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1
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Namura N, Kamada K, Hagiwara T, Takahashi K, Matsui K. Disease activity and changes in the fibrosis-4 index in patients with rheumatoid arthritis treated with methotrexate for a short period. Arch Rheumatol 2025; 40:53-62. [PMID: 40264486 PMCID: PMC12010268 DOI: 10.46497/archrheumatol.2025.10702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 01/27/2025] [Indexed: 04/24/2025] Open
Abstract
Objectives This study aims to investigate the relationship between disease activity and changes in the fibrosis-4 index (FIB-4) in patients with rheumatoid arthritis (RA) who received methotrexate as Phase I treatment for a short period. Patients and methods In this retrospective study, 144 patients (106 females, 38 males; median age: 68.05 years; range, 58.3 to 76.0 years) diagnosed with RA who had not received methotrexate before their diagnosis were included between April 2015 and September 2020. The patients' clinical data were recorded at baseline, six months, and 12 months. Patients with hepatitis, alcoholism, severe obesity, hypercholesterolemia, or overlapping autoimmune diseases and those receiving a maximum methotrexate dose of ≤10 mg/week were excluded. Multiple regression analysis was performed to identify predictors of the changes in FIB-4 values from baseline. Mediation analysis was employed to determine the association between Disease Activity Score-28 for RA with erythrocyte sedimentation rate (DAS28-ESR) and changes in FIB-4 values, with the cumulative methotrexate dose as a mediator. Results FIB-4 values increased significantly from baseline to 12 months after methotrexate initiation. The cumulative methotrexate dose did not independently influence changes in FIB-4 values. After adjusting for confounding factors, the factor independently influencing the change in fibrosis-4 values from baseline was DAS28-ESR at six and 12 months (β=0.107 and β=0.086, respectively). The cumulative methotrexate dose did not mediate the relationship between DAS28-ESR at baseline and changes in FIB-4 values, and it did not affect changes in FIB-4 values over a short period. Conclusion Rheumatoid arthritis disease activity before methotrexate administration independently affected changes in FIB-4 values. We suggest monitoring FIB-4 values in patients with RA with high disease activity, even for a short period after methotrexate administration, as FIB-4 values in these patients may be underestimated.
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Affiliation(s)
- Noriyuki Namura
- Department of Diabetes, Endocrinology and Clinical Immunology, Division of Allergology and Rheumatology, School of Medicine, Hyogo Medical University, Nishinomiya, Japan
- Department of Rheumatology, Takarazuka City Hospital, Takarazuka City, Japan
| | - Kazuya Kamada
- Department of Rheumatology, Takarazuka City Hospital, Takarazuka City, Japan
| | - Takahumi Hagiwara
- Department of Rheumatology, Takarazuka City Hospital, Takarazuka City, Japan
| | - Kanae Takahashi
- Department of Biostatistics, School of Medicine, Hyogo Medical University, Nishinomiya, Japan
| | - Kiyoshi Matsui
- Department of Diabetes, Endocrinology and Clinical Immunology, Division of Allergology and Rheumatology, School of Medicine, Hyogo Medical University, Nishinomiya, Japan
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2
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Buckholz AP, Brown RS. Noninvasive Fibrosis Testing in Chronic Liver Disease Including Caveats. Clin Liver Dis 2023; 27:117-131. [PMID: 36400461 DOI: 10.1016/j.cld.2022.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Assessment of liver fibrosis is important as the range of liver disease management has expanded, rendering biopsy both imperfect and impractical in many situations. Noninvasive tests of fibrosis leverage laboratory, imaging and elastography techniques to estimate disease extent, often with the goal of identifying advanced fibrosis. This review attempts to summarize their utility across a broad range of possible clinical scenarios while considering the central tenets of health care quality: access, quality, and cost. For each test, it also discusses the caveats whereby each test may have reduced effectiveness and how to consider each in a typical clinical setting.
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Affiliation(s)
- Adam P Buckholz
- Division of Gastroenterology and Hepatology, NewYork-Presbyterian/Weill Cornell Medical Center, 1305 York Avenue 4th Floor, New York, NY 10021, USA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, NewYork-Presbyterian/Weill Cornell Medical Center, 1305 York Avenue 4th Floor, New York, NY 10021, USA.
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3
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Martinou E, Pericleous M, Stefanova I, Kaur V, Angelidi AM. Diagnostic Modalities of Non-Alcoholic Fatty Liver Disease: From Biochemical Biomarkers to Multi-Omics Non-Invasive Approaches. Diagnostics (Basel) 2022; 12:407. [PMID: 35204498 PMCID: PMC8871470 DOI: 10.3390/diagnostics12020407] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/31/2022] [Accepted: 02/02/2022] [Indexed: 02/05/2023] Open
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and its prevalence is increasing globally. NAFLD is a multifaceted disorder, and its spectrum includes steatosis to steatohepatitis, which may evolve to advanced fibrosis and cirrhosis. In addition, the presence of NAFLD is independently associated with a higher cardiometabolic risk and increased mortality rates. Considering that the vast majority of individuals with NAFLD are mainly asymptomatic, early diagnosis of non-alcoholic steatohepatitis (NASH) and accurate staging of fibrosis risk is crucial for better stratification, monitoring and targeted management of patients at risk. To date, liver biopsy remains the gold standard procedure for the diagnosis of NASH and staging of NAFLD. However, due to its invasive nature, research on non-invasive tests is rapidly increasing with significant advances having been achieved during the last decades in the diagnostic field. New promising non-invasive biomarkers and techniques have been developed, evaluated and assessed, including biochemical markers, imaging modalities and the most recent multi-omics approaches. Our article provides a comprehensive review of the currently available and emerging non-invasive diagnostic tools used in assessing NAFLD, also highlighting the importance of accurate and validated diagnostic tools.
