the odds (adjusted odds ratio, 4.15; 95% CI, 1.71-10.04) of significant fibrosis compared HBsAg-negatives. Both significant fibrosis (adjusted hazard ratio 1.41, 95% CI, 1.21-1.64) and cirrhosis (adjusted hazard ratio 1.57, 95% CI, 1.31-1.89) were associated with increased all-cause mortality. CONCLUSION Liver fibrosis may be a risk factor for mortality during ART among HIV-infected individuals in Africa. APRI is an inexpensive and potentially useful test for liver fibrosis in resource-constrained settings.
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Affiliation(s)
- Michael J. Vinikoor
- Department of Medicine, University of North Carolina at Chapel Hill, North Carolina, USA,Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
| | - Edford Sinkala
- Department of Medicine, University of Zambia, Lusaka, Zambia,University Teaching Hospital, Lusaka, Zambia
| | - Aggrey Mweemba
- Department of Medicine, University of Zambia, Lusaka, Zambia,University Teaching Hospital, Lusaka, Zambia
| | - Arianna Zanolini
- Department of Medicine, University of North Carolina at Chapel Hill, North Carolina, USA,Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
| | - Lloyd Mulenga
- Centre for Infectious Disease Research in Zambia, Lusaka, Zambia,Department of Medicine, University of Zambia, Lusaka, Zambia,University Teaching Hospital, Lusaka, Zambia
| | - Izukanji Sikazwe
- Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
| | - Michael W. Fried
- Department of Medicine, University of North Carolina at Chapel Hill, North Carolina, USA
| | - Joseph J. Eron
- Department of Medicine, University of North Carolina at Chapel Hill, North Carolina, USA
| | - Gilles Wandeler
- Institute of Social and Preventive Medicine, University of Bern, Switzerland,Department of Infectious Diseases, University Hospital Bern, Switzerland
| | - Benjamin H. Chi
- Centre for Infectious Disease Research in Zambia, Lusaka, Zambia,Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, North Carolina, USA
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Abstract
In HIV-infected individuals, coinfection with HBV and/or HCV is common because of shared modes of transmission. It is known that HIV accelerates progression of liver disease and results in increased morbidity and mortality associated with viral hepatitis, but it is less clear if viral hepatitis has a direct effect on HIV. Treatment of viral hepatitis improves outcomes and should be considered in all HIV-infected patients. Treatment of HBV without concurrent treatment of HIV is risky because resistance can occur in both viruses if regimens are not carefully chosen.
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Diagnostic performance of collagen IV and laminin for the prediction of fibrosis and cirrhosis in chronic hepatitis C patients: a multicenter study. Eur J Gastroenterol Hepatol 2015; 27:378-85. [PMID: 25874509 DOI: 10.1097/meg.0000000000000298] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIM To date, liver biopsy has been the gold standard used for the assessment of liver fibrosis in patients with chronic hepatitis C. Our aim was to evaluate the diagnostic performance of a panel of simple blood markers of liver fibrosis and the development a novel score to replace liver biopsy. PATIENTS AND METHODS Liver biochemical profile including transaminases, bilirubin, alkaline phosphatase, and albumin, in addition to platelet count, was evaluated using standard methods in 305 chronic hepatitis C patients. Serum type IV collagen and laminin were assayed using the ELISA technique. Liver biopsies were performed. Statistical analyses were carried out by logistic regression and receiver operating characteristic curves to assess and compare the diagnostic accuracy of blood markers. A stepwise combination algorithm was developed and validated in 317 additional patients. RESULTS The Fibrosis Discriminant Score (FDS) was developed combining collagen, laminin, aspartate aminotransferase/platelet ratio index, and albumin. FDS produced an area under receiver operating characteristic curve of 0.831 for significant fibrosis, 0.791 for advanced fibrosis, and 0.881 for cirrhosis. The FDS was correctly classified in 82% of patients with significant fibrosis with 79% sensitivity and 88% specificity at cut-off 0.66 or more. Similar results were obtained in a validation study in which, of 317 patients, liver biopsy could have been avoided in 81%. CONCLUSION A simple fibrosis index can be useful to select hepatitis C virus-infected patients with a very low risk of significant fibrosis in whom the protocol of liver biopsies may be avoided.
