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Liguori A, Zoncapè M, Casazza G, Easterbrook P, Tsochatzis EA. Staging liver fibrosis and cirrhosis using non-invasive tests in people with chronic hepatitis B to inform WHO 2024 guidelines: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2025; 10:332-349. [PMID: 39983746 DOI: 10.1016/s2468-1253(24)00437-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 12/14/2024] [Accepted: 12/18/2024] [Indexed: 02/23/2025]
Abstract
BACKGROUND Non-invasive tests (aspartate aminotransferase-to-platelet ratio index [APRI] and transient elastography [FibroScan]) were recommended in the 2015 WHO guidelines to guide treatment decisions in people with chronic hepatitis B. We updated the systematic review and meta-analysis that informed the 2015 guidelines to inform new cutoffs for non-invasive tests for the diagnosis of significant fibrosis and cirrhosis for the 2024 WHO guidelines for chronic hepatitis B. METHODS We searched PubMed (MEDLINE), Embase, and Science Citation Index Expanded (Web of Science) for studies published in any language between Jan 1, 2014, and Feb 15, 2023. We included all studies that reported cross-sectional data on the staging of fibrosis or cirrhosis with APRI, Fibrosis-4 (FIB-4), and FibroScan compared with liver biopsy as the reference standard in people with chronic hepatitis B. We excluded studies in which the maximum interval between liver biopsy and non-invasive fibrosis test was more than 6 months; that reported on fewer than ten patients with advanced fibrosis or cirrhosis; that were done exclusively in children; and did not report diagnostic accuracy across our prespecified ranges of test cutoffs. The results of this updated search were collated with the meta-analysis that informed the 2015 guidelines. Outcomes of interest were the sensitivity and specificity of non-invasive tests using defined index test cutoffs for detecting significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4) based on the METAVIR staging system. We performed meta-analyses using a bivariate random-effects model. FINDINGS Of 19 933 records identified by our search strategy, 195 were eligible for our systematic review and combined with the 69 studies from the previous meta-analysis to total 264. Two studies were at low risk of bias, 31 studies had unclear risk of bias, and 231 studies had a high risk of bias. Of these 264, 211 studies with 61 665 patients were used in the meta-analysis. For the diagnosis of significant fibrosis (≥F2), sensitivity and specificity were 72·9% (95% CI 70·2-75·5) and 64·7% (95% CI 61·0-68·2) for the APRI low cutoff (>0·3 to 0·7), 30·5% (23·7-38·3) and 92·3% (89·3-94·6) for the APRI high cutoff (>1·3 to 1·7), and 75·1% (72·2-77·7) and 79·3% (76·2-82·2) for FibroScan (>6·0 to 8·0 kPa), respectively. For the diagnosis of cirrhosis (F4), sensitivity and specificity were 59·4% (53·2-65·2) and 73·9% (70·1-77·4) for the APRI low cutoff (>0·8 to 1·2), 30·2% (24·2-36·9) and 88·2% (85·4-90·6) for the APRI high cutoff (>1·8 to 2·2), and 82·6% (77·8-86·5) and 89·0% (86·3-91·2) for FibroScan (>11·0 to 14·0 kPa), respectively. Using a hypothetical population of 1000 unselected patients with chronic hepatitis B with a 25% prevalence of significant fibrosis (≥F2), the APRI low cutoff for significant fibrosis (≥F2) would result in 262 (26·2%) false positives but only 68 (6·8%) false negatives. The FibroScan cutoff would result in 158 (15·8%) false positives and 63 (6·3%) false negatives. In a population with a 5% prevalence of cirrhosis (F4), the APRI low cutoff for cirrhosis (F4) would result in 247 (24·7%) false positives and 21 (2·1%) false negatives and the FibroScan cutoff would result in 105 (10·5%) false positives and nine (0·9%) false negatives. INTERPRETATION These findings have informed new thresholds of APRI and FibroScan for diagnosis of significant fibrosis and cirrhosis in the 2024 WHO guidelines on chronic hepatitis B, with an APRI score greater than 0·5 or a FibroScan value greater than 7·0 kPa considered to identify most adults with significant fibrosis (≥F2) and an APRI score greater than 1·0 or a FibroScan value greater than 12·5 kPa to identify most adults with cirrhosis (F4). These patients are a priority for antiviral treatment. FUNDING WHO.
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Affiliation(s)
- Antonio Liguori
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London, UK; Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
| | - Mirko Zoncapè
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London, UK; Liver Unit, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giovanni Casazza
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Philippa Easterbrook
- Department of Global HIV, Hepatitis and STI Programmes, World Health Organization, Geneva, Switzerland
| | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London, UK.
