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Tomino T, Itoh S, Toshima T, Yoshiya S, Bekki Y, Iseda N, Izumi T, Tsutsui Y, Toshida K, Yoshizumi T. Clinical validation of preoperative serum markers for liver fibrosis in living donor liver transplantation recipients. Surg Today 2025; 55:627-637. [PMID: 39317845 DOI: 10.1007/s00595-024-02941-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 09/05/2024] [Indexed: 09/26/2024]
Abstract
PURPOSE To validate the reliability of fibrosis markers as predictors of graft survival in living donor liver transplantation (LDLT) recipients. METHODS We reviewed data retrospectively, from 163 patients who underwent adult LDLT with preoperative measurements of type IV collagen (CIV), Mac-2 binding protein glycosylation isomer (M2BPGi), and hyaluronic acid (HA). Patients were divided into high and low groups for each biomarker, based on optimal cutoff values, and graft loss within 6 months was evaluated in each group. RESULTS The high CIV level group showed significantly lower 6-month graft survival rates and significantly higher rates of postoperative sepsis and sepsis from pneumonia. However, the groups with high and low M2BPGi levels and those with high and low HA levels did not show significant differences in 6-month graft survival rates or rates of postoperative sepsis. Multivariate analysis revealed that a CIV level ≥ 590 was a significant predictor of graft loss within 6 months, postoperative sepsis, and sepsis from pneumonia. CONCLUSION Unlike other fibrosis markers, preoperative CIV levels can predict graft survival, postoperative sepsis, and sepsis from pneumonia after LDLT.
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Affiliation(s)
- Takahiro Tomino
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Shohei Yoshiya
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yuki Bekki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Norifumi Iseda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Takuma Izumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yuriko Tsutsui
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Katsuya Toshida
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
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Wakabayashi S, Kimura T, Tamaki N, Iwadare T, Okumura T, Kobayashi H, Yamashita Y, Tanaka N, Kurosaki M, Umemura T. AI-Based Platelet-Independent Noninvasive Test for Liver Fibrosis in MASLD Patients. JGH Open 2025; 9:e70150. [PMID: 40191781 PMCID: PMC11969565 DOI: 10.1002/jgh3.70150] [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] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 03/14/2025] [Accepted: 03/21/2025] [Indexed: 04/09/2025]
Abstract
Background and Aim Noninvasive tests (NITs), such as platelet-based indices and ultrasound/MRI elastography, are widely used to assess liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). However, platelet counts are not routinely included in Japanese health check-ups, limiting their utility in large-scale screenings. Additionally, elastography, while effective, is costly and less accessible in routine practice. Most existing AI-based models incorporate these markers, restricting their applicability. This study aimed to develop a simple yet accurate AI model for liver fibrosis staging using only routine demographic and biochemical markers. Methods This retrospective study analyzed biopsy-proven data from 463 Japanese MASLD patients. Patients were randomly assigned to training (N = 370, 80%) and test (N = 93, 20%) cohorts. The AI model incorporated age, sex, BMI, diabetes, hypertension, hyperlipidemia, and routine blood markers (AST, ALT, γ-GTP, HbA1c, glucose, triglycerides, cholesterol). Results The Support Vector Machine model demonstrated high diagnostic performance, with an area under the curve (AUC) of 0.886 for detecting significant fibrosis (≥ F2). The AUCs for advanced fibrosis (≥ F3) and cirrhosis (F4) were 0.882 and 0.916, respectively. Compared to FIB-4, APRI, and FAST score (0.80-0.96), SVM achieved comparable accuracy while eliminating the need for platelet count or elastography. Conclusion This AI model accurately assesses liver fibrosis in MASLD patients without requiring platelet count or elastography. Its simplicity, cost-effectiveness, and strong diagnostic performance make it well-suited for large-scale health screenings and routine clinical use.
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Affiliation(s)
- Shun‐ichi Wakabayashi
- Department of Medicine, Division of GastroenterologyShinshu University School of MedicineMatsumotoJapan
| | - Takefumi Kimura
- Department of Medicine, Division of GastroenterologyShinshu University School of MedicineMatsumotoJapan
- Consultation Center for Liver DiseasesShinshu University HospitalMatsumotoJapan
| | - Nobuharu Tamaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Takanobu Iwadare
- Department of Medicine, Division of GastroenterologyShinshu University School of MedicineMatsumotoJapan
| | - Taiki Okumura
- Department of Medicine, Division of GastroenterologyShinshu University School of MedicineMatsumotoJapan
| | - Hiroyuki Kobayashi
- Department of Medicine, Division of GastroenterologyShinshu University School of MedicineMatsumotoJapan
| | - Yuki Yamashita
- Department of Medicine, Division of GastroenterologyShinshu University School of MedicineMatsumotoJapan
| | - Naoki Tanaka
- Department of Global Medical Research PromotionShinshu University Graduate School of MedicineMatsumotoJapan
- International Relations OfficeShinshu University School of MedicineMatsumotoJapan
- Research Center for Social SystemsShinshu UniversityMatsumotoJapan
| | - Masayuki Kurosaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Takeji Umemura
- Department of Medicine, Division of GastroenterologyShinshu University School of MedicineMatsumotoJapan
- Consultation Center for Liver DiseasesShinshu University HospitalMatsumotoJapan
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Ananchuensook P, Moonlisarn K, Boonkaew B, Bunchorntavakul C, Tangkijvanich P. Diagnostic Performance of Serum Mac-2-Binding Protein Glycosylation Isomer as a Fibrosis Biomarker in Non-Obese and Obese Patients with MASLD. Biomedicines 2025; 13:415. [PMID: 40002828 PMCID: PMC11853689 DOI: 10.3390/biomedicines13020415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 01/30/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Serum mac-2-binding protein glycosylation isomer (M2BPGi) is a new biomarker for liver fibrosis. However, its performance in metabolic dysfunction-associated steatotic liver disease (MASLD), particularly in obese patients, remains to be explored. Methods: This study evaluated the role of M2BPGi in predicting liver fibrosis in 205 patients with MASLD using magnetic resonance elastography (MRE) as a reference. The performance of M2BPGi was compared to vibration-controlled transient elastography (VCTE), FIB-4, APRI, and NFS. The PNPLA3, TM6SF2, and HSD17B13 polymorphisms were assessed by allelic discrimination assays. Results: The area under the ROC curves for VCTE, M2BPGi FIB-4, APRI, and NFS in differentiating significant fibrosis were 0.95 (95% CI; 0.91-0.98), 0.85 (0.79-0.92), 0.81 (0.74-0.89), 0.79 (0.71-0.87), and 0.80 (0.72-0.87) (all p < 0.001), respectively. The optimal cut-off values of M2BPGi in predicting significant fibrosis, advanced fibrosis, and cirrhosis were 0.82, 0.95, and 1.23 cut-off index (COI); yielding satisfactory sensitivity, specificity, and diagnostic accuracy. The performance of M2BPGi was consistent among subgroups according to BMI, while the AUROCs of FIB-4, APRI, and NFS were remarkably decreased in patients with BMI ≥ 30 kg/m2. Patients with the PNPLA3 GG genotype had significantly higher M2BPGi than those with the CC/CG genotypes. In multivariate analysis, the independent factors associated with significant liver fibrosis were VCTE, M2BPGi, and PNPLA3 rs738409. Conclusions: Our data demonstrated that serum M2BPGi accurately assessed liver fibrosis across different BMI, indicating that this biomarker could apply to non-obese and obese patients with MASLD in clinical settings.
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Affiliation(s)
- Prooksa Ananchuensook
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand;
- Academic Affair, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kamonchanok Moonlisarn
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Chulalongkorn University, Bangkok 10330, Thailand; (K.M.); (B.B.)
| | - Bootsakorn Boonkaew
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Chulalongkorn University, Bangkok 10330, Thailand; (K.M.); (B.B.)
| | | | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Chulalongkorn University, Bangkok 10330, Thailand; (K.M.); (B.B.)
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Shinozaki S, Miura K, Tahara T, Yamamoto H. Effectiveness of Pemafibrate Dose Escalation on Metabolic Dysfunction-Associated Steatotic Liver Disease Refractory to Standard Dose. Metabolites 2025; 15:100. [PMID: 39997725 PMCID: PMC11857616 DOI: 10.3390/metabo15020100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 01/27/2025] [Accepted: 02/03/2025] [Indexed: 02/26/2025] Open
Abstract
Background and Aim: Controlling the hepatic inflammation of metabolic dysfunction-associated steatotic liver disease (MASLD) is important to prevent serious condition. Pemafibrate, a selective peroxisome proliferator-activated receptor-α modulator, has demonstrated effectiveness at a standard dose (0.2 mg daily). The aim of this study is to evaluate the effectiveness of pemafibrate dose escalation from 0.2 mg to 0.4 mg daily in patients with MASLD who are refractory to standard-dose therapy. Methods: This study included patients with MASLD who had a persistent elevation of alanine aminotransferase (ALT) levels despite more than one year of standard-dose pemafibrate therapy (0.2 mg daily). All patients underwent dose escalation to 0.4 mg once daily. Hepatic inflammation was assessed using serum ALT levels, hepatic function was evaluated with the albumin-bilirubin score, and hepatic fibrosis was estimated using Mac-2 binding protein glycosylation isomer (M2BPGi) levels. A one-year treatment period was investigated, including six months before dose escalation and six months after dose escalation. Results: Eleven patients were included. The median treating period with standard-dose pemafibrate was 3.2 years. Weight did not show significant change throughout the observation period. Regarding the hepatobiliary enzyme, the aspartate aminotransferase, ALT, and γ-glutamyl transpeptidase levels significantly improved six months after the dose escalation. Specifically, ALT improved in all patients, and the ALT levels normalized in four patients (36%). The lipid profiles, the albumin-bilirubin score, and M2BPGi did not significantly change after the dose escalation. Conclusions: The dose escalation of pemafibrate from 0.2 mg to 0.4 mg daily may improve hepatic inflammation in patients with MASLD refractory to standard-dose therapy.
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Affiliation(s)
- Satoshi Shinozaki
- Shinozaki Medical Clinic, Utsunomiya 321-3223, Japan
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke 329-0431, Japan
| | - Kouichi Miura
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke 329-0431, Japan
| | | | - Hironori Yamamoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke 329-0431, Japan
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Wang Y, Song SJ, Jiang Y, Lai JCT, Wong GLH, Wong VWS, Yip TCF. Role of noninvasive tests in the prognostication of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol 2025; 31:S51-S75. [PMID: 38934108 PMCID: PMC11925434 DOI: 10.3350/cmh.2024.0246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 06/20/2024] [Accepted: 06/26/2024] [Indexed: 06/28/2024] Open
Abstract
In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.
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Affiliation(s)
- Yue Wang
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Sherlot Juan Song
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Yichong Jiang
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Jimmy Che-To Lai
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Grace Lai-Hung Wong
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Vincent Wai-Sun Wong
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Terry Cheuk-Fung Yip
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
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Kamada Y, Sumida Y, Takahashi H, Fujii H, Miyoshi E, Nakajima A. Utility of Mac-2 binding protein glycosylation isomer as an excellent biomarker for the prediction of liver fibrosis, activity, and hepatocellular carcinoma onset: an expert review. J Gastroenterol 2025; 60:10-23. [PMID: 39652103 DOI: 10.1007/s00535-024-02179-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 11/10/2024] [Indexed: 01/11/2025]
Abstract
Mac-2 binding protein glycosylation isomer (M2BPGi) is a liver fibrosis biomarker that originated in Japan and has been covered by health insurance for 10 years. M2BPGi is useful not only for liver fibrosis stage prediction but also for assessment of the degree of liver inflammation and prediction of hepatocellular carcinoma development. The usefulness of M2BPGi for assessing disease progression in patients with various chronic liver diseases has been demonstrated over the past decade in a large number of patients. Recently, there have been many reports from outside Japan, including reports from South Korea, Taiwan, Hong Kong, and China. These studies demonstrated that M2BPGi is an excellent biomarker that can evaluate the progression of liver fibrosis in chronic liver disease. It is also an excellent indicator of liver activity. Recently, a quantitative M2BPGi (M2BPGi-Qt) assay was developed, and future validation in real-world settings is expected. This will enable diagnosis of the progression of liver fibrosis based on more precise test results and is expected to contribute to the early detection and follow-up of diseases caused by chronic hepatitis, as well as post-treatment monitoring. The significance of the M2BPGi-Qt assay will likely become clearer as real-world data accumulate. If new cutoff values for each chronic liver disease stage and activity level using the M2BPGi-Qt assay are set based on real-world data, it is expected that this will become a useful tool to identify cases of liver fibrosis and monitor the progression of chronic liver disease.