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Affiliation(s)
- Eirini Martinou
- Hepatobiliary and Pancreatic Surgery Department, Royal Surrey County Hospital, Guildford GU2 7XX, UK
- Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK;
| | - Marinos Pericleous
- Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK;
- Department of Gastroenterology and Hepatology, Royal Surrey County Hospital, Guildford GU2 7XX, UK
| | - Irena Stefanova
- Department of General Surgery, Frimley Health NHS Foundation Trust, Camberley GU16 7UJ, UK;
| | - Vasha Kaur
- Department of Upper Gastrointestinal and Bariatric Surgery, St George’s Hospital, London SW17 0QT, UK;
| | - Angeliki M. Angelidi
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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4
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A comparative study of cirrhosis sub-staging using the Laennec system, Beijing classification, and morphometry. Mod Pathol 2021; 34:2175-2182. [PMID: 34381188 DOI: 10.1038/s41379-021-00881-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 07/07/2021] [Accepted: 07/12/2021] [Indexed: 02/04/2023]
Abstract
There is constant remodeling in a cirrhotic liver resulting in cirrhosis being spatially heterogeneous. The Laennec system, and, more recently the Beijing classification, have been used to sub-classify various degrees of cirrhosis. It is unknown how these two schemes compare with each other, how they are impacted by geographic variation, and how they correlate with clinical outcomes. Five needle biopsies were obtained from 20 explanted cirrhotic HCV livers at the time of transplantation. Collagen proportionate area (CPA) was measured by computerized quantitative morphometry. The Laennec system (4A-4C indicating increasing degrees of cirrhosis) and Beijing classification (P-progressive, R-regressive, I-indeterminate) were assessed and then correlated with CPA. Geographical variation using CPAs was calculated by the coefficient of variation (CoV). CPA of Laennec 4C cirrhosis was higher than 4A (p = 0.00008) or 4B (p = 0.0002). The CPA of the P pattern was greater than the R (p = 0.002) or I patterns (p = 0.037). The mean CoV of the five CPAs was 47.3 ± 4.5%, suggesting a significant degree of geographic variation. There was 100% overlap between the Beijing R pattern and Laennec 4A, and 80% overlap between the P pattern and Laennec 4C. Patients' platelet counts of P pattern were lower than R pattern (p = 0.008) or I pattern (p = 0.024), while Laennec 4C was lower than 4A (p = 0.036) and 4B patients (p = 0.7). There was no correlation between CPA, Laennec stage, or Beijing classification and MELD score, liver weights, total bilirubin, or albumin levels. The Laennec system and the Beijing classification are highly correlated with CPA in cirrhosis. This study confirms that there is a significant degree of geographic variation in terms of fibrosis content and cirrhosis morphology throughout the liver.
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5
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Varchetta S, Mele D, D'Ambrosio R, Perbellini R, Lombardi A, Rojas A, Paolucci S, Baldanti F, Oliviero B, Mantovani S, Tinelli C, De Silvestri A, Romero Gomez M, Lampertico P, Mondelli MU. A new algorithm shows superior ability to discriminate liver fibrosis stages in chronic hepatitis C. J Viral Hepat 2021; 28:1443-1451. [PMID: 34228858 DOI: 10.1111/jvh.13570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/11/2021] [Accepted: 06/30/2021] [Indexed: 12/09/2022]
Abstract
Previous evidence suggests that sialic acid-binding Ig-like lectin 7 (Siglec-7) protein is significantly increased in patients with chronic hepatitis C virus (HCV) infection and directly correlates with clinical parameters of liver inflammation and fibrosis. The aim of this study was to determine the diagnostic value of Siglec-7 as a non-invasive tool to assess liver fibrosis in patients with chronic hepatitis C in a cross-sectional study. Serum levels of Siglec-7 were retrospectively tested in 1007 consecutive patients with chronic HCV infection recruited at three different European sites and data examined by the 'imperfect gold-standard' statistical analysis. Liver stiffness obtained by transient elastography (TE) was considered the standard reference. Liver fibrosis was staged according to published cut-offs of liver stiffness measurement by TE. Accuracy of detection of liver fibrosis stage was not increased by Siglec-7 alone. However, we developed a new index (SiGAP) including Siglec-7, γ-glutamyl transferase, age and platelet count which showed increased sensitivity and specificity in predicting fibrosis compared with APRI or FIB4 indices. The AUROC of SiGAP for the diagnosis of significant (≥F2) and advanced liver fibrosis (≥F3) showed significantly higher values than those of APRI and FIB-4. Siglec-7 may be useful as a complementary tool to assess liver fibrosis stage in patients with chronic hepatitis C when included in a specifically designed algorithm, which showed high level of accuracy in the detection of F2 and F3 fibrosis stage.
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Affiliation(s)
- Stefania Varchetta
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Dalila Mele
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Roberta D'Ambrosio
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Riccardo Perbellini
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Andrea Lombardi
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Angela Rojas
- SeLiver Group, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Stefania Paolucci
- Molecular Virology Unit, Division of Microbiology and Virology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Fausto Baldanti
- Molecular Virology Unit, Division of Microbiology and Virology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Barbara Oliviero
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Stefania Mantovani
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Carmine Tinelli
- Biostatistics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Manuel Romero Gomez
- SeLiver Group, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,UGC de Enfermedades Digestivas, Hospital Universitario Virgen del Rocío, Sevilla, Spain
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.,Department of Pathophysiology and Transplantation, CRC "A.M. and A. Migliavacca" Centre for Liver Disease, University of Milan, Milan, Italy
| | - Mario U Mondelli
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
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Dai X, Zeng Y, Zhang H, Gu Z, Gong Q, Luo K. Advances on Nanomedicines for Diagnosis and Theranostics of Hepatic Fibrosis. ADVANCED NANOBIOMED RESEARCH 2021. [DOI: 10.1002/anbr.202000091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Affiliation(s)
- Xinghang Dai
- Huaxi MR Research Center (HMRRC) Department of Radiology Functional and molecular imaging Key Laboratory of Sichuan Province West China Hospital Sichuan University Chengdu 610041 China
- West China School of Medicine Sichuan University Chengdu 610041 China
| | - Yujun Zeng
- Huaxi MR Research Center (HMRRC) Department of Radiology Functional and molecular imaging Key Laboratory of Sichuan Province West China Hospital Sichuan University Chengdu 610041 China
| | - Hu Zhang
- Huaxi MR Research Center (HMRRC) Department of Radiology Functional and molecular imaging Key Laboratory of Sichuan Province West China Hospital Sichuan University Chengdu 610041 China
- Amgen Bioprocessing Centre Keck Graduate Institute CA 91711 USA
| | - Zhongwei Gu
- Research Unit of Psychoradiology Chinese Academy of Medical Sciences Chengdu 610041 China
| | - Qiyong Gong
- Huaxi MR Research Center (HMRRC) Department of Radiology Functional and molecular imaging Key Laboratory of Sichuan Province West China Hospital Sichuan University Chengdu 610041 China
- Research Unit of Psychoradiology Chinese Academy of Medical Sciences Chengdu 610041 China
| | - Kui Luo
- Huaxi MR Research Center (HMRRC) Department of Radiology Functional and molecular imaging Key Laboratory of Sichuan Province West China Hospital Sichuan University Chengdu 610041 China
- Research Unit of Psychoradiology Chinese Academy of Medical Sciences Chengdu 610041 China
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7
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Noninvasive biomarkers predict improvement in liver fibrosis after successful generic DAAs based therapy of chronic hepatitis C in Egypt. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2020. [DOI: 10.1016/j.cegh.2020.04.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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8
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Lin B, Ma Y, Wu S, Liu Y, Liu L, Wu L. Novel Serum Biomarkers for Noninvasive Diagnosis and Screening of Nonalcoholic Fatty Liver Disease-Related Hepatic Fibrosis. OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY 2019; 23:181-189. [PMID: 30932742 DOI: 10.1089/omi.2019.0035] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing global public health concern and becoming the leading cause of liver disease worldwide. The estimated global prevalence of NAFLD is ∼25% depending on the country and the assessment method used to establish the diagnosis. Meta-analyses suggest that the highest prevalence is in the Middle East (31.8%) and South America (30.4%), and the lowest in Africa (13.5%). In the United States, between 75 and 100 million individuals were estimated to have NAFLD. This important disease is associated with increased incidence of liver-related deaths, hepatocarcinoma, and overall mortality. Fibrosis stage, among other histological characteristics, is the most critical factor in predicting all-cause and disease-specific mortality in NAFLD. The ability to detect fibrosis early in NAFLD patients is critical in controlling mortality associated with this highly prevalent disease. We present here an expert review on recent advances in novel blood biomarkers, for example, the Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP), type IV collagen 7S, chitinase 3 like 1 (CHI3L1; YKL-40), and insulin-like growth factor-1 (IGF-1). Algorithms using multiple biomarkers such as alpha-2-macroglobulin, mir34a, YKL-40, and hemoglobin A1c (HbA1c; NIS4), enhanced liver fibrosis (ELF), Hepascore, FibroMeter, FibroTest, FIBROSpect, FIB-C3, and ADPAPT are highlighted. Novel technologies such as tandem mass spectrometry to directly measure protein turnover rate of the key proteins involved in hepatic fibrosis, as an indicator of fibrogenesis, are also discussed. In conclusion, NAFLD is a growing global health problem that warrants long-term funding, research, and training of scholars across the fields of public health diagnostics, systems sciences, nutrition, hepatology, and clinical oncology.