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Patel K, Asrani SK, Fiel MI, Levine D, Leung DH, Duarte-Rojo A, Dranoff JA, Nayfeh T, Hasan B, Taddei TH, Alsawaf Y, Saadi S, Majzoub AM, Manolopoulos A, Alzuabi M, Ding J, Sofiyeva N, Murad MH, Alsawas M, Rockey DC, Sterling RK. Accuracy of blood-based biomarkers for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline. Hepatology 2025; 81:358-379. [PMID: 38489517 DOI: 10.1097/hep.0000000000000842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 02/19/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND AND AIMS Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease. APPROACH AND RESULTS We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in HBV and HCV, HIV-HCV/HBV coinfection, and NAFLD. Positive (LR+) and negative (LR-) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86, respectively; LR+ and LR- for NAFLD F2-4, F3-4, and F4 were 2.65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15, respectively. Overall, the proportional odds ratio indicated FIB-4 <1.45 was better than aspartate aminotransferase-to-platelet ratio index <0.5 for F2-4. FIB-4 >3.25 was also better than aspartate aminotransferase-to-platelet ratio index >1.5 for F3-4 and F4. There was limited data for combined tests. CONCLUSIONS Blood-based biomarkers are associated with small-to-moderate change in pretest probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV coinfection, and NAFLD, with limited comparative or combination studies for other chronic liver diseases.
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Affiliation(s)
- Keyur Patel
- Department of Medcine, Division of Gastroenterology and Hepatology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Sumeet K Asrani
- Department of Medicine, Division of Hepatology, Baylor University Medical Center, Dallas, Texas, USA
| | - Maria Isabel Fiel
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Deborah Levine
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Daniel H Leung
- Department of Pediatrics, Baylor College of Medicine and Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern Medicine and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Jonathan A Dranoff
- Yale School of Medicine, Department of Internal Medicine, Section of Digestive Diseases, New Haven, Connecticut, USA
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Tarek Nayfeh
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar Hasan
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Tamar H Taddei
- Yale School of Medicine, Department of Internal Medicine, Section of Digestive Diseases, New Haven, Connecticut, USA
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Yahya Alsawaf
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Samer Saadi
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Muayad Alzuabi
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Jingyi Ding
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Nigar Sofiyeva
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Mohammad H Murad
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Mouaz Alsawas
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
- Department of Medicine, Section of Hepatology, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Don C Rockey
- Department of Medicine, Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Richard K Sterling
- Department of Medicine, Section of Hepatology, Virginia Commonwealth University, Richmond, Virginia, USA
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Liu X, Zhang W, Ma B, Lv C, Sun M, Shang Q. The value of serum Mac-2 binding protein glycosylation isomer in the diagnosis of liver fibrosis: a systematic review and meta-analysis. Front Physiol 2024; 15:1382293. [PMID: 39558944 PMCID: PMC11570841 DOI: 10.3389/fphys.2024.1382293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 09/30/2024] [Indexed: 11/20/2024] Open
Abstract
Background The early detection and intervention of liver fibrosis (LF) in patients with chronic liver disease is critical to their management. The accuracy of serum Mac-2 binding protein glycosylation isomer (M2BPGi) in the diagnosis of LF remains controversial. This study aimed to comprehensively assess the value of serum M2BPGi in diagnosing LF. Methods The PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library databases were searched. The effect values were combined using a random-effects model. Meta-regression and subgroup analysis were used to explore the sources of heterogeneity. In addition, publication bias assessment and sensitivity analysis were conducted. Results This study includes 12 studies with 2,416 patients. The pooled sensitivity, specificity, and AUROC of M2BPGi in the diagnosis of significant fibrosis (≥F2) were 0.65 (95% CI: 0.57-0.71), 0.79 (95% CI: 0.72-0.84), and 0.78 (95% CI: 0.74-0.81), respectively, while those for predicting extensive fibrosis (≥F3) were 0.76 (95% CI: 0.71-0.80), 0.75 (95% CI: 0.68-0.81), and 0.81 (95% CI: 0.77-0.84). Sensitivity analysis indicated stable results in this study. The disease type, cut-off values, study country, average age, and male proportion were the sources of heterogeneity in diagnosing significant fibrosis of M2BPGi (p < 0.05). Sample size, disease type, study country, publication year, cut-off values, average age, and male proportion were important sources of heterogeneity in diagnosing extensive fibrosis (p < 0.05). Conclusion Serum M2BPGi has good diagnostic performance for significant fibrosis and extensive fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), or nonalcoholic fatty liver disease (NAFLD) and is an effective, non-invasive, and convenient marker. Systematic Review Registration https://inplasy.com/inplasy-2023-10-0086/.