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Affiliation(s)
- Yoshihiro Kamada
- Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, 1-7, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshio Sumida
- Graduate School of Healthcare Management, International University of Healthcare and Welfare, 4-1-26, Akasaka, Minato-ku, Tokyo, 107-8402, Japan.
| | - Hirokazu Takahashi
- Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Hideki Fujii
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3, Asahimachi, Abeno, Osaka, 545-8585, Japan
| | - Eiji Miyoshi
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
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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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Ishikawa T, Terai N, Sato R, Jimbo R, Kobayashi Y, Sato T, Iwanaga A, Sano T, Yokoyama J, Honma T. Clinical Efficacy and Body Composition Changes with Sodium Glucose Cotransporter 2 Inhibitor/Glucagon-like Peptide-1 Antagonist Combination Therapy in Patients with Type 2 Diabetes Mellitus-associated Nonalcoholic Fatty Liver Disease. Intern Med 2024; 63:2491-2497. [PMID: 38346734 PMCID: PMC11473285 DOI: 10.2169/internalmedicine.3259-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 12/14/2023] [Indexed: 09/18/2024] Open
Abstract
Objective Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) treatment guidelines recommend sodium glucose cotransporter 2 inhibitor (SGLT2I) and glucagon-like peptide-1 agonist (GLP-1A) therapy in patients with type 2 diabetes mellitus (T2DM). SGLT2I improves the pathological condition of NAFLD/NASH in T2DM patients. However, cases of rebound during long-term SGLT2I treatment have been reported. This study investigated the efficacy of SGLT2I and GLP-1A combination therapy in diabetic patients with NAFLD by examining changes in computed tomography (CT)-based body composition and clinical outcomes. Methods Fifteen patients (5 men/10 women) with T2DM-associated NAFLD who had not responded to SGLT2I treatment and were being treated with GLP-1A combination therapy were included. Changes in the liver function, visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were compared using CT to evaluate the body composition. Results SGLT2I significantly improved alanine aminotransferase (28.0 to 13.0 IU/L), alkaline phosphatase (250.0 to 77.0 IU/L), and gamma glutamyl transpeptidase (23.0 to 12.0 IU/L) levels. The body mass index (BMI) decreased from 25.7 to 25.2 kg/m2. A CT-based analysis showed a significant improvement in SATI (80.9 to 66.1, p=0.002), with no significant change in VATI (53.2 to 51.5). GLP-1A addition improved the BMI (25.2 to 23.5 kg/m2) and hemoglobin A1c (6.5% to 6.2%, p=0.001). A further analysis revealed additional improvement in SATI (66.1 to 56.6, p=0.007) and a significant decrease in VATI (51.5 to 48.3, p=0.001). Conclusion SGLT2I and GLP-1A combination therapy improved the liver function, body composition, and glycemic control in diabetic patients with NAFLD/NASH, as well as SATI and VATI. The optimal timing of combination therapy remains to be determined.
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Affiliation(s)
- Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Japan
| | - Nanako Terai
- Department of Radiographer, Saiseikai Niigata Hospital, Japan
| | - Ryo Sato
- Department of Gastroenterology, Saiseikai Niigata Hospital, Japan
| | - Ryo Jimbo
- Department of Gastroenterology, Saiseikai Niigata Hospital, Japan
| | - Yuji Kobayashi
- Department of Gastroenterology, Saiseikai Niigata Hospital, Japan
| | - Toshifumi Sato
- Department of Gastroenterology, Saiseikai Niigata Hospital, Japan
| | - Akito Iwanaga
- Department of Gastroenterology, Saiseikai Niigata Hospital, Japan
| | - Tomoe Sano
- Department of Gastroenterology, Saiseikai Niigata Hospital, Japan
| | - Junji Yokoyama
- Department of Gastroenterology, Saiseikai Niigata Hospital, Japan
| | - Terasu Honma
- Department of Gastroenterology, Saiseikai Niigata Hospital, Japan
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Suzuki T, Matsuura K, Nagura Y, Ito K, Ogawa S, Kawamura H, Fujiwara K, Nagaoka K, Iio E, Watanabe T, Kataoka H, Tanaka Y. MicroRNA-223-3p levels in serum-derived extracellular vesicles predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents. J Gastroenterol 2024; 59:719-731. [PMID: 38739200 DOI: 10.1007/s00535-024-02115-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 05/02/2024] [Indexed: 05/14/2024]
Abstract
BACKGROUND We retrospectively investigated microRNA (miRNA) levels in serum-derived extracellular vesicles (EVs) as predictive indicators for regression of liver fibrosis, after achievement of a sustained virological response (SVR) by direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC). METHODS The study subjects were recruited from a historical cohort of 108 CHC patients whose pretreatment serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels were ≥ 2.0 cut-off index (COI). We classified patients with M2BPGi levels < 1.76 and ≥ 1.76 COI at 2 years after the end of treatment (EOT) into the regression and non-regression groups, respectively. Eleven of the patients were assigned to the discovery set, and we comprehensively investigated the miRNAs contained in serum-derived EVs at 24 weeks after the EOT (EOT24W), using RNA sequencing. The remaining 97 patients were assigned to the validation set, and reproducibility was verified by quantitative real-time PCR. RESULTS Through analysis of the discovery and validation sets, we identified miR-223-3p and miR-1290 as candidate predictors. Subsequently, we analyzed various clinical data, including these candidate miRNAs. Multivariate analyses revealed that the levels of miR-223-3p at EOT24W were significantly associated with regression of M2BPGi-based liver fibrosis (Odds ratio: 1.380; P = 0.024). Consistent results were obtained, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis (pretreatment M2BPGi levels ≥ 3.3 COI). CONCLUSIONS The miR-223-3p level in serum-derived EVs at EOT24W is a feasible predictor of regression of M2BPGi-based liver fibrosis after achievement of an SVR by DAA therapy.
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Affiliation(s)
- Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan.
| | - Yoshihito Nagura
- Department of Gastroenterology, Kasugai Municipal Hospital, Kasugai, Japan
| | - Kyoko Ito
- Department of Virology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shintaro Ogawa
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hayato Kawamura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Katsuya Nagaoka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Etsuko Iio
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Takehisa Watanabe
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
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10
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Uojima H, Yamasaki K, Sugiyama M, Kage M, Ishii N, Shirabe K, Hidaka H, Kusano C, Murakawa M, Asahina Y, Nishimura T, Iijima H, Sakamoto K, Ito K, Amano K, Kawaguchi T, Tamaki N, Kurosaki M, Suzuki T, Matsuura K, Taketomi A, Joshita S, Umemura T, Nishina S, Hino K, Toyoda H, Yatsuhashi H, Mizokami M. Quantitative measurements of M2BPGi depend on liver fibrosis and inflammation. J Gastroenterol 2024; 59:598-608. [PMID: 38625546 DOI: 10.1007/s00535-024-02100-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 03/19/2024] [Indexed: 04/17/2024]
Abstract
BACKGROUND The relationship between liver fibrosis and inflammation and Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with chronic liver disease (CLD) other than hepatitis C remains uncertain, owing to the limitations of qualitative methods. Here, we evaluated the influence of liver fibrosis and inflammation on quantitative M2BPGi (M2BPGi-Qt) in CLD, considering each etiology. METHODS We recruited 1373 patients with CLD. To evaluate the influence of liver fibrosis and inflammation on M2BPGi-Qt levels, we assessed M2BPGi-Qt levels at each fibrosis and activity stage within different etiologies of CLD based on pathological findings. Subsequently, we evaluated if the accuracy of fibrosis staging based on M2BPGi-Qt could be improved by considering the influence of liver inflammation. RESULTS In patients with viral hepatitis, non-alcoholic fatty liver disease, and primary biliary cholangitis, the median M2BPGi-Qt levels increased liver fibrosis progression. Median M2BPGi-Qt levels were not associated with the degree of fibrosis in patients with autoimmune hepatitis (AIH). Median M2BPGi-Qt levels increased with the progression of liver activity in all etiologies. A significant difference was found at each stage in AIH. Considering the liver inflammation, we established an algorithm, M2BPGi-Qt, to determine the alanine aminotransferase-to-platelet ratio (MAP-R) in liver cirrhosis (LC). The area under the receiver operating characteristic curve (AUC) of MAP-R was higher than that of the M2BPGi-Qt for detecting LC (AUC MAP-R = 0.759 and M2BPGi-Qt = 0.700, p < 0.001). CONCLUSIONS The quantitative measurement system for M2BPGi depends on liver fibrosis and inflammation, regardless of etiology. Liver inflammation complicates the interpretation of M2BPGi-Qt results when assessing the fibrosis stage.
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Affiliation(s)
- Haruki Uojima
- Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan.
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
| | - Kazumi Yamasaki
- Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Ōmura, Japan
| | - Masaya Sugiyama
- Department of Viral Pathogenesis and Controls, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
| | - Masayoshi Kage
- Department of Pathology, Junshin Gakuen University, Fukuoka, Japan
| | - Norihiro Ishii
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Ken Shirabe
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Hisashi Hidaka
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Chika Kusano
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Miyako Murakawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Yushima, Bunkyo-Ku, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Yushima, Bunkyo-Ku, Tokyo, Japan
- Department of Liver Disease Control, Tokyo Medical and Dental University, Yushima, Bunkyo-Ku, Tokyo, Japan
| | - Takashi Nishimura
- Division of Hepatobiliary and Pancreatic Disease, Department of Gastroenterology, Hyogo Medical University, Nishinomiya, Hyogo, Japan
| | - Hiroko Iijima
- Division of Hepatobiliary and Pancreatic Disease, Department of Gastroenterology, Hyogo Medical University, Nishinomiya, Hyogo, Japan
| | - Kazumasa Sakamoto
- Department of Gastroenterology, Aichi Medical University, Nagakute, Aichi, Japan
| | - Kiyoaki Ito
- Department of Gastroenterology, Aichi Medical University, Nagakute, Aichi, Japan
| | - Keisuke Amano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Asahi-Machi, Kurume, Fukuoka, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Asahi-Machi, Kurume, Fukuoka, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan
| | - Takanori Suzuki
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Satoru Joshita
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Asahi, Matsumoto, Japan
| | - Takeji Umemura
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Asahi, Matsumoto, Japan
| | - Sohji Nishina
- Department of Hepatology and Pancreatology, Kawasaki Medical School, Aichi, Japan
| | - Keisuke Hino
- Department of Hepatology and Pancreatology, Kawasaki Medical School, Aichi, Japan
- Digestive Disease Center, Shunan Memorial Hospital, Yamaguchi, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hiroshi Yatsuhashi
- Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Ōmura, Japan
| | - Masashi Mizokami
- Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan
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11
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Kong F, Dong R, Chen G, Sun S, Yang Y, Jiang J, Meng L, Chen H, Zhu J, Zheng S. Progress in Biomarkers Related to Biliary Atresia. J Clin Transl Hepatol 2024; 12:305-315. [PMID: 38426193 PMCID: PMC10899875 DOI: 10.14218/jcth.2023.00260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 12/12/2023] [Accepted: 01/02/2024] [Indexed: 03/02/2024] Open
Abstract
Biliary atresia (BA) is a congenital cholestatic disease that can seriously damage children's liver function. It is one of the main reasons for liver transplantation in children. Early diagnosis of BA is crucial to the prognosis of patients, but there is still a lack of reliable non-invasive diagnostic methods. Additionally, as some children are in urgent need of liver transplantation, evaluating the stage of liver fibrosis and postoperative native liver survival in children with BA using a straightforward, efficient, and less traumatic method is a major focus of doctors. In recent years, an increasing number of BA-related biomarkers have been identified and have shown great potential in the following three aspects of clinical practice: diagnosis, evaluation of the stage of liver fibrosis, and prediction of native liver survival. This review focuses on the pathophysiological function and clinical application of three novel BA-related biomarkers, namely MMP-7, FGF-19, and M2BPGi. Furthermore, progress in well-known biomarkers of BA such as gamma-glutamyltransferase, circulating cytokines, and other potential biomarkers is discussed, aiming to provide a reference for clinical practice.