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Kassaye S, Li Y, Huhn G, Peters MG, French AL, Tien PC, Luxon B, Plankey MW. Direct and Indirect Serum Markers of Liver Fibrosis Compared with Transient Elastography among Women in the Women's Interagency HIV Study. JOURNAL OF AIDS & CLINICAL RESEARCH 2015; 6:446. [PMID: 26251759 PMCID: PMC4524652 DOI: 10.4172/2155-6113.1000446] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The aim of this study was to determine the test characteristics of direct and indirect biomarkers for liver fibrosis compared with transient elastography (TE) among a group of human immunodeficiency virus (HIV)-infected and uninfected women with or without Hepatitis C virus (HCV) infection. METHODS Women enrolled in the Women's Interagency HIV Study (WIHS) from Washington DC, San Francisco, and Chicago with a body mass index (BMI)<35 underwent liver stiffness measurement using TE between October, 2010 and September, 2012. Serum samples were tested for hyaluronic acid to calculate the SHASTA and aspartate aminotransferase to platelet ratio index (APRI). Receiver operator characteristics (ROC) of significant liver fibrosis (liver stiffness ≥ 7.1 kPa by TE, correlating with a METAVIR fibrosis score of F2-F4) predicted by SHASTA and APRI were compared. RESULTS Among 308 women, the median age was 48 years, BMI was 25.6, 67% were non-Hispanic black, 27% HCV+, and 78% HIV+. The overall prevalence of significant liver fibrosis was 20%, and among HIV+ women, 22%. Overall, there was no statistically significant difference in the area under ROC curve (AUROC) between SHASTA and APRI relative to significant fibrosis by TE. Among HCV+ women (with or without HIV), the AUROC ranged from 0.70-0.73 for both the SHASTA and APRI compared to TE. Both SHASTA and APRI were associated with significant misclassification with a false negative rate of 33-40% for significant fibrosis compared with TE among women with HCV infection, with or without HIV. CONCLUSION Both the SHASTA and APRI, direct and indirect serum biomarkers of liver fibrosis respectively, are comparable at detection of significant liver fibrosis among women with HCV infection, regardless of HIV status. However, there was a high false negative rate in detection of significant liver fibrosis of up to 40% which is a significant limitation of use of these biomarkers.
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Affiliation(s)
- Seble Kassaye
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Ying Li
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Gregory Huhn
- CORE Center/Department of Medicine, Stroger Hospital of Cook County, Chicago, Illinois, USA
| | - Marion G Peters
- Department of Medicine, University of California, San Francisco, California, USA
| | - Audrey L French
- CORE Center/Department of Medicine, Stroger Hospital of Cook County, Chicago, Illinois, USA
| | - Phyllis C Tien
- Department of Medicine, University of California, San Francisco, California, USA
- Medical Service, Department of Veterans Affairs Medical Center, San Francisco, California, USA
| | - Bruce Luxon
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Michael W Plankey
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
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Abstract
Newer noninvasive tests have begun to replace liver biopsy for staging purposes. The clinician must evaluate these tools and apply them to individual patients. None of these modalities give the exact same staging of fibrosis as a liver biopsy, but they are excellent tools for risk stratification. Still, it should be recognized that there are disease-specific issues with different utilizations and cutoffs for different clinical diseases. This article provides a framework for incorporating the use of serum biomarkers and elastography-based approaches to stage fibrosis into clinical practice. This review also covers recent developments in this rapidly advancing area.
