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Otero Sanchez L, Moreno C. Noninvasive Tests in Assessment of Patients with Alcohol-Associated Liver Disease. Clin Liver Dis 2024; 28:715-729. [PMID: 39362717 DOI: 10.1016/j.cld.2024.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/05/2024]
Abstract
Alcohol-associated liver disease (ALD) remains a significant public health concern, accounting for at least half of cirrhosis cases in Europe. Historically, liver biopsy has been considered the gold standard method for both diagnosing and staging ALD. However, in the past 3 decades, there has been a growing interest in developing noninvasive biomarkers for identifying high-risk patients prone to develop liver-related complications, including elastography methods or blood-based biomarkers. This review aims to summarize currently available noninvasive testing methods that are clinically available for assessing patients with ALD, including notably steatosis and fibrosis.
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Affiliation(s)
- Lukas Otero Sanchez
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Universitaire de Bruxelles, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Universitaire de Bruxelles, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
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Lai JCT, Liang LY, Wong GLH. Noninvasive tests for liver fibrosis in 2024: are there different scales for different diseases? Gastroenterol Rep (Oxf) 2024; 12:goae024. [PMID: 38605932 PMCID: PMC11009030 DOI: 10.1093/gastro/goae024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/25/2024] [Accepted: 03/11/2024] [Indexed: 04/13/2024] Open
Abstract
Liver fibrosis is the common pathway from various chronic liver diseases and its progression leads to cirrhosis which carries a significant risk for the development of portal hypertension-related complications and hepatocellular carcinoma. It is crucial to identify and halt the worsening of liver fibrosis given its important prognostic implication. Liver biopsy is the gold standard for assessing the degree of liver fibrosis but is limited due to its invasiveness and impracticality for serial monitoring. Many noninvasive tests have been developed over the years trying to assess liver fibrosis in a practical and accurate way. The tests are mainly laboratory- or imaging-based, or in combination. Laboratory-based tests can be derived from simply routine blood tests to patented laboratory parameters. Imaging modalities include ultrasound and magnetic resonance elastography, in which vibration-controlled transient elastography is the most widely validated and adopted whereas magnetic resonance elastography has been proven the most accurate liver fibrosis assessment tool. Nonetheless, noninvasive tests do not always apply to all liver diseases, nor does a common cut-off value of a test mean the same degree of liver fibrosis in different scenarios. In this review, we discuss the diagnostic and prognostic performance, as well as the confounders and limitations, of different noninvasive tests on liver fibrosis assessment in various liver diseases.
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Affiliation(s)
- Jimmy Che-To Lai
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lilian Yan Liang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
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Schreiner AD, Zhang J, Moran WP, Koch DG, Marsden J, Livingston S, Mauldin PD, Gebregziabher M. FIB-4 and incident severe liver outcomes in patients with undiagnosed chronic liver disease: A Fine-Gray competing risk analysis. Liver Int 2023; 43:170-179. [PMID: 35567761 PMCID: PMC9659674 DOI: 10.1111/liv.15295] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 04/18/2022] [Accepted: 05/09/2022] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND AIMS The Fibrosis-4 index (FIB-4) can reliably assess fibrosis risk in patients with chronic liver disease, and advanced fibrosis is associated with severe liver disease (SLD) outcomes. However, CLD is underdiagnosed in primary care. We examined the association between FIB-4 risk strata and the incidence of SLD preceding a CLD diagnosis while considering incident CLD diagnoses as competing risks. METHODS Using primary care clinic data between 2007 and 2018, we identified patients with two FIB-4 scores and no liver disease diagnoses preceding the index FIB-4. Patients were followed from index FIB-4 until an incident SLD (a composite of cirrhosis, hepatocellular carcinoma or liver transplantation), CLD or were censored. Hazard ratios were computed using a Fine-Gray competing risk model. RESULTS Of 20 556 patients, there were 54.8% in the low, 34.8% in the indeterminate, 6.6% in the high and 3.8% in the persistently high-risk FIB-4 strata. During a mean 8.2 years of follow-up, 837 (4.1%) patients experienced an SLD outcome and 11.5% of the sample received a CLD diagnosis. Of patients with an SLD event, 49% received no preceding CLD diagnosis. In the adjusted Fine-Gray model, the indeterminate (HR 1.41, 95% CI 1.17-1.71), high (HR 4.65, 95% CI 3.76-5.76) and persistently high-risk (HR 7.60, 95% CI 6.04-9.57) FIB-4 risk strata were associated with a higher incidence of SLD compared to the low-risk stratum. CONCLUSIONS FIB-4 scores with indeterminate- and high-risk values are associated with an increased incidence of SLD in primary care patients without known CLD.
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Affiliation(s)
- Andrew D. Schreiner
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425
| | - Jingwen Zhang
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425
| | - William P. Moran
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425
| | - David G. Koch
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425
| | - Justin Marsden
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425
| | - Sherry Livingston
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425
| | - Patrick D. Mauldin
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425
| | - Mulugeta Gebregziabher
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425
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Allaire M, Bruix J, Korenjak M, Manes S, Maravic Z, Reeves H, Salem R, Sangro B, Sherman M. What to do about hepatocellular carcinoma: Recommendations for health authorities from the International Liver Cancer Association. JHEP Rep 2022; 4:100578. [PMID: 36352896 PMCID: PMC9638834 DOI: 10.1016/j.jhepr.2022.100578] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 08/26/2022] [Accepted: 08/29/2022] [Indexed: 12/02/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a major public health problem worldwide for which the incidence and mortality are similar, pointing to the lack of effective treatment options. Knowing the different issues involved in the management of HCC, from risk factors to screening and management, is essential to improve the prognosis and quality of life of affected individuals. This document summarises the current state of knowledge and the unmet needs for all the different stakeholders in the care of liver cancer, meaning patients, relatives, physicians, regulatory agencies and health authorities so that optimal care can be delivered to patients. The document was commissioned by the International Liver Cancer Association and was reviewed by senior members, including two ex-presidents of the Association. This document lays out the recommended approaches to the societal management of HCC based on the economic status of a given region.
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Key Words
- AASLD, American Association for the Study of Liver Disease
- AFP, alpha-fetoprotein
- ALT, alanine aminotransferase
- APRI, aspartate aminotransferase-to-platelet ratio index
- Alcohol consumption
- BCLC, Barcelona clinic liver cancer
- DCP, des-gammacarboxy prothrombin
- DEB-TACE, TACE with drug-eluting beads
- EASL, European Association for the study of the Liver
- EBRT, external beam radiation therapy
- ELF, enhanced liver fibrosis
- GGT, gamma-glutamyltransferase
- HCC, hepatocellular carcinoma
- Hepatocellular carcinoma
- Hepatocellular carcinoma surveillance
- Hepatocellular carcinoma treatment
- Li-RADS, Liver Imaging Reporting and Data System
- NAFLD, non-alcoholic fatty liver disease
- Obesity
- RFA, radiofrequency ablation
- TACE, transarterial chemoembolisation
- TARE, transarterial radioembolisation
- TKI, tyrosine kinase inhibitor
- Viral hepatitis
- cTACE, conventional TACE
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Affiliation(s)
- Manon Allaire
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d’Hépato-gastroentérologie, Paris, France
| | - Jordi Bruix
- University Hospital Clinic IDIBAPS, Barcelona, Spain
| | - Marko Korenjak
- European Liver Patients' Association (ELPA), Brussels, Belgium
| | - Sarah Manes
- Global Liver Institute Washington District of Columbia, USA
| | | | - Helen Reeves
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, IL 60611, USA
| | - Bruno Sangro
- Liver Unit and HPB Oncology Area, Clinica Universidad de Navarra and CIBEREHD, Pamplona, Spain
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Haque LY, Fiellin DA, Tate JP, Esserman D, Bhattacharya D, Butt AA, Crystal S, Edelman EJ, Gordon AJ, Lim JK, Tetrault JM, Williams EC, Bryant K, Cartwright EJ, Rentsch CT, Justice AC, Lo Re V, McGinnis KA. Association Between Alcohol Use Disorder and Receipt of Direct-Acting Antiviral Hepatitis C Virus Treatment. JAMA Netw Open 2022; 5:e2246604. [PMID: 36515952 PMCID: PMC9856353 DOI: 10.1001/jamanetworkopen.2022.46604] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 10/19/2022] [Indexed: 12/15/2022] Open
Abstract
Importance Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection is associated with lower mortality and is effective in individuals with alcohol use disorder (AUD). However, despite recommendations, patients with AUD may be less likely to receive DAAs. Objective To assess the association between alcohol use and receipt of DAA treatment among patients with HCV within the Veterans Health Administration (VHA). Design, Setting, and Participants This cohort study included 133 753 patients with HCV born from 1945 to 1965 who had completed the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and had at least 1 outpatient visit in the VHA from January 1, 2014, through May 31, 2017, with maximal follow-up of 3 years until May 31, 2020; DAA receipt; or death, whichever occurred first. Exposures Alcohol use categories generated using responses to the AUDIT-C questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses: current AUD, abstinent with AUD history, at-risk drinking, lower-risk drinking, and abstinent without AUD history. Demographic, other clinical, and pharmacy data were also collected. Main Outcomes and Measures Associations between alcohol use categories and DAA receipt within 1 and 3 years estimated using Cox proportional hazards regression stratified by calendar year. Results Of 133 753 patients (130 103 men [97%]; mean [SD] age, 60.6 [4.5] years; and 73 493 White patients [55%]), 38% had current AUD, 12% were abstinent with a history of AUD, 6% reported at-risk drinking, 14% reported lower-risk drinking, and 30% were abstinent without a history of AUD. Receipt of DAA treatment within 1 year was 7%, 33%, 53%, and 56% for patients entering the cohort in 2014, 2015, 2016, and 2017, respectively. For patients entering in 2014, those with current AUD (hazard ratio [HR], 0.72 [95%, CI, 0.66-0.77]) or who were abstinent with an AUD history (HR, 0.91 [95% CI, 0.84-1.00]) were less likely to receive DAA treatment within 1 year compared with patients with lower-risk drinking. For those entering in 2015-2017, patients with current AUD (HR, 0.75 [95% CI, 0.70-0.81]) and those who were abstinent with an AUD history (HR, 0.76 [95% CI, 0.68-0.86]) were less likely to receive DAA treatment within 1 year compared with patients with lower-risk drinking. Conclusions and Relevance This cohort study suggests that individuals with AUD, regardless of abstinence, were less likely to receive DAA treatment. Improved access to DAA treatment for persons with AUD is needed.
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Affiliation(s)
- Lamia Y. Haque
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Yale Program in Addiction Medicine, Yale School of Medicine, New Haven, Connecticut
| | - David A. Fiellin
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Yale Program in Addiction Medicine, Yale School of Medicine, New Haven, Connecticut
- Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
| | - Janet P. Tate
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Veterans Affairs Connecticut Health Care System, West Haven
| | - Denise Esserman
- Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut
| | - Debika Bhattacharya
- Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles
- Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California
| | - Adeel A. Butt
- Department of Medicine, Weill Cornell Medicine, New York, New York
- Department of Population Health Sciences, Weill Cornell Medicine, New York, New York
- Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
| | - Stephen Crystal
- Center for Health Services Research, Rutgers University, New Brunswick, New Jersey
| | - E. Jennifer Edelman
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Yale Program in Addiction Medicine, Yale School of Medicine, New Haven, Connecticut
- Department of Social and Behavioral Sciences, Yale School of Public Health, New Haven, Connecticut
| | - Adam J. Gordon
- Informatics, Decision-Enhancement, and Analytic Sciences Center, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah
- Program for Addiction Research, Clinical Care, Knowledge, and Advocacy, Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City
| | - Joseph K. Lim
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Jeanette M. Tetrault
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Yale Program in Addiction Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Emily C. Williams
- Seattle-Denver Center of Innovation for Veteran-Centered and Value-Driven Care, Veterans Affairs Puget Sound Health Care System, Seattle, Washington
- Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, Washington
- Department of Health Systems and Population Health, University of Washington, Seattle
| | - Kendall Bryant
- HIV/AIDS and Alcohol Research Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
| | - Emily J. Cartwright
- Department of Medicine, Emory School of Medicine, Atlanta, Georgia
- Veterans Affairs Atlanta Health Care System, Atlanta, Georgia
| | - Christopher T. Rentsch
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Veterans Affairs Connecticut Health Care System, West Haven
- London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Amy C. Justice
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
- Veterans Affairs Connecticut Health Care System, West Haven
| | - Vincent Lo Re
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, Philadelphia, Pennsylvania
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, Philadelphia, Pennsylvania
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, Philadelphia, Pennsylvania
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Chen Z, Ma Y, Cai J, Sun M, Zeng L, Wu F, Zhang Y, Hu M. Serum biomarkers for liver fibrosis. Clin Chim Acta 2022; 537:16-25. [PMID: 36174721 DOI: 10.1016/j.cca.2022.09.022] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 09/21/2022] [Accepted: 09/22/2022] [Indexed: 11/03/2022]
Abstract
Liver fibrosis is a common pathway in most chronic liver diseases, characterized by excessive extracellular matrix accumulation. Without treatment, fibrosis will ultimately result in cirrhosis, portal hypertension, and even liver failure. It is considered that liver fibrosis is reversible while cirrhosis is not, making it significant to diagnose and evaluate liver fibrogenesis timely. As the gold standard, liver biopsy is imperfect due to its invasiveness and sampling error. Therefore, attempts at uncovering noninvasive tests have become a hot topic in liver fibrosis. Nowadays, as an important category of noninvasive tests, serum biomarkers, which are safer, convenient, repeatable, and more acceptable, are widely discussed and commonly used in clinical practice. Serum biomarkers of liver fibrosis can be divided into class I (direct) and classⅡ (indirect) markers. However, the diagnostic efficiency still varies among studies. This article summarizes the most established and newly discovered serum biomarkers for hepatic fibrogenesis.