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Affiliation(s)
- Fanyang Kong
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Rui Dong
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Gong Chen
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Song Sun
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Yifan Yang
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Jingying Jiang
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Lingdu Meng
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Huifen Chen
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Jiajie Zhu
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Shan Zheng
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
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12
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Moon SY, Baek YH, Jang SY, Jun DW, Yoon KT, Cho YY, Jo HG, Jo AJ. Proposal of a Novel Serological Algorithm Combining FIB-4 and Serum M2BPGi for Advanced Fibrosis in Nonalcoholic Fatty Liver Disease. Gut Liver 2024; 18:283-293. [PMID: 37574956 PMCID: PMC10938160 DOI: 10.5009/gnl230128] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 06/12/2023] [Accepted: 06/13/2023] [Indexed: 08/15/2023] Open
Abstract
Background/Aims Noninvasive methods have become increasingly critical in the diagnosis of fibrosis in chronic liver diseases. Herein, we compared the diagnostic performance of serum Mac2 binding protein glycosylation isomer (M2BPGi) and other serological panels for fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and proposed an improved two-step diagnostic algorithm for advanced fibrosis. Methods We enrolled 231 patients diagnosed with NAFLD who underwent a liver biopsy. We subsequently evaluated the diagnostic performance of serological panels, including serum M2BPGi, a fibrosis index based on four factors (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), and NAFLD fibrosis score (NFS), in predicting the stage of liver fibrosis. We then constructed a two-step algorithm to better differentiate advanced fibrosis. Results The areas under the receiver operating characteristic curves of serum M2BPGi, FIB-4, APRI, and NFS for advanced fibrosis (≥F3) were 0.823, 0.858, 0.779, and 0.827, respectively. To reduce the performance of unnecessary liver biopsy, we propose a two-step algorithm using FIB-4 as an initial diagnostic tool and serum M2BPGi (≥0.6) as an additional diagnostic method for patients classified as intermediate (23%). Using the proposed algorithm, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.812, 0.814, 0.814, 0.600, and 0.927, respectively. Conclusions Serum M2BPGi is a simple and effective test for advanced fibrosis in patients with NAFLD. Application of the two-step algorithm based on FIB-4 and M2BPGi proposed here can improve diagnostic performance and reduce unnecessary tests, making diagnosis easily accessible, especially in primary medical centers.
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Affiliation(s)
- Sang Yi Moon
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Yang Hyun Baek
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Se Young Jang
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
- Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Korea
- Liver Center, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Young Youn Cho
- Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea
| | - Hoon Gil Jo
- Division of Gastroenterology, Department of Internal Medicine, Wonkwang University Hospital, Wonkwang University College of Medicine, Iksan, Korea
| | - Ae Jeong Jo
- Department of Information Statistics, Andong National University, Andong, Korea
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13
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López Tórrez SM, Ayala CO, Ruggiro PB, Costa CAD, Wagner MB, Padoin AV, Mattiello R. Accuracy of prognostic serological biomarkers in predicting liver fibrosis severity in people with metabolic dysfunction-associated steatotic liver disease: a meta-analysis of over 40,000 participants. Front Nutr 2024; 11:1284509. [PMID: 38419854 PMCID: PMC10899345 DOI: 10.3389/fnut.2024.1284509] [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: 12/05/2023] [Accepted: 01/25/2024] [Indexed: 03/02/2024] Open
Abstract
Introduction A prognostic model to predict liver severity in people with metabolic dysfunction-associated steatotic liver disease (MASLD) is very important, but the accuracy of the most commonly used tools is not yet well established. Objective The meta-analysis aimed to assess the accuracy of different prognostic serological biomarkers in predicting liver fibrosis severity in people with MASLD. Methods Adults ≥18 years of age with MASLD were included, with the following: liver biopsy and aspartate aminotransferase-to-platelet ratio (APRI), fibrosis index-4 (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score (BARD score), FibroMeter, FibroTest, enhanced liver fibrosis (ELF), Forns score, and Hepascore. Meta-analyses were performed using a random effects model based on the DerSimonian and Laird methods. The study's risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Results In total, 138 articles were included, of which 86 studies with 46,514 participants met the criteria for the meta-analysis. The results for the summary area under the receiver operating characteristic (sAUROC) curve, according to the prognostic models, were as follows: APRI: advanced fibrosis (AF): 0.78, any fibrosis (AnF): 0.76, significant fibrosis (SF): 0.76, cirrhosis: 0.72; FIB-4: cirrhosis: 0.83, AF: 0.81, AnF: 0.77, SF: 0.75; NFS: SF: 0.81, AF: 0.81, AnF: 0.71, cirrhosis: 0.69; BARD score: SF: 0.77, AF: 0.73; FibroMeter: SF: 0.88, AF: 0.84; FibroTest: SF: 0.86, AF: 0.78; and ELF: AF: 0.87. Conclusion The results of this meta-analysis suggest that, when comparing the scores of serological biomarkers with liver biopsies, the following models showed better diagnostic accuracy in predicting liver fibrosis severity in people with MASLD: FIB-4 for any fibrosis, FibroMeter for significant fibrosis, ELF for advanced fibrosis, and FIB-4 for cirrhosis.Clinical trial registration: [https://clinicaltrials.gov/], identifier [CRD 42020180525].
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Affiliation(s)
- Sergio M. López Tórrez
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Camila O. Ayala
- School of Medicine, Postgraduate Program in Pediatrics and Child Health, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Paula Bayer Ruggiro
- School of Medicine, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Caroline Abud Drumond Costa
- School of Medicine, Postgraduate Program in Pediatrics and Child Health, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Mario B. Wagner
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
- School Medicine, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Alexandre Vontobel Padoin
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Rita Mattiello
- School Medicine, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- School of Medicine, Postgraduate Program in Epidemiology, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
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14
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Bui HH, Nguyen STB, Phan ST, Nguyen KM, Nguyen CD. Evaluating M2BPGi as a Marker for Liver Fibrosis in Patients with Chronic Hepatitis B. Dig Dis Sci 2023; 68:4407-4417. [PMID: 37861877 PMCID: PMC10635958 DOI: 10.1007/s10620-023-08143-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 10/02/2023] [Indexed: 10/21/2023]
Abstract
BACKGROUND The accurate evaluation of liver fibrosis is crucial for the treatment and follow up of chronic hepatitis B (CHB) patients. AIM We examined the efficiency of serum Mac-2 Binding Protein Glycosylation isomer (M2BPGi) in diagnosing liver fibrosis stages in CHB patients. METHODS A cross-sectional study was conducted on 177 adult CHB patients visiting the University Medical Center Ho Chi Minh City, Vietnam between October 2019 and December 2021. M2BPGi, ARFI, APRI, and FIB-4 were tested against FibroScan® for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The optimal M2BPGi cut-off values were identified based on the area under the receiver operating characteristic (AUROC) curve. RESULTS There was a strong agreement between M2BPGi and FibroScan® (r = 0.77, P < 0.001). The optimal M2BPGi cut-off index (C.O.I) for detecting significant fibrosis (F ≥ 2) was 0.79 with an AUROC of 0.77, 67.3% sensitivity, 70% specificity, 60.6% NPV, and 75.3% PPV. Compared with APRI (61%) and FIB-4 (47%), M2BPGi had the greatest sensitivity for diagnosing F ≥ 2. M2BPGi combined with APRI yielded highest diagnosis performance for F ≥ 2 with an AUROC of 0.87. The optimal cut-off index of M2BPGi for diagnosing cirrhosis (F4) was 1.3 with an AUROC of 0.91, 88% sensitivity, 87.4% specificity, 97% NPV, and 61% PPV. The AUROC of M2BPGi for diagnosing F4 was comparable to that of ARFI (0.93). CONCLUSIONS With cut-off values of 0.79 C.O.I and 1.3 C.O.I, M2BPGi could be an effective method for diagnosing significant fibrosis and cirrhosis in CHB patients, respectively.
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Affiliation(s)
- Hoang Huu Bui
- Department of Gastroenterology, University Medical Center Ho Chi Minh City, 215 Hong Bang Street, Ward 11, District 5, Ho Chi Minh City, 70000, Vietnam
- Department of Internal Medicine, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
| | - Suong Thi-Bang Nguyen
- Department of Clinical Laboratory, University Medical Center Ho Chi Minh City, 215 Hong Bang Street, Ward 11, District 5, Ho Chi Minh City, 70000, Vietnam
- Department of Biochemistry, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
| | - Sang The Phan
- Department of Gastroenterology, University Medical Center Ho Chi Minh City, 215 Hong Bang Street, Ward 11, District 5, Ho Chi Minh City, 70000, Vietnam
| | - Khue Minh Nguyen
- Vietnam National University, 227 Nguyen Van Cu Street, District 5, Ho Chi Minh City, 700000, Vietnam
| | - Chuong Dinh Nguyen
- Department of Gastroenterology, University Medical Center Ho Chi Minh City, 215 Hong Bang Street, Ward 11, District 5, Ho Chi Minh City, 70000, Vietnam.
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15
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Uojima H, Nakabayashi K, Yamasaki K, Sugiyama M, Ishii N, Shirabe K, Kyoutou T, Ueda K, Takahama Y, Tamaki N, Kurosaki M, Hidaka H, Kusano C, Amano K, Kawaguchi T, Taketomi A, Joshita S, Umemura T, Murakawa M, Asahina Y, Suzuki T, Matsuura K, Nishimura T, Iijima H, Sakamoto K, Ito K, Nishina S, Hino K, Toyoda H, Yatsuhashi H, Kage M, Mizokami M. New chemiluminescent enzyme immunoassay for quantitative measurement of Mac-2 binding protein glycosylation isomer in chronic liver disease. J Gastroenterol 2023; 58:1252-1260. [PMID: 37812281 DOI: 10.1007/s00535-023-02043-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 09/12/2023] [Indexed: 10/10/2023]
Abstract
BACKGROUND This study aimed to evaluate the quantitative measurement of Mac-2 binding protein glycosylation isomer (M2BPGi) levels using the new chemiluminescent enzyme immunoassay. METHODS The data of a total of 347 patients with hepatitis C virus (HCV) infection and 150 health volunteers from 13 locations in Japan were evaluated. The quantitative system for measuring M2BPGi-Qt levels was based on a new chemiluminescent enzyme immunoassay. We evaluated the reproducibility and quantitation range in quantitative M2BPGi-Qt measurement. We also investigated the confidence ratio of M2BPGi-Qt levels measured by the new quantitative system to M2BPGi levels measured by the current semi-quantitative system for validating the clinical utility of the new method. RESULTS The reproducibility of M2BPGi-Qt in HCV samples with negative, positive 1+, and positive 2+ was 0.77 ± 0.02 AU/mL, 2.25 ± 0.03 AU/mL, and 6.55 ± 0.21 AU/mL, respectively, and the corresponding coefficient of variation (CV)s were 2.1%, 1.3%, and 3.2%, respectively. The range of quantification assessment resulted that all CVs showed less than 5% in investigated range. Sample stability testing found that the mean percentage difference between the pre- and post-storage values of 6 samples ranged between 96.2 and 103.9%. The correlation coefficient between M2BPGi and M2BPGi-Qt in patients with HCV and the healthy volunteers was 0.986 and 0.991, respectively. M2BPGi-Qt could be quantitatively assessed in a patient with over 20 C.O.I. CONCLUSION Compared with qualitative methods, the M2BPGi quantitative measurement system could provide a numerical value unaffected by interpretation bias, and measurements are more precise at high M2BPGi levels.
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Affiliation(s)
- Haruki Uojima
- Department of Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan.