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Affiliation(s)
- Xinyu Liu
- College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Wei Zhang
- Department of Liver Disease, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China
| | - Baofeng Ma
- The third department of encephalopathy, Jinan Integrated Traditional Chinese and Western Medicine Hospital, Jinan, China
| | - Chunlei Lv
- Diagnosis and Treatment Center for Liver Diseases, Tai’an 88 Hospital, Taian, China
| | - Mimi Sun
- Diagnosis and Treatment Center for Liver Diseases, Tai’an 88 Hospital, Taian, China
| | - Qinghua Shang
- Department of Liver Disease, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China
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Bestari MB, Haryono H, Wijaya MP, Girawan D, Agustanti N, Nugraha ES. Revisiting Mac-2-Binding Protein Glycosylation Isomer (M2BPGi) for Diagnosing High-Risk Liver Fibrosis in Chronic Hepatitis B Patients: A Stepwise Diagnostic Analysis. F1000Res 2024; 13:280. [PMID: 39099607 PMCID: PMC11294808 DOI: 10.12688/f1000research.147153.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/10/2024] [Indexed: 08/06/2024] Open
Abstract
Background The level of liver fibrosis is the basis for the treatment of chronic hepatitis B (CHB), and it is necessary to adapt non-invasive liver fibrosis modalities. We aimed to investigate the use of M2BPGi as a single or combined diagnostic modality for liver fibrosis in CHB patients through a stepwise diagnostic analysis. Methods Cross-sectional data were taken from patients between October 2021 and August 2022. Demographic data, blood profile, liver function, and liver stiffness were measured in CHB patients over 18 years old, willing to take part in the research, and had complete data. APRI, FIB-4, and AAR were calculated using the well-known formulas. Serum M2BPGi-levels were converted into a cut-off index (COI). The patients were divided into low-risk (LR) and high-risk fibrosis (HR) groups. A cut-off for each predictor variable to differentiate between the LR and HR groups was determined. The obtained cut-off was assessed for its association with the grouping of liver elastography results. Models to diagnose the liver stiffness measurement (LSM) ≥8 kPa were created and compared through multivariate and ROC analyses. Results The number of patients that met the inclusion and exclusion criteria was 143 (HR = 65, LR = 78). The cut-off for diagnosing LSM ≥8kPa was 0.311, 0.742, 0.635, and 1.434 for APRI, FIB-4, AAR, and M2BPGi, respectively. This cut-off was significantly associated with the results of the HR and LR groupings. A multivariate analysis found that FIB4, AAR, and M2BPGi added significantly to the model. Statistically, the most optimal use of M2BPGi was combined with FIB-4, with an AUC of 0.835. Conclusions The optimal cut-off of M2BPGi for diagnosing high-risk liver fibrosis in this study was 1.434. M2BPGi should be used with FIB-4 as a diagnostic tool for diagnosing liver fibrosis, especially in the absence of a liver biopsy or elastography.
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Affiliation(s)
| | - Haryono Haryono
- Internal Medicine, Padjadjaran University, Bandung, West Java, 40161, Indonesia
| | | | - Dolvy Girawan
- Internal Medicine, Padjadjaran University, Bandung, West Java, 40161, Indonesia
| | - Nenny Agustanti
- Internal Medicine, Padjadjaran University, Bandung, West Java, 40161, Indonesia
| | - Eka Surya Nugraha
- Internal Medicine, Padjadjaran University, Bandung, West Java, 40161, Indonesia
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Vincent JP, Ndow G, Ogawa S, Ceesay A, Njie R, Sanneh B, Baldeh I, D’Alessandro U, Mendy M, Thursz M, Chemin I, Tanaka Y, Lemoine M, Shimakawa Y. Mac-2 binding protein glycosylation isomer (M2BPGi) to evaluate liver fibrosis and cancer in HBV-infected patients in West Africa. J Glob Health 2022; 12:04076. [PMID: 36370422 PMCID: PMC9653177 DOI: 10.7189/jogh.12.04076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND To reduce mortality associated with hepatitis B virus (HBV) infection, timely detection of cirrhosis and early-stage hepatocellular carcinoma (HCC) is essential. In low-income countries, however, HBV-infected people have limited access to liver histopathology, a reference test. Recently, Asian studies have suggested the usefulness of an inexpensive serum biomarker called Mac-2 binding protein glycosylation isomer (M2BPGi) in staging liver fibrosis and predicting HCC in HBV-infected patients. METHODS We systematically searched PubMed for studies examining the performance of M2BPGi in staging liver fibrosis in HBV-infected people, published up to September 21, 2021, to elucidate the knowledge gap. We then conducted a cross-sectional study of 339 HBV-infected patients in The Gambia (cirrhosis = 65, HCC = 73, non-cirrhosis non-HCC = 201). We evaluated the association of M2BPGi with cirrhosis and HCC by computing odds ratios (ORs) derived from logistic regression. We also assessed the performance of M2BPGi to stage liver fibrosis in 49 patients who underwent liver biopsy (derivation set) and 217 patients with transient elastography (validation set). Using the derivation set we drew the receiver operating characteristics (ROC) curves to identify optimal M2BPGi thresholds to indicate significant fibrosis and cirrhosis using biopsy as a reference. We then applied these cut-offs to the validation set to obtain its sensitivity and specificity for indicating significant fibrosis and cirrhosis using transient elastography as a reference. RESULTS The systematic review identified 13 studies, all of which were conducted in East Asia and none in Africa. In The Gambia, positive M2BPGi was significantly associated with both cirrhosis (adjusted OR = 7.8, 95% CI = 3.1-19.7) and HCC (adjusted OR = 10.1, 2.6-40.2). The areas under the ROC curve (AUROC) in the derivation and validation set were 0.62 and 0.78, respectively, to diagnose significant fibrosis, and 0.80 and 0.89, respectively, to diagnose cirrhosis. By applying the optimal cut-offs, the sensitivity and specificity in the validation set were 61.5% and 93.4%, respectively, to diagnose significant fibrosis, and 72.5% and 92.2%, respectively, for cirrhosis. CONCLUSIONS To the best of our knowledge, this is the first evaluation of M2BPGi in HBV-infected African population. The findings supported its accuracy in the diagnosis of cirrhosis in HBV-infected patients in West Africa.