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Affiliation(s)
- Biaoyang Lin
- 1 Zhejiang-California International Nanosystems Institute (ZCNI), Proprium Research Center, Zhejiang University, Hangzhou, China.,2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.,3 Department of Urology, University of Washington School of Medicine, Seattle, Washington
| | - Yingying Ma
- 1 Zhejiang-California International Nanosystems Institute (ZCNI), Proprium Research Center, Zhejiang University, Hangzhou, China.,2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Shengjun Wu
- 4 School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Yunhua Liu
- 5 Department of Liver Diseases, The Second Hospital of Yunnan Province, Kunming, China
| | - Longgen Liu
- 6 The Third People's Hospital of Changzhou, Changzhou, China
| | - Lihua Wu
- 7 State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The Research Center for Clinical Pharmacy, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
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9
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Navrotsky AN. [Diagnostic possibilities of methods for the evaluation of liver fibrosis in chronic viral hepatitis]. TERAPEVT ARKH 2018. [PMID: 28635835 DOI: 10.17116/terarkh20168811149-155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The paper reviews the diagnostic possibilities of different methods for the evaluation of liver fibrosis in chronic viral hepatitis from the point of view of their clinical application. Histological examination retains its value as the gold standard method in evaluating the liver. Transient elastography is a rather effective tool for identifying severe liver fibrosis.
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Affiliation(s)
- A N Navrotsky
- Omsk State Medical University, Ministry of Health of Russia, Omsk, Russia
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10
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Cheng JC, Tseng CP, Liao MH, Peng CY, Yu JS, Chuang PH, Huang JT, Chen JJW. Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes. Sci Rep 2017; 7:4448. [PMID: 28667290 PMCID: PMC5493679 DOI: 10.1038/s41598-017-04259-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 05/11/2017] [Indexed: 12/17/2022] Open
Abstract
Hepatitis C virus (HCV) infection of hepatocytes promotes liver fibrosis by activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix in liver tissue. Whether or not host factors released from the HCV-infected hepatocytes play role in HSCs activation is unclear. In this study, HSCs were activated by the conditioned medium derived from HCV replicon cells. Secretomic profiling of HCV replicon cells and the parental Huh7 cells revealed ubiquitin carboxy-terminal hydrolase L1 (UCHL1) as a novel secreted protein from HCV-infected hepatocytes. UCHL1 expression in hepatocytes was induced by HCV infection. UCHL1 was expressed in the liver and found in the plasma of patients with chronic hepatitis C. Molecular analysis by use of the anti-UCHL1 neutralization antibody and purified UCHL1 protein showed that secreted UCHL1 protein was bound to the cell surface of HSCs and activated JNK signaling leading to overexpression of alpha-smooth muscle actin and the activation of HSCs. These results provide further for understanding the underlying mechanism in HCV-mediated hepatic fibrogenesis.
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Affiliation(s)
- Ju-Chien Cheng
- Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, 40402, Taiwan.
| | - Ching-Ping Tseng
- Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, 33302, Taiwan.,Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan.,Molecular Medicine Research Center, Chang Gung University, Taoyuan, 33302, Taiwan.,Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, 33302, Taiwan
| | - Mei-Huei Liao
- Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, 40402, Taiwan.,Institute of Biomedical Sciences, National Chung Hsing University, Taichung, 40402, Taiwan
| | - Cheng-Yuan Peng
- Department of Internal Medicine, China Medical University Hospital, Taichung, 40402, Taiwan
| | - Jau-Song Yu
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan.,Molecular Medicine Research Center, Chang Gung University, Taoyuan, 33302, Taiwan.,Liver Research Center, Chang Gung Memorial Hospital, Linkou, 33302, Taiwan
| | - Po-Heng Chuang
- Department of Internal Medicine, China Medical University Hospital, Taichung, 40402, Taiwan
| | - Jing-Tang Huang
- Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, 40402, Taiwan
| | - Jeremy J W Chen
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung, 40402, Taiwan
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11
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12
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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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13
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Tama M, Naylor P, Patel S, Altawil J, Gulati D, Antaki F, Mutchnick MG, Ehrinpreis M. Overestimate of Fibrosis by FIBROSpect® II in African Americans Complicates the Management of their Chronic Hepatitis C. J Clin Transl Hepatol 2016; 4:12-9. [PMID: 27047767 PMCID: PMC4807138 DOI: 10.14218/jcth.2015.00053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2015] [Revised: 02/02/2016] [Accepted: 02/04/2016] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Evaluation of advanced fibrosis in patients with hepatitis C virus (HCV) infection is used to facilitate decisions on treatment strategy and to initiate additional screening measures. Unfortunately, most studies have predominately Caucasian (Cau) patients and may not be as relevant for African Americans (AA). AIMS This study specifically addresses the issue of defining minimal vs. significant fibrosis in African Americans (AA) with chronic hepatitis C (CHC) using noninvasive assays. METHODS All patients (n = 319) seen between 1 January 2008 and 30 June 2013 for whom a FibroSpect II® (FSII) assay was performed and had data for calculation of aspartate aminotransferase (AST) platelet ratio index (APRI) and Fibrosis-4 (FIB-4) were identified using the medical records. RESULTS When liver biopsy score and FSII assay results for the AA patients with CHC were compared, 31% of AA had advanced FSII fibrosis scores (F2-F4) despite a biopsy score of F0-F1. In contrast, 10% of Cau over-scored. The AA false positive rate was 14% for APRI and 34% for FIB-4. Combining FSII with either APRI (7% false positive) or FIB-4 (10% false positive) improved the false positive rate in AA to 7% (FSII + APRI) and 10% (FSII + FIB-4) but reduced the sensitivity for significant fibrosis. CONCLUSIONS The FSII assay overestimates fibrosis in AA and should be used with caution since these patients may not have significant fibrosis. If the APRI or FIB-4 assay is combined with the FSII assay, minimal fibrosis in AA can be defined without subjecting the patients to a subsequent biopsy.