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
| | | | - Kazumi Yamasaki
- Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Ōmura, Japan
| | - Masaya Sugiyama
- Department of Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan
| | - Norihiro Ishii
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University, Graduate School of Medicine, Gunma, Japan
| | - Ken Shirabe
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University, Graduate School of Medicine, Gunma, Japan
| | - Takuya Kyoutou
- Department of Reagent Engineering, Sysmex Corporation, Kobe, Japan
| | - Koji Ueda
- Department of Reagent Engineering, Sysmex Corporation, Kobe, Japan
| | - Yoichi Takahama
- Department of Reagent Engineering, Sysmex Corporation, Kobe, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hisashi Hidaka
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Chika Kusano
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Keisuke Amano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Asahi-Machi, Kurume, Fukuoka, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Asahi-Machi, Kurume, Fukuoka, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Satoru Joshita
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Takeji Umemura
- Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine. Asahi, Matsumoto, Japan
| | - Miyako Murakawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan
- Department of Liver Disease Control, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan
| | - Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takashi Nishimura
- Division of Hepatobiliary and Pancreatic Disease, Department of Gastroenterology, Hyogo Medical University, Nishinomiya, Japan
| | - Hiroko Iijima
- Division of Hepatobiliary and Pancreatic Disease, Department of Gastroenterology, Hyogo Medical University, Nishinomiya, Japan
| | - Kazumasa Sakamoto
- Department of Gastroenterology, Aichi Medical University, Aichi, Japan
| | - Kiyoaki Ito
- Department of Gastroenterology, Aichi Medical University, Aichi, Japan
| | - Sohji Nishina
- Department of Hepatology and Pancreatology, Kawasaki Medical University, Kurashiki, Japan
| | - Keisuke Hino
- Department of Hepatology and Pancreatology, Kawasaki Medical University, Kurashiki, Japan
- Digestive Disease Center, Shunan Memorial Hospital, Kudamatsu, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hiroshi Yatsuhashi
- Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Ōmura, Japan
| | | | - Masashi Mizokami
- Department of Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan
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16
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Terracciani F, Falcomatà A, Gallo P, Picardi A, Vespasiani-Gentilucci U. Prognostication in NAFLD: physiological bases, clinical indicators, and newer biomarkers. J Physiol Biochem 2023; 79:851-868. [PMID: 36472795 DOI: 10.1007/s13105-022-00934-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 11/23/2022] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is becoming an epidemic in Western countries. Notably, while the majority of NAFLD patients will not evolve until advanced liver disease, a minority of them will progress towards liver-related events. Therefore, risk stratification and prognostication are emerging as fundamental in order to optimize human and economic resources for the care of these patients.Liver fibrosis has been clearly recognized as the main predictor of poor hepatic and extrahepatic outcomes. However, a prediction based only on the stage of fibrosis is near-sighted and static, as it does not capture the propensity of disease to further progress, the speed of progression and their changes over time. These determinants, which result from the interaction between genetic predisposition and acquired risk factors (obesity, diabetes, etc.), express themselves in disease activity, and can be synthesized by biomarkers of hepatic inflammation and fibrogenesis.In this review, we present the currently available clinical tools for risk stratification and prognostication in NAFLD specifically with respect to the risk of progression towards hard hepatic outcomes, i.e., liver-related events and death. We also discuss about the genetic and acquired drivers of disease progression, together with the physiopathological bases of their come into action. Finally, we introduce the most promising biomarkers in the direction of repeatedly assessing disease activity over time, mainly in response to future therapeutic interventions.
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Affiliation(s)
- Francesca Terracciani
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Andrea Falcomatà
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Paolo Gallo
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy.
| | - Antonio Picardi
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy
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Shinozaki S, Tahara T, Miura K, Lefor AK, Yamamoto H. Effectiveness of One-Year Pemafibrate Therapy on Non-Alcoholic Fatty Liver Disease Refractory to Long-Term Sodium Glucose Cotransporter-2 Inhibitor Therapy: A Pilot Study. Life (Basel) 2023; 13:1327. [PMID: 37374110 DOI: 10.3390/life13061327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 06/02/2023] [Accepted: 06/03/2023] [Indexed: 06/29/2023] Open
Abstract
Background: Both pemafibrate and sodium glucose cotransporter-2 (SGLT2) inhibitor can decrease serum transaminase levels in patients with non-alcoholic fatty liver disease (NAFLD) complicated with dyslipidemia and type 2 diabetes mellitus (T2DM), respectively. However, the effectiveness of combined therapy has been rarely reported. Methods: This is a two-center retrospective observational study. NAFLD patients complicated with T2DM treated with pemafibrate for >1 year were included, in whom prior treatment with SGLT2 inhibitor > 1 year failed to normalize serum alanine aminotransferase (ALT) levels. Hepatic inflammation, function, and fibrosis were assessed by ALT, albumin-bilirubin (ALBI) score, and Mac-2 binding protein glycosylation isomer (M2BPGi) levels, respectively. Results: Seven patients were included. The median duration of prior treatment with SGLT2 inhibitors was 2.3 years. During the one year before starting pemafibrate therapy, the therapy did not significantly change hepatic enzymes. All patients received pemafibrate 0.1 mg twice daily without dose escalations. During one year of pemafibrate therapy, triglyceride, aspartate aminotransferase, ALT, γ-glutamyl transpeptidase, ALBI score, and M2BPGi levels significantly improved (p < 0.05), although weight or hemoglobin A1c did not significantly change. Conclusions: One year of pemafibrate therapy improves markers of hepatic inflammation, function, and fibrosis in NAFLD patients in whom long-term SGLT2 inhibitor therapy failed to normalize serum ALT.
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Affiliation(s)
- Satoshi Shinozaki
- Shinozaki Medical Clinic, Utsunomiya 321-3223, Japan
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Tochigi 329-0431, Japan
| | - Toshiyuki Tahara
- Saiseikai Utsunomiya Hospital, 911-1 Takebayashi, Utsunomiya 321-0974, Japan
| | - Kouichi Miura
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Tochigi 329-0431, Japan
| | - Alan Kawarai Lefor
- Department of Surgery, Jichi Medical University, Tochigi 329-0431, Japan
| | - Hironori Yamamoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Tochigi 329-0431, Japan
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18
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Sulaiman AS, Hasan I, Hustrini NM, Lydia A, Hanifa RS, Gani RA. Diagnostic performance of Mac-2-binding protein glycosylation isomer (M2BPGi) as a liver fibrosis marker in chronic hepatitis C patients with chronic kidney disease on hemodialysis. Clin Exp Nephrol 2023; 27:557-564. [PMID: 36995542 DOI: 10.1007/s10157-023-02319-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 01/16/2023] [Indexed: 03/31/2023]
Abstract
BACKGROUND/AIM Liver fibrosis assessment is essential to determine the initiation, duration, and evaluation of chronic hepatitis C treatment. Therefore, the study aimed to assess the role of Mac-2-binding protein glycosylation isomer (M2BPGi) as a biomarker to measure liver fibrosis in chronic hepatitis C patients with chronic kidney disease on hemodialysis. METHODS This study used a cross-sectional design. Serum M2BPGi level and transient elastography results were evaluated in 102 chronic hepatitis C patients with CKD on HD, 36 CKD on HD patients, and 48 healthy controls. ROC analysis was conducted to identify the optimal cutoff values to assess significant fibrosis and cirrhosis among chronic hepatitis C patients with CKD on HD. RESULTS In chronic hepatitis C patients with CKD on HD, the level of serum M2BPGi had a moderately significant correlation with transient elastography (r = 0.447, p < 0.001). The median serum M2BPGi was higher among CKD on HD patients compared to healthy controls (1.260 COI vs. 0.590 COI, p < 0.001) and was even higher in chronic hepatitis C patients with CKD on HD compared to CKD on HD group (2.190 COI vs. 1.260 COI, p < 0.001). It is also increased according to the severity of liver fibrosis: 1.670 COI, 2.020 COI, and 5.065 COI for F0-F1, significant fibrosis, and cirrhosis, respectively. The optimal cutoff values for diagnosing significant fibrosis and cirrhosis were 2.080 and 2.475 COI, respectively. CONCLUSION Serum M2BPGi could be a simple and reliable diagnostic tool for evaluating cirrhosis in chronic hepatitis C patients with CKD on HD.
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Affiliation(s)
- Andri Sanityoso Sulaiman
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia.
| | - Irsan Hasan
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
| | - Ni Made Hustrini
- Nephrology and Hypertension Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
| | - Aida Lydia
- Nephrology and Hypertension Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
| | - Rachmadianti Sukma Hanifa
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
| | - Rino Alvani Gani
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
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Fuji T, Kojima T, Kajioka H, Sakamoto M, Oka R, Katayama T, Narahara Y, Niguma T. The preoperative M2BPGi score predicts operative difficulty and the incidence of postoperative complications in laparoscopic liver resection. Surg Endosc 2023; 37:1262-1273. [PMID: 36175698 DOI: 10.1007/s00464-022-09664-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 09/18/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND Liver fibrosis or cirrhosis frequently makes parenchymal transection more difficult, but the difficulty score of laparoscopic liver resection (LLR), including the IWATE criteria, does not include a factor related to liver fibrosis. Therefore, this study aimed to evaluate M2BPGi as a predictor of the difficulty of parenchymal transection and the incidence of postoperative complications in LLR. METHODS Data from 54 patients who underwent laparoscopic partial liver resection (LLR-P) and 24 patients who underwent laparoscopic anatomical liver resection between 2017 and 2019 in our institution were retrospectively analyzed. All cases were classified according to M2BPGi scores, and reserve liver function, intraoperative blood loss, and postoperative complications were compared among these groups. RESULTS Sixteen cases (29.6%) were M2BPGi negative (cut-off index < 1.0), 25 cases (46.3%) were 1+ (1.0 ≤ cut-off index < 3.0), and 13 cases (24.1%) were 2+ (cut-off index ≥ 3.0). M2BPGi-positive cases had significantly worse hepatic reserve function (K-ICG: 0.16 vs 0.14 vs 0.08, p < 0.0001). Intraoperative bleeding was significantly greater in M2BPGi-positive cases [50 ml vs 150 ml vs 200 ml, M2BPGi (-) or (1+) vs M2BPGi (2+), p = 0.045]. Postoperative complications (Clavien-Dindo ≥ II) were significantly more frequent in M2BPGi-positive cases [0% vs 4% vs 33%, M2BPGi (-) or (1+) vs M2BPGi (2+), p = 0.001]. CONCLUSION M2BPGi could predict surgical difficulty and complications in LLR-P. In particular, it might be better not to select M2BPGi (2+) cases as teaching cases because of the massive bleeding during parenchymal transection.
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Affiliation(s)
- Tomokazu Fuji
- Department of Surgery, Okayama Saiseikai General Hospital, 2-25 Kokutaicho, Kita-ku, Okayama, 700-8511, Japan
| | - Toru Kojima
- Department of Surgery, Okayama Saiseikai General Hospital, 2-25 Kokutaicho, Kita-ku, Okayama, 700-8511, Japan.
| | - Hiroki Kajioka
- Department of Surgery, Okayama Saiseikai General Hospital, 2-25 Kokutaicho, Kita-ku, Okayama, 700-8511, Japan
| | - Misaki Sakamoto
- Department of Surgery, Okayama Saiseikai General Hospital, 2-25 Kokutaicho, Kita-ku, Okayama, 700-8511, Japan
| | - Ryoya Oka
- Department of Surgery, Okayama Saiseikai General Hospital, 2-25 Kokutaicho, Kita-ku, Okayama, 700-8511, Japan
| | - Tetsuya Katayama
- Department of Surgery, Okayama Saiseikai General Hospital, 2-25 Kokutaicho, Kita-ku, Okayama, 700-8511, Japan
| | - Yuki Narahara
- Department of Surgery, Okayama Saiseikai General Hospital, 2-25 Kokutaicho, Kita-ku, Okayama, 700-8511, Japan
| | - Takefumi Niguma
- Department of Surgery, Okayama Saiseikai General Hospital, 2-25 Kokutaicho, Kita-ku, Okayama, 700-8511, Japan
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20
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Inoue T, Tanaka Y. Noninvasive assessments of liver disease severity based on biomarkers. COMPREHENSIVE GUIDE TO HEPATITIS ADVANCES 2023:31-60. [DOI: 10.1016/b978-0-323-98368-6.00009-4] [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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Early detection of liver fibrosis with serum Mac-2 binding protein glycosylation-modified isomer (M2BPGi) during follow-up intestinal failure patients without intestinal failure-associated liver disease (IFALD). Pediatr Surg Int 2022; 38:1807-1813. [PMID: 36125546 DOI: 10.1007/s00383-022-05240-w] [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] [Accepted: 09/09/2022] [Indexed: 10/14/2022]
Abstract
PURPOSE Mac-2 binding protein glycosylation-modified isomer (M2BPGi) is a new marker for hepatic fibrosis progression. We examined the relationship between serum M2BPGi levels and liver histological findings in intestinal failure (IF) patients without IF-associated liver disease (IFALD). METHODS This study included IF patients without IFALD followed at our hospital. All patients underwent routine liver biopsies per protocol every 1-2 years. We examined M2BPGi levels and histological findings in relation to aspartate aminotransferase (AST) to platelet ratio index, fibrosis-4 index, and AST/ALT ratio. Liver fibrosis was evaluated based on the METAVIR score. RESULTS Total 18 liver biopsies out of eight patients were included. The median age was 11.5 years. Mean M2BPGi was 0.44 cutoff index (COI) in patients with F0 fibrosis, 0.78 COI in patients with F1 fibrosis and 1.63 COI in patients with F2 fibrosis. Mean M2BPGi was significantly higher in patients with F2 versus F1 or F0 fibrosis (P < 0.016 and P < 0.028, respectively). M2BPGi levels were more strongly correlated with fibrosis stage than with other conventional fibrosis markers. CONCLUSION Serum M2BPGi is a novel marker of liver fibrosis in patients with IF. It is useful for follow-up prior to IFALD. Serum M2BPGi levels can support the interpretation of liver status.