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Affiliation(s)
| | - Gibril Ndow
- Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom
- Disease Control & Elimination, MRC Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Shintaro Ogawa
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Amie Ceesay
- Disease Control & Elimination, MRC Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Ramou Njie
- Edward Francis Small Teaching Hospital, Banjul, The Gambia
- School of Medicine & Allied Health Sciences, University of The Gambia, Serekunda, The Gambia
| | - Bakary Sanneh
- National Public Health Laboratories, Ministry of Health, Serekunda, The Gambia
| | - Ignatius Baldeh
- National Public Health Laboratories, Ministry of Health, Serekunda, The Gambia
| | - Umberto D’Alessandro
- Disease Control & Elimination, MRC Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Maimuna Mendy
- International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France
| | - Mark Thursz
- Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom
| | - Isabelle Chemin
- INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie, Université Claude Bernard, Lyon, France
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Maud Lemoine
- Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom
| | - Yusuke Shimakawa
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France
- International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan
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Lian MJ, Chen ZQ, Wang QM, Zheng GS, Hong GL. Diagnostic accuracy of mac-2-binding protein glycosylation isomer for diagnosing hepatitis B-related fibrosis: A meta-analysis. J Dig Dis 2022; 23:550-560. [PMID: 36251470 DOI: 10.1111/1751-2980.13140] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/24/2022] [Accepted: 10/13/2022] [Indexed: 12/30/2022]
Abstract
OBJECTIVES Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis. The aim of this meta-analysis was to evaluate the accuracy of M2BPGi for predicting hepatitis B virus (HBV)-related liver fibrosis. METHODS EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure, SinoMED, VIP Database for Chinese Technical Periodicals databases were searched comprehensively for articles published up to March 2022. Quality assessment was carried out in accordance with the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The pooled diagnostic estimates including sensitivity, specificity, the area under the summary receiver operating characteristic curve (AUROC) were calculated. Before pooling the estimates, the threshold effect was assessed. Subgroup analysis was performed as well. RESULTS In all, 11 studies including 1836 patients were included. None of the 11 studies met all the criteria of QUADAS-2. The threshold effect was found (r = 0.757, P = 0.011) for predicting HBV-related severe fibrosis. The sensitivity, specificity and AUROC of M2BPGi for the prediction of significant fibrosis were 0.68 (0.65-0.71), 0.67 (0.64-0.70) and 0.741, respectively, while those for predicting cirrhosis were 0.65 (0.57-0.72), 0.79 (0.77-0.81) and 0.792. Additionally, the AUROC of M2BPGi for predicting severe fibrosis reached 0.766. No publication bias was observed. The results of subgroup analyses were similar to the overall results. CONCLUSIONS M2BPGi has moderate diagnostic accuracy for predicting HBV-related significant fibrosis, severe fibrosis, and cirrhosis. Further studies stratified by etiology, liver inflammation, treatment, etc, are urgently needed.
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Affiliation(s)
- Ming Jian Lian
- Department of Clinical Laboratory, Xiamen Key Laboratory of Genetic Testing, The First Affiliated Hospital Of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian Province, China
| | - Zhi Qi Chen
- Department of Clinical Laboratory, Xiamen Key Laboratory of Genetic Testing, The First Affiliated Hospital Of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian Province, China
| | - Qian Ming Wang
- Department of Clinical Laboratory, Xiamen Key Laboratory of Genetic Testing, The First Affiliated Hospital Of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian Province, China
| | - Gang Sen Zheng
- Department of Clinical Laboratory, Xiamen Key Laboratory of Genetic Testing, The First Affiliated Hospital Of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian Province, China
| | - Guo Lin Hong
- Department of Clinical Laboratory, Xiamen Key Laboratory of Genetic Testing, The First Affiliated Hospital Of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian Province, China
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Jang TY, Huang CF, Yeh ML, Huang CI, Dai CY, Tsai PC, Hsu PY, Wei YJ, Hou NJ, Liang PC, Lin YH, Wang CW, Hsieh MY, Lin ZY, Huang JF, Yu ML, Chuang WL. Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein expression predicts disease severity in nonalcoholic steatohepatitis patients. Kaohsiung J Med Sci 2022; 38:261-267. [PMID: 34786828 DOI: 10.1002/kjm2.12474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 10/05/2021] [Accepted: 10/15/2021] [Indexed: 01/18/2023] Open
Abstract
The role of Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) in the prediction of disease severity in nonalcoholic fatty liver disease (NAFLD) remains elusive. This study evaluated the performance of WFA+ -M2BP in predicting fibrosis in patients with NAFLD. A total of 80 patients with biopsy-proven nonalcoholic steatohepatitis (NASH) were enrolled. Serum WFA+ -M2BP levels were measured using standard methods. The fibrosis-4 (FIB-4) index was also measured. The mean values of WFA+ -M2BP were 1.0, 1.0, 0.8, and 2.2 in Metavir fibrosis stage F0, F1, F2, and F3-4, respectively (linear trend p = 0.005). The optimal cut-off value of WFA+ -M2BP in predicting advanced fibrosis (F3-4) was 1.37 cut-off index (COI), yielding the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy of 75.0, 79.4, 39.1, 94.7, and 78.7%, respectively (p < 0.001). Combining WFA+ -M2BP with FIB-4 significantly increased the diagnostic performance for advanced fibrosis, yielding specificity, PPV, and accuracy of 100, 100, and 93%, respectively. The significant factors predicting advanced liver fibrosis in the multivariate regression analysis were WFA+ -M2BP ≥ 1.37 COI (OR/confidence interval [CI]: 9.49/1.63-55.21, p = 0.01) and FIB-4 ≥ 2.80 (OR/CI: 38.18/4.89-297.93, p = 0.001). Monitoring WFA+ -M2BP is suitable for noninvasive assessment of liver fibrosis in NASH patients, particularly in combination with FIB-4.