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Affiliation(s)
- Zhiyang Chen
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yichen Ma
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Jingyao Cai
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Mei Sun
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Ling Zeng
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Fengxi Wu
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yiru Zhang
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Min Hu
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
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Zhang Y, Zhang Y, Liang H, Zhuo Z, Fan P, Chen Y, Zhang Z, Zhang W. Serum N-terminal DDR1: A Novel Diagnostic Marker of Liver Fibrosis Severity. J Clin Transl Hepatol 2021; 9:702-710. [PMID: 34722185 PMCID: PMC8516844 DOI: 10.14218/jcth.2021.00024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 03/11/2021] [Accepted: 04/05/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND AND AIMS The expression of discoidin domain receptor 1 (DDR1) is commonly up-regulated and undergoes collagen-induced ectodomain (N-terminal) shedding during the progression of liver fibrosis. This study aimed to evaluate the clinical utility of N-terminal DDR1 as a diagnostic biomarker for liver fibrosis. METHODS N-terminal DDR1 shedding was evaluated using cell lines, liver fibrosis mouse models, clinical data of 298 patients collected from February 2019 to June 2020. The clinical data were divided into test and validation cohorts to evaluate the diagnostic performance of serum N-terminal DDR1. RESULTS Time- and dosage-dependent N-terminal DDR1 shedding stimulated by collagen I was observed in a hepatocyte cell line model. The type I collagen deposition and serum N-terminal DDR1 levels concurrently increased in the development of liver fibrosis in mouse models. Clinical data demonstrated a significant diagnostic power of serum N-terminal DDR1 levels as an accurate biomarker of liver fibrosis and cirrhosis. The diagnostic performance was further increased when applying N-DDR1/albumin ratio, achieving area under the curve of 0.790, 0.802, 0.879, and 0.865 for detecting histological fibrosis stages F ≥2, F ≥3, F 4 with liver biopsy as a reference method, and cirrhosis according to imaging techniques, respectively. With a cut-off of 55.6, a sensitivity, specificity, positive predictive value, and negative predictive value of 82.7%,76.6%, 67.4%, and 88.3% were achieved for the detection of cirrhosis. CONCLUSIONS Serum N-terminal DDR1 appears to be a novel diagnostic marker for liver fibrosis.
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Affiliation(s)
- Yuxin Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hubei Key Laboratory of Hepato-Biliary-Pancreatic Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yujie Zhang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Huifang Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hubei Key Laboratory of Hepato-Biliary-Pancreatic Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zeng Zhuo
- Department of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Pan Fan
- Department of Surgery, University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Yifa Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hubei Key Laboratory of Hepato-Biliary-Pancreatic Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhanguo Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hubei Key Laboratory of Hepato-Biliary-Pancreatic Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Correspondence to: Zhanguo Zhang and Wanguang Zhang, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China. Tel: +86-2783665213, Fax: +86-27-83662640, E-mail: (ZZ) and (WZ)
| | - Wanguang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hubei Key Laboratory of Hepato-Biliary-Pancreatic Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Correspondence to: Zhanguo Zhang and Wanguang Zhang, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China. Tel: +86-2783665213, Fax: +86-27-83662640, E-mail: (ZZ) and (WZ)
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Fujita K, Masaki T. Serum Biomarkers of Liver Fibrosis Staging in the Era of the Concept "Compensated Advanced Chronic Liver Disease". J Clin Med 2021; 10:3340. [PMID: 34362121 PMCID: PMC8347037 DOI: 10.3390/jcm10153340] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 07/12/2021] [Accepted: 07/25/2021] [Indexed: 12/12/2022] Open
Abstract
Non-invasive indexes of liver fibrosis based on blood examinations have been developed for decades, partially replacing liver biopsy examinations. Recently, the concept of liver cirrhosis was revised and converted to "compensated advanced chronic liver diseases" since the Baveno VI consensus statement in 2015. The term "compensated advanced chronic liver diseases" was established based on the premise that serum biomarkers were not able to differentiate cirrhosis from severe fibrosis. The difficulty to histologically distinguish cirrhosis from severe fibrosis had been pointed out in 1977, when the definition and nomenclatures of cirrhosis had been determined by the World Health Organization. That was decades before serum biomarkers available at present were investigated. Though we are accustomed to differentiating the fibrosis stage as stage 1, 2, 3 (severe fibrosis), and 4 (cirrhosis), differentiation of cirrhosis from severe fibrosis is difficult even by histopathological examination. The current review will provide readers a framework to revise how to apply serum biomarkers on liver fibrosis staging in an era of the concept of "compensated advanced chronic liver disease".
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Affiliation(s)
- Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita District, Kagawa 761-0793, Japan;
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Hashem A, Awad A, Shousha H, Alakel W, Salama A, Awad T, Mabrouk M. Validation of a machine learning approach using FIB-4 and APRI scores assessed by the metavir scoring system: A cohort study. Arab J Gastroenterol 2021; 22:88-92. [PMID: 33985905 DOI: 10.1016/j.ajg.2021.04.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 02/01/2021] [Accepted: 04/25/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND STUDY AIM The study aim was to improve and validate the accuracy of the fibrosis-4 (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI) scores for use in a potential machine-learning (ML) method that accurately predicts the extent of liver fibrosis. PATIENTS AND METHODS This retrospective multicenter study included 69,106 patients with chronic hepatitis C planned for antiviral therapy from January 2010-December 2014 with liver biopsy results. FIB-4 and APRI scores were calculated and their performance for predicting significant liver fibrosis (F3-F4) assessed against the Metavir scoring system. ML was used for feature selection and reduction to identify the most relevant attributes (CfsSubseteval/best first) for prediction. RESULTS In this study, 57,492 (83.2%) patients were F0-F2, and 11,615 (16.8%) patients were F3-F4. The revalidation of FIB-4 and APRI showed lower accuracy and higher disagreement with the biopsy results, with AUCs of 0.68 and 0.58, respectively. FIB-4 diagnosed fewer (14%) F3-F4 patients, and the high specificity and negative predictive values of FIB-4 and APRI reflected the low prevalence of F3-F4 in the study population. Out of 15 attributes, age (>35 years), AFP (>6.5 ng/ml), and platelet count (<150,000/mm3) were the most relevant risk attributes, and patients with one or more of these risk factors were likely to be F3-F4, with a classification accuracy of ≤ 92% and receiver operating characteristics area of 0.74. CONCLUSION FIB-4 and APRI scores were not very accurate and missed diagnosing most of the F3-F4 patients. ML implementation improved medical decisions and minimized the required clinical data to three risk factors.
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Affiliation(s)
- Ahmed Hashem
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Abubakr Awad
- School of Natural and Computing Sciences, University of Aberdeen, Aberdeen, UK
| | - Hend Shousha
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Wafaa Alakel
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt; National Hepatology and Tropical Medicine Research Institute, Ministry of Health and Population, Cairo, Egypt
| | - Ahmed Salama
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Tahany Awad
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mahasen Mabrouk
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Mijač D, Krstić MN, Marković AP, Popović DD, Krstić JM, Milosavljević T. Abnormal Liver Blood Tests: Primary Care Approach. Dig Dis 2021; 40:215-222. [PMID: 33951646 DOI: 10.1159/000517016] [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: 02/18/2021] [Accepted: 05/04/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND According to recent epidemiological data, annual deaths due to liver disease have increased dramatically, while predictions show that trends will continue to rise in the upcoming years. SUMMARY Abnormal liver blood tests are one of the most common challenges encountered in the primary care setting. The prevalence of mildly elevated transaminase levels is around 10-20% in the general population. The most common causes for the rising burden of liver disease are nonalcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ARLD), and viral hepatitis. With improvements in the management of viral hepatitis over the last decades, the causes for the rising burden of liver disease are shifting toward ARLD and NAFLD. It is well-known that liver disease usually progresses silently for years or decades until the complications of cirrhosis occur. The majority of patients will not require referral to a specialist but will need further assessment in primary care. They should be evaluated for the etiology of liver disease irrespective of the duration of abnormal liver blood tests or unmarked clinical presentation. The evaluation should include a history of alcohol use, a history of medicines or herbal supplements, testing for viral hepatitis, and assessment for NAFLD, especially in obese patients and patients with type 2 diabetes. Abdominal ultrasound should be performed. Key Messages: The general practitioner may contribute significantly by identifying and screening patients at risk for chronic liver disease, as well as prioritize individuals with symptoms or signs of advanced liver disease to the specialist clinic.
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Affiliation(s)
- Dragana Mijač
- Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, Medical School, University of Belgrade, Belgrade, Serbia
| | - Miodrag N Krstić
- Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, Medical School, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Pavlović Marković
- Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, Medical School, University of Belgrade, Belgrade, Serbia
| | - Dušan D Popović
- Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, Medical School, University of Belgrade, Belgrade, Serbia
| | - Jovan M Krstić
- Clinic for Digestive Surgery, University Clinical Center of Serbia, Medical School, University of Belgrade, Belgrade, Serbia
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Ballestri S, Mantovani A, Baldelli E, Lugari S, Maurantonio M, Nascimbeni F, Marrazzo A, Romagnoli D, Targher G, Lonardo A. Liver Fibrosis Biomarkers Accurately Exclude Advanced Fibrosis and Are Associated with Higher Cardiovascular Risk Scores in Patients with NAFLD or Viral Chronic Liver Disease. Diagnostics (Basel) 2021; 11:diagnostics11010098. [PMID: 33435415 PMCID: PMC7827076 DOI: 10.3390/diagnostics11010098] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 12/29/2020] [Accepted: 01/06/2021] [Indexed: 02/07/2023] Open
Abstract
Liver fibrosis predicts liver-related and cardiovascular outcomes in chronic liver disease patients. We compared the diagnostic performance of various liver fibrosis biomarkers for identifying histological significant/advanced fibrosis. Additionally, the correlations of such liver fibrosis biomarkers with cardiovascular risk (CVR) scores were evaluated. 173 patients with viral hepatitis (157 HCV and 16 HBV) and 107 with a non-alcoholic fatty liver disease (NAFLD) were consecutively enrolled. Various liver fibrosis biomarkers: aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (ARR), AST to Platelet Ratio Index (APRI), Fibrosis-4 (FiB-4), Forns index, NAFLD fibrosis score (NFS), BARD (body mass index (BMI), AAR, Diabetes) score, and Hepamet fibrosis score (HFS), were used to identify significant/advanced fibrosis. CVR was assessed by using the SCORE, the Progetto CUORE, or the Framingham risk scoring systems. Liver fibrosis biomarkers performed better in predicting advanced rather than significant liver fibrosis in all patients, regardless of chronic liver disease aetiology. Forns index and HFS performed best in predicting advanced fibrosis in patients with viral chronic liver disease and NAFLD. Lower cut-offs of these liver fibrosis biomarkers had high negative predictive values for advanced fibrosis overall, as well as in patients with NAFLD or viral chronic liver disease. FIB-4, Forns index, NFS, and HFS were positively correlated with SCORE and Framingham risk scores. In conclusion, liver fibrosis biomarkers accurately exclude advanced fibrosis and positively correlate with CVR scores in patients with chronic liver disease.
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Affiliation(s)
- Stefano Ballestri
- Internal Medicine Unit, Pavullo Hospital, Azienda USL, 41026 Modena, Italy;
- Correspondence: ; Tel.: +39-0536-29409
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy; (A.M.); (G.T.)
| | - Enrica Baldelli
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy;
| | - Simonetta Lugari
- Metabolic Medicine Unit, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria, 41126 Modena, Italy; (S.L.); (M.M.); (F.N.)
| | - Mauro Maurantonio
- Metabolic Medicine Unit, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria, 41126 Modena, Italy; (S.L.); (M.M.); (F.N.)
| | - Fabio Nascimbeni
- Metabolic Medicine Unit, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria, 41126 Modena, Italy; (S.L.); (M.M.); (F.N.)
| | | | - Dante Romagnoli
- Gastroenterology Unit, Ospedale Policlinico di Modena, Azienda Ospedaliero-Universitaria, 41126 Modena, Italy;
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy; (A.M.); (G.T.)
| | - Amedeo Lonardo
- Metabolic Syndrome Unit, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria, 41126 Modena, Italy;
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12
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Ferguson TF, Rosen E, Carr R, Brashear M, Simon L, Theall KP, Ronis MJ, Welsh DA, Molina PE. Associations of Liver Disease with Alcohol Use among People Living with HIV and the Role of Hepatitis C: The New Orleans Alcohol Use in HIV Study. Alcohol Alcohol 2020; 55:28-36. [PMID: 31812989 DOI: 10.1093/alcalc/agz089] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 09/19/2019] [Accepted: 10/11/2019] [Indexed: 02/06/2023] Open
Abstract
AIM This cross-sectional analysis of the New Orleans Alcohol Use in HIV (NOAH) study assesses whether current and lifetime alcohol use in people living with HIV (PLWH) are associated with greater liver disease and how hepatitis C-viral (HCV) co-infection (HIV/HCV+) modifies the association. METHODS Alcohol use was measured by Lifetime Drinking History (LDH), a 30-day Timeline Followback calendar, the Alcohol Use Disorder Identification Test, and phosphatidylethanol. Liver disease was estimated by alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST platelet ratio-index (APRI), fibrosis-4 index (FIB-4) and nonalcoholic fatty liver disease-fibrosis score. Associations between alcohol consumption and liver disease were estimated with multivariable logistic regression. Models were adjusted for age, sex, body-mass index, hepatitis B and HIV viral load. RESULTS Participants (N = 353) were majority male (69%) and black (84%) with a mean age of 48.3 ± 10 years. LDH was significantly associated with advanced liver fibrosis (FIB-4 aOR = 22.22 [1.22-403.72]) only among HIV/HCV+ participants with an LDH of 100-600 kg. HIV/HCV+ participants had a higher prevalence of intermediate and advanced liver disease markers than HIV/HCV- (P < 0.0001). Advanced markers of liver disease were most strongly associated with hazardous drinking (≥40(women)/60(men) grams/day) (APRI aOR = 15.87 (3.22-78.12); FIB-4 aOR = 6.76 (1.81-7.16)) and PEth ≥400 ng/ml (APRI aOR = 17.52 (2.55-120.54); FIB-4 aOR = 17.75 (3.30-95.630). CONCLUSION Results indicate a greater association of current alcohol use with liver disease than lifetime alcohol use, which varied by HCV status. These findings stress the importance of reducing alcohol use in PLWH to decrease risk of liver disease and fibrosis.