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22
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Mac-2 binding protein glycosylation isomer, the FIB-4 index, and a combination of the two as predictors of non-alcoholic steatohepatitis. PLoS One 2022; 17:e0277380. [DOI: 10.1371/journal.pone.0277380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 10/25/2022] [Indexed: 11/12/2022] Open
Abstract
Approximately 10% non-alcoholic fatty liver disease (NAFLD) cases progress to non-alcoholic steatohepatitis (NASH). Liver biopsy, the gold standard for diagnosing NASH and associated liver fibrosis, is invasive with a risk of life-threatening complications. Therefore, reliable non-invasive biomarkers for predicting NASH are required to prevent unnecessary liver biopsies. We evaluated the performance of two non-invasive fibrosis markers, Mac-2 binding protein glycosylation isomer (M2BPGi) and the FIB-4 index for predicting the fibrosis staging, NAFLD activity scoring (NAS) index, and NASH. We also analyzed the correlation between the two markers. The sensitivities, specificities, positive predictive values (PPV), and negative predictive values of the FIB-4 index, M2BPGi, and a combination of both markers for NASH diagnosis were evaluated. The M2BPGi and FIB-4 index showed a good performance in diagnosing NASH, the fibrosis stage, and the NAS index in NAFLD patients. While both markers were well-correlated with each other in most cases, no correlation was found in some patients. Compared with the FIB-4 index or the M2BPGi alone, a combination of the two showed a higher specificity, PPV, and accuracy for NASH diagnosis. The M2BPGi and the FIB-4 index are easily accessible and reliable liver fibrosis markers. Diseases other than liver disease may cause dissociation between the two markers, causing failure to predict NASH. However, the combination of both markers can compensate for their disadvantages. Because the PPV of the combination was relatively high, patients who test positive for both markers should undergo liver biopsy for NASH diagnosis.
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Park HJ, Seo KI, Lee SU, Han BH, Yun BC, Park ET, Lee J, Hwang H, Yoon M. Clinical usefulness of Mac-2 binding protein glycosylation isomer for diagnosing liver cirrhosis and significant fibrosis in patients with chronic liver disease: A retrospective single-center study. Medicine (Baltimore) 2022; 101:e30489. [PMID: 36221351 PMCID: PMC9542736 DOI: 10.1097/md.0000000000030489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Accurate diagnosis of liver cirrhosis (LC) and significant fibrosis in patients with chronic liver disease (CLD) is important. The Mac-2 binding protein glycosylation isomer (M2BPGi) has emerged as a novel serum biomarker for liver fibrosis; however, insufficient clinical data of M2BPGi are available in patients with CLD. Therefore, we performed a retrospective cohort study to investigate the clinical usefulness of serum M2BPGi for assessing LC and significant fibrosis in CLD patients. We retrospectively reviewed the CLD patients with measured serum M2BPGi at Kosin University Gospel Hospital between January 2016 and December 2019. Multivariate logistic regression analyses were conducted to identify the independent factors associated with LC. The diagnostic power of serum M2BPGi for LC and significant fibrosis (≥F2) was evaluated and compared to that of other serum biomarkers using receiver operating characteristic curve and area under the curve (AUC). A total of 454 patients enrolled in this study. M2BPGi (adjusted odds ratio [aOR], 1.77; 95% confidence interval [CI], 1.52-2.07) and fibrosis index based on four factors (aOR, 1.23; 95% CI, 1.11-1.37) were identified as significant independent factors for LC. The AUC of M2BPGi for LC (0.866) and significant fibrosis (0.816) were comparable to those of fibrosis index based on four factors (0.860, 0.773), aspartate aminotransferase-to-platelet ratio index (0.806, 0.752), and gamma-glutamyl transpeptidase-to-platelet ratio (0.759, 0.710). The optimal cut-off values for M2BPGi for LC and significant fibrosis were 1.37 and 0.89, respectively. Serum M2BPGi levels were significantly correlated with liver stiffness measurements (ρ = 0.778). Serum M2BPGi is a reliable noninvasive method for the assessment of LC and significant fibrosis in patients with CLD.
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Affiliation(s)
- Hyun Joon Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea
- Chang Kee-Ryo Memorial Liver Institute, Kosin University College of Medicine, Busan, South Korea
| | - Kwang Il Seo
- Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea
- Chang Kee-Ryo Memorial Liver Institute, Kosin University College of Medicine, Busan, South Korea
- *Correspondence: Kwang Il Seo, MD, PhD, Department of Internal Medicine, Kosin University College of Medicine, 262 Gamcheon-ro, Seo-gu, Busan, 49267, South Korea. (e-mail: )
| | - Sang Uk Lee
- Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea
- Chang Kee-Ryo Memorial Liver Institute, Kosin University College of Medicine, Busan, South Korea
| | - Byung Hoon Han
- Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea
- Chang Kee-Ryo Memorial Liver Institute, Kosin University College of Medicine, Busan, South Korea
| | - Byung Cheol Yun
- Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea
- Chang Kee-Ryo Memorial Liver Institute, Kosin University College of Medicine, Busan, South Korea
| | - Eun Taek Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea
- Chang Kee-Ryo Memorial Liver Institute, Kosin University College of Medicine, Busan, South Korea
| | - Jinwook Lee
- Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea
- Chang Kee-Ryo Memorial Liver Institute, Kosin University College of Medicine, Busan, South Korea
| | - Hyunyong Hwang
- Department of Laboratory Medicine, Kosin University College of Medicine, Busan, South Korea
| | - Myunghee Yoon
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery Biomedical Research Institute, Pusan National University, College of Medicine, Busan, South Korea
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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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Nakai M, Morikawa K, Hosoda S, Yoshida S, Kubo A, Tokuchi Y, Kitagataya T, Yamada R, Ohara M, Sho T, Suda G, Ogawa K, Sakamoto N. Pre-sarcopenia and Mac-2 binding protein glycosylation isomer as predictors of recurrence and prognosis of early-stage hepatocellular carcinoma. World J Hepatol 2022; 14:1480-1494. [PMID: 36158914 PMCID: PMC9376769 DOI: 10.4254/wjh.v14.i7.1480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 04/20/2022] [Accepted: 06/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The Mac-2 binding protein glycosylation isomer (M2BPGi), a fibrosis marker in various liver diseases, is reportedly a prognostic marker in patients with hepatocellular carcinoma (HCC) who underwent hepatectomy.
AIM To evaluate whether the M2BPGi value, M2BP, and pre-sarcopenia before radiofrequency ablation (RFA) could be useful recurrence and prognostic markers in patients with early-stage HCC.
METHODS In total, 160 patients with early-stage primary HCC treated with RFA were separately analyzed as hepatitis C virus (HCV)-positive and HCV-negative. Factors contributing to recurrence and liver-related death, including M2BP, M2BPGi, and skeletal muscle mass index, were statistically analyzed. Eighty-three patients were HCV-positive and 77 were HCV-negative.
RESULTS In HCV-positive patients, only des-γ-carboxy-prothrombin ≥ 23 mAU/mL was a significant poor prognostic factor affecting survival after RFA. In HCV-negative patients, M2BPGi ≥ 1.86 cutoff index was significantly associated with tumor recurrence, while M2BP was not. M2BPGi ≥ 1.86 cutoff index (hazard ratio, 4.89; 95% confidence interval: 1.97-12.18; P < 0.001) and pre-sarcopenia (hazard ratio, 3.34, 95% confidence interval: 1.19-9.37; P = 0.022) were independent significant poor prognostic factors in HCV-negative patients.
CONCLUSION In HCV-negative patients with primary HCC treated with RFA, lower M2BPGi contributed to a lower tumor recurrence rate and longer survival period. Pre-sarcopenia contributed to the poor prognosis independently in HCV-negative patients. These factors might be useful recurrence and prognostic markers for early-stage primary HCC.
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Affiliation(s)
- Masato Nakai
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Shunichi Hosoda
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Sonoe Yoshida
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Akinori Kubo
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Yoshimasa Tokuchi
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Takashi Kitagataya
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Ren Yamada
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo 060-8638, Japan
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Arai T, Atsukawa M, Tsubota A, Ono H, Kawano T, Yoshida Y, Okubo T, Hayama K, Nakagawa‐Iwashita A, Itokawa N, Kondo C, Nagao M, Iwakiri K. Efficacy and safety of oral semaglutide in patients with non‐alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study. JGH Open 2022; 6:503-511. [PMID: 35822119 PMCID: PMC9260206 DOI: 10.1002/jgh3.12780] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 05/27/2022] [Accepted: 06/05/2022] [Indexed: 12/13/2022]
Abstract
Background and Aim This study aimed to clarify the efficacy and safety of oral semaglutide treatment in patients with non‐alcoholic fatty liver disease (NAFLD) complicated by type 2 diabetes mellitus (T2DM). Methods This was a single‐arm, open‐label pilot study. Sixteen patients with NAFLD who received oral semaglutide for T2DM were included in the analysis. Oral semaglutide was initiated at a dose of 3 mg once daily, and the dose was sequentially increased to 7 mg at 4 weeks and 14 mg at 8 weeks (maintenance dose) until the end of the 24‐week trial. Results Body weight and levels of liver‐related biochemistry, plasma glucose, and hemoglobin A1c decreased significantly from baseline to 12 weeks. These significant decreases were maintained until the end of the trial. Additionally, levels of the homeostasis model assessment‐insulin resistance and triglyceride significantly decreased at 24 weeks. Controlled attenuation parameter (CAP) values significantly decreased from baseline to 24 weeks. Changes in body weight were correlated with those in levels of alanine aminotransferase (r = 0.52) and CAP (r = 0.72). As for liver fibrosis markers, significant decreases from baseline to 24 weeks in levels of the fibrosis‐4 index, ferritin, and type IV collagen 7 s were found; however, the liver stiffness measurement did not significantly decrease. Most adverse events were grade 1–2 transient gastrointestinal disorders. Conclusions Oral semaglutide treatment in patients with NAFLD complicated by T2DM improved impaired liver function, hypertriglyceridemia, insulin resistance, and hepatic steatosis, as well as improving diabetic status and reducing body weight.