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Affiliation(s)
- Tyng-Yuan Jang
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Po-Yau Hsu
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yi-Ju Wei
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Nai-Jen Hou
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chih-Wen Wang
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division and Hepatitis Center, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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8
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Lin MT, Chiu SYH, Chang KC, Li WF, Yong CC, Liu YW, Wang JH, Kuo FY, Huang CC, Wang CC, Hsiao CC, Hu TH. Significant association between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein and prognosis of hepatocellular carcinoma after surgical treatment. Am J Cancer Res 2022; 12:601-614. [PMID: 35261790 PMCID: PMC8899980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 01/10/2022] [Indexed: 06/14/2023] Open
Abstract
Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) is a novel marker for evaluating fibrosis and predicting the development of hepatocellular carcinoma (HCC). However, the role of WFA+-M2BP in the prognosis of HCC patients after curative surgery remains unknown. In this study, we aimed to evaluate the prognostic role of serum WFA+-M2BP in HCC patients after curative resection and liver transplantation. We enrolled 460 HCC patients (357 resection and 103 transplantation) to analyze the risk factors for HCC recurrence and patient's survival. We employed time-to-event models using univariate and multivariable Cox proportional hazards regression analyses and calculated the hazard ratios (HRs) and adjusted HRs with their corresponding 95% confidence intervals (CIs). The levels of WFA+-M2BP were 0.19-14.51 COI (median 1.08) in patients of hepatectomy and 0.47-19.90 COI (median 6.0) in transplant patients. The levels of WFA+-M2BP in liver transplant patients is much higher than that of hepatectomy patients. Overall, liver fibrotic stage was positively correlated to WFA+-M2BP levels (P<0.0001). This study demonstrated that elevated WFA+-M2BP level (COI ≥0.75) was associated with a higher HCC recurrence rate in the resection group (P<0.001). Survival analysis showed that an elevated WFA+-M2BP level (COI ≥1.43) is associated with a higher mortality risk after surgical resection (P=0.0088) in the univariate analysis only. In liver transplant patients, WFA+-M2BP level (COI ≥3.81) did not predict HCC recurrence at all, but was associated poor survival after transplantation, with a borderline significance (P=0.0943). Serum WFA+-M2BP is a reliable marker for liver fibrosis in the present study. It is also reliable marker to predict prognosis of HCC after surgical resection. However, the prognostic role of WFA+-M2BP in HCC related transplants is equivocal, which is different from that of surgical resection.
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Affiliation(s)
- Ming-Tsung Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung UniversityTaoyuan 33302, Taiwan
| | - Sherry Yueh-Hsia Chiu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
- Department of Health Care Management, College of Management and Healthy Aging Research Center, Chang Gung UniversityTaoyuan 33302, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
| | - Wei-Feng Li
- Department of Surgery, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
| | - Chee-Chien Yong
- Department of Surgery, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
| | - Yueh-Wei Liu
- Department of Surgery, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
| | - Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
| | - Fang-Ying Kuo
- Department of Pathology, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
| | - Chao-Cheng Huang
- Department of Pathology, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
| | - Chih-Chi Wang
- Department of Surgery, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
| | - Chang-Chun Hsiao
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung UniversityTaoyuan 33302, Taiwan
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan
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9
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Serum Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Can Predict Mild or Significant Liver Fibrosis in Non-alcoholic Fatty Liver Disease. HEPATITIS MONTHLY 2021. [DOI: 10.5812/hepatmon.115400] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: The serum levels of M2BPGi increase with liver fibrosis progression in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. However, the diagnostic performance of M2BPGi in non-alcoholic fatty liver disease (NAFLD) patients remains unclear. Objectives: To assess the severity of liver fibrosis in NAFLD patients and healthy controls by M2BPGi using acoustic radiation force impulse (ARFI) as the standard reference. Methods: Those suffering from NAFLD and healthy controls were recruited. NAFLD diagnosis was confirmed using fatty liver in imaging after excluding HCV, HBV, alcohol, drug, or other known causes of chronic liver disease. ARFI was used as the standard reference to determine the stage of liver fibrosis. Results: A total of 226 subjects were recruited, including 130 (57.5%) NAFLD patients who were divided into three groups according to the stage of liver fibrosis: F0, F1, and F ≥ 2. The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST to platelet ratio index (APRI), M2BPGi, and the fatty liver grade were significantly different between the three groups. The levels of M2BPGi were correlated with median ARFI value (P < 0.001), APRI (P = 0.011), and fibrosis 4 index (FIB-4) (P < 0.001). The area under the curve (AUC) of M2BPGi test was 0.58 for F ≥ 1 and 0.68 for F ≥ 2, respectively (P = 0.039 and P = 0.024). Conclusions: The M2BPGi levels were correlated with ARFI, APRI, and FIB-4 scores in this study population. The level of M2BPGi could predict mild (F ≥ 1) and significant liver fibrosis (F ≥ 2) in NAFLD patients, suggesting a surrogate marker to differentiate between normal, mild, and significant fibrosis.