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Affiliation(s)
- Tekeda F Ferguson
- Louisiana State University Health Sciences Center, Comprehensive Alcohol Research Center, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA.,Louisiana State University Health - New Orleans, School of Public Health, Department of Epidemiology, School of Public Health, 2020 Gravier Street, LEC - 3rd Floor, New Orleans, Louisiana 70112, LA, USA
| | - Erika Rosen
- Louisiana State University Health Sciences Center, Comprehensive Alcohol Research Center, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA.,Louisiana State University Health - New Orleans, School of Public Health, Department of Epidemiology, School of Public Health, 2020 Gravier Street, LEC - 3rd Floor, New Orleans, Louisiana 70112, LA, USA
| | - Rotonya Carr
- University of Pennsylvania, Perelman School of Medicine, Division of Gastroenterology, 421 Curie Boulevard, 907 Biomedical Research Building II/III, Philadelphia, Pennsylvania 19104, PA, USA
| | - Meghan Brashear
- Louisiana State University Health Sciences Center, Comprehensive Alcohol Research Center, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA.,Tulane University, School of Public Health and Tropical Medicine, Department of Global Community Health and Behavioral Sciences, 1440 Canal Street, Suite 2210, New Orleans, LA 70112, USA
| | - Liz Simon
- Louisiana State University Health Sciences Center, Comprehensive Alcohol Research Center, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA.,Louisiana State University Health - New Orleans, School of Medicine, Physiology, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA
| | - Katherine P Theall
- Louisiana State University Health Sciences Center, Comprehensive Alcohol Research Center, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA.,Tulane University, School of Public Health and Tropical Medicine, Department of Global Community Health and Behavioral Sciences, 1440 Canal Street, Suite 2210, New Orleans, LA 70112, USA
| | - Martin J Ronis
- Louisiana State University Health Sciences Center, Comprehensive Alcohol Research Center, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA.,Louisiana State University Health - New Orleans, School of Medicine, Pharmacology, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA, and
| | - David A Welsh
- Louisiana State University Health Sciences Center, Comprehensive Alcohol Research Center, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA.,Louisiana State University Health - New Orleans, School of Medicine, Pulmonology, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA
| | - Patricia E Molina
- Louisiana State University Health Sciences Center, Comprehensive Alcohol Research Center, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA.,Louisiana State University Health - New Orleans, School of Medicine, Physiology, 1901 Perdido Street, New Orleans, Louisiana 70112, LA, USA
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13
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Liver fibrosis assessments using FibroScan, virtual-touch tissue quantification, the FIB-4 index, and mac-2 binding protein glycosylation isomer levels compared with pathological findings of liver resection specimens in patients with hepatitis C infection. BMC Gastroenterol 2020; 20:314. [PMID: 32977741 PMCID: PMC7519502 DOI: 10.1186/s12876-020-01459-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 09/17/2020] [Indexed: 02/07/2023] Open
Abstract
Background Evaluation of fibrosis stage is important to monitor progression of liver disease and risk of hepatocellular carcinoma (HCC). While liver biopsy is the gold standard, the method is invasive and faces several limitations. The aim of this study was to determine correlations among METAVIR scores and FibroScan, Virtual-Touch tissue quantification (VTQ), fibrosis index based on four factors (FIB-4 index), and Mac-2 binding protein glycosylation isomer (M2BPGi) level, and for examine differences in the reliability of non-invasive methods to evaluate fibrosis. Methods We used liver resection specimens from patients with hepatitis C virus (HCV), correlations were assessed between METAVIR scores and non-invasive method. Receiver operating characteristic (ROC) curves were generated to determine the sensitivity, specificity, and cut off values of the methods. Results All Patients group: In F0–2 vs F3–4, the areas under the ROC curve (AUC) (0.85) of FibroScan was significantly higher than that (0.67) of FIB-4 index (p = 0.002) and that (0.67) of M2BPGi (p = 0.001). The AUC (0.83) of VTQ was significantly higher than that (0.67) of FIB-4 index (p = 0.01) and that (0.67) of M2BPGi (p = 0.002). In F0–3 vs F4, the AUC (0.86) of VTQ was significantly higher than that (0.65) of FIB-4 index (p = 0.04). The AUC (0.89) of FibroScan was significantly higher than that (0.65) of FIB-4 index (p = 0.002) and that (0.76) of M2BPGi (p = 0.02). Non-SVR group: In F0–2 vs F3–4, the AUC (0.85) of FibroScan was significantly higher than that (0.84) of FIB-4 index (p = 0.02) and that (0.73) of M2BPGi (p = 0.003). The AUC (0.84) of VTQ was significantly higher than that (0.74) of FIB-4 index (p = 0.04). In F0–3 vs F4, the AUC (0.91) of FibroScan was significantly higher than that (0.67) of FIB-4 index (p = 0.003) and that (0.78) of M2BPGi (p = 0.02). The AUC (0.88) of VTQ was significantly higher than that of FIB-4 index (0.67) and that of M2BPGi (0.78) (p = 0.04). Conclusions FibroScan and VTQ best reflected the results of hepatic fibrosis diagnosis using liver resection specimens among the four examination methods evaluated.
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14
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Rosato V, Masarone M, Aglitti A, Persico M. The diagnostic conundrum in non-alcoholic fatty liver disease. EXPLORATION OF MEDICINE 2020. [DOI: 10.37349/emed.2020.00018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the most common liver alteration worldwide. It encompasses a spectrum of disorders that range from simple steatosis to a progressive form, defined non-alcoholic steatohepatitis (NASH), that can lead to advanced fibrosis and eventually cirrhosis and hepatocellular carcinoma. On liver histology, NASH is characterized by the concomitant presence of significant fat accumulation and inflammatory reaction with hepatocellular injury. Until now, liver biopsy is still required to differentiate simple steatosis from NASH and evaluate the degree of liver fibrosis. Unfortunately, this technique has well-known limitations, including invasiveness and expensiveness. Moreover, it may be biased by sampling error and intra- or inter-observed variability. Furthermore, due to the increasing prevalence of NAFLD worldwide, to program a systematic screening with liver biopsy is not imaginable. In recent years, different techniques were developed and validated with the aim of non-invasively identifying NASH and assess liver fibrosis degrees. The non-invasive tests range from simple blood-tests analyses to composite scores and complex imaging techniques. Nevertheless, even if they could represent cost-effective strategies for diagnosing NASH, advanced fibrosis and cirrhosis, their accuracy and consequent usefulness are to be discussed. With this aim, in this review the authors summarize the current state of non-invasive assessment of NAFLD. In particular, in addition to the well-established tests, the authors describe the future perspectives in this field, reporting the latest tests based on OMICS, gut-miocrobioma and micro-RNAs. Finally, the authors provide an accurate assessment of how these non-invasive tools perform in clinical practice depending on the clinical context, with the aim of giving the clinicians a useful tool to try to resolve the diagnostic conundrum of NAFLD.
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Affiliation(s)
- Valerio Rosato
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Odontostomatology “Scuola Medica Salernitana”- University of Salerno, Street Salvador Allende, 43, Fisciano, 84084 Campania, Italy
| | - Mario Masarone
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Odontostomatology “Scuola Medica Salernitana”- University of Salerno, Street Salvador Allende, 43, Fisciano, 84084 Campania, Italy
| | - Andrea Aglitti
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Odontostomatology “Scuola Medica Salernitana”- University of Salerno, Street Salvador Allende, 43, Fisciano, 84084 Campania, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Odontostomatology “Scuola Medica Salernitana”- University of Salerno, Street Salvador Allende, 43, Fisciano, 84084 Campania, Italy
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15
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Chen Q, Li Q, Li D, Chen X, Liu Z, Hu G, Wang J, Ling W. Association between liver fibrosis scores and the risk of mortality among patients with coronary artery disease. Atherosclerosis 2020; 299:45-52. [PMID: 32240838 DOI: 10.1016/j.atherosclerosis.2020.03.010] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 02/09/2020] [Accepted: 03/11/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Fatty liver diseases are highly prevalent in patients with coronary artery disease (CAD) and might progress to irreversible liver fibrosis. Whether baseline liver fibrosis (LF) scores are associated with long-term mortality among patients with CAD requires investigation. METHODS The analysis was conducted based on a prospective cohort study among 3263 patients with CAD in China. Cox models were used to assess the association of baseline levels of LF scores, including non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis 4 score (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), gamma-glutamyltransferase to platelet ratio (GPR), and Forns score, with the risk of all-cause and cardiovascular mortality among CAD patients. RESULTS During a median follow-up period of 7.56 (inter-quartile range: 6.86-8.31) years, 538 deaths were identified, 319 of those were due to cardiovascular diseases. Compared with patients with lowest score levels, multivariable-adjusted HRs (95% CI) for those with highest levels of NFS, FIB-4, APRI, GPR and Forns score were 2.89 (2.14-3.91), 2.84 (2.14-3.76), 1.77 (1.33-2.36), 1.47 (1.19-1.83) and 3.10 (1.88-5.11) for all-cause mortality, 3.02 (2.05-4.45), 3.34 (2.29-4.86), 1.99 (1.40-2.83), 1.80 (1.36-2.39) and 2.43 (1.28-4.61) for cardiovascular mortality, respectively. These associations were consistent when we excluded those who died within the first year of follow-up or stratified patients by different sex, age, BMI, diabetes status, metabolic syndrome status, CAD type and hsCRP level. CONCLUSIONS Higher LF scores are associated with increased risks of all-cause and cardiovascular mortality among CAD patients. LF scores might play a potential role in CAD prognosis prediction.
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Affiliation(s)
- Qian Chen
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China
| | - Qing Li
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong, 510080, China
| | - Dan Li
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong, 510080, China; Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, Guangdong, 510080, China
| | - Xuechen Chen
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong, 510080, China
| | - Zhaomin Liu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong, 510080, China; Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, Guangdong, 510080, China
| | - Gang Hu
- Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, 70808, United States
| | - Jingfeng Wang
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China.
| | - Wenhua Ling
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong, 510080, China; Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, Guangdong, 510080, China.
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Fayed HM, Mahmoud HS, Elaiw Mohamed Ali A. The Utility of Retinol-Binding Protein 4 in Predicting Liver Fibrosis in Chronic Hepatitis C Patients in Response to Direct-Acting Antivirals. Clin Exp Gastroenterol 2020; 13:53-63. [PMID: 32110084 PMCID: PMC7041599 DOI: 10.2147/ceg.s229689] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 01/14/2020] [Indexed: 12/15/2022] Open
Abstract
Background Hepatic fibrosis grading is crucial for chronic hepatitis C (CHC) patients in monitoring liver disease progression and antiviral treatment indication. Retinol-binding protein 4 (RBP4), an adipokine secreted by adipocytes and hepatocytes, has variable levels in health and disease. Purpose To comparatively evaluate RBP4 serum levels in predicting liver fibrosis in CHC versus fibroscan, noninvasive fibrosis, and inflammatory indices. Patients and Methods Cohort study included 50 naive non-obese CHC patients and 20 age-, sex- and body mass index-matched healthy subjects. Fibroscan, RBP4, and noninvasive fibrosis as APRI, CDS, FIB-4, GUCI, Lok index indices based on serological markers, and inflammatory indices as platelet to lymphocyte ratio (PLR) and liver regeneration markers as; alpha-fetoprotein (AFP) and APRI, were evaluated in response to direct-acting antivirals (DAAs). Results RBP4 was significantly lower in patients than in controls (P=0.0001) and progressively decreased with the increase in fibrosis grade (F0-F=41.42±3.08), (F2=39.32±1.43), (F3-F4= 35.31±0.5), (P=0.0001). Liver function, stiffness, and RBP4 significantly improved after treatment (P=0.0001). RBP4 negatively correlated with viral load (r=−0.78, p=0.0001), fibroscan fibrosis grade (r=−0.52, p=0.0001), AFP (r=−0.63, p=0.0001), and positively correlated with platelet (r=0.424, p=0.0001), and white cell count (r=0.298, p=0.002). RBP4 at a cutoff value <40.55 ng/mL might predict significant fibrosis (90.48% sensitivity, 62.5% specificity, AUROC=0.811, 95% CI=67.5–90.0) and at a cutoff value <35.9 ng/mL could predict advanced fibrosis (100% sensitivity, 100% specificity, AUROC =1.0, 95% CI=0.929–1). Conclusion RBP4 showed excellent accuracy, sensitivity, specificity, PPV, and NPV. RBP4 has a superior diagnostic performance in predicting advanced fibrosis grads in CHC patients and hence can replace expensive invasive procedures.