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Affiliation(s)
- Alan Bonder
- Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Elliot B Tapper
- Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Nezam H Afdhal
- Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
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Huang ZL, Chen XP, Zhao QY, Zheng YB, Peng L, Gao ZL, Zhao ZX. An albumin, collagen IV, and longitudinal diameter of spleen scoring system superior to APRI for assessing liver fibrosis in chronic hepatitis B patients. Int J Infect Dis 2015; 31:18-22. [DOI: 10.1016/j.ijid.2014.10.030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 10/05/2014] [Accepted: 10/20/2014] [Indexed: 12/20/2022] Open
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Shaheen AAM, Myers RP. Systematic Review and Meta–Analysis of the Diagnostic Accuracy of Fibrosis Marker Panels in Patients with HIV/Hepatitis C Coinfection. HIV CLINICAL TRIALS 2015; 9:43-51. [DOI: 10.1310/hct0901-43] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Crossan C, Tsochatzis EA, Longworth L, Gurusamy K, Davidson B, Rodríguez-Perálvarez M, Mantzoukis K, O'Brien J, Thalassinos E, Papastergiou V, Burroughs A. Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation. Health Technol Assess 2015; 19:1-vi. [PMID: 25633908 PMCID: PMC4781028 DOI: 10.3310/hta19090] [Citation(s) in RCA: 109] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822. LIMITATIONS A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION This study is registered as PROSPERO CRD42011001561. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Catriona Crossan
- Health Economics Research Group, Brunel University London, Uxbridge, UK
| | - Emmanuel A Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Louise Longworth
- Health Economics Research Group, Brunel University London, Uxbridge, UK
| | | | | | - Manuel Rodríguez-Perálvarez
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Konstantinos Mantzoukis
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Julia O'Brien
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Evangelos Thalassinos
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Vassilios Papastergiou
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Andrew Burroughs
- Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
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Gowda C, Compher C, Amorosa VK, Re VL. Association between chronic hepatitis C virus infection and low muscle mass in US adults. J Viral Hepat 2014; 21:938-43. [PMID: 24989435 PMCID: PMC4236264 DOI: 10.1111/jvh.12273] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Accepted: 05/17/2014] [Indexed: 12/15/2022]
Abstract
Given that low muscle mass can lead to worse health outcomes in patients with chronic infections, we assessed whether chronic hepatitis C virus (HCV) infection was associated with low muscle mass among US adults. We performed a cross-sectional study of the National Health Examination and Nutrition Study (1999-2010). Chronic HCV-infected patients had detectable HCV RNA. Low muscle mass was defined as <10th percentile for mid-upper arm circumference (MUAC). Multivariable logistic regression was used to determine adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of low muscle mass associated with chronic HCV. Among 18 513 adults, chronic HCV-infected patients (n = 303) had a higher prevalence of low muscle mass than uninfected persons (13.8% vs 6.7%; aOR, 2.22; 95% CI, 1.39-3.56), and this association remained when analyses were repeated among persons without significant liver fibrosis (aOR, 2.12; 95% CI, 1.30-3.47). This study demonstrates that chronic HCV infection is associated with low muscle mass, as assessed by MUAC measurements, even in the absence of advanced liver disease.
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Affiliation(s)
- Charitha Gowda
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA (C.G., V.K.A., V.L.R.), Department of Biostatistics and Epidemiology and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA (C.G., V.L.R.)
| | - Charlene Compher
- Department of Nutrition, University of Pennsylvania School of Nursing, Philadelphia, PA (C.C.)
| | - Valerianna K. Amorosa
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA (C.G., V.K.A., V.L.R.), Philadelphia Veterans Affairs Medical Center, Philadelphia, PA (V.K.A.)
| | - Vincent Lo Re
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA (C.G., V.K.A., V.L.R.), Department of Biostatistics and Epidemiology and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA (C.G., V.L.R.)