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Affiliation(s)
- Maher Tama
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Paul Naylor
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
- Correspondence to: Paul Naylor, Gastroenterology, 603 Hudson Bldg, Harper University Hospital, 3990 John R, Detroit, MI 48201, USA. Tel: +1-313-745-8601, Fax: +1-313-745-8843, E-mail:
| | - Suhag Patel
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Johnny Altawil
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Dhiraj Gulati
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Fadi Antaki
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Milton G. Mutchnick
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Murray Ehrinpreis
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
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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: 19] [Impact Index Per Article: 2.1] [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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Teriaky A, Reau N. Evaluation of Hepatitis C Patients in the Direct-Acting Antiviral Era. Clin Liver Dis 2015; 19:591-604, v. [PMID: 26466649 DOI: 10.1016/j.cld.2015.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis C is a major worldwide cause of liver morbidity and mortality. A substantial proportion of infected patients will develop chronic disease, which may progress over decades to cirrhosis. This can lead to decompensation and hepatocellular carcinoma. With the advent of the direct-acting antivirals, hepatitis C has become increasingly curable with limited adverse events and a shorter duration of therapy. This review discusses the evaluation process of the hepatitis C patient in the direct-acting antiviral era, including screening, clinical evaluation, drug-drug interactions, treatment urgency, and counseling.
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Affiliation(s)
- Anouar Teriaky
- Department of Medicine, Center for Liver Diseases, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
| | - Nancy Reau
- Department of Medicine, Center for Liver Diseases, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA
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Abstract
Liver-related biomarkers have been developed and validated mainly in patients with chronic hepatitis C for the prediction of liver fibrosis or cirrhosis, which is a final pathway of chronic liver injury. They are noninvasive, traceable, and easy-to-use. Biomarkers provide implications related to screening, diagnosis, treatment, and prognosis of chronic hepatitis. For the improvement of performance and coverage, biomarker panels, imaging biomarkers, and even genetic biomarkers have been developed. With the advancement of genomics and proteomics, earlier and more precise prediction is expected in the near future. In this review, multiple biomarker panels for the estimation of the degree of fibrosis in chronic hepatitis C, biomarkers for the screening and diagnosis of hepatitis C, biomarkers for the treatment of hepatitis C, biomarkers for the prediction of complications related to the chronic hepatitis C, and future perspectives will be summarized.
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Affiliation(s)
- Seung Ha Park
- Department of Internal Medicine, Inje University College of Medicine, Busan, South Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea.
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Koller T, Kollerova J, Huorka M, Meciarova I, Payer J. Noninvasive scoring algorithm to identify significant liver fibrosis among treatment-naive chronic hepatitis C patients. Eur J Gastroenterol Hepatol 2014; 26:1108-1115. [PMID: 25188444 DOI: 10.1097/meg.0000000000000182] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIMS Staging for liver fibrosis is recommended in the management of hepatitis C as an argument for treatment priority. Our aim was to construct a noninvasive algorithm to predict the significant liver fibrosis (SLF) using common biochemical markers and compare it with some existing models. METHODS The study group included 104 consecutive cases; SLF was defined as Ishak fibrosis stage greater than 2. The patient population was assigned randomly to the training and the validation groups of 52 cases each. The training group was used to construct the algorithm from parameters with the best predictive value. Each parameter was assigned a score that was added to the noninvasive fibrosis score (NFS). The accuracy of NFS in predicting SLF was tested in the validation group and compared with APRI, FIB4, and Forns models. RESULTS Our algorithm used age, alkaline phosphatase, ferritin, APRI, α2 macroglobulin, and insulin and the NFS ranged from -4 to 5. The probability of SLF was 2.6 versus 77.1% in NFS<0 and NFS>0, leaving NFS=0 in a gray zone (29.8% of cases). The area under the receiver operating curve was 0.895 and 0.886, with a specificity, sensitivity, and diagnostic accuracy of 85.1, 92.3, and 87.5% versus 77.8, 100, and 87.9% for the training and the validation group. In comparison, the area under the receiver operating curve for APRI=0.810, FIB4=0.781, and Forns=0.703 with a diagnostic accuracy of 83.9, 72.3, and 62% and gray zone cases in 46.15, 37.5, and 44.2%. CONCLUSION We devised an algorithm to calculate the NFS to predict SLF with good accuracy, fewer cases in the gray zone, and a straightforward clinical interpretation. NFS could be used for the initial evaluation of the treatment priority.
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Affiliation(s)
- Tomas Koller
- a5th Department of Internal Medicine, Comenius University Medical Faculty and University Hospital Bratislava bDepartment of Pathology, Alpha Medical s.r.o., Bratislava, Slovakia
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Sebastiani G, Gkouvatsos K, Pantopoulos K. Chronic hepatitis C and liver fibrosis. World J Gastroenterol 2014; 20:11033-11053. [PMID: 25170193 PMCID: PMC4145747 DOI: 10.3748/wjg.v20.i32.11033] [Citation(s) in RCA: 159] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Revised: 04/14/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy.
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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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Parameters associated with significant liver histological changes in patients with chronic hepatitis B. ISRN GASTROENTEROLOGY 2014; 2014:913890. [PMID: 24616815 PMCID: PMC3927580 DOI: 10.1155/2014/913890] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2013] [Accepted: 11/12/2013] [Indexed: 12/17/2022]
Abstract
This study aimed to evaluate factors associated with significant liver histological changes. Liver biopsies from 157 CHB patients were retrospectively analyzed. Only ALB was significantly correlated with advanced liver necroinflammatory (P = 0.001). Age, ALB, GLOB, AST, PLT, and PT were independent predictors of significant fibrosis (P = 0.002, P < 0.001, P = 0.001, P = 0.048, P < 0.001, and P = 0.001, resp.). AST, WBC, and HBV DNA were significantly correlated with advanced fibrosis in normal ALT patients (P < 0.001, P = 0.041, and P = 0.012, resp.) and age, ALB, GLOB, PLT, and PT in patients with abnormal ALT (P = 0.003, P < 0.001, P = 0.004, P < 0.001, and P = 0.002, resp.). Age, AST, GGT, PLT, and PT were significantly associated with advanced fibrosis in HBeAg+ patients (P = 0.01, P = 0.016, P = 0.027, P = 0.016, and P = 0.009, resp.) and ALB, GLOB, WBC, PLT, and PT in HBeAg− patients (P < 0.001, P = 0.004, P = 0.005, P < 0.001, and P = 0.035, resp.). PLT was an excellent predictor for cirrhosis (P < 0.001 and AUROC = 0.805). ALT was not predictive of advanced fibrosis for patients with HBeAg+ or HBeAg− (P = 0.273 and P = 0.599, resp.). PLT was an excellent predictor for cirrhosis in CHB patients. Liver histopathology can be recommended for chronic HBV carriers of older age, with normal ALT, lower PLT, and lower ALB.