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Affiliation(s)
- Hanan Mahmoud Fayed
- Clinical and Chemical Pathology Department, Qena Faculty of Medicine, South Valley University, Qena, Egypt
| | - Hasan Sedeek Mahmoud
- Tropical Medicine and Gastroenterology Department, Qena Faculty of Medicine, South Valley University, Qena, Egypt
| | - Abdallah Elaiw Mohamed Ali
- Clinical and Chemical Pathology Department, Qena Faculty of Medicine, South Valley University, Qena, Egypt
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17
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Singh SP, Barik RK. NonInvasive Biomarkers in Nonalcoholic Fatty Liver Disease: Are We There Yet? J Clin Exp Hepatol 2020; 10:88-98. [PMID: 32025168 PMCID: PMC6995889 DOI: 10.1016/j.jceh.2019.09.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Accepted: 09/15/2019] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD encompasses a spectrum of disease ranging from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. However, despite the growing recognition of this important disease burden, there are significant challenges to accurately and noninvasively diagnose the various forms of NAFLD, especially to differentiate benign steatosis from the progressive NASH. This is of utmost importance because although liver biopsy is considered the current imperfect 'gold' standard for diagnosing NASH and staging fibrosis, it is an invasive procedure with significant limitations. Although, a number of noninvasive markers have been or are currently undergoing investigation, until date, no highly sensitive and specific tests are available to differentiate NASH from simple steatosis. At the moment, further investigations are needed before prediction models or blood-based biomarkers become available and acceptable for routine clinical care. There is a great need for developing inexpensive, easily accessible, highly sensitive and specific biomarkers that permit not only the identification of patients at high risk of adverse outcomes, but also the monitoring of disease progression and response after therapeutic interventions.
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Affiliation(s)
- Shivaram P. Singh
- Address for correspondence: Shivaram Prasad Singh, Professor, Dept. of Gastroenterology, S.C.B. Medical College, Cuttack, Odisha, 753007, India.
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18
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Death after diagnosis of noncommunicable disease comorbid conditions, stratified by injection drug use. AIDS 2019; 33:285-293. [PMID: 30325772 DOI: 10.1097/qad.0000000000002054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Describe all-cause mortality associated with history of injection drug use (IDU) after a validated diagnosis of four noncommunicable disease (NCD) diagnoses: end-stage liver disease (ESLD); end-stage renal disease (ESRD); cancer; or myocardial infarction (MI) or stroke. DESIGN We followed four cohorts of persons in continuity HIV care in the Johns Hopkins HIV Clinic with a validated diagnosis of ESLD (n = 67), ESRD (n = 187), cancer (n = 424), and MI or stroke (n = 213) from 1996 through approximately 2014. METHODS Crude and adjusted Cox proportional hazards models to estimate hazard ratios for death after a validated diagnosis of one of four NCD diagnoses associated with history of IDU as an HIV acquisition risk factor. RESULTS History of IDU was not associated with death after ESRD (adjusted hazard ratio 0.98, 95% confidence interval (CI) 0.57-1.68). Associations between history of IDU and death after ESLD and MI or stroke were weak, imprecise and not statistically significant (hazard ratio 1.17, 95% CI 0.63-2.19; hazard ratio 1.21, 95% CI 0.80-1.83). History of IDU was not associated with death after cancer in the first 6 months, but subsequently, the adjusted hazard ratio was 2.03 (95% CI 1.26-3.27). CONCLUSION Persons with a history of injection drug use and non-IDU had strikingly similar risk and hazard of mortality after several major NCD diagnoses. Mortality after cancer diagnosis in this cohort was higher for persons with a history of IDU than those without; this may be because of being diagnosed with a different mix of specific sites and stages of cancers.
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Montasser MF, Zaky S, Salaheldin M, Johar D, Abushouk AI, El-Raey F, Al-Husseini M, Mohammed EG. Fib-4 Predicts Early Hematological Adverse Events Induced by Interferon-Based Triple Therapy in Chronic Hepatitis C Virus Patients. J Interferon Cytokine Res 2019; 39:85-94. [PMID: 30657408 DOI: 10.1089/jir.2018.0131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Interferon-alpha (IFN-α)-based therapy is associated with several hematological adverse events in hepatitis C virus (HCV)-infected patients with advanced fibrosis. We performed this study to evaluate the association between Fibrosis-4 (Fib-4) index and hematological adverse events in patients with chronic HCV infection, undergoing IFN-α-based triple therapy. We included 120 HCV-infected patients, receiving triple therapy: weekly PegIFN-α, daily ribavirin (1,000-1,200 mg), and daily sofosbuvir (400 mg) for 12 weeks. We compared Fib-4 scores for patients who developed hematological adverse events at weeks 4 (w4) and w12 of treatment and w12 post-treatment versus those who did not. Treatment with the aforementioned triple regimen was associated with a sustained virological response (SVR)-12 rate of 93.9%. We found no significant associations (P > 0.05) between SVR12 rate and the degree of fibrosis or the risk of hematological adverse events. The Fib-4 score could predict patients who developed hematological adverse events (anemia, leukopenia, and neutropenia) in the first month of treatment, but not in later stages. A Fib-4 cutoff value of 3.59 had high specificity for anemia, leukopenia, and neutropenia (85.1%, 87.2%, and 88.2%, respectively), but had low sensitivity for detecting the 3 events. In conclusion, the Fib-4 score may predict early hematological adverse effects in HCV-infected patients on IFN-based triple therapy.
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Affiliation(s)
- Mohamed F Montasser
- 1 Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Samy Zaky
- 2 Tropical Medicine Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Mohamed Salaheldin
- 1 Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Dina Johar
- 3 Physiology and Pathophysiology Department, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada
| | | | - Fathiya El-Raey
- 4 Tropical Medicine Department, Faculty of Medicine, Al-Azhar University, Damietta, Egypt
| | - Muneer Al-Husseini
- 1 Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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20
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Bavaro DF, Saracino A, Fiordelisi D, Bruno G, Ladisa N, Monno L, Angarano G. Influence of HLA-B18 on liver fibrosis progression in a cohort of HIV/HCV coinfected individuals. J Med Virol 2019; 91:751-757. [PMID: 30578670 DOI: 10.1002/jmv.25385] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Accepted: 12/20/2018] [Indexed: 02/06/2023]
Abstract
Liver fibrosis is accelerated in human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected compared with HCV monoinfected patients, due to multiple cofactors. Recently, HLA-B18 haplotype has been associated with short-term liver disease progression in this population. Our aim was to assess the influence of HLA-B18 on the fibrosis process in HIV/HCV coinfected individuals, untreated for HCV, during a long-term follow-up. All consecutive HIV/HCV co-infectedcoinfected patients followed in our center, with positive HCV-RNA and available human leukocyte antigen (HLA) haplotypes (determined by sequence-specific oligonucleotide primed polymerase chain reaction and simple sequence repeats polymerase chain reaction using Luminex Technology) were included. Liver fibrosis progression was assessed by means of fibrosis-4 index for liver fibrosis (FIB-4) and AST to platelet ratio index. The association between FIB-4 score over time and laboratory and clinical parameters, including HLA, was evaluated by univariate and multivariate multilevel generalized linear models. A total of 29 out of 148 screened patients were excluded because of spontaneous HCV clearance (27% were HLA-B18+). Among the remaining 119 individuals (82% males; median age at first visit = 30 years [interquartile range, IQR, 26-35]; median follow-up = 21.5 years [IQR, 15-25]), 26% were HLA-B18+. No baseline differences were evidenced between HLA-B18+ and B18- patients. Fibrosis progression was significantly faster in HLA-B18+ than in HLA-B18- patients ( P < 0.001) (Figure 1). At univariate analysis, age ( P < 0.001), HLA-B18 haplotype ( P = 0.02) and HIV-RNA viral load overtime ( P < 0.001) were associated with liver disease progression. At multivariate analysis, only age ( P < 0.001) remained independently associated with liver fibrosis progression. Our data suggest a possible association between HLA-B18 and an accelerated liver fibrosis in HIV/HCV coinfected with a long-term follow-up.
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Affiliation(s)
- Davide Fiore Bavaro
- Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari "Aldo Moro,", Bari, Italy
| | - Annalisa Saracino
- Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari "Aldo Moro,", Bari, Italy
| | - Deborah Fiordelisi
- Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari "Aldo Moro,", Bari, Italy
| | - Giuseppe Bruno
- Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari "Aldo Moro,", Bari, Italy
| | - Nicoletta Ladisa
- Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari "Aldo Moro,", Bari, Italy
| | - Laura Monno
- Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari "Aldo Moro,", Bari, Italy
| | - Gioacchino Angarano
- Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari "Aldo Moro,", Bari, Italy
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Choi CB, Park YB, Lee SW. Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in Korea: A Narrative Review. Yonsei Med J 2019; 60:10-21. [PMID: 30554486 PMCID: PMC6298898 DOI: 10.3349/ymj.2019.60.1.10] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Indexed: 12/15/2022] Open
Abstract
Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of systemic necrotising vasculitides, which often involve small vessels, and which lead to few or no immune deposits in affected organs. According to clinical manifestations and pathological features, AAV is classified into three variants: microscopic polyangiitis, granulomatosis with polyangiitis (GPA), and eosinophilic GPA. The American College of Rheumatology 1990 criteria contributed to the classification of AAV, although currently the algorithm suggested by the European Medicines Agency in 2007 and the Chapel Hill Consensus Conference Nomenclature of Vasculitides proposed in 2012 have encouraged physicians to classify AAV patients properly. So far, there have been noticeable advancements in studies on the pathophysiology of AAV and the classification criteria for AAV in Western countries. However, studies analysing clinical features of Korean patients with AAV have only been conducted and reported since 2000. One year-, 5 year-, and 10 year-cumulative patient survival rates are reported as 96.1, 94.8, and 92.8%. Furthermore, initial vasculitis activity, prognostic factor score, age and specific organ-involvement have been found to be associated with either all-cause mortality or poor disease course. The rate of serious infection is 28.6%, and 1 year-, 5 year- and 10 year-cumulative hospitalised infection free survival rates range from 85.1% to 72.7%. The overall standardised incidence ratio of cancer in AAV patients was deemed 1.43 compared to the general Korean population.
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Affiliation(s)
- Chan Bum Choi
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
| | - Yong Beom Park
- Division of Rheumatology, Department of Internal Medicine, and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Won Lee
- Division of Rheumatology, Department of Internal Medicine, and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea.
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22
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Lee HW, Oh SR, Kim DY, Jeong Y, Kim S, Kim BK, Kim SU, Kim DY, Ahn SH, Han KH, Park JY. Daclatasvir Plus Asunaprevir for the Treatment of Patients with Hepatitis C Virus Genotype 1b Infection: Real-World Efficacy, Changes in Liver Stiffness and Fibrosis Markers, and Safety. Gut Liver 2018; 12:324-330. [PMID: 29409309 PMCID: PMC5945264 DOI: 10.5009/gnl17298] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Revised: 09/20/2017] [Accepted: 09/20/2017] [Indexed: 12/17/2022] Open
Abstract
Background/Aims The treatment with daclatasvir plus asunaprevir (DCV+ASV) is associated with potent antiviral effects in patients with genotype 1b hepatitis C virus (HCV) infection. We investigated the real-world efficacy, changes in liver stiffness and noninvasive fibrosis markers, and the safety of DCV+ASV treatment in Korean patients. Methods In total, 363 patients with chronic hepatitis C were treated with DCV+ASV between August 2015 and January 2017. Finally, we analyzed the data of 270 patients who were monitored for at least 12 weeks after the end of treatment. Results The mean age was 60.7 years, and females predominated (60.4%). Most patients (64.8%) were treatment-naïve, and 56 patients (20.7%) had cirrhosis. Two hundred fifty-seven (95.2%) and 251 (93.0%) patients achieved end-of-treatment responses and sustained virological responses at 12 weeks posttreatment (SVR12), respectively. The SVR12 rates were higher in patients who were <65 years of age, males, without cirrhosis and had lower HCV RNA levels. All LS values and fibrosis-4 and aspartate aminotransferase-to-platelet ratio index values declined from baseline to the time of assessment of SVR12. Conclusions The DCV+ASV therapy resulted in a high SVR12 and improved liver fibrosis; the treatment was well tolerated in patients with genotype 1b HCV infections.
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Affiliation(s)
- Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Se Rim Oh
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Yun Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Yechan Jeong
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Brain Korea 21 PLUS Project for Medical Science College of Medicine, Seoul, Korea
| | - Seungtaek Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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23
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Mazzitelli M, Torti C, Sabatino J, D'Ascoli GL, Costa C, Pisani V, Raffetti E, De Rosa S, Strazzulla A, Focà A, Liberto MC, Indolfi C. Evaluation of cardiac function by global longitudinal strain before and after treatment with sofosbuvir-based regimens in HCV infected patients. BMC Infect Dis 2018; 18:518. [PMID: 30326844 PMCID: PMC6192073 DOI: 10.1186/s12879-018-3426-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 10/01/2018] [Indexed: 01/08/2023] Open
Abstract
Background Possible cardiotoxicity of sofosbuvir in humans has not been demonstrated yet. Also, since HCV can exert deleterious effects on hearth function, it is of interest to know whether HCV eradication provides any benefits using global longitudinal strain (GLS), a measure of left ventricular function more reliable than ejection fraction (EF). Methods Patients eligible for treatment with the combination therapy for HCV were invited to perform a transthoracic cardiac ultrasound at four different time points: before starting treatment, after one month, at the end of treatment and, after six month. Left ventricular function was measured with both EF and GLS. Results From March 2015 to December 2016, 82 patients were enrolled. Fifty-six percent patients were males. Mean age was 66.12 (SD: 9.25) years. About 20% patients did not present any cardiovascular risk factors or comorbidities. A worsening trend of GLS was observed. Variations were not found to be statistically significant when EF was studied along the follow-up. However, when GLS was studied, its variations were found to be statistically significant indicating a worsening effect, albeit with different trends in patients who underwent treatment for three months compared to six months. Worsening of GLS was found to be statistically significant even after adjusting for body mass index and liver fibrosis, independently from treatment duration. Conclusions Our results showed unexpected worsening of left ventricular function when measured through GLS after HCV treatment response induced by DAAs including sofosbuvir. Although this result is not proven to be clinically significant, the safety profile of sofosbuvir-based regimens needs to be studied further. Electronic supplementary material The online version of this article (10.1186/s12879-018-3426-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Maria Mazzitelli
- Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Carlo Torti
- Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy.
| | - Jolanda Sabatino
- Cardiovascular Institute, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Greta Luana D'Ascoli
- Cardiovascular Institute, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Chiara Costa
- Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Vincenzo Pisani
- Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Elena Raffetti
- Unit of Hygiene, Epidemiology and Public Health, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health, Viale Europa, 25123, Brescia, Italy
| | - Salvatore De Rosa
- Cardiovascular Institute, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Alessio Strazzulla
- Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Alfredo Focà
- Institute of Microbiology, Department of Health Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Maria Carla Liberto
- Institute of Microbiology, Department of Health Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Ciro Indolfi
- Cardiovascular Institute, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
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24
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Ravaioli F, Conti F, Brillanti S, Andreone P, Mazzella G, Buonfiglioli F, Serio I, Verrucchi G, Bacchi Reggiani ML, Colli A, Marasco G, Colecchia A, Festi D. Hepatocellular carcinoma risk assessment by the measurement of liver stiffness variations in HCV cirrhotics treated with direct acting antivirals. Dig Liver Dis 2018; 50:573-579. [PMID: 29567413 DOI: 10.1016/j.dld.2018.02.010] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Revised: 02/14/2018] [Accepted: 02/15/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Direct-acting antivirals (DAA) are an effective treatment for hepatitis C virus infection. However, sustained virologic response (SVR) after DAA treatment does not seem to reduce the risk of hepatocellular carcinoma (HCC) development in these patients. Liver stiffness measurement (LSM) may predict the risk of developing HCC in liver cirrhosis patients. AIMS The aim of our study was to evaluate the role of LSM variation as predictor of HCC development in patients treated with DAA. METHODS In 139 HCV-related cirrhotic patients, LSM and laboratory tests were carried out at baseline (BL) and at the end of DAA treatment (EOT). Patients were followed for at least 6 months after the EOT. LSM reduction was expressed as Delta LS (∆LS). Cox regression analysis was used to identify prognostic factors for HCC development after DAA. RESULTS Median LSM values were significantly reduced from BL to EOT (from 18.6 to 13.8 kPa; p < 0.001). The median ∆LS was -26.7% (IQR: -38.4% -13.6%). During a median follow-up of 15 months after DAA treatment, 20 (14.4%) patients developed HCC. Significant LSM reduction was observed both in patients who developed HCC and in those who did not, but this was significantly lower in the patients who developed HCC (-18.0% vs -28.9% p = 0.005). At multivariate analysis, ∆LS lower than -30%, Child-Turcotte-Pugh-B and history of HCC were independently associated with HCC development. CONCLUSION Our results indicate that ∆LS is a useful non-invasive marker for predicting HCC development after DAA treatment.
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Affiliation(s)
- Federico Ravaioli
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Fabio Conti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Stefano Brillanti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Pietro Andreone
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Giuseppe Mazzella
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Ilaria Serio
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Gabriella Verrucchi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Agostino Colli
- Department of Internal Medicine, General Hospital "A. Manzoni", Lecco, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Antonio Colecchia
- UOC. Gastroenterology Unit, Borgo Trento University Hospital, Verona, Italy
| | - Davide Festi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
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25
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Diagnostic Accuracy of Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis 4 Scores in Predicting Advanced Liver Fibrosis in Patients with End-stage Renal Disease and Chronic Viral Hepatitis: Experience from Pakistan. J Transl Int Med 2018; 6:38-42. [PMID: 29607303 DOI: 10.2478/jtim-2018-0008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Objectives The aim was to assess the diagnostic accuracy of APRI and FIB-4 in assessing the stage of liver fibrosis in end stage renal disease (ESRD) patients with chronic viral hepatitis and to compare the two tests with standard tru-cut liver biopsy. Material and Methods The study was conducted at Sindh Institute of Urology and Transplantation Karachi (SIUT) from May 2010 to May 2014. All ESRD patients, being considered as candidates for renal transplantation and in whom liver biopsy was performed were included. Fibrosis stage was assessed on liver biopsy using Ishak scoring system. The serum transaminases and platelet counts were used to calculate APRI and FIB-4 scores. Results Out of 109 patients, hepatitis C and B virus infections were present in 104 (95.4%) and 3(2.8%), respectively, while 2 (1.8%) patients had both infections. The mean Ishak fibrosis score was 1.95 ± 2. Advanced fibrosis was noted in 37 (34%) patients. Univariate analysis showed that advanced liver fibrosis was associated with lower platelets counts (P=0.001) and higher aspartate aminotransferase (AST) (P=0.001), alanine aminotransferase (ALT) (P=0.022), APRI score (P=0.001) and FIB-4 score (P=0.001). On logistic regression analysis, only APRI score (P < 0.001) was found to be the independent variable associated with advanced liver fibrosis. APRI score cutoff ≥1 indicating advanced fibrosis showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 91.9%, 90.3%, 82.9%, 95.6%, respectively with area under the curve (AUC) of 0.97. Similarly, a FIB-4 score cutoff ≥1.1 had sensitivity, specificity, PPV and NPV of 70.27%, 66.67%, 52% and 81.36%, respectively with AUC of 0.74. Conclusion APRI is more accurate noninvasive test for assessing advanced liver fibrosis in ESRD patients as compared to FIB-4. It can be used to obviate the need for liver biopsy in this high risk population.
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26
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Shear-wave elastography for the assessment of liver fibrosis in liver transplant recipients treated for hepatitis C virus recurrence. Eur J Gastroenterol Hepatol 2018; 30:27-32. [PMID: 29049126 DOI: 10.1097/meg.0000000000001003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES Direct-acting antiviral agents have revolutionized hepatitis C therapy, and are also found to be effective in the liver transplant setting. The extent of liver fibrosis influences patient management and is used to monitor therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging-based method that has not yet been studied extensively in liver transplant patients. Our aim was to study the effect of direct-acting antivirals in heaptitis C recurrence on liver stiffness determined by SWE. PATIENTS AND METHODS A total of 23 liver transplant patients with hepatitis C recurrence were enrolled in this prospective study. The patients underwent 24 weeks of ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin combination therapy. Elastographic examinations, serological tests and laboratory tests were performed, and serum biomarkers of liver fibrosis were calculated the day before treatment (baseline) and at the end of the treatment. RESULTS All our patients became hepatitis C virus RNA negative by the end of the treatment. Median liver stiffness values decreased significantly after treatment compared with baseline (8.72±3.77 vs. 7.19±2.4 kPa; P<0.001). Among the studied laboratory values, a significant decrease was observed in the levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase, whereas international normalized ratio levels increased. Serum biomarkers, namely aspartate aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly after treatment compared with baseline. CONCLUSION In the present study, SWE was succesfully used to monitor the beneficial therapeutic effects of direct-acting antivirals in hepatitis C recurrence following liver transplantation. We believe that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C treatment in liver transplant patients.
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Newsome PN, Cramb R, Davison SM, Dillon JF, Foulerton M, Godfrey EM, Hall R, Harrower U, Hudson M, Langford A, Mackie A, Mitchell-Thain R, Sennett K, Sheron NC, Verne J, Walmsley M, Yeoman A. Guidelines on the management of abnormal liver blood tests. Gut 2018; 67:6-19. [PMID: 29122851 PMCID: PMC5754852 DOI: 10.1136/gutjnl-2017-314924] [Citation(s) in RCA: 297] [Impact Index Per Article: 42.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 10/06/2017] [Accepted: 10/15/2017] [Indexed: 12/13/2022]
Abstract
These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. These guidelines deal specifically with the management of abnormal liver blood tests in children and adults in both primary and secondary care under the following subheadings: (1) What constitutes an abnormal liver blood test? (2) What constitutes a standard liver blood test panel? (3) When should liver blood tests be checked? (4) Does the extent and duration of abnormal liver blood tests determine subsequent investigation? (5) Response to abnormal liver blood tests. They are not designed to deal with the management of the underlying liver disease.
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Affiliation(s)
- Philip N Newsome
- National Institute for Health Research (NIHR), Birmingham Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK,Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Rob Cramb
- National Institute for Health Research (NIHR), Birmingham Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - Suzanne M Davison
- Leeds Children’s Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - John F Dillon
- Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK
| | | | - Edmund M Godfrey
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | | | - Mark Hudson
- Regional Liver and Transplant Unit, Freeman Hospital, Newcastle Upon Tyne, UK,Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK
| | | | | | | | - Karen Sennett
- Killick Street Health Centre, London, UK,NHS Islington Clinical Commissioning Group, London, UK
| | - Nicholas C Sheron
- Clinical and Experimental Science, Faculty of Medicine, University of Southampton, Southampton, UK
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Staufer K, Dengler M, Huber H, Marculescu R, Stauber R, Lackner C, Dienes HP, Kivaranovic D, Schachner C, Zeitlinger M, Wulkersdorfer B, Rauch P, Prager G, Trauner M, Mikulits W. The non-invasive serum biomarker soluble Axl accurately detects advanced liver fibrosis and cirrhosis. Cell Death Dis 2017; 8:e3135. [PMID: 29072690 PMCID: PMC5680921 DOI: 10.1038/cddis.2017.554] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 07/28/2017] [Accepted: 09/13/2017] [Indexed: 02/07/2023]
Abstract
Soluble Axl (sAxl) was recently shown to be strongly released into the blood during liver fibrogenesis and hepatocellular carcinoma suggesting sAxl as a biomarker of liver diseases. In this study we are the first to evaluate sAxl in human serum in comparison to Enhanced Liver Fibrosis (ELF) test and transient elastography (TE; Fibroscan) for its value to detect significant (F≥2), advanced fibrosis (F≥3), and cirrhosis (F4) in different liver disease etiologies and healthy controls. To properly determine the diagnostic accuracy of sAxl, a test cohort as well as a validation cohort was employed using liver biopsy as a reference method. Most notably, sAxl was confirmed to be an accurate biomarker of liver fibrosis and cirrhosis. Its accuracy was increased, if total serum albumin was added to build a sAxl/albumin ratio. Thereby an AUC of 0.763, 0.776, 0.826, and 0.832 was achieved corresponding to histological fibrosis stages F≥2, F≥3, F4 with liver biopsy as a reference method, and cirrhosis according to imaging techniques, respectively. With a cut-off of 1.29, a sensitivity, specificity, PPV, and NPV of 78.5%, 80.1%, 44%, 94.9% for the detection of cirrhosis was achieved. In comparison, ELF test and TE showed an AUC of 0.910, and 0.934, respectively, for the detection of cirrhosis. However, performance of TE was not possible in 14.4% of patients and both, ELF™ test and TE bear the disadvantage of high costs. In conclusion, the sAxl/albumin ratio is suggested as an accurate biomarker of liver fibrosis and cirrhosis. Due to its easy applicability and low costs it is suitable as screening parameter for significant to advanced liver fibrosis and cirrhosis, especially if TE is not available or not applicable.
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Affiliation(s)
- Katharina Staufer
- Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mirko Dengler
- Department of Internal Medicine I, Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
| | - Heidemarie Huber
- Department of Internal Medicine I, Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
| | - Rodrig Marculescu
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Rudolf Stauber
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Carolin Lackner
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Hans-Peter Dienes
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Danijel Kivaranovic
- Department of Statistics and Operations Research, University of Vienna, Vienna, Austria
| | - Christian Schachner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Markus Zeitlinger
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | | | - Peter Rauch
- Candor Bioscience GmbH, Wangen im Allgäu, Germany
| | - Gerhard Prager
- Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Mikulits
- Department of Internal Medicine I, Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
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29
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Valkov I, Ivanova R, Alexiev A, Antonov K, Mateva L. Association of Serum Lipids with Hepatic Steatosis, Stage of Liver Fibrosis and Viral Load in Chronic Hepatitis C. J Clin Diagn Res 2017; 11:OC15-OC20. [PMID: 28969178 DOI: 10.7860/jcdr/2017/28609.10459] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 06/19/2017] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Hepatitis C Virus (HCV) relies on host lipids for its life cycle contributing to lipid abnormalities and hepatic steatosis. Disease progression is influenced by viral factors interacting with host immune and metabolic pathways. The significance of serum lipids for Chronic Hepatitis C (CHC) assessment is not clearly established yet. AIM Our aim was to investigate serum lipids' association with stage of liver fibrosis, steatosis and genotypes in patients with CHC. MATERIALS AND METHODS A total of 112 CHC patients (54 male, 58 female, aged 48.6±13.7 years) were studied - 98 genotype 1 (G1) and 14 genotype 3 (G3). Liver cirrhosis (F4) was diagnosed in 31 cases. Steatosis was present in 75 of all patients on ultrasound. Liver biopsy was done in 65 patients and histology showed steatosis in 28, stages of fibrosis (F1-F3) in 56 and F4 in 9 patients (METAVIR). Laboratory panel included complete blood count, liver tests and serum lipid levels (mmol/l) with Friedewald equation estimations. Indirect noninvasive fibrosis scores FIB-4, Aspartate aminotransferase to Platelet Ratio Index (APRI) and Forns index were calculated. HCV RNA was quantified by RT-PCR. Statistical analysis included Spearman's rho, Mann-Whitney U test, Receiver Operating Characteristic (ROC) curve. RESULTS Total Cholesterol (TCh) (p=0.002) and Low-Density Lipoprotein (LDL) (p=0.003) in G1 patients were higher when steatosis was present. TCh (p<0.001), High-Density Lipoprotein (HDL) (p=0.018) and LDL (p=0.003) were lower in G1 F4 compared with F1-F3 patients. Triglyceride (TG) levels correlated with FIB-4 (r=0.364, p=0.029), APRI (r=0.333, p=0.047) and Forns index (r=0.423, p=0.010) in G1 patients without steatosis. TG to LDL ratio (TG/LDL) (p=0.001) was higher in F4 than in F1-F3 patients. TG/LDL ratio predicted the presence of F4 in G1 patients without steatosis by an area under the ROC curve 0.900 (p<0.001). TG/LDL ratio > 0.52 was highly specific for F4 without steatosis. Specificity dropped to 76% when steatosis was present. TG/LDL < 0.32 negatively predicted liver cirrhosis. HCV RNA correlated with TG levels (r=0.330, p=0.009) in G1 patients with steatosis and with histological percent of fatty hepatocytes (r=0.585, p=0.028) in G3 patients. CONCLUSION Lipid levels in CHC G1 patients depend on the presence of steatosis and cirrhosis. HCV RNA is associated with TG levels in G1 patients with steatosis, but not in G3 patients. In cirrhotic CHC G1 patients cholesterol is low with relatively increased TG. TG/LDL ratio is a potential marker of liver cirrhosis in CHC G1 patients.
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Affiliation(s)
- Ivan Valkov
- Resident and PhD Student, Clinic of Gastroenterology, University Hospital "St.Ivan Rilski", Medical University-Sofia, Bulgaria
| | - Radina Ivanova
- Associate Professor, Laboratory of Clinical Pathology, University Hospital "St.Ivan Rilski", Medical University-Sofia, Bulgaria
| | - Assen Alexiev
- Professor, Clinic of Gastroenterology, University Hospital "St.Ivan Rilski", Medical University-Sofia, Bulgaria
| | - Krasimir Antonov
- Professor, Clinic of Gastroenterology, University Hospital "St.Ivan Rilski", Medical University-Sofia, Bulgaria
| | - Lyudmila Mateva
- Professor, Head of Clinic of Gastroenterology, University Hospital "St.Ivan Rilski", Medical University-Sofia, Bulgaria
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30
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Unalp-Arida A, Ruhl CE. Liver fibrosis scores predict liver disease mortality in the United States population. Hepatology 2017; 66:84-95. [PMID: 28195363 PMCID: PMC7005915 DOI: 10.1002/hep.29113] [Citation(s) in RCA: 178] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Accepted: 02/09/2017] [Indexed: 12/07/2022]
Abstract
Fatty liver disease is common in the United States and worldwide due to changing lifestyles and can progress to fibrosis and cirrhosis contributing to premature death. We examined whether liver fibrosis scores were associated with increased overall and disease-specific mortality in a United States population-based prospective survey with up to 23 years of linked-mortality data. Data were analyzed from 14,841 viral hepatitis-negative adult participants in the third National Health and Nutrition Examination Survey, 1988-1994. Liver fibrosis was predicted using the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and Forns score. Participants were passively followed for mortality, identified by death certificate underlying or contributing causes, by linkage to National Death Index records through 2011. Hazard ratios (HR) for mortality were calculated using Cox proportional hazards regression to adjust for mortality risk factors. During follow-up, cumulative mortality was 28.0% from all causes and 0.82% with liver disease, including primary liver cancer. Elevated liver disease mortality was found with an intermediate to high APRI (HR, 9.44; 95% confidence interval [CI], 5.02-17.73), intermediate (HR, 3.15; 95% CI, 1.33-7.44) or high (HR, 25.14; 95% CI, 8.38-75.40) FIB-4 score, high NFS (HR, 6.52; 95% CI, 2.30-18.50), and intermediate (HR, 3.58; 95% CI, 1.78-7.18) or high (HR, 63.13; 95% CI, 22.16-179.78) Forns score. Overall mortality was also greater with higher fibrosis scores. CONCLUSION In the United States population, higher liver fibrosis scores were associated with increased liver disease and overall mortality. Liver health management with common clinical measures of fibrosis risk stratification merits further investigation. (Hepatology 2017;66:84-95).
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Affiliation(s)
- Aynur Unalp-Arida
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD
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31
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Herman M, Okoji O, Castaneda D, Jirru E, Kotler D. Letter: APRI and FIB-4 do not correlate with Fibrosure in the evaluation of liver fibrosis in hepatitis C patients. Aliment Pharmacol Ther 2017; 45:190-191. [PMID: 27910146 DOI: 10.1111/apt.13836] [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: 12/08/2022]
Affiliation(s)
- M Herman
- Department of Medicine, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA
| | - O Okoji
- Department of Medicine, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA.,Department of Gastroenterology, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA
| | - D Castaneda
- Department of Medicine, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA
| | - E Jirru
- Department of Medicine, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA
| | - D Kotler
- Department of Medicine, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA.,Department of Gastroenterology, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA
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32
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Liver fibrosis in HIV-infected individuals on long-term antiretroviral therapy: associated with immune activation, immunodeficiency and prior use of didanosine. AIDS 2016; 30:1771-80. [PMID: 27088320 DOI: 10.1097/qad.0000000000001119] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND It is unclear whether HIV infection is associated with liver fibrosis in the absence of chronic hepatitis B or C virus (HBV/HCV) coinfection. We compared prevalence of liver fibrosis, noninvasively assessed by the Fibrosis-4 (FIB-4) index, between HIV-infected patients and uninfected controls, and explored determinants of a higher FIB-4 score, indicative of more liver fibrosis. METHODS FIB-4 was assessed in HIV-uninfected and HIV-1-infected, predominantly virologically suppressed participants of the AGEhIV Cohort Study without HBV and/or HCV coinfection, and aged at least 45. Using multivariable regression, we investigated associations between FIB-4 and HIV-status, HIV-disease characteristics, antiretroviral drugs and markers of microbial translocation and immune activation. RESULTS Prevalence of advanced liver fibrosis (FIB-4 ≥ 3.25) was low: 1.4% in HIV-infected and 1.0% in HIV-uninfected participants. After adjustment for age, sex, ethnicity, detectable anti-hepatitis B core/anti-HCV antibodies and excessive alcohol intake, HIV remained significantly associated with higher FIB-4 (+4.2%, P = 0.05). Prior exposure to didanosine, longer duration of a CD4 cell count below 500 cells/μl and a lower CD4 cell count at enrollment were each associated with a higher FIB-4. Markers of immune activation (soluble CD163, activated CD8 T-lymphocytes and regulatory T-lymphocytes) were associated with a higher FIB-4 in HIV-infected but not HIV-uninfected study participants. CONCLUSION HIV infection was independently associated with higher FIB-4 scores, indicating more advanced liver fibrosis, though the difference in FIB-4 scores between HIV-infected and HIV-uninfected was small. Higher levels of immune activation were associated with liver fibrosis in HIV-infected, even in the absence of HBV or HCV infection, but not in HIV-uninfected individuals.
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33
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Diktas H, Karacaer Z, Özturk II, Cicek H. Comparison of relationship between histopathological, serological and biochemical parameters in patients with chronic hepatitis B infection. Postgrad Med J 2016; 92:693-696. [PMID: 27170311 DOI: 10.1136/postgradmedj-2016-134069] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2016] [Revised: 04/18/2016] [Accepted: 04/24/2016] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To demonstrate the relationship between liver histology, alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and hepatitis B virus (HBV) DNA levels based on hepatitis B e antigen (HBeAg) seropositivity status in naive patients with chronic hepatitis B (CHB). MATERIALS AND METHOD Naive patients with CHB admitted to our hospital between January 2012 and April 2014 were evaluated retrospectively. The patients were allocated into one of two groups based on HBeAg-seropositivity status. RESULTS Two hundred and fourteen patients were enrolled in the study. Of these 214 patients, 103 (48.1%) were HBeAg-positive and 111 (51.9%) were HBeAg-negative. In the HBeAg-positive group, positive correlations were found between histologic activity index (HAI) scores and ALT (t=3.3, r=0.31, p=0.001), AST (t=2.8, r=0.27, p=0.005) and HBV DNA load (t=2.5, r=0.24, p=0.014). Additionally, in this group, fibrosis scores had positive correlations with ALT (t=3.3, r=0.32, p=0.001) and AST (t=2.7, r=0.26, p=0.008). In the HBeAg-negative group, positive correlations were found between HAI scores and ALT (t=3, r=0. 28, p=0.003), AST (t=3, r=0. 28, p=0.003) and HBV DNA (t=5.3, r=0. 45, p=0). In this same group, fibrosis scores had a positive correlation with HBV DNA (t=2.2, r=0. 21, p=0.024). Multivariate logistic regression analysis showed a positive relationship between fibrosis and ALT in the HBeAg-positive group and a positive relationship between fibrosis and HBV DNA load in the HBeAg-negative group. CONCLUSIONS This study showed that HBV DNA load is an independent predictive factor for evaluating HAI and fibrosis in the HBeAg-negative group. Also, ALT is an independent predictive factor for evaluating fibrosis in the HBeAg-positive group.
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Affiliation(s)
- Husrev Diktas
- Department of Infectious Diseases and Clinical Microbiology, Tatvan Military Hospital, Bitlis, Turkey
| | - Zehra Karacaer
- Department of Infectious Diseases and Clinical Microbiology, Etimesgut Military Hospital, Ankara, Turkey
| | - I Ilker Özturk
- Department of Infectious Diseases and Clinical Microbiology, Beytepe Military Hospital, Ankara, Turkey
| | - Huseyin Cicek
- Department of Infectious Diseases and Clinical Microbiology, Etimesgut Military Hospital, Ankara, Turkey
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34
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Kaswala DH, Lai M, Afdhal NH. Fibrosis Assessment in Nonalcoholic Fatty Liver Disease (NAFLD) in 2016. Dig Dis Sci 2016; 61:1356-64. [PMID: 27017224 DOI: 10.1007/s10620-016-4079-4] [Citation(s) in RCA: 96] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Accepted: 02/04/2016] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver pathologies characterized by hepatic steatosis with a history of little to no alcohol consumption or secondary causes of hepatic steatosis. The prevalence of NAFLD is 20-25 % of the general population in the Western countries and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. The spectrum of disease ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis. Advanced fibrosis is the most significant predictor of mortality in NAFLD. It is crucial to assess for the presence and degree of hepatic fibrosis in order to make therapeutic decisions and predict clinical outcomes. Liver biopsy, the current gold standard to assess the liver fibrosis, has a number of drawbacks such as invasiveness, sampling error, cost, and inter-/intra-observer variability. There are currently available a number of noninvasive tests as an alternative to liver biopsy for fibrosis staging. These noninvasive fibrosis tests are increasingly used to rule out advanced fibrosis and help guide disease management. While these noninvasive tests perform relatively well for ruling out advanced fibrosis, they also have limitations. Understanding the strengths and limitations of liver biopsy and the noninvasive tests is necessary for deciding when to use the appropriate tests in the evaluation of patients with NAFLD.
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Affiliation(s)
- Dharmesh H Kaswala
- Liver Center, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, 110 Francis St #8e, Boston, MA, 0221, USA
| | - Michelle Lai
- Liver Center, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, 110 Francis St #8e, Boston, MA, 0221, USA
| | - Nezam H Afdhal
- Liver Center, Department of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, 110 Francis St #8e, Boston, MA, 0221, USA.
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35
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Andrés-Otero MJ, De-Blas-Giral I, Puente-Lanzarote JJ, Serrano-Aulló T, Morandeira MJ, Lorente S, Lou-Bonafonte JM. Multiple approaches to assess fourteen non-invasive serum indexes for the diagnosis of liver fibrosis in chronic hepatitis C patients. Clin Biochem 2016; 49:560-5. [PMID: 26968102 DOI: 10.1016/j.clinbiochem.2015.12.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Revised: 12/15/2015] [Accepted: 12/19/2015] [Indexed: 12/28/2022]
Abstract
BACKGROUND The aim of this study was to compare fourteen non-invasive indexes/scores: AAR, APRI, Fibroindex, MODEL3, Forns index, FIB4, GUCI, FI, FCI, Pohl score, AP index, CDS, HGM-1 and HGM-2, in order to diagnose the hepatic fibrosis stage in a survey of patients with chronic hepatitis C. METHODS 84 patients with chronic hepatitis C were studied. Liver fibrosis was staged according to the Scheuer scoring system. The diagnostic accuracy of these indexes/scores was evaluated by AUROC, contingency tables and logistic regression analysis. RESULTS The best AUROCs (>0.9) to discriminate cirrhosis (F=4), were observed for CDS, FI, AAR, MODEL3, FIB4, HGM-2 and FCI. To discriminate at least advance fibrosis (F≥3), the best AUROCs (>0.89) were for CDS, FI, FIB4, HGM2-2, MODEL3 and FCI. To discriminate at least significant fibrosis (F≥2), the best AUROCs (>0.8) were for FIB4, GUCI, APRI, FI, Forns index, HGM-2 and FCI. Contingency tables and logistic regression analysis supported the results obtained by AUROC. CONCLUSIONS This study compares the diagnostic performance of fourteen indexes for the diagnosis of liver fibrosis stage in the same group of CHC patients. These results allow the selection of the best indexes for further studies in larger populations, in order to build diagnostic algorithms as an alternative to liver biopsy for fibrosis staging in patients with chronic HCV infection. These algorithms would allow to take therapeutical decisions and the continuous follow-up of hepatic fibrosis in these patients.
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Affiliation(s)
| | - Ignacio De-Blas-Giral
- Dpto. Patología Animal, Universidad de Zaragoza, Zaragoza, Spain; Instituto Agroalimentario de Aragón, Zaragoza, Spain
| | - Juan José Puente-Lanzarote
- Servicio de Bioquímica Clínica, HCU Lozano Blesa, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain
| | - Trinidad Serrano-Aulló
- Servicio de Digestivo, HCU Lozano Blesa, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain
| | - María José Morandeira
- Servicio Anatomía patológica, HCU Lozano Blesa, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain
| | - Sara Lorente
- Servicio de Digestivo, HCU Lozano Blesa, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain
| | - José Manuel Lou-Bonafonte
- Dpto. Farmacología y Fisiología, Universidad de Zaragoza, Zaragoza, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain; Instituto Agroalimentario de Aragón, Zaragoza, Spain.
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36
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Jiang ZG, Feldbrügge L, Tapper EB, Popov Y, Ghaziani T, Afdhal N, Robson SC, Mukamal KJ. Aspirin use is associated with lower indices of liver fibrosis among adults in the United States. Aliment Pharmacol Ther 2016; 43:734-43. [PMID: 26749582 DOI: 10.1111/apt.13515] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2015] [Revised: 11/02/2015] [Accepted: 12/13/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND Recent animal studies have shown that platelets directly activate hepatic stellate cells to promote liver fibrosis, whereas anti-platelet agents decrease liver fibrosis. It is unknown whether platelet inhibition by aspirin prevents liver fibrosis in humans. AIM To examine the association between aspirin use and liver fibrosis among adults with suspected chronic liver disease. METHODS We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey III. We identified 1856 individuals with suspected chronic liver disease (CLD). The degree of liver fibrosis was determined using four validated fibrosis indices and a composite index. RESULTS The use of aspirin was associated with a significantly lower composite liver fibrosis index calculated from FIB4, APRI, Forns and NFS [0.24 standard deviation (s.d.) units lower; 95% CI -0.42 to -0.06, P = 0.009]. The association of aspirin with lower fibrosis scores was significantly larger among those with suspected CLD compared to those without (-0.23 vs. -0.03 s.d. units; P interaction = 0.05). The negative association between aspirin use and lower fibrosis index was consistent across all four fibrosis indices (P = 0.002-0.08) in individuals with chronic viral hepatitis, suspected alcoholic liver disease and NASH. In comparison, no negative associations with liver fibrosis were seen with ibuprofen in parallel analyses. CONCLUSIONS The use of aspirin was associated with significantly lower indices of liver fibrosis among US adults with suspected chronic liver diseases. Aspirin and other anti-platelet drugs warrant further investigation for the prevention and treatment of liver fibrosis.
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Affiliation(s)
- Z Gordon Jiang
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - L Feldbrügge
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - E B Tapper
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Y Popov
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - T Ghaziani
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - N Afdhal
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - S C Robson
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - K J Mukamal
- Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Grebely J, Alavi M, Micallef M, Dunlop AJ, Balcomb AC, Phung N, Weltman MD, Day CA, Treloar C, Bath N, Haber PS, Dore GJ. Treatment for hepatitis C virus infection among people who inject drugs attending opioid substitution treatment and community health clinics: the ETHOS Study. Addiction 2016; 111:311-9. [PMID: 26451534 DOI: 10.1111/add.13197] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2015] [Revised: 06/02/2015] [Accepted: 09/30/2015] [Indexed: 12/12/2022]
Abstract
AIMS To estimate adherence and response to therapy for chronic hepatitis C virus (HCV) infection among people with a history of injecting drug use. A secondary aim was to identify predictors of HCV treatment response. DESIGN Prospective cohort recruited between 2009 and 2012. Participants were treated with peg-interferon alfa-2a/ribavirin for 24 (genotypes 2/3, G2/3) or 48 weeks (genotype 1, G1). SETTING Six opioid substitution treatment (OST) clinics, two community health centres and one Aboriginal community-controlled health organization providing drug treatment services in New South Wales, Australia. PARTICIPANTS Among 415 people with a history of injecting drug use and chronic HCV assessed by a nurse, 101 were assessed for treatment outcomes (21% female). MEASUREMENTS Study outcomes were treatment adherence and sustained virological response (SVR, undetectable HCV RNA >24 weeks post-treatment). FINDINGS Among 101 treated, 37% (n = 37) had recently injected drugs (past 6 months) and 62% (n = 63) were receiving OST. Adherence ≥ 80% was 86% (n = 87). SVR was 74% (75 of 101), with no difference observed by sex (males: 76%, females: 67%, P = 0.662). In adjusted analysis, age < 35 (versus ≥ 45 years) [adjusted odds ratio (aOR) = 5.06, 95% confidence interval (CI) = 1.47, 17.40] and on-treatment adherence ≥ 80% independently predicted SVR (aOR = 19.41, 95% CI = 3.61, 104.26]. Recent injecting drug use at baseline was not associated with SVR. CONCLUSIONS People with a history of injecting drug use and chronic hepatitis C virus attending opioid substitution treatment and community health clinics can achieve adherence and responses to interferon-based therapy similar to other populations, despite injecting drugs at baseline. Younger age and adherence are predictive of improved response to hepatitis C virus therapy.
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Affiliation(s)
- Jason Grebely
- The Kirby Institute, UNSW Australia, Sydney, NSW, Australia
| | - Maryam Alavi
- The Kirby Institute, UNSW Australia, Sydney, NSW, Australia
| | | | - Adrian J Dunlop
- University of Newcastle, Newcastle, NSW, Australia.,Drug and Alcohol Clinical Services, Hunter New England Local Health District, Newcastle, NSW, Australia
| | - Anne C Balcomb
- Clinic 96, Kite St Community Health Centre, Orange, NSW, Australia
| | - Nghi Phung
- Drug Health Services, Western Sydney Local Health District, NSW, Australia
| | - Martin D Weltman
- Gastroenterology and Hepatology, Nepean Hospital, Kingswood, NSW, Australia.,Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Carolyn A Day
- Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,Drug Health Service, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Carla Treloar
- Centre for Social Research in Health, UNSW Australia, Sydney, NSW, Australia
| | | | - Paul S Haber
- Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Gregory J Dore
- The Kirby Institute, UNSW Australia, Sydney, NSW, Australia
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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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Imanieh MH, Hakimzadeh M, Dehghani SM, Geramizadeh B, Safarpour A, Sepehrimanesh M, Haghighat M. Aspartate aminotransferase to platelet ratio index and severity of hepatic fibrosis in children. COMPARATIVE CLINICAL PATHOLOGY 2015. [DOI: 10.1007/s00580-015-2124-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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Alboraie M, Khairy M, Elsharkawy M, Asem N, Elsharkawy A, Esmat G. Value of Egy-Score in diagnosis of significant, advanced hepatic fibrosis and cirrhosis compared to aspartate aminotransferase-to-platelet ratio index, FIB-4 and Forns' index in chronic hepatitis C virus. Hepatol Res 2015; 45:560-70. [PMID: 24995544 DOI: 10.1111/hepr.12385] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 06/24/2014] [Accepted: 06/25/2014] [Indexed: 01/14/2023]
Abstract
AIM Serum markers and developed scores are of rising importance in non-invasive diagnosis of hepatic fibrosis. Aspartate aminotransferase-to-platelet ratio index (APRI), FIB-4 and Forns' index are validated scores used for diagnosis of liver fibrosis. The Egy-Score is a newly developed score for detection of hepatic fibrosis with promising results. We aimed to assess the accuracy of the Egy-Score in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis compared to APRI, FIB-4 and Forns' in chronic hepatitis C virus (HCV) patients. METHODS A retrospective study including 100 chronic hepatitis C naïve Egyptian patients was performed. Patients were classified according to stages of fibrosis into three groups: significant fibrosis (≥ F2), advanced fibrosis (≥ F3) and cirrhosis (F4). Egy-Score, APRI, FIB-4 and Forns' index were calculated. Regression analysis and receiver-operator curves were plotted to assess the sensitivity, specificity and predictive values for the significant scores with the best cut-off for diagnosis. RESULTS An Egy-Score of 3.28 or more was superior to APRI, FIB-4 and Forns' index for detecting advanced fibrosis with a sensitivity of 91% and specificity of 78%. An Egy-Score of 3.67 or more was superior to APRI, FIB-4 and Forns' index for detecting cirrhosis with a sensitivity of 82% and specificity of 87%. Forns' index was superior to Egy-Score, FIB-4 and APRI for detecting significant fibrosis. CONCLUSION The Egy-Score is a promising, accurate, easily calculated, cost-effective score in the prediction of hepatic fibrosis in chronic HCV patients with superiority over APRI, FIB-4 and Forns' index in advanced hepatic fibrosis and cirrhosis.
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Affiliation(s)
- Mohamed Alboraie
- Internal Medicine Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; Egyptian Liver Fibrosis Study Group, Cairo, Egypt
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Moorman AC, Xing J, Ko S, Rupp LB, Xu F, Gordon SC, Lu M, Spradling PR, Teshale EH, Boscarino JA, Vijayadeva V, Schmidt MA, Holmberg SD. Late diagnosis of hepatitis C virus infection in the Chronic Hepatitis Cohort Study (CHeCS): Missed opportunities for intervention. Hepatology 2015; 61:1479-84. [PMID: 25131217 PMCID: PMC5675516 DOI: 10.1002/hep.27365] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Accepted: 08/07/2014] [Indexed: 01/08/2023]
Abstract
UNLABELLED To determine the stage of liver disease at initial diagnosis of hepatitis C virus (HCV) infection, we analyzed data from the Chronic Hepatitis Cohort Study (CHeCS), a large U.S. observational study. We examined the temporal relationships of initial HCV infection diagnosis with cirrhosis-defined by liver biopsy or mean FIB-4 score >5.88-and time to onset of cirrhotic decompensation in electronic medical records. We determined time in the health system prior to HCV diagnosis and rates of hospitalization and death following HCV diagnosis. Of 14,717 patients with chronic HCV seen during 2006-2011, 6,166 (42%) had a definable time of initial HCV diagnosis. Of these, 1,056 (17%) patients met our definition for "late diagnosis" with either cirrhosis concurrent with initial HCV diagnosis (n = 550), a first diagnosis of hepatic decompensation before or within 12 months after initial HCV diagnosis (n = 506), or both (n = 314). Patients with late diagnosis had an average of 6 years in the health system before their HCV diagnosis. In a comparison with patients without late diagnosis, hospitalization (59% versus 35%) and death (33% versus 9%) were more frequent among patients with late diagnosis. Among all who died, mean (median) time from initial HCV diagnosis to death was 4.8 (4.2) years. CONCLUSION Many CHeCS patients had advanced liver disease concurrent with their initial HCV diagnosis despite many years of engagement with the healthcare system, and these patients had high rates of hospitalization and mortality.
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Affiliation(s)
| | - Jian Xing
- Division of Viral Hepatitis, CDC, Atlanta, GA
| | - Stephen Ko
- Division of Viral Hepatitis, CDC, Atlanta, GA
| | | | - Fujie Xu
- Division of Viral Hepatitis, CDC, Atlanta, GA
| | | | - Mei Lu
- Henry Ford Health System, Detroit, MI
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Sanal MG. Biomarkers in nonalcoholic fatty liver disease-the emperor has no clothes? World J Gastroenterol 2015; 21:3223-3231. [PMID: 25805928 PMCID: PMC4363751 DOI: 10.3748/wjg.v21.i11.3223] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2014] [Revised: 01/16/2015] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
Fatty liver is present in over ten percentage of the world population and it is a growing public health problem. Nonalcoholic fatty liver disease (NAFLD) is not a single disease, but encompasses a spectrum of diseases of different etiologies. It is difficult to find highly specific and sensitive diagnostic biomarkers when a disease is very complex. Therefore, we should aim to find relevant prognostic markers rather than accurate diagnostic markers which will help to minimize the frequency of liver biopsies to evaluate disease progression. There are several biomarker panels commercially available, however, there is no clear evidence that more sophisticated panels are better compared to simple criteria such as, presence of diabetes over five years, metabolic syndrome, obesity, obstructive sleep apnea, aspartate transaminase/alanine transaminase (ALT) ratio > 0.8 or ferritin levels > 1.5 times normal in patients with over six month history of raised ALT and/or ultrasonological evidence of fat in the liver. Currently the biomarker panels are not a replacement for a liver biopsy. However the need and benefit of liver biopsy in NAFLD is questionable because there is no convincing evidence that biopsy and detailed staging of NAFLD improves the management of NAFLD and benefits the patient. After all there is no evidence based treatment for NAFLD other than management of lifestyle and components of “metabolic syndrome”.
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Abdollahi M, Pouri A, Ghojazadeh M, Estakhri R, Somi M. Non-invasive serum fibrosis markers: A study in chronic hepatitis. ACTA ACUST UNITED AC 2015; 5:17-23. [PMID: 25901293 PMCID: PMC4401163 DOI: 10.15171/bi.2015.05] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Revised: 12/05/2014] [Accepted: 01/04/2015] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Chronic hepatitis is specified as inflammatory disease of the liver lasting for more than six months. Role of noninvasive fibrosis markers as prognostication factors of the presence or absence of significant fibrosis on liver biopsy of patients with chronic hepatitis is the aim of this study. METHODS Two hundred twenty-one patients with chronic hepatitis involved in the study between 2011 and 2013. Routine biochemical indices and serum fibrosis markers such as aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI) and Fibrosis 4 score (FIB-4) were evaluated, and the histological grade and stage of the liver biopsy specimens were scored according to the Ishak scoring system. Diagnostic accuracies of these markers for prediction of significant fibrosis were assessed by Receiver Operating Characteristic (ROC) curve analysis. RESULTS Contemporaneous laboratory indices for imputing AAR, APRI, and FIB-4 were identified with liver biopsies. From all, 135 males (61.1%) and 86 females (38.9%), with mean age of 39.6±14.4 were studied. Significant correlation between stages of fibrosis and FIB-4, APRI and AAR were detected, with a correlation coefficient higher than that of other markers in the patients with Hepatitis B (r = 0.46), C (r = 0.58) and autoimmune hepatitis (r = 0.28). FIB-4 (AUROC = 0.84) and APRI (AUROC = 0.78) were superior to AAR at distinguishing severe fibrosis from mild-to-moderate fibrosis and gave the highest diagnostic accuracy. CONCLUSION Application of these markers was good at distinguishing significant fibrosis and decreased the need for staging liver biopsy specimens among patients with chronic hepatitis.
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Affiliation(s)
| | - Aliasghar Pouri
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Morteza Ghojazadeh
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rasoul Estakhri
- Department of Pathology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammadhossein Somi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Saito M, Yano Y, Hirano H, Momose K, Yoshida M, Azuma T. Serum NX-DCP as a New Noninvasive Model to Predict Significant Liver Fibrosis in Chronic Hepatitis C. HEPATITIS MONTHLY 2015; 15:e22978. [PMID: 25788955 PMCID: PMC4350249 DOI: 10.5812/hepatmon.22978] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Revised: 11/11/2014] [Accepted: 01/03/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Finding a noninvasive method to predict liver fibrosis using inexpensive and easy-to-use markers is important. OBJECTIVES We aimed to clarify whether NX-des-γ-carboxyprothrombin (NX-DCP) could become a new noninvasive model to predict liver fibrosis in hepatitis C virus (HCV) related liver disease. PATIENTS AND METHODS We performed a prospective cohort study on a consecutive group of 101 patients who underwent liver biopsy for HCV-related liver disease at Kobe University Hospital. Laboratory measurements were performed on the same day as the biopsy. Factors associated with significant fibrosis (F3-4) were assessed by multivariate analyses. A comparison of predictive ability between multivariate factors and abovementioned noninvasive models was also performed. RESULTS Increase in serum NX-DCP was significantly related to increase in fibrosis stage (P = 0.006). Moreover, NX-DCP was a multivariate factor associated with the presence of significant fibrosis F 3-4 (median 21 of F0-2 group vs. median 22 of F3-4 group with P = 0.002). The AUC of NX-DCP showed no significant differences compared with those of the AST-to-platelet ratio index (APRI), modified-APRI, the Göteborg University Cirrhosis Index (GUCI), the Lok index, the Hui score, cirrhosis discriminating score (CDS) and the Pohl score (P > 0.05). CONCLUSIONS NX-DCP correlated positively with fibrosis stage and could discriminate well between HCV-related patients with or without significant fibrosis. Moreover, NX-DCP had a similar predictive ability to the abovementioned models, and thereby could be a new noninvasive prediction tool for fibrosis.
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Affiliation(s)
- Masaya Saito
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- Corresponding Author: Masaya Saito, Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. Tel: +81-783826305, Fax: +81-783826309, E-mail:
| | - Yoshihiko Yano
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hirotaka Hirano
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kenji Momose
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masaru Yoshida
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- Division of Metabolomics Research, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takeshi Azuma
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
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Li J, Gordon SC, Rupp LB, Zhang T, Boscarino JA, Vijayadeva V, Schmidt MA, Lu M. The validity of serum markers for fibrosis staging in chronic hepatitis B and C. J Viral Hepat 2014; 21:930-7. [PMID: 24472062 DOI: 10.1111/jvh.12224] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Accepted: 10/30/2013] [Indexed: 12/16/2022]
Abstract
Assessment of liver fibrosis is critical for successful individualized disease management in persons with chronic hepatitis B (CHB) or chronic hepatitis C (CHC). We expanded and validated serum marker indices to provide accurate, reproducible and easily applied methods of fibrosis assessment. Liver biopsy results from over 284 CHB and 2304 CHC patients in the Chronic Hepatitis Cohort Study ('CHeCS') were mapped to a F0-F4 equivalent scale. APRI and FIB-4 scores within a 6-month window of biopsy were mapped to the same scale. A novel algorithm was applied to derive and validate optimal cut-offs for differentiating fibrosis levels. For the prediction of advanced fibrosis and cirrhosis, the FIB-4 score outperformed the other serum marker indices in the CHC cohort and was similar to APRI in the CHB cohort. The area under the receiver operating characteristic curves (AUROC) for FIB-4 in differentiating F3-F4 from F0-F2 was 0.86 (95% CI: 0.80-0.92) for CHB and 0.83 (95% CI: 0.81-0.85) for CHC. The suggested cut-offs based on FIB-4 model produced high positive predictive values [CHB: 90.0% for F0-F2, 100.0% for cirrhosis (F4); CHC: 89.7% for F0-F2; 82.9% for cirrhosis (F4)]. In this large observational cohort, FIB-4 predicted the upper and lower end of liver fibrosis stage (cirrhosis and F0-F2, respectively) with a high degree of accuracy in both CHB and CHC patients.
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Affiliation(s)
- J Li
- Henry Ford Health System, Detroit, MI, USA
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Impact of contacting study authors to obtain additional data for systematic reviews: diagnostic accuracy studies for hepatic fibrosis. Syst Rev 2014; 3:107. [PMID: 25239493 PMCID: PMC4185334 DOI: 10.1186/2046-4053-3-107] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 08/29/2014] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Seventeen of 172 included studies in a recent systematic review of blood tests for hepatic fibrosis or cirrhosis reported diagnostic accuracy results discordant from 2 × 2 tables, and 60 studies reported inadequate data to construct 2 × 2 tables. This study explores the yield of contacting authors of diagnostic accuracy studies and impact on the systematic review findings. METHODS Sixty-six corresponding authors were sent letters requesting additional information or clarification of data from 77 studies. Data received from the authors were synthesized with data included in the previous review, and diagnostic accuracy sensitivities, specificities, and positive and likelihood ratios were recalculated. RESULTS Of the 66 authors, 68% were successfully contacted and 42% provided additional data for 29 out of 77 studies (38%). All authors who provided data at all did so by the third emailed request (ten authors provided data after one request). Authors of more recent studies were more likely to be located and provide data compared to authors of older studies. The effects of requests for additional data on the conclusions regarding the utility of blood tests to identify patients with clinically significant fibrosis or cirrhosis were generally small for ten out of 12 tests. Additional data resulted in reclassification (using median likelihood ratio estimates) from less useful to moderately useful or vice versa for the remaining two blood tests and enabled the calculation of an estimate for a third blood test for which previously the data had been insufficient to do so. We did not identify a clear pattern for the directional impact of additional data on estimates of diagnostic accuracy. CONCLUSIONS We successfully contacted and received results from 42% of authors who provided data for 38% of included studies. Contacting authors of studies evaluating the diagnostic accuracy of serum biomarkers for hepatic fibrosis and cirrhosis in hepatitis C patients impacted conclusions regarding diagnostic utility for two blood tests and enabled the calculation of an estimate for a third blood test. Despite relatively extensive efforts, we were unable to obtain data to resolve discrepancies or complete 2 × 2 tables for 62% of studies.
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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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Silva Junior RG, Schmillevitch J, Nascimento MDFA, Miranda MLQ, Brant PEAC, Schulz PO, Vieira A, Szutan LA. Acoustic radiation force impulse elastography and serum fibrosis markers in chronic hepatitis C. Scand J Gastroenterol 2014; 49:986-92. [PMID: 24742130 DOI: 10.3109/00365521.2014.909528] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Liver biopsy (LB) remains the gold standard for the assessment of liver fibrosis, although it is invasive and can have complications. The present study compares several noninvasive methods of fibrosis assessment in chronic hepatitis C (CHC), including acoustic radiation force impulse (ARFI) elastography, aspartate aminotransferase:platelet ratio index (APRI), Forns, FIB-4, and King scores versus percutaneous LB. MATERIAL AND METHODS This prospective study enrolled 51 untreated CHC patients. Biological tests necessary for the calculation of the scores (according to the classic formulas) were performed within a week of LB. The time interval between LB and tissue stiffness, assessed according to the Metavir score, was <6 months. Cutoff values were determined using area under receiver-operating characteristic curves (AUROC). RESULTS The best test for predicting significant fibrosis (F ≥2 Metavir) was ARFI elastography with an AUROC of 0.90, followed by FIB-4 (AUROC = 0.86), King (AUROC = 0.85), Forns (AUROC = 0.84), and APRI (AUROC = 0.82). For a cutoff of 1.31 m/s, ARFI had 89.3% sensitivity (Se) and 87% specificity (Sp). The best test for predicting cirrhosis was ARFI elastography with an AUROC of 0.98, followed by FIB-4 (AUROC = 0.94), King (AUROC = 0.90), APRI (AUROC = 0.82), and Forns (AUROC = 0.81). For a cutoff of 1.95 m/s, ARFI had 100% Se and 95.2% Sp. CONCLUSION ARFI elastography had very good accuracy for the assessment of liver fibrosis. It was more effective than APRI, Forns, King, and FIB-4 scores for the prediction of significant fibrosis and cirrhosis in CHC patients.
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Affiliation(s)
- Roberto Gomes Silva Junior
- Liver and Portal Hypertension Group, Santa Casa de São Paulo School of Medical Sciences , São Paulo , Brazil
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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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Lim JK, Tate JP, Fultz SL, Goulet JL, Conigliaro J, Bryant KJ, Gordon AJ, Gibert C, Rimland D, Goetz MB, Klein MB, Fiellin DA, Justice AC, Lo Re V. Relationship between alcohol use categories and noninvasive markers of advanced hepatic fibrosis in HIV-infected, chronic hepatitis C virus-infected, and uninfected patients. Clin Infect Dis 2014; 58:1449-58. [PMID: 24569533 DOI: 10.1093/cid/ciu097] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND It is unclear if the risk of liver disease associated with different levels of alcohol consumption is higher for patients infected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV). We evaluated associations between alcohol use categories and advanced hepatic fibrosis, by HIV and chronic HCV status. METHODS We performed a cross-sectional study among participants in the Veterans Aging Cohort Study who reported alcohol consumption at enrollment (701 HIV/HCV-coinfected; 1410 HIV-monoinfected; 296 HCV-monoinfected; 1158 HIV/HCV-uninfected). Alcohol use category was determined by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and alcohol-related diagnoses and was classified as nonhazardous drinking, hazardous/binge drinking, or alcohol-related diagnosis. Advanced hepatic fibrosis was defined by FIB-4 index >3.25. RESULTS Within each HIV/HCV group, the prevalence of advanced hepatic fibrosis increased as alcohol use category increased. For each alcohol use category, advanced hepatic fibrosis was more common among HIV-infected than uninfected (nonhazardous: 6.7% vs 1.4%; hazardous/binge: 9.5% vs 3.0%; alcohol-related diagnosis: 19.0% vs 8.6%; P < .01) and chronic HCV-infected than uninfected (nonhazardous: 13.6% vs 2.5%; hazardous/binge: 18.2% vs 3.1%; alcohol-related diagnosis: 22.1% vs 6.5%; P < .01) participants. Strong associations with advanced hepatic fibrosis (adjusted odds ratio [95% confidence interval]) were observed among HIV/HCV-coinfected patients with nonhazardous drinking (14.2 [5.91-34.0]), hazardous/binge drinking (18.9 [7.98-44.8]), and alcohol-related diagnoses (25.2 [10.6-59.7]) compared with uninfected nonhazardous drinkers. CONCLUSIONS Advanced hepatic fibrosis was present at low levels of alcohol consumption, increased with higher alcohol use categories, and was more prevalent among HIV-infected and chronic HCV-infected patients than uninfected individuals. All alcohol use categories were strongly associated with advanced hepatic fibrosis in HIV/HCV-coinfected patients.
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Affiliation(s)
- Joseph K Lim
- Veterans Affairs (VA) Connecticut Healthcare System, West Haven
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