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10
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Nascimento da Silva LC, Mendonça JSP, de Oliveira WF, Batista KLR, Zagmignan A, Viana IFT, Dos Santos Correia MT. Exploring lectin-glycan interactions to combat COVID-19: Lessons acquired from other enveloped viruses. Glycobiology 2021; 31:358-371. [PMID: 33094324 PMCID: PMC7665446 DOI: 10.1093/glycob/cwaa099] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 08/30/2020] [Accepted: 09/26/2020] [Indexed: 01/08/2023] Open
Abstract
The emergence of a new human coronavirus (SARS-CoV-2) has imposed great pressure on the health system worldwide. The presence of glycoproteins on the viral envelope opens a wide range of possibilities for application of lectins to address some urgent problems involved in this pandemic. In this work, we discuss the potential contributions of lectins from non-mammalian sources in the development of several fields associated with viral infections, most notably COVID-19. We review the literature on the use of non-mammalian lectins as a therapeutic approach against members of the Coronaviridae family, including recent advances in strategies of protein engineering to improve their efficacy. The applications of lectins as adjuvants for antiviral vaccines are also discussed. Finally, we present some emerging strategies employing lectins for the development of biosensors, microarrays, immunoassays and tools for purification of viruses from whole blood. Altogether, the data compiled in this review highlights the importance of structural studies aiming to improve our knowledge about the basis of glycan recognition by lectins and its repercussions in several fields, providing potential solutions for complex aspects that are emerging from different health challenges.
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Affiliation(s)
- Luís Cláudio Nascimento da Silva
- Programa de Pós-graduação em Biologia Microbiana, Laboratório de Patogenicidade Bacteriana, Universidade CEUMA, São Luís 65075-120, Brazil.,Programa de Pós-graduação em Biodiversidade e Biotecnologia da Amazônia Legal, Laboratório de Patogenicidade Bacteriana, Universidade CEUMA, São Luís 65075-120, Brazil
| | - Juliana Silva Pereira Mendonça
- Programa de Pós-graduação em Biologia Microbiana, Laboratório de Patogenicidade Bacteriana, Universidade CEUMA, São Luís 65075-120, Brazil
| | - Weslley Felix de Oliveira
- Departamento de Bioquímica, Centro de Biociências, Universidade Federal de Pernambuco, Recife 50.670-901, Brazil
| | - Karla Lílian Rodrigues Batista
- Programa de Pós-graduação em Biodiversidade e Biotecnologia da Amazônia Legal, Laboratório de Patogenicidade Bacteriana, Universidade CEUMA, São Luís 65075-120, Brazil
| | - Adrielle Zagmignan
- Programa de Pós-graduação em Biodiversidade e Biotecnologia da Amazônia Legal, Laboratório de Patogenicidade Bacteriana, Universidade CEUMA, São Luís 65075-120, Brazil
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11
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Yeh ML, Huang JF, Yu ML, Chuang WL. Hepatitis b infection: progress in identifying patients most likely to respond to peginterferon alfa. Expert Rev Gastroenterol Hepatol 2021; 15:427-435. [PMID: 33338385 DOI: 10.1080/17474124.2021.1866985] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 12/17/2020] [Indexed: 02/07/2023]
Abstract
Introduction: Despite the disadvantage of side effects, pegylated interferon alpha (Peg-IFN α) remains an indispensable agent for chronic hepatitis B (CHB) due to its immunomodulatory effect. The selection of a patient most likely to have a favorable response becomes an essential issue for Peg-IFN α therapy.Areas covered: Recent progress in the prediction of the treatment response to Peg-IFN α.Expert opinion: Before Peg-IFN α therapy, baseline host and viral factors, including female sex, younger age, a high alanine aminotransferase level, HBV genotype A or B, and low viral load, predict a favorable response. In addition, on-treatment viral kinetics of hepatitis B surface antigen (HBsAg), e antigen (HBeAg) and HBV DNA help clinicians determine whether to continue or discontinue Peg-IFN α therapy. The novel HBV markers hepatitis B core-related antigen and HBV RNA have recently been investigated as useful predictors. The limited efficacy of Peg-IFN α monotherapy facilitated the development of new strategies of 'add-on' or 'switch to' Peg-IFN α in patients receiving long-term nucleot(s)ide analog treatment, which may lead to an increase in HBeAg and HBsAg loss. In summary, tailored Peg-IFN α therapeutic strategies based on predictors extended the landscape for CHB treatment.
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Affiliation(s)
- Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, Lipid Science and Aging Research Center, and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, Lipid Science and Aging Research Center, and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, Lipid Science and Aging Research Center, and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, Lipid Science and Aging Research Center, and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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12
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Behairy OG, El-Gendy SA, Ibrahim DY, Mansour AI, El-Shimi OS. Mac-2 binding protein glycan isomer as noninvasive tool to assess liver fibrosis in children with chronic liver disease. Hepatol Res 2021; 51:277-283. [PMID: 33393720 DOI: 10.1111/hepr.13608] [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: 09/28/2020] [Revised: 11/03/2020] [Accepted: 12/04/2020] [Indexed: 12/19/2022]
Abstract
AIM This study is aimed to measure the value of serum Mac-2 binding protein glycan isomer (M2BPGI) in children with chronic liver diseases in comparison with liver biopsy and serum biomarkers. METHODS Comparative cross-sectional study included 100 children with chronic liver diseases and 50 healthy age/sex-matched control group. All subjects were evaluated via medical history, clinical, radiological and laboratory examinations. Liver biopsy was performed for studied patients and serum M2BPGI level was measured by Enzyme Linked Immune Sorbent Assay (ELISA) in all studied subjects. RESULTS Serum M2BPGI level increased more significantly in chronic liver disease patients (6.04 ± 2.72 ng/ml) than in healthy controls (1.12 ± 0.83 ng/ml) (P < 0.001). M2BPGI level was significantly elevated with progressive fibrosis (P < 0.001), and differed significantly between high and low Child-Pugh score, pediatric end-stage liver disease score and model for end-stage liver disease score score. Serum M2BPGI was correlated with serum biomarkers and degree of fibrosis in patients. CONCLUSION M2BPGI could be used as one of noninvasive tools for detecting and staging of hepatic fibrosis in Egyptian children with chronic liver disease.
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Affiliation(s)
- Ola G Behairy
- Department of Pediatrics, Faculty of Medicine, Benha University, Benha, Egypt
| | - Soha A El-Gendy
- Department of Pediatrics, Faculty of Medicine, Benha University, Benha, Egypt
| | | | - Amira I Mansour
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Benha University, Benha, Eygpt
| | - Ola S El-Shimi
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Benha University, Benha, Eygpt
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13
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Kimura Y, Taura K, Hai Nam N, Uemoto Y, Yoshino K, Ikeno Y, Okuda Y, Nishio T, Yamamoto G, Tanabe K, Koyama Y, Anazawa T, Fukumitsu K, Ito T, Yagi S, Kamo N, Seo S, Iwaisako K, Hata K, Imai T, Uemoto S. Utility of Mac-2 Binding Protein Glycosylation Isomer to Evaluate Graft Status After Liver Transplantation. Liver Transpl 2021; 27:403-415. [PMID: 32780942 DOI: 10.1002/lt.25870] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 07/12/2020] [Accepted: 07/28/2020] [Indexed: 01/13/2023]
Abstract
Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel liver fibrosis biomarker, but there are few studies on M2BPGi in liver transplantation (LT) recipients. This study aimed to evaluate the utility of M2BPGi measurement in LT recipients. We collected the clinicopathological data of 233 patients who underwent a liver biopsy at Kyoto University Hospital after LT between August 2015 and June 2019. The median values of M2BPGi in patients with METAVIR fibrosis stages F0, F1, F2, and ≥F3 were 0.61, 0.76, 1.16, and 1.47, respectively, whereas those in patients with METAVIR necroinflammatory indexes A0, A1, and ≥A2 were 0.53, 1.145, and 2.24, respectively. Spearman rank correlation test suggested that the necroinflammatory index had a stronger correlation to the M2BPGi value than the fibrosis stage. The area under the receiver operating characteristic curve of M2BPGi to predict ≥A1 was 0.75, which was significantly higher than that of any other liver fibrosis and inflammation marker. Patients with a rejection activity index (RAI) of ≥3 had a higher M2BPGi value than those with RAI ≤ 2 (P = 0.001). Patients with hepatitis C virus viremia had a higher M2BPGi value than sustained virological responders or those with other etiologies. In conclusion, the present study demonstrated that M2BPGi values are more strongly influenced by necroinflammatory activity and revealed M2BPGi, which has been thought to be a so-called fibrosis marker, as a disease activity marker in transplant recipients. M2BPGi measurement may be useful to detect early stage liver inflammation that cannot be detected by routine blood examination of LT recipients.
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Affiliation(s)
- Yusuke Kimura
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Nguyen Hai Nam
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Yusuke Uemoto
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Kenji Yoshino
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Yoshinobu Ikeno
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Yukihiro Okuda
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Takahiro Nishio
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Gen Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Kazutaka Tanabe
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Yukinori Koyama
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Takayuki Anazawa
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Ken Fukumitsu
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Takashi Ito
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Shintaro Yagi
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Naoko Kamo
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Satoru Seo
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Keiko Iwaisako
- Department of Medical Life Systems, Doshisha University, Kyoto, Japan
| | - Koichiro Hata
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Takumi Imai
- Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan
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14
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Yang HC, Su TH. Viral and Host Factors Affecting Disease Progression of Hepatitis B Virus Infection. HEPATITIS B VIRUS AND LIVER DISEASE 2021:205-230. [DOI: 10.1007/978-981-16-3615-8_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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15
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Tamaki N, Kurosaki M, Loomba R, Izumi N. Clinical Utility of Mac-2 Binding Protein Glycosylation Isomer in Chronic Liver Diseases. Ann Lab Med 2020; 41:16-24. [PMID: 32829576 PMCID: PMC7443525 DOI: 10.3343/alm.2021.41.1.16] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 06/15/2020] [Accepted: 07/29/2020] [Indexed: 12/15/2022] Open
Abstract
An accurate evaluation of liver fibrosis is clinically important in chronic liver diseases. Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum marker for liver fibrosis. In this review, we discuss the role of M2BPGi in diagnosing liver fibrosis in chronic hepatitis B and C, chronic hepatitis C after sustained virologic response (SVR), and nonalcoholic fatty liver disease (NAFLD). M2BPGi predicts not only liver fibrosis but also the hepatocellular carcinoma (HCC) development and prognosis in patients with chronic hepatitis B and C, chronic hepatitis C after SVR, NAFLD, and other chronic liver diseases. M2BPGi can also be used to evaluate liver function and prognosis in patients with cirrhosis. M2BPGi levels vary depending on the etiology and the presence or absence of treatment. Therefore, the threshold of M2BPGi for diagnosing liver fibrosis and predicting HCC development has to be adjusted according to the background and treatment status.
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Affiliation(s)
- Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,NAFLD Research Center, Division of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Rohit Loomba
- NAFLD Research Center, Division of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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16
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Wisteria floribunda agglutinin-positive Mac-2-binding protein as a diagnostic biomarker in liver cirrhosis: an updated meta-analysis. Sci Rep 2020; 10:10582. [PMID: 32601332 PMCID: PMC7324360 DOI: 10.1038/s41598-020-67471-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 06/04/2020] [Indexed: 02/05/2023] Open
Abstract
Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) had been suggested as a possible glycobiomarker for assessing liver fibrosis. Here, we conducted this updated meta-analysis to systematically investigate the predictive accuracy of WFA+-M2BP for diagnosing liver fibrosis and hepatocellular carcinoma (HCC) by comparing with multiple non-invasive indicators. We searched relevant literatures from Pubmed, Web of Science, EMBASE and Cochrane Library and enrolled 36 eligible studies involving 7,362 patients. Summary results were calculated using bivariate random effects model. The pooled sensitivities, specificities and areas under the summary receiver operating characteristic curves (AUSROCs) of WFA+-M2BP for identifying mild fibrosis, significant fibrosis, advanced fibrosis, cirrhosis, and HCC were 0.70/0.68/0.75, 0.71/0.75/0.79, 0.75/0.76/0.82, 0.77/0.86/0.88, and 0.77/0.80/0.85, respectively. The accuracy of WFA+-M2BP was strongly affected by etiology and it was not better than other non-invasive indicators for predicting early fibrosis. It showed similar diagnostic performance to hyaluronic acid and FibroScan for cirrhosis, but was equivalent to α-fetoprotein for HCC. In conclusion, WFA+-M2BP was suitable to diagnose late stage of liver fibrosis, especially cirrhosis. Individual cutoff value of WFA+-M2BP could be used to grade liver fibrosis in different etiology. Combined diagnostic model was suggested to improve its predictive accuracy for HCC.
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17
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Kim M, Jun DW, Park H, Kang BK, Sumida Y. Sequential Combination of FIB-4 Followed by M2BPGi Enhanced Diagnostic Performance for Advanced Hepatic Fibrosis in an Average Risk Population. J Clin Med 2020; 9:jcm9041119. [PMID: 32295166 PMCID: PMC7230806 DOI: 10.3390/jcm9041119] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/12/2020] [Accepted: 04/13/2020] [Indexed: 12/12/2022] Open
Abstract
The fibrosis-4 (FIB-4) index is the most widely used estimated formula to screen for advanced hepatic fibrosis; however, it has a considerable intermediate zone. Here, we propose an algorithm to reduce the intermediate zone and improve the diagnostic performance of screening for advanced liver fibrosis by incorporating Mac-2-binding protein glycan isomer (M2BPGi) into a FIB-4 based screening strategy in an average risk group. Four-hundred eighty-eight healthy and chronic liver disease subjects were analyzed using a 1:1 propensity score matched for age and sex. Advanced liver fibrosis (≥F3) was defined by magnetic resonance elastography (MRE, ≥3.6 kPa). Classification tree analysis was employed to improve diagnostic performance using a combination of the FIB-4 index and M2BPGi. The median serum M2BPGi levels of healthy subjects, patients without advanced fibrosis, and those with the condition were 0.48, 0.94, and 2.93, respectively. The area under the receiver operating characteristic (AUROC) curve of M2BPGi (0.918) for advanced fibrosis was the highest compared to those of the FIB-4 index (0.887), APRI (0.873), and AST/ALT ratio (0.794). When M2BPGi was incorporated following the FIB-4 index, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 87.1%, 82.5%, 54.0%, and 96.4%, respectively. Moreover, 74.3% (133/179) of cases in the intermediate zone of the FIB-4 index avoided unnecessary referrals. Two-step pathway (FIB-4 followed by M2BPGi) could reduce unnecessary referrals and/or liver biopsies in an average-risk population.
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Affiliation(s)
- Mimi Kim
- Department of Radiology, Hanyang University College of Medicine, Seoul 04763, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, Korea
- Correspondence: ; Tel.: +82 2 2290 8338; Fax: +82 2 972 0068
| | - Huiyul Park
- Department of Family medicine, Hanyang University College of Medicine, Seoul 04763, Korea
| | - Bo-Kyeong Kang
- Department of Radiology, Hanyang University College of Medicine, Seoul 04763, Korea
| | - Yoshio Sumida
- Centre for Digestive and Liver Diseases, Nara City Hospital, Nara 630-8305, Japan
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