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Xu MY, Jia XF, Qu Y, Zheng RD, Yuan ZH, Weng HL, Dooley S, Wang XP, Zhang LJ, Lu LG. Serum dihydroxyacetone kinase peptide m/z 520.3 as predictor of disease severity in patients with compensated chronic hepatitis B. J Transl Med 2013; 11:234. [PMID: 24289155 PMCID: PMC3851457 DOI: 10.1186/1479-5876-11-234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 09/13/2013] [Indexed: 01/06/2023] Open
Abstract
Background & aim Due to known limitations of liver biopsy, reliable non-invasive serum biomarkers for chronic liver diseases are needed. We performed serum peptidomics for such investigation in compensated chronic hepatitis B (CHB) patients. Methods Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed peptides in sera from 40 CHB patients (20 with S0G0-S1G1 and 20 with S3G3-S4G4). Ion pair quantification from differentially expressed peptides in a validation set of sera from 86 CHB patients was done with multiple reaction monitoring (MRM). Results 21 differentially represented peptide peaks were found through LC-MS/MS. Ion pairs generated from eleven of these peptides (m/z < 800) were quantified by MRM. Summed peak area ratios of 6 ion pairs from peptide m/z 520.3 (176.1, 353.7, 459.8, 503.3, 351.3, 593.1), which was identified as dihydroxyacetone kinase (DAK) fragment, decreased from mild to advanced stages of fibrosis or inflammation. Area Under Receiver Operating Characteristic Curves (AUROCs) of five ion models discriminating fibrosis degrees were 0.871 ~ 0.915 (S2-4 versus S0-1) and 0.804 ~ 0.924 (S3-4 versus S0-2). AUROCs discriminating inflammation grades were 0.840 ~ 0.902 (G2-4 versus G0-1) and 0.787 ~ 0.888 (G3-4 versus G0-2). The diagnostic power of these models provides improved sensitivity and specificity for predicting disease progression as compared to aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Forn’s index and serum DAK protein. Conclusions The peptide fragment (m/z 520.3) of DAK is a promising biomarker to guide timing of antiviral treatment and to avoid liver biopsy in compensated CHB patients.
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22
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Rosselli M, MacNaughtan J, Jalan R, Pinzani M. Beyond scoring: a modern interpretation of disease progression in chronic liver disease. Gut 2013; 62:1234-41. [PMID: 23645629 DOI: 10.1136/gutjnl-2012-302826] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Matteo Rosselli
- Division of Medicine, University College London, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
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23
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Levenson RM, Fornari A, Loda M. Multispectral imaging and pathology: seeing and doing more. ACTA ACUST UNITED AC 2013; 2:1067-81. [PMID: 23495926 DOI: 10.1517/17530059.2.9.1067] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND The current appreciation of the biological complexity of disease has led to increasing demands on pathologists to provide clinically relevant, quantitative morphological and molecular information while preserving cellular and tissue context. This can be technically challenging, especially when signals of interest are colocalized. With fluorescence-based methods, sensitivity and quantitative reliability may be compromised by spectral cross-talk between labels and by autofluorescence. In brightfield microscopy, overlapping chromogenic signals pose similar imaging difficulties. APPROACH These challenges can be addressed using commercially available multispectral imaging technologies attached to standard microscope platforms, or alternatively, integrated into whole-slide scanning instruments. ASSESSMENT Multispectral techniques, along with other developments in digital analysis, will allow pathologists to deliver appropriate quantitative and multiplexed analyses in a reproducible and timely manner. Caveats apply - as the complexity of the sample preparation and analysis components increases, commensurate attention must be paid to the use of appropriate controls for all stages of the process.
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Affiliation(s)
- Richard M Levenson
- CRI, 35B Cabot Road, Woburn, MA 01801, USA +1 781 935 9099, ext. 204 ; +1 781 935 3388 ;
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Abstract
Nonalcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide, encompasses a spectrum of abnormal liver histology ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Population studies show that NAFLD is strongly associated with insulin resistance, obesity, type 2 diabetes mellitus, and lipid abnormalities. In the context of hepatic steatosis, factors that promote cell injury, inflammation, and fibrosis include oxidative stress, early mitochondrial dysfunction, endoplasmic reticulum stress, iron accumulation, apoptosis, adipocytokines, and stellate cell activation. The exact NASH prevalence is unknown because of the absence of simple noninvasive diagnostic tests. Although liver biopsy is the "gold standard" for the diagnosis of NASH, other tests are needed to facilitate the diagnosis and greatly reduce the requirement for invasive liver biopsy. In addition, the development of new fibrosis markers in NASH is needed to facilitate the assessment of its progression and the effectiveness of new therapies. The aim of this chapter, which is overview of biomarkers in NASH, is to establish a systematic approach to laboratory findings of the disease.