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Prevalence and predictors of elevated aspartate aminotransferase-to-platelet ratio index in Latin American perinatally HIV-infected children. Pediatr Infect Dis J 2014. [PMID: 23799515 DOI: 10.1097/inf] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Chronic liver disease has emerged as an important problem in adults with longstanding HIV infection, but data are lacking for children. We characterized elevated aspartate aminotransferase-to-platelet ratio index (APRI), a marker of possible liver fibrosis, in perinatally HIV-infected children. METHODS The National Institute of Child Health and Human Development International Site Development Initiative enrolled HIV-infected children (ages 0.1-20.1 years) from 5 Latin American countries in an observational cohort from 2002 to 2009. Twice yearly visits included medical history, physical examination and laboratory evaluations. The prevalence (95% confidence interval) of APRI > 1.5 was calculated, and associations with demographic, HIV-related and liver-related variables were investigated in bivariate analyses. RESULTS APRI was available for 1012 of 1032 children. APRI was >1.5 in 32 (3.2%, 95% confidence interval: 2.2%-4.4%) including 2 of 4 participants with hepatitis B virus infection. Factors significantly associated with APRI > 1.5 (P < 0.01 compared with APRI ≤ 1.5) included country, younger age, past or current hepatitis B virus, higher alanine aminotransferase, lower total cholesterol, higher log10 current viral load, lower current CD4 count, lower nadir CD4 count, use of hepatotoxic nonantiretroviral (ARV) medications and no prior ARV use. Rates of APRI > 1.5 varied significantly by current ARV regimen (P = 0.0002), from 8.0% for no ARV to 3.2% for non-protease inhibitor regimens to 1.5% for protease inhibitor-based regimens. CONCLUSIONS Elevated APRI occurred in approximately 3% of perinatally HIV-infected children. Protease inhibitor-based ARVs appeared protective whereas inadequate HIV control appeared to increase risk of elevated APRI. Additional investigations are needed to better assess potential subclinical, chronic liver disease in HIV-infected children.
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Abstract
Liver fibrosis is the final common pathway for almost all causes of chronic liver injury. Liver fibrosis is now known to be a dynamic process having significant potential for resolution. Therefore, fibrosis prediction is an essential part of the assessment and management of patients with chronic liver disease. As such, there is strong demand for reliable liver biomarkers that provide insight into disease etiology, diagnosis, therapy, and prognosis in lieu of more invasive approaches such as liver biopsy. Current diagnostic strategies range from use of serum biomarkers to more advanced imaging techniques including transient elastography and magnetic resonance imaging. In addition to these modalities, there are other approaches including the use of novel, but yet to be validated, biomarkers. In this chapter, we discuss the biomarkers of liver fibrosis including the use of invasive and noninvasive biomarkers and disease-specific biomarkers in various chronic liver diseases.
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Schiavon LDL, Narciso-Schiavon JL, Carvalho-Filho RJD. Non-invasive diagnosis of liver fibrosis in chronic hepatitis C. World J Gastroenterol 2014; 20:2854-2866. [PMID: 24659877 PMCID: PMC3961992 DOI: 10.3748/wjg.v20.i11.2854] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/10/2013] [Accepted: 01/14/2014] [Indexed: 02/06/2023] Open
Abstract
Assessment of liver fibrosis in chronic hepatitis C virus (HCV) infection is considered a relevant part of patient care and key for decision making. Although liver biopsy has been considered the gold standard for staging liver fibrosis, it is an invasive technique and subject to sampling errors and significant intra- and inter-observer variability. Over the last decade, several noninvasive markers were proposed for liver fibrosis diagnosis in chronic HCV infection, with variable performance. Besides the clear advantage of being noninvasive, a more objective interpretation of test results may overcome the mentioned intra- and inter-observer variability of liver biopsy. In addition, these tests can theoretically offer a more accurate view of fibrogenic events occurring in the entire liver with the advantage of providing frequent fibrosis evaluation without additional risk. However, in general, these tests show low accuracy in discriminating between intermediate stages of fibrosis and may be influenced by several hepatic and extra-hepatic conditions. These methods are either serum markers (usually combined in a mathematical model) or imaging modalities that can be used separately or combined in algorithms to improve accuracy. In this review we will discuss the different noninvasive methods that are currently available for the evaluation of liver fibrosis in chronic hepatitis C, their advantages, limitations and application in clinical practice.