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Affiliation(s)
- Taeang Arai
- Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, Research Center for Medical Sciences The Jikei University School of Medicine Tokyo Japan
| | - Hirotaka Ono
- Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan
| | - Tadamichi Kawano
- Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan
| | - Yuji Yoshida
- Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan
| | - Tomomi Okubo
- Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan
| | - Korenobu Hayama
- Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan
| | | | - Norio Itokawa
- Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan
| | - Mototsugu Nagao
- Division of Endocrinology, Diabetes and Metabolism Nippon Medical School Tokyo Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan
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Tamaki N, Kurosaki M, Huang DQ, Loomba R. Noninvasive assessment of liver fibrosis and its clinical significance in nonalcoholic fatty liver disease. Hepatol Res 2022; 52:497-507. [PMID: 35352460 PMCID: PMC9718363 DOI: 10.1111/hepr.13764] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 03/11/2022] [Accepted: 03/28/2022] [Indexed: 01/26/2023]
Abstract
Liver fibrosis is the most important prognostic factor in patients with nonalcoholic fatty liver disease (NAFLD). Several noninvasive markers for fibrosis, including blood-based markers and imaging based-markers have been developed. Indirect fibrosis markers (e.g., fibrosis-4 index and NAFLD fibrosis score) consist of standard laboratory data and clinical parameters. Given its availability and high negative predictive value for advanced fibrosis, these markers are suitable for screening at primary care. Blood-based fibrogenesis markers (enhanced liver fibrosis and N-terminal propeptide of type 3 collagen), ultrasound-based modalities (vibration-controlled transient elastography, point shear wave elastography [SWE], and two-dimensional SWE), and magnetic resonance elastography have high diagnostic accuracy for liver fibrosis and are suitable for diagnosing liver fibrosis at secondary care centers. Sequential use of these markers can increase diagnostic accuracy and reduce health care costs. Furthermore, combining noninvasive makers may assist in identifying candidates for pharmacological trials and reducing screening failure. Emerging data suggest that these noninvasive markers are associated with liver-related events (hepatocellular carcinoma and decompensation) and mortality. Furthermore, delta change in noninvasive markers over time is also associated with time-course change in fibrosis, liver-related event risk, and mortality risk. However, the association between liver fibrosis and cardiovascular disease (CVD) risk is still controversial. CVD risk may decrease in patients with decompensated liver disease and noninvasive markers may be useful for assessing CVD risk in these patients. Therefore, noninvasive markers may be utilized as measures of fibrosis as well as real-time prognostic tools, in place of liver biopsy.
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Affiliation(s)
- Nobuharu Tamaki
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Daniel Q. Huang
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, National University of Singapore, Singapore, Singapore
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California, USA
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Toyoda H, Yasuda S, Shiota S, Sone Y, Maeda A, Kaneoka Y, Kumada T, Tanaka J. Identification of the suitable candidates for EOB-MRI with the high risk of the presence of non-hypervascular hypointense nodules in patients with HCV infection. Eur Radiol 2022; 32:5016-5023. [PMID: 35142900 DOI: 10.1007/s00330-022-08570-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 12/08/2021] [Accepted: 01/07/2022] [Indexed: 12/24/2022]
Abstract
OBJECTIVES Non-hypervascular hypointense nodules (NHHNs) depicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have a high likelihood of progressing to hepatocellular carcinoma (HCC). The presence of NHHNs is a strong risk factor for HCC development in patients with chronic hepatitis C virus (HCV) infection after the achievement of sustained virologic response (SVR). However, it is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection. We therefore explored serum markers that potentially indicate the presence of NHHNs. METHODS Three serum markers, alpha-fetoprotein (AFP), FIB-4 index, and Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi), were measured in 481 patients with HCV infection and no history of HCC who underwent EOB-MRI. The associations between these serum marker levels and the presence of NHHNs were investigated. RESULTS All three markers were associated with the presence of NHHNs. M2BPGi predicted the presence of NHHNs more accurately than AFP and FBB-4 index; M2BPGi had the highest area under the receiver operating characteristic curve. Multivariate analysis identified male gender and high M2BPGi as factors associated with the presence of NHHNs. When patients were stratified by the degree of liver fibrosis, M2BPGi increased with the progression of fibrosis. In addition, NHHNs were more prevalently detected in patients with higher M2BPGi (COI > 3.46) in patients with similar fibrosis degree. CONCLUSIONS M2BPGi is a serum marker that potentially identifies HCV patients with high risk of the presence of NHHNs, for whom EOB-MRI should be considered. KEY POINTS • Non-hypervascular hypointense nodule on EOB-DTPA-enhanced MRI is pre-HCC nodule with high likelihood of progressing to HCC, which is a strong predictor for HCC that develops after the eradication of HCV in patients with HCV infection. • It is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection due to limited access, limited availability of MRI equipment, and high costs. • Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi) levels effectively indicate the presence of NHHNs and can be used to identify patients with high risk of their presence, for whom EOB-DTPA-enhanced MRI should be considered.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan.
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan
| | - Shohei Shiota
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan
| | - Yasuhiro Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Atsuyuki Maeda
- Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yuji Kaneoka
- Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Cheng Y, Wang C. Comparison of Mac‐2 binding protein glycosylation isomer (M2BPGi) with AST to Platelet Ratio Index (APRI), Fibrosis 4 Score (FIB‐4), and Non‐alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) for NAFLD patients. ADVANCES IN DIGESTIVE MEDICINE 2022. [DOI: 10.1002/aid2.13315] [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: 11/10/2022]
Affiliation(s)
- Yu‐Ming Cheng
- Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine Tzu Chi University Hualien Taiwan
| | - Chia‐Chi Wang
- Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine Tzu Chi University Hualien Taiwan
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Smirne C, Croce E, Di Benedetto D, Cantaluppi V, Comi C, Sainaghi PP, Minisini R, Grossini E, Pirisi M. Oxidative Stress in Non-Alcoholic Fatty Liver Disease. LIVERS 2022; 2:30-76. [DOI: 10.3390/livers2010003] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it still remains an orphan of adequate therapies. This review highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive oxygen species generators, including those produced in the gastrointestinal tract, contribute to the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the physiological antioxidant response. Therefore, modulation of this defense system emerges as an interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics, diet, and fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual genetic and epigenetic factors as well. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors, coupled with new OS biomarkers, will likely assist in noninvasive diagnosis and monitoring of NAFLD progression and in further personalizing treatments.
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Affiliation(s)
- Carlo Smirne
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Eleonora Croce
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Davide Di Benedetto
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Vincenzo Cantaluppi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Cristoforo Comi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Pier Paolo Sainaghi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Rosalba Minisini
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Elena Grossini
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
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Kwon Y, Kim ES, Choe YH, Kim MJ. Stratification by Non-invasive Biomarkers of Non-alcoholic Fatty Liver Disease in Children. Front Pediatr 2022; 10:846273. [PMID: 35444966 PMCID: PMC9013938 DOI: 10.3389/fped.2022.846273] [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: 12/31/2021] [Accepted: 02/21/2022] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from isolated hepatic steatosis to non-alcoholic steatohepatitis to fibrosis. We aimed to introduce useful biomarkers released during liver inflammation and fibrogenesis that are easy to use in outpatient clinic and adjust to children to evaluate each NAFLD stage without biopsy. METHODS This prospective study included 60 patients aged under 19 years whose alanine aminotransferase (ALT) levels were elevated from March 2021. All patients were proven to have NAFLD by ultrasonography and laboratory work-up to exclude other causes of hepatitis. Fibroscan and additional laboratory tests for biomarkers [procollagen type1 amino-terminal propeptide (P1NP), osteocalcin, interleukin-6 (IL-6), and Mac-2 binding protein glycosylated isomer (M2BPGi)] were performed. Fibroscan-AST (FAST) score was used for the comparison of steatohepatitis and liver stiffness measurement (kPa) was used for the comparison of advanced fibrosis. RESULTS The biomarker that showed a significant difference between the FAST-positive and negative groups was the P1NP/osteocalcin ratio with a p-value of 0.008. The area under receiver operating characteristic (AUROC) of P1NP/osteocalcin ratio*ALT values (values obtained through multivariate analysis) was 0.939 with the cut-off value of 305.38. The biomarkers that showed a significant difference between the LSM-positive and negative groups were IL-6 and M2BPGi with a p-values of 0.005 and <0.001. AUROC of IL-6 *AST values (values obtained through multivariate analysis) was 0.821 with the cut-off value of 228.15. M2BPGi showed a significant linear relationship with LSM in Pearson correlation analysis (Pearson correlation coefficient = 0.382; p = 0.003). The diagnostic capability of M2BPGi to evaluate advanced fibrosis showed an acceptable result (AUROC = 0.742; p = 0.022). CONCLUSIONS Non-invasive biomarkers can be used to predict each stage of NAFLD in children. The measurements of P1NP, IL-6 or M2BPGi along with the basic chemistry tests would help determine the stage of NAFLD they correspond to at the time of initial diagnosis and predict responsiveness after the treatment.
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Affiliation(s)
- Yiyoung Kwon
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Eun Sil Kim
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yon Ho Choe
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Mi Jin Kim
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Suzuki T, Matsuura K, Nagura Y, Iio E, Ogawa S, Fujiwara K, Nojiri S, Kataoka H, Tanaka Y. Development of hepatocellular carcinoma from various phases of chronic hepatitis B virus infection. PLoS One 2021; 16:e0261878. [PMID: 34962955 PMCID: PMC8714106 DOI: 10.1371/journal.pone.0261878] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 12/11/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND & AIMS There is insufficient data on the clinical course of chronic hepatitis B (CHB) patients in the immune-tolerant (IT) and immune-clearance, inactive (IC) phases over a long follow-up period. DESIGN We enrolled 466 CHB patients from our historical cohort, including 56 IT+MA (mildly active), 134 IC, 230 with chronic active hepatitis (CH) and 46 with liver cirrhosis (LC), who were categorized to each phase by at least one year of follow-up period from the first visit to our hospital. We investigated long-term risks, and their factors, of developing hepatocellular carcinoma (HCC), and the transition between the clinical phases, especially in the IT+MA and IC groups. RESULTS Of the 56 patients in the IT+MA group, 27 remained the IT+MA phase, but 29 transitioned to the CH phase and started nucleot(s)ide analogue (NA) treatment during the follow-up period. Meanwhile, of the 134 patients in the IC group, only 5 started NA treatment after progressing to the CH phase. The development of HCC from the IT+MA, IC, CH, and LC groups was observed in 2, 2, 9, and 20 cases, respectively. The cumulative incidence rates of developing HCC in the IT+MA, IC, CH, and LC groups were 9.9, 1.8, 3.0, and 53.1% at 10 years. In the CH and LC group, patients who developed HCC were older, had higher levels of FIB-4 index, M2BPGi, HBcrAg and AFP, and had lower levels of albumin and platelet counts. In CH patients, FIB-4 index levels were elevated at the diagnosis of HCC compared to baseline, whereas these decreased during the follow-up period in non-HCC patients. CONCLUSIONS HCC occurred at a certain rate among patients in the IT+MA and IC groups. Careful follow-up is required for CH patients with higher levels of FIB-4 index and/or M2BPGi because of the high incidence of HCC development. (299 words).
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Affiliation(s)
- Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yoshihito Nagura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Etsuko Iio
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shintaro Ogawa
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shunsuke Nojiri
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- 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
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Ouchida T, Takamatsu S, Maeda M, Asuka T, Morita C, Kondo J, Ueda K, Miyoshi E. Challenges in the Application of Glyco-Technology to Hepatitis B Virus Therapy and Diagnosis. Viruses 2021; 13:1860. [PMID: 34578441 PMCID: PMC8473023 DOI: 10.3390/v13091860] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 09/13/2021] [Accepted: 09/14/2021] [Indexed: 01/05/2023] Open
Abstract
Hepatitis B virus (HBV) is a major pathogen that causes acute/chronic hepatitis. Continuous HBV infection can lead to the development of hepatocellular carcinoma (HCC). Although several different anti-HBV treatments are available for chronic hepatitis B patients, discontinuing these medications is difficult. Patients with chronic hepatitis B at high risk for HCC therefore require close observation. However, no suitable biomarkers for detecting high-risk groups for HCC exist, except for serum HBV-DNA, but a number of HCC biomarkers are used clinically, such as alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II). Glycosylation is an important post-translational protein modification involved in many human pathologic conditions. HBV surface proteins contain various oligosaccharides, and several reports have described their biological functions. Inhibition of HBV glycosylation represents a potential novel anti-HBV therapy. It is thought that glycosylation of hepatocytes/hepatoma cells is also important for HBV infection, as it prevents HBV from infecting cells other than hepatocytes, even if the cells express the HBV receptor. In this review, we summarize considerable research regarding the relationship between HBV and glycosylation as it relates to the development of novel diagnostic tests and therapies for HBV.
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Affiliation(s)
- Tsunenori Ouchida
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita 565-0871, Japan; (T.O.); (S.T.); (M.M.); (T.A.); (C.M.); (J.K.)
| | - Shinji Takamatsu
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita 565-0871, Japan; (T.O.); (S.T.); (M.M.); (T.A.); (C.M.); (J.K.)
| | - Megumi Maeda
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita 565-0871, Japan; (T.O.); (S.T.); (M.M.); (T.A.); (C.M.); (J.K.)
| | - Tatsuya Asuka
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita 565-0871, Japan; (T.O.); (S.T.); (M.M.); (T.A.); (C.M.); (J.K.)
| | - Chiharu Morita
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita 565-0871, Japan; (T.O.); (S.T.); (M.M.); (T.A.); (C.M.); (J.K.)
- Department of Microbiology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan;
| | - Jumpei Kondo
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita 565-0871, Japan; (T.O.); (S.T.); (M.M.); (T.A.); (C.M.); (J.K.)
| | - Keiji Ueda
- Department of Microbiology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan;
| | - Eiji Miyoshi
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita 565-0871, Japan; (T.O.); (S.T.); (M.M.); (T.A.); (C.M.); (J.K.)
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Sugimoto K, Lee DH, Lee JY, Yu SJ, Moriyasu F, Sakamaki K, Oshiro H, Takahashi H, Kakegawa T, Tomita Y, Abe M, Yoshimasu Y, Takeuchi H, Choi BI, Itoi T. Multiparametric US for Identifying Patients with High-Risk NASH: A Derivation and Validation Study. Radiology 2021; 301:625-634. [PMID: 34519576 DOI: 10.1148/radiol.2021210046] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is common in the general population but identifying patients with high-risk nonalcoholic steatohepatitis (NASH) who are candidates for pharmacologic therapy remains a challenge. Purpose To develop a score to identify patients with high-risk NASH, defined as NASH with an NAFLD activity score (NAS) of 4 or greater and clinically significant fibrosis (stage 2 [F2] or higher). Materials and Methods This was a cross-sectional secondary analysis of data prospectively collected between April 2017 and March 2019 for a group of patients with NAFLD in Japan (Japan NAFLD, the derivation data set) with contemporaneous two-dimensional shear-wave elastography and biopsy-proven NAFLD (age range, 20-89 years). Three US markers (liver stiffness [LS, measured in kilopascals], attenuation coefficient [AC, measured in decibels per centimeter per megahertz], and dispersion slope [DS, measured in meters per second per kilohertz]) were determined, together with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and the AST-to-ALT ratio. The best-fit multivariate logistic regression model for identifying patients with high-risk NASH was determined. Diagnostic performance was assessed by using the area under the receiver operating characteristic curve (AUC). The findings were validated in an independent data set (Korea NAFLD; age range, 20-78 years). Results The Japan NAFLD data set included 111 patients (mean age, 53 years ± 18 [standard deviation]; 57 men), 84 (76%) with NASH. The Korea NAFLD data set included 102 patients (mean age, 48 years ± 18; 43 men), 55 (36%) with NASH. The most predictive model (LAD NASH score) combined LS, AC, and DS. Performance was satisfactory in both the derivation sample (AUC, 0.86; 95% CI: 0.79, 0.93) and the validation sample (AUC, 0.88; 95% CI: 0.80, 0.95). The LAD NASH score showed a positive predictive value of 86.5% and a negative predictive value of 87.5% for high-risk NASH in the derivation sample. Conclusion A score combining three US markers may be useful for noninvasive identification of patients with high-risk nonalcoholic steatohepatitis for inclusion in clinical trials and pharmacologic therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lockhart in this issue.
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Affiliation(s)
- Katsutoshi Sugimoto
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Dong Ho Lee
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Jae Young Lee
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Su Jong Yu
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Fuminori Moriyasu
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Kentaro Sakamaki
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Hisashi Oshiro
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Hiroshi Takahashi
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Tatsuya Kakegawa
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Yusuke Tomita
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Masakazu Abe
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Yu Yoshimasu
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Hirohito Takeuchi
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Byung Ihn Choi
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
| | - Takao Itoi
- From the Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan (K. Sugimoto, H. Takahashi, T.K., Y.T., M.A., Y.Y., H. Takeuchi, T.I.); Departments of Radiology (D.H.L., J.Y.L.) and Internal Medicine, Division of Gastroenterology and Hepatology (S.J.Y.), Seoul National University, Seoul, Korea; Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan (F.M.); Center for Data Science, Yokohama City University, Kanagawa, Japan (K. Sakamaki); Department of Pathology, Jichi Medical University, Tochigi, Japan (H.O.); Department of Radiology, Chung-Ang University Hospital, Seoul, Korea (B.I.C.)
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Atsukawa M, Tsubota A, Kondo C, Uchida-Kobayashi S, Takaguchi K, Tsutsui A, Nozaki A, Chuma M, Hidaka I, Ishikawa T, Iwasa M, Tamai Y, Tobari M, Matsuura K, Nagura Y, Abe H, Kato K, Suzuki K, Okubo T, Arai T, Itokawa N, Toyoda H, Enomoto M, Tamori A, Tanaka Y, Kawada N, Takei Y, Iwakiri K. A novel noninvasive formula for predicting cirrhosis in patients with chronic hepatitis C. PLoS One 2021; 16:e0257166. [PMID: 34506563 PMCID: PMC8432856 DOI: 10.1371/journal.pone.0257166] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 08/24/2021] [Indexed: 12/26/2022] Open
Abstract
Evaluating liver fibrosis is crucial for disease severity assessment, treatment decisions, and hepatocarcinogenic risk prediction among patients with chronic hepatitis C. In this retrospective multicenter study, we aimed to construct a novel model formula to predict cirrhosis. A total of 749 patients were randomly allocated to training and validation sets at a ratio of 2:1. Liver stiffness measurement (LSM) was made via transient elastography using FibroScan. Patients with LSM ≥12.5 kPa were regarded as having cirrhosis. The best model formula for predicting cirrhosis was constructed based on factors significantly and independently associated with LSM (≥12.5 kPa) using multivariate regression analysis. Among the 749 patients, 198 (26.4%) had LSM ≥12.5 kPa. In the training set, multivariate analysis identified logarithm natural (ln) type IV collagen 7S, ln hyaluronic acid, and ln Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+-Mac-2 BP) as the factors that were significantly and independently associated with LSM ≥12.5 kPa. Thus, the formula was constructed as follows: score = -6.154 + 1.166 × ln type IV collagen 7S + 0.526 × ln hyaluronic acid + 1.069 × WFA+-Mac-2 BP. The novel formula yielded the highest area under the curve (0.882; optimal cutoff, -0.381), specificity (81.5%), positive predictive values (62.6%), and predictive accuracy (81.6%) for predicting LSM ≥12.5 kPa among fibrosis markers and indices. These results were almost similar to those in the validated set, indicating the reproducibility and validity of the novel formula. The novel formula scores were significantly, strongly, and positively correlated with LSM values in both the training and validation data sets (correlation coefficient, 0.721 and 0.762; p = 2.67 × 10-81 and 1.88 × 10-48, respectively). In conclusion, the novel formula was highly capable of diagnosing cirrhosis in patients with chronic hepatitis C and exhibited better diagnostic performance compared to conventional fibrosis markers and indices.
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Affiliation(s)
- Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Akihito Tsubota
- Core Research Facilities, The Jikei University School of Medicine, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | | | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Kanagawa, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Kanagawa, Japan
| | - Isao Hidaka
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Tsuyoshi Ishikawa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
| | - Yasuyuki Tamai
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
| | - Maki Tobari
- Department of Internal Medicine and Gastroenterology, Tokyo Women’s Medical University Yachiyo Medical Center, Chiba, Japan
| | - Kentaro Matsuura
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Aichi, Japan
| | - Yoshihito Nagura
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Aichi, Japan
| | - Hiroshi Abe
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Keizo Kato
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Kenta Suzuki
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Tomomi Okubo
- Department of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Chiba, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Masaru Enomoto
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Akihiro Tamori
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Kumamoto University, Kumamoto, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Yoshiyuki Takei
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
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Jang SY, Tak WY, Park SY, Kweon YO, Lee YR, Kim G, Hur K, Han MH, Lee WK. Diagnostic Efficacy of Serum Mac-2 Binding Protein Glycosylation Isomer and Other Markers for Liver Fibrosis in Non-Alcoholic Fatty Liver Diseases. Ann Lab Med 2021; 41:302-309. [PMID: 33303715 PMCID: PMC7748098 DOI: 10.3343/alm.2021.41.3.302] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/23/2020] [Accepted: 11/30/2020] [Indexed: 02/07/2023] Open
Abstract
Background Mac-2 binding protein glycosylation isomer (M2BPGi) has been established as a non-invasive biomarker for liver fibrosis. We evaluated the diagnostic efficacy of M2BPGi compared with those of other liver fibrosis markers in liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Methods We analyzed serum M2BPGi levels in 113 NAFLD patients. A pathologist graded liver fibrosis histopathologically. The diagnostic efficacies of serum M2BPGi and other liver fibrosis markers (aspartate aminotransferase to platelet ratio index, fibrosis index based on four factors, and NAFLD fibrosis score [NFS]) were evaluated using correlation, area under the ROC curve (AUC), logistic regression, and C-statistics. Results Serum M2BPGi level and other liver fibrosis markers showed a moderate correlation with fibrosis grade. The AUC values of M2BPGi were 0.761, 0.819, 0.866, and 0.900 for diagnosing fibrosis (F)>0, F>1, F>2, and F>3, respectively. Logistic regression analysis showed M2BPGi as the only independent factor associated with F>2 and F>3. Although C-statistics showed that NFS was the best diagnostic factor for F>2 and F>3, M2BPGi with NFS had an increased C-statistics value, indicating that it is a better diagnostic model. Conclusions The serum M2BPGi level increased with liver fibrosis severity and could be a good biomarker for diagnosing advanced fibrosis and cirrhosis in NAFLD patients. A well-controlled, prospective study with a larger sample size is needed to validate the diagnostic power of M2BPGi and other fibrosis markers in NAFLD.
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Affiliation(s)
- Se Young Jang
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
| | - Young-Oh Kweon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
| | - Yu Rim Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
| | - Gyeonghwa Kim
- Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Keun Hur
- Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Man-Hoon Han
- Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
| | - Won Kee Lee
- Department of Medical Informatics, School of Medicine, Kyungpook National University, Daegu, Korea
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Kawaguchi K, Sakai Y, Terashima T, Shimode T, Seki A, Orita N, Takeshita Y, Shimakami T, Takatori H, Arai K, Kitamura K, Yamashita T, Yamashita T, Takamura M, Mizukoshi E, Takamura T, Honda M, Wada T, Kaneko S. Decline in serum albumin concentration is a predictor of serious events in nonalcoholic fatty liver disease. Medicine (Baltimore) 2021; 100:e26835. [PMID: 34397849 PMCID: PMC8341320 DOI: 10.1097/md.0000000000026835] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 06/20/2021] [Accepted: 07/19/2021] [Indexed: 02/07/2023] Open
Abstract
ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which includes diabetes mellitus and hyperlipidemia. A fraction of NAFLD patients develop nonalcoholic steatohepatitis, leading to cirrhosis associated with various serious complications, including hepatocellular carcinoma, gastroesophageal varices, cardiovascular events, and other organ malignancy. Although the incidence of chronic viral hepatitis with associated complications has gradually decreased as highly effective antiviral therapies have been established, the number of patients with steatohepatitis has been increasing.This retrospective study examined data of 229 patients from 22 hospitals in our region. We examined 155 cases of chronological data and assessed the development of liver fibrosis and evaluated hepatic reserve-related markers such as platelet count, FIB-4 index, prothrombin time, and serum albumin concentration. We analyzed the relationship of these chronological changes and the incidence of NAFLD related serious complications.Data related to liver fibrosis progression, albumin, and prothrombin time were significantly associated with the occurrence of serious complications associated with cirrhosis. We compared 22 event and 133 nonevent cases of chronological changes in the data per year and found that serum albumin concentration was significantly lower in the group that developed serious complications (event cases: -0.21 g/dL/year, nonevent cases: -0.04 g/dL/year (P < .001)). This albumin decline was only the associated factor with the event incidence by multivariate analysis (P < .01).Annual decline in serum albumin concentration in patients with NAFLD is associated with serious events from the outcome of multicenter retrospective study. This highlights its potential utility as a surrogate marker to assess the efficacy of prediction of NAFLD related serious events.
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Affiliation(s)
- Kazunori Kawaguchi
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Yoshio Sakai
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
- Department of Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences
| | - Takeshi Terashima
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Tetsuhiro Shimode
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Akihiro Seki
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Noriaki Orita
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Yumie Takeshita
- Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences
| | - Tetsuro Shimakami
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Hajime Takatori
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Kuniaki Arai
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Kazuya Kitamura
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Taro Yamashita
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Tatsuya Yamashita
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Masayuki Takamura
- Department of Cardiology, Kanazawa University Graduate School of Medical Sciences
| | - Eishiro Mizukoshi
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Toshinari Takamura
- Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences
| | - Masao Honda
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
| | - Takashi Wada
- Department of Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences
| | - Shuichi Kaneko
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences
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Liver fibrosis is associated with carotid atherosclerosis in patients with liver biopsy-proven nonalcoholic fatty liver disease. Sci Rep 2021; 11:15938. [PMID: 34354193 PMCID: PMC8342487 DOI: 10.1038/s41598-021-95581-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 07/26/2021] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is related to subclinical atherosclerosis. However, whether the severity of the disease (or which histopathological component) is associated with subclinical atherosclerosis remains controversial. This study aimed to investigate the association between the histopathological severity of NAFLD and carotid intima-media thickness (CIMT) in Japanese patients with liver biopsy-proven NAFLD. Maximum-CIMT (max-CIMT) was measured as an index of carotid atherosclerosis in 195 biopsy-proven NAFLD patients. A significant association was observed between the severity of fibrosis (but not steatosis, inflammation, and ballooning) and max-CIMT. Older age, male gender, hypertension, and advanced fibrosis were independently linked to max-CIMT ≥ 1.2 mm. The prevalence of max-CIMT ≥ 1.2 mm was significantly higher in the advanced fibrosis group than in the non-advanced fibrosis group (75.4% versus 44.0%; p < 0.01). Non-invasive liver fibrosis markers and scoring systems, including fibrosis-4 index, NAFLD fibrosis score, hyaluronic acid, and Wisteria floribunda agglutinin positive Mac-2-binding protein, demonstrated that the diagnostic performance for max-CIMT ≥ 1.2 mm was similar to that of biopsy-based fibrosis staging. In conclusion, advanced fibrosis is significantly and independently associated with high-risk CIMT. Non-invasive fibrosis markers and scoring systems could help estimate the risk of atherosclerosis progression in patients with NAFLD.
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Saito N, Hatanaka T, Nakano Y, Nakano S, Hazama Y, Yoshida S, Hachisu Y, Tanaka Y, Yoshinaga T, Kashiwabara K, Tojima H, Sato K, Kakizaki S, Uraoka T. Usefulness of FibroScan-AST (FAST) score in Japanese patients with non-alcoholic fatty liver disease: A single-center retrospective experience. KANZO 2021; 62:393-402. [DOI: 10.2957/kanzo.62.393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
Affiliation(s)
- Naoto Saito
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital
| | - Yuya Nakano
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital
| | - Sachi Nakano
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital
| | - Yoichi Hazama
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital
| | - Sachiko Yoshida
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital
| | - Yoko Hachisu
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital
| | - Yoshiki Tanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital
| | - Teruo Yoshinaga
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital
| | | | - Hiroki Tojima
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine
| | - Ken Sato
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine
| | - Satoru Kakizaki
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine
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Miyoshi T, Hamaguchi M, Kitagawa N, Hashimoto Y, Fukui M. Correlation between Liver Stiffness by Two-Dimensional Shear Wave Elastography and Waist Circumference in Japanese Local Citizens with Abdominal Obesity. J Clin Med 2021; 10:jcm10091971. [PMID: 34064337 PMCID: PMC8125660 DOI: 10.3390/jcm10091971] [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] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/23/2021] [Accepted: 04/30/2021] [Indexed: 12/13/2022] Open
Abstract
Background: Various factors other than fibrosis could affect liver stiffness (LS), measured by two-dimensional shear wave elastography (2D-SWE). We aimed to clarify the factors affecting LS in local citizens. Methods: We performed a cross-sectional study among local citizens of a health checkup program. Abdominal obesity was defined as waist circumference ≥85 cm for men and ≥90 cm for women. We evaluated the correlation between LS by 2D-SWE (Aplio 500) and waist circumference with linear regression analyses. We selected the following items as variables in the multivariate analysis: waist circumference, sex, hypertension, diabetes, diagnostic components of metabolic syndrome, γ−glutamyl transpeptidase, total bilirubin, NAFLD fibrosis score, and an indicator of a fatty liver, evaluated ultrasonographically. Results: Overall, 345 individuals were included; 318 (181 men and 137 women; age, 63.4 years; waist circumference, 84.0 cm; LS, 5.79 kPa) were analyzed, 128 of whom had abdominal obesity and significantly higher LS than non-abdominally obese individuals. In the multivariate analysis, waist circumference was positively, independently, and significantly correlated with LS only in abdominally obese individuals. Conclusions: Liver stiffness by 2D-SWE could increase with increases in waist circumference in local citizens with abdominal obesity. Physicians should pay attention when assessing the LS of abdominally obese individuals.
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Affiliation(s)
- Tomoki Miyoshi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
- Correspondence: ; Tel.: +81-75-251-5506
| | - Noriyuki Kitagawa
- Department of Diabetology, Kameoka Municipal Hospital, Kameoka 621-8585, Japan;
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
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Nouso K, Furubayashi Y, Kariyama K, Wakuta A, Miyake N, Inoue K, Nagai Y, Murakami S, Adachi T, Oyama A, Wada N, Takeuchi Y, Sakata M, Yasunaka T, Onishi H, Shiraha H, Takaki A, Shiota S, Yasuda S, Toyoda H, Kawanaka M, Kumada T, Okada H. Abnormal fucosylation of alpha-fetoprotein in patients with nonalcoholic steatohepatitis. Hepatol Res 2021; 51:548-553. [PMID: 33596344 DOI: 10.1111/hepr.13626] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/03/2021] [Accepted: 02/08/2021] [Indexed: 12/21/2022]
Abstract
AIM Nonalcoholic steatohepatitis (NASH) is a risk factor for nonvirus-related hepatocellular carcinoma, which is increasing in prevalence. The aim of this study was to clarify the clinical application of fucosylated alpha-fetoprotein (AFP-L3) in the process of nonalcoholic fatty liver (NAFL) disease development. METHODS Serum samples from 115 diabetes mellitus (DM), 36 NAFL, and 119 NASH patients were analyzed for AFP-L3 expression using raw data of a micro total analysis system. These data were then compared with the clinical characteristics of the patients. A validation study was also undertaken with 55 samples (17 NAFL and 38 NASH). RESULTS Trace amounts of AFP-L3 were detected in 3.5%, 16.7%, and 58.0% of patients with DM, NAFL, and NASH, respectively. The odds ratio of AFP-L3 positivity for the diagnosis of NASH in multivariate analysis was 9.81 (95% confidence interval, 3.77-25.5). The rates in patients without fibrosis or with stage 1, stage 2, stage 3, and stage 4 fibrosis were 14.7%, 31.3%, 63.0%, 86.2%, and 100%, respectively. The rates were significantly increased according to the advancement of liver fibrosis (p < 0.001); however, no difference in the positive rate of AFP-L3 was observed between patients with and without fatty livers and between patients with normal and abnormal transaminase. The same relationship was also observed in the validation cohort. CONCLUSION Abnormal fucosylation of AFP occurred in patients with NASH, so it could be useful for the screening of NASH in patients with DM, as well as for the differential diagnosis of NASH and the evaluation of fibrosis.
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Affiliation(s)
- Kazuhiro Nouso
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.,Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | | | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Akiko Wakuta
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Nozomi Miyake
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Kanae Inoue
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Yuta Nagai
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Shiho Murakami
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Takuya Adachi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Atsushi Oyama
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Nozomu Wada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Yasuto Takeuchi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Masahiro Sakata
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Tetsuya Yasunaka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Hideki Onishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Hidenori Shiraha
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Akinobu Takaki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Shohei Shiota
- Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan
| | - Miwa Kawanaka
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Takashi Kumada
- Department of Nursing, Faculty of Nursing, Gifu Kyoritsu University, Gifu, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
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Eso Y, Nakano S, Mishima M, Arasawa S, Iguchi E, Takeda H, Takai A, Takahashi K, Taura K, Seno H. Mac-2 binding protein glycosylation isomer predicts tolerability and clinical outcome of lenvatinib therapy for hepatocellular carcinoma. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:498-507. [PMID: 33787071 DOI: 10.1002/jhbp.954] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/09/2021] [Accepted: 03/10/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Many patients with hepatocellular carcinoma present with impaired hepatic function, which often requires interruption or withdrawal of lenvatinib due to associated adverse events. We aimed to identify pre-treatment predictors of tolerability and clinical outcome of lenvatinib therapy. METHODS Eighty patients who received lenvatinib at our institution between 2018 and 2020 were included in this study. We assessed essential factors associated with prolonged progression-free survival (PFS), using Cox proportional hazards model. We also investigated the correlation between the factor identified as contributing most to PFS and the relative dose intensity (RDI), response rate, and duration of treatment with lenvatinib. RESULTS Pre-treatment level of Mac-2-binding protein glycosylation isomer (M2BPGi) showed significant association with PFS (hazard ratio = 0.52, P = .0358). Low M2BPGi levels (<1.5) correlated significantly with longer PFS than higher levels (P = .0003). Patients with M2BPGi <1.5 achieved significantly higher RDI, objective response rate, and disease control rate, and maintained lenvatinib treatment for longer than those with baseline values ≥1.5. Patients with M2BPGi ≥1.5 had a higher incidence of adverse events such as fatigue and anorexia. CONCLUSIONS Baseline M2BPGi levels may predict the tolerability and treatment response to lenvatinib. Patients with high M2BPGi levels may less likely to benefit from lenvatinib therapy.
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Affiliation(s)
- Yuji Eso
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shigeharu Nakano
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Masako Mishima
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Soichi Arasawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Eriko Iguchi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Haruhiko Takeda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Atsushi Takai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ken Takahashi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Mizuno K, Haga H, Okumoto K, Hoshikawa K, Katsumi T, Nishina T, Saito T, Katagiri H, Ueno Y. Intrahepatic distribution of nerve fibers and alterations due to fibrosis in diseased liver. PLoS One 2021; 16:e0249556. [PMID: 33852613 PMCID: PMC8046205 DOI: 10.1371/journal.pone.0249556] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 03/21/2021] [Indexed: 01/23/2023] Open
Abstract
Autonomic nerve fibers in the liver are distributed along the portal tract, being involved in the regulation of blood flow, bile secretion and hepatic metabolism, thus contributing to systemic homeostasis. The present study investigated changes in hepatic nerve fibers in liver biopsy specimens from patients with normal liver, viral hepatitis and non-alcoholic steatohepatitis, in relation to clinical background. The areal ratio of nerve fibers to the total portal area was automatically calculated for each sample. The nerve fiber areal ratios (NFAR) for total nerve fibers and sympathetic nerve fibers were significantly lower in liver affected by chronic hepatitis, particularly viral hepatitis, and this was also the case for advanced liver fibrosis. However, the degree of inflammatory activity did not affect NFAR for either whole nerves or sympathetic nerves. Comparison of samples obtained before and after antiviral treatment for HCV demonstrated recovery of NFAR along with improvement of liver fibrosis.
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Affiliation(s)
- Kei Mizuno
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
- Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan
| | - Hiroaki Haga
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
- Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan
| | - Kazuo Okumoto
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Kyoko Hoshikawa
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
- Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan
| | - Tomohiro Katsumi
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
- Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan
| | - Taketo Nishina
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
- Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan
| | - Takafumi Saito
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Hideki Katagiri
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
- Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan
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Proteomic screening of plasma identifies potential noninvasive biomarkers associated with significant/advanced fibrosis in patients with nonalcoholic fatty liver disease. Biosci Rep 2021; 40:221652. [PMID: 31860081 PMCID: PMC6944676 DOI: 10.1042/bsr20190395] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 11/16/2019] [Accepted: 12/19/2019] [Indexed: 12/13/2022] Open
Abstract
Noninvasive biomarkers are