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Liu XD, Wu JL, Liang J, Zhang T, Sheng QS. Globulin-platelet model predicts minimal fibrosis and cirrhosis in chronic hepatitis B virus infected patients. World J Gastroenterol 2012; 18:2784-2792. [PMID: 22719186 PMCID: PMC3374981 DOI: 10.3748/wjg.v18.i22.2784] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2012] [Revised: 03/20/2012] [Accepted: 04/09/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To establish a simple model consisting of the routine laboratory variables to predict both minimal fibrosis and cirrhosis in chronic hepatitis B virus (HBV)-infected patients. METHODS We retrospectively investigated 114 chronic HBV-infected patients who underwent liver biopsy in two different hospitals. Thirteen parameters were analyzed by step-wise regression analysis and correlation analysis. A new fibrosis index [globulin/platelet (GP) model] was developed, including globulin (GLOB) and platelet count (PLT). GP model = GLOB (g/mL) × 100/PLT (× 10(9)/L). We evaluated the receiver operating characteristics analysis used to predict minimal fibrosis and compared six other available models. RESULTS Thirteen clinical biochemical and hematological variables [sex, age, PLT, alanine aminotransferase, aspartate aminotransferase (AST), albumin, GLOB, total bilirubin (T.bil), direct bilirubin (D.bil), glutamyltransferase, alkaline phosphatase, HBV DNA and prothrombin time (PT)] were analyzed according to three stages of liver fibrosis (F0-F1, F2-F3 and F4). Bivariate Spearman's rank correlation analysis showed that six variables, including age, PLT, T.bil, D.bil, GLOB and PT, were correlated with the three fibrosis stages (FS). Correlation coefficients were 0.23, -0.412, 0.208, 0.220, 0.314 and 0.212; and P value was 0.014, < 0.001, 0.026, 0.018, 0.001 and 0.024, respectively. Univariate analysis revealed that only PLT and GLOB were significantly different in the three FS (PLT: F = 11.772, P < 0.001; GLOB: F = 6.612, P = 0.002). Step-wise multiple regression analysis showed that PLT and GLOB were also independently correlated with FS (R(2) = 0.237). By Spearman's rank correlation analysis, GP model was significantly correlated with the three FS (r = 0.466, P < 0.001). The median values in F0-F1, F2-F3 and F4 were 1.461, 1.720 and 2.634. Compared with the six available models (fibrosis index, AST-platelet ratio, FIB-4, fibrosis-cirrhosis index and age-AST model and age-PLT ratio), GP model showed a highest correlation coefficient. The sensitivity and positive predictive value at a cutoff value < 1.68 for predicting minimal fibrosis F0-F1 were 72.4% and 71.2%, respectively. The specificity and negative predictive value at a cutoff value < 2.53 for the prediction of cirrhosis were 84.5% and 96.7%. The area under the curve (AUC) of GP model for predicting minimal fibrosis and cirrhosis was 0.762 [95% confidence interval (CI): 0.676-0.848] and 0.781 (95% CI: 0.638-0.924). Although the differences were not statistically significant between GP model and the other models (P all > 0.05), the AUC of GP model was the largest among the seven models. CONCLUSION By establishing a simple model using available laboratory variables, chronic HBV-infected patients with minimal fibrosis and cirrhosis can be diagnosed accurately, and the clinical application of this model may reduce the need for liver biopsy in HBV-infected patients.
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Sebastiani G, Alberti A. How far is noninvasive assessment of liver fibrosis from replacing liver biopsy in hepatitis C? J Viral Hepat 2012; 19 Suppl 1:18-32. [PMID: 22233410 DOI: 10.1111/j.1365-2893.2011.01518.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Chronic hepatitis C represents a major cause of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications. Formation and accumulation of fibrosis in the liver is the common pathway that leads to evolutive liver disease. Precise staging of liver fibrosis is essential for patient management in clinical practice because the presence of bridging fibrosis represents a strong indication for antiviral therapy, while cirrhosis requires a specific follow-up. Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis, but it has limitations: it is invasive, costly and prone to sampling errors. Recently, blood markers and instrumental methods have been proposed for the noninvasive assessment of liver fibrosis in hepatitis C. However, international guidelines do not recommend the widespread use of noninvasive methods for liver fibrosis in clinical practice. This is because of, in some cases, unsatisfactory accuracy and incomplete validation of others. Some studies suggest that the effectiveness of noninvasive methods for assessing liver fibrosis may increase when they are combined, and a number of sequential and synchronous algorithms have been proposed for this purpose, with the aim of reducing rather than substituting liver biopsies. This may represent a rational and reliable approach for implementing noninvasive assessment of liver fibrosis in clinical practice. It could allow more comprehensive first-line screening of liver fibrosis in hepatitis C than would be feasible with liver biopsy alone.
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Affiliation(s)
- G Sebastiani
- VIMM-Venetian Institute of Molecular Medicine, Padua, Italy
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Baranova A, Lal P, Birerdinc A, Younossi ZM. Non-invasive markers for hepatic fibrosis. BMC Gastroenterol 2011; 11:91. [PMID: 21849046 PMCID: PMC3176189 DOI: 10.1186/1471-230x-11-91] [Citation(s) in RCA: 204] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2011] [Accepted: 08/17/2011] [Indexed: 01/18/2023] Open
Abstract
With great advancements in the therapeutic modalities used for the treatment of chronic liver diseases, the accurate assessment of liver fibrosis is a vital need for successful individualized management of disease activity in patients. The lack of accurate, reproducible and easily applied methods for fibrosis assessment has been the major limitation in both the clinical management and for research in liver diseases. However, the problem of the development of biomarkers capable of non-invasive staging of fibrosis in the liver is difficult due to the fact that the process of fibrogenesis is a component of the normal healing response to injury, invasion by pathogens, and many other etiologic factors. Current non-invasive methods range from serum biomarker assays to advanced imaging techniques such as transient elastography and magnetic resonance imaging (MRI). Among non-invasive methods that gain strongest clinical foothold are FibroScan elastometry and serum-based APRI and FibroTest. There are many other tests that are not yet widely validated, but are none the less, promising. The rate of adoption of non-invasive diagnostic tests for liver fibrosis differs from country to country, but remains limited. At the present time, use of non-invasive procedures could be recommended as pre-screening that may allow physicians to narrow down the patients' population before definitive testing of liver fibrosis by biopsy of the liver. This review provides a systematic overview of these techniques, as well as both direct and indirect biomarkers based approaches used to stage fibrosis and covers recent developments in this rapidly advancing area.
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Affiliation(s)
- Ancha Baranova
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
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Sebastiani G, Gkouvatsos K, Plebani M. Non-invasive assessment of liver fibrosis: it is time for laboratory medicine. Clin Chem Lab Med 2010; 49:13-32. [PMID: 20961196 DOI: 10.1515/cclm.2011.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Chronic liver diseases (CLDs) represent a major cause of morbidity and mortality worldwide. In all etiologies of CLDs, staging of liver fibrosis is essential for both prognosis and management. Until a few years ago, liver biopsy was the only tool for the diagnosis of liver fibrosis in patients with CLDs. However, liver biopsy is an invasive and costly procedure. More recently, various serum biomarkers and laboratory tests have been proposed as surrogates of liver histology. Due to inadequate diagnostic accuracy or to lack of sufficient validation, guidelines still do not recommend them as a substitute for liver biopsy that is still considered the gold standard for the diagnosis of liver fibrosis. Notably, non-invasive serum biomarkers, when combined, may reduce by 50%-80% the number of liver biopsies needed for correctly classifying hepatic fibrosis. However, liver biopsy cannot be avoided completely, but should be used in those cases in which non-invasive methods show poor accuracy. In this view, serum biomarkers and liver biopsy represent a union between laboratory medicine and hepatology.
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Affiliation(s)
- Giada Sebastiani
- Department of Digestive Diseases, Hepatology and Clinical Nutrition, Dell'Angelo Hospital, Venice, Venetian Institute of Molecular Medicine (VIMM), Padova, Italy
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Jarcuska P, Janicko M, Veselíny E, Jarcuska P, Skladaný L. Circulating markers of liver fibrosis progression. Clin Chim Acta 2010; 411:1009-1017. [PMID: 20399764 DOI: 10.1016/j.cca.2010.04.009] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2009] [Revised: 04/11/2010] [Accepted: 04/11/2010] [Indexed: 01/18/2023]
Abstract
INTRODUCTION Fibrogenesis is a typical reaction of the liver to injury. In the case of overstimulation of fibrogenesis clinically significant fibrosis and, eventually, cirrhosis occur. Treatment of liver cirrhosis is limited, therefore it is important to screen and monitor patients at risk of cirrhosis. Noninvasive parameters are ideal for this purpose due to their risk profile and repeatability. METHODS Systematic review of literature. RESULTS Among large number of proposed biomarkers, there is a distinct difference between two groups or classes. Class I biomarkers are associated with the process of fibrogenesis, their presence in the serum is the result of the increased turnover of extracellular matrix. Class II biomarkers and their combinations are mostly markers of liver function or structural damage. We have identified 27 Class I and 13 Class II biomarkers that have been proposed in the literature. We have evaluated in detail those which reached limited clinical application. CONCLUSION General clinical acceptance of these biomarkers is low because of various drawbacks. Simple and readily available biomarkers have low accuracy in predicting liver fibrosis and more advanced markers have low cost-benefit ratio. Therefore liver biopsy remains the "gold standard" for diagnosis of fibrosis. However potential noninvasive alternatives exist and their implementation could be valuable.
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Affiliation(s)
- Peter Jarcuska
- 1st Department of Internal Medicine, P.J. Safárik University, Kosice, Slovakia.
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Poynard T, Muntenau M, Morra R, Ngo Y, Imbert-Bismut F, Thabut D, Messous D, Massard J, Lebray P, Moussalli J, Benhamou Y, Ratziu V. Methodological aspects of the interpretation of non-invasive biomarkers of liver fibrosis: a 2008 update. ACTA ACUST UNITED AC 2009; 32:8-21. [PMID: 18973843 DOI: 10.1016/s0399-8320(08)73990-3] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
This review summarizes the methodological aspects of the interpretation of non-invasive biomarkers in liver fibrosis. A scoring system has been updated to better compare the quality of fibrosis biomarkers. Several methodological issues are related to the classical methodology using biopsy, as this is considered the gold standard. However, from evidence-based data, it appears that the methodology needs to change to prevent flawed conclusions among key opinion leaders as well as in obsolete guidelines. As waiting for the perfect biomarker for the diagnosis of advanced fibrosis to come along is probably a waste of time, in the meantime, methods can be improved. The main proposals for improving the methodology are, to take into account the spectrum bias, to assess accuracy between adjacent stages, to compare biomarkers in the same patient, to assess the cause of failure among discordant cases and to use specific statistical methods adapted for imperfect gold standards.
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Affiliation(s)
- T Poynard
- APHP Service d'Hépato-Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, Université Paris 6, CNRS ESA 8149 Paris, France.
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Abstract
An intensive research effort in the field of non-invasive evaluation of liver fibrosis has recently permitted the description and validation of several serum markers of fibrosis, mainly in chronic hepatitis C patients. In addition to the commonly used tests such as FibroTest or FibroMeters, other either indirect (aspartate aminotransferase, prothrombin time, platelets) or direct (PIIINP, hyaluronic acid, metalloproteinases) markers, usually used in combination, have been evaluated. Simple scores such as APRI or FIB-4 have also been widely studied and have revealed interesting, albeit non-comprehensive, data on liver fibrosis, especially in terms of significant, extensive fibrosis or cirrhosis. These simple scores may be proposed as a first-line investigation, bearing in mind their limitations and comparing them with more accurate methods for evaluating liver fibrosis if necessary. Other scores, including direct serum markers, which can be difficult to assess, have given disappointing results that, in general, were either similar to, or only slightly better than, the results of the simpler tests. Further studies are needed to identify new markers that are more accurate and, above all, able to predict the outcome of liver fibrosis.
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Smith JO, Sterling RK. Systematic review: non-invasive methods of fibrosis analysis in chronic hepatitis C. Aliment Pharmacol Ther 2009; 30:557-76. [PMID: 19519733 DOI: 10.1111/j.1365-2036.2009.04062.x] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Accurate determination of the presence and degree of liver fibrosis is essential for prognosis and for planning treatment of patients with chronic hepatitis C virus (HCV). Non-invasive methods of assessing fibrosis have been developed to reduce the need for biopsy. AIM To perform a review of these non-invasive measures and their ability to replace biopsy for assessing hepatic fibrosis in patients with chronic HCV. METHODS A systematic review of PUBMED and EMBASE was performed through 2008 using the following search terms: HCV, liver, elastography, hepatitis, Fibroscan, SPECT, noninvasive liver fibrosis, ultrasonography, Doppler, MRI, Fibrotest, Fibrosure, Actitest, APRI, Forns and breath tests, alone or in combination. RESULTS We identified 151 studies: 87 using biochemical, 57 imaging and seven breath tests either alone or in combination. CONCLUSIONS Great strides are being made in the development of accurate non-invasive methods for determination of fibrosis. Although no single non-invasive test or model developed to date can match that information obtained from actual histology (i.e. inflammation, fibrosis, steatosis), combinations of two modalities of non-invasive methods can reliably differentiate between minimal and significant fibrosis, and thereby avoid liver biopsy in a significant percentage of patients.
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Affiliation(s)
- J O Smith
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University Health System, Richmond, VA 23298-0341, USA
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Cheung KJ, Tilleman K, Deforce D, Colle I, Van Vlierberghe H. The HCV serum proteome: a search for fibrosis protein markers. J Viral Hepat 2009; 16:418-29. [PMID: 19226329 DOI: 10.1111/j.1365-2893.2009.01083.x] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Liver fibrosis/cirrhosis is a serious health issue in hepatitis C virus (HCV-) infected patients and is currently diagnosed by the invasive liver biopsy. The aim of this study was to find useful fibrosis markers in HCV-patients' sera of different fibrosis degrees (METAVIR F0-F4) based on proteomics. Serum proteome profiles were created by two-dimensional gel electrophoresis. Profiles were analysed between different degrees of fibrosis (F0-F4) and between early (F0F1) and late (F2F3F4) fibrosis by univariate analyses (P <or= 0.05). Differentially expressed proteins were subsequently identified by mass spectrometry. Mac-2-binding protein, alpha-2-macroglobulin and hemopexin were increased in F4 opposite F0/F1. A-1-antitrypsin, leucine-rich alpha-2-glycoprotein and fetuin-A were decreased in F4 opposite F0/F1. Late fibrosis was characterized by an increase in Mac-2-binding protein, alpha-2-macroglobulin and alpha-1B-glycoprotein expression and a decrease in haptoglobin expression. Mac-2-binding protein expression was confirmed by dot blot assay and enzyme-linked immunosorbent assay in a secondary population. In conclusion, serum proteome analysis enabled the detection/identification of existing and new candidate markers in line with fibrosis progression in HCV-patients.
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Affiliation(s)
- K J Cheung
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium.
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35
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Molecular and Contextual Markers of Hepatitis C Virus and Drug Abuse. Mol Diagn Ther 2009. [DOI: 10.1007/bf03256323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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36
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Nelson DR, Davis GL, Jacobson I, Everson GT, Fried MW, Harrison SA, Hassanein T, Jensen DM, Lindsay KL, Terrault N, Zein N. Hepatitis C virus: a critical appraisal of approaches to therapy. Clin Gastroenterol Hepatol 2009; 7:397-414; quiz 366. [PMID: 19114127 DOI: 10.1016/j.cgh.2008.11.016] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2008] [Accepted: 11/16/2008] [Indexed: 02/07/2023]
Affiliation(s)
- David R Nelson
- Hepatology and Liver Transplantation, University of Florida, Gainesville, Florida 32610, USA.
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37
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Patel K, Benhamou Y, Yoshida EM, Kaita KD, Zeuzem S, Torbenson M, Pulkstenis E, Subramanian GM, McHutchison JG. An independent and prospective comparison of two commercial fibrosis marker panels (HCV FibroSURE and FIBROSpect II) during albinterferon alfa-2b combination therapy for chronic hepatitis C. J Viral Hepat 2009; 16:178-86. [PMID: 19175870 DOI: 10.1111/j.1365-2893.2008.01062.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Noninvasive markers that accurately follow changes in fibrosis may provide alternatives to liver biopsy for assessment of histological endpoints of antiviral therapy in chronic hepatitis C (CHC). This study compared two commercially available serum marker panels (HCV FibroSURE and FIBROSpect II) during interferon-based therapy. Ninety-five interferon-naïve patients with genotype 1 CHC were enrolled in a phase 2b, active-controlled study of albinterferon alfa-2b/ribavirin for 48 weeks. Proprietary and simple biochemical marker panels were independently evaluated in serum before and during the study. Baseline liver biopsies were evaluated for METAVIR fibrosis by a single pathologist. Index scores were obtained for HCV FibroSURE (n = 84) and FIBROSpect II (n = 95); mean biopsy length: 17.8 +/- 8.0 mm. For detecting fibrosis stages 2-4 (prevalence 23% [22/95] and 21% [18/84]), HCV FibroSURE and FIBROSpect II indicated high sensitivity (1.00 and 0.95, respectively), lower but comparable specificity (0.61 and 0.66, respectively), and a good area under the receiver operating characteristic curve (0.89 and 0.90, respectively). Simple indices had high indeterminate rates (31-40%) at baseline. Patients with a sustained virological response had lower baseline scores than nonresponders, and reduced median percent changes in index scores for HCV FibroSURE (-20.0%vs 2.9%; P = 0.14) and FIBROS Spect II (-6.8%vs 18.4%; P = 0.05). The panels demonstrated comparable performance characteristics for differentiating mild from moderate-severe stage disease in CHC. Lower index scores at baseline that continue to decline likely reflect reduced fibrogenesis activity in patients with successful antiviral responses to therapy.
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Affiliation(s)
- K Patel
- Duke Clinical Research Institute and Duke University Medical Center, Durham, NC 27715, USA.
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38
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Shapshak P, Somboonwit C, Drumright LN, Frost SDW, Commins D, Tellinghuisen TL, Scott WK, Duncan R, McCoy C, Page JB, Giunta B, Fernandez F, Singer E, Levine A, Minagar A, Oluwadara O, Kotila T, Chiappelli F, Sinnott JT. Molecular and contextual markers of hepatitis C virus and drug abuse. Mol Diagn Ther 2009; 13:153-79. [PMID: 19650670 PMCID: PMC4447498 DOI: 10.2165/01250444-200913030-00002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The spread of hepatitis C virus (HCV) infection involves a complex interplay of social risks, and molecular factors of both virus and host. Injection drug abuse is the most powerful risk factor for HCV infection, followed by sexual transmission and additional non-injection drug abuse factors such as co-infection with other viruses and barriers to treatment. It is clearly important to understand the wider context in which the factors related to HCV infection occur. This understanding is required for a comprehensive approach leading to the successful prevention, diagnosis, and treatment of HCV. An additional consideration is that current treatments and advanced molecular methods are generally unavailable to socially disadvantaged patients. Thus, the recognition of behavioral/social, viral, and host factors as components of an integrated approach to HCV is important to help this vulnerable group. Equally important, this approach is key to the development of personalized patient treatment - a significant goal in global healthcare. In this review, we discuss recent findings concerning the impact of drug abuse, epidemiology, social behavior, virology, immunopathology, and genetics on HCV infection and the course of disease.
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Affiliation(s)
- Paul Shapshak
- Division of Infectious Disease and International Medicine, Department of Internal Medicine, Tampa General Hospital, University of South Florida, College of Medicine, Tampa, Florida, USA.
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Talwalkar JA, Sanderson SO. Role of computerized image morphometry for assessing noninvasive methods to detect hepatic fibrosis. Clin Gastroenterol Hepatol 2008; 6:958-9. [PMID: 18774531 DOI: 10.1016/j.cgh.2008.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2008] [Accepted: 06/10/2008] [Indexed: 02/07/2023]
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Van Leeuwen DJ, Balabaud C, Crawford JM, Bioulac-Sage P, Dhillon AP. A clinical and histopathologic perspective on evolving noninvasive and invasive alternatives for liver biopsy. Clin Gastroenterol Hepatol 2008; 6:491-6. [PMID: 18455694 DOI: 10.1016/j.cgh.2008.02.023] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2007] [Revised: 01/31/2008] [Accepted: 02/04/2008] [Indexed: 02/07/2023]
Abstract
Noninvasive or minimally invasive alternatives are proposed as substitutes for liver biopsy and include clinical indices, cross-sectional imaging, serum biomarkers, liver stiffness measurement, and portal pressure measurement. Most alternatives to liver biopsy assess one aspect of liver disease and translate this into a numeric score. Overlap between categories may limit applications. Liver biopsy provides information about numerous variables: tissue architectural changes; necroinflammatory injury; fibrotic stage; alterations of parenchyma and bile duct epithelium; accumulation of fat, copper, and iron; and molecular and genetic changes. Liver biopsy may identify multiple disease etiologies. A single numeric score cannot be a substitute for complete histologic assessment. However, within defined clinical contexts, noninvasive assessment is an attractive alternative for many patients given the ease, avoidance of risk from invasive procedures, and validated contribution to clinical management. Serum biomarkers and liver stiffness assessment may become indispensable in longitudinal studies and to document outcome of treatments. The accuracy of the more reliable techniques is typically around 80%. Neither liver biopsy nor any single alternative option represents an absolute assessment of liver disease. Biopsy and alternatives are not mutually exclusive options. Liver biopsy and the noninvasive alternatives require a clear understanding of significance and limitations of each investigation. This places a responsibility on the clinician to consider fully the results of any of the investigative options used within the diagnostic and prognostic context of each individual patient, and to choose critically the most appropriate investigations for the patient's needs.
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Affiliation(s)
- Dirk J Van Leeuwen
- Section of Gastroenterology and Hepatology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire 03756, USA.
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