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Siberry GK, Cohen RA, Harris DR, Cruz MLS, Oliveira R, Peixoto MF, Cervi MC, Hazra R, Pinto JA. Prevalence and predictors of elevated aspartate aminotransferase-to-platelet ratio index in Latin American perinatally HIV-infected children. Pediatr Infect Dis J 2014; 33:177-82. [PMID: 23799515 PMCID: PMC3875831 DOI: 10.1097/inf.0b013e3182a01dfb] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Chronic liver disease has emerged as an important problem in adults with longstanding HIV infection, but data are lacking for children. We characterized elevated aspartate aminotransferase-to-platelet ratio index (APRI), a marker of possible liver fibrosis, in perinatally HIV-infected children. METHODS The National Institute of Child Health and Human Development International Site Development Initiative enrolled HIV-infected children (ages 0.1-20.1 years) from 5 Latin American countries in an observational cohort from 2002 to 2009. Twice yearly visits included medical history, physical examination and laboratory evaluations. The prevalence (95% confidence interval) of APRI > 1.5 was calculated, and associations with demographic, HIV-related and liver-related variables were investigated in bivariate analyses. RESULTS APRI was available for 1012 of 1032 children. APRI was >1.5 in 32 (3.2%, 95% confidence interval: 2.2%-4.4%) including 2 of 4 participants with hepatitis B virus infection. Factors significantly associated with APRI > 1.5 (P < 0.01 compared with APRI ≤ 1.5) included country, younger age, past or current hepatitis B virus, higher alanine aminotransferase, lower total cholesterol, higher log10 current viral load, lower current CD4 count, lower nadir CD4 count, use of hepatotoxic nonantiretroviral (ARV) medications and no prior ARV use. Rates of APRI > 1.5 varied significantly by current ARV regimen (P = 0.0002), from 8.0% for no ARV to 3.2% for non-protease inhibitor regimens to 1.5% for protease inhibitor-based regimens. CONCLUSIONS Elevated APRI occurred in approximately 3% of perinatally HIV-infected children. Protease inhibitor-based ARVs appeared protective whereas inadequate HIV control appeared to increase risk of elevated APRI. Additional investigations are needed to better assess potential subclinical, chronic liver disease in HIV-infected children.
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Affiliation(s)
- George K Siberry
- From the *Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda; †Westat, Rockville, MD; ‡Department of Infectious Diseases, Hospital Federal dos Servidores do Estado; §Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro; ¶Vertical Transmission Unit, Femina Hospital, Porto Alegre; ‖Department of Pediatrics, University of São Paulo Faculty of Medicine of Ribeirão Preto, Ribeirão Preto; and **Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil
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Nakeeb NAE, Helmy A, Saleh SA, Abdellah HM, Aleem MHA, Elshennawy D. Comparison between FIB-4 Index and Fibroscan as Marker of Fibrosis in Chronic HCV Infection in Egyptian Patients. ACTA ACUST UNITED AC 2014. [DOI: 10.4236/ojgas.2014.412052] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Cui XW, Friedrich-Rust M, Molo CD, Ignee A, Schreiber-Dietrich D, Dietrich CF. Liver elastography, comments on EFSUMB elastography guidelines 2013. World J Gastroenterol 2013; 19:6329-6347. [PMID: 24151351 PMCID: PMC3801303 DOI: 10.3748/wjg.v19.i38.6329] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Revised: 08/11/2013] [Accepted: 09/16/2013] [Indexed: 02/06/2023] Open
Abstract
Recently the European Federation of Societies for Ultrasound in Medicine and Biology Guidelines and Recommendations have been published assessing the clinical use of ultrasound elastography. The document is intended to form a reference and to guide clinical users in a practical way. They give practical advice for the use and interpretation. Liver disease forms the largest section, reflecting published experience to date including evidence from meta-analyses with shear wave and strain elastography. In this review comments and illustrations on the guidelines are given.
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Peters L, Mocroft A, Soriano V, Rockstroh J, Rauch A, Karlsson A, Knysz B, Pradier C, Zilmer K, Lundgren JD. Hyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients. PLoS One 2013; 8:e64283. [PMID: 23724041 PMCID: PMC3664579 DOI: 10.1371/journal.pone.0064283] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Accepted: 04/13/2013] [Indexed: 12/14/2022] Open
Abstract
Background Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid’s (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study. Methods Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0–75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls). Results During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2–62.6) and 221.6 ng/mL (74.9–611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75–250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86–9.26, p<0.0007) and 28.22 (95% CI 14.95–46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR –5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001). Conclusions An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications.
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Affiliation(s)
- Lars Peters
- Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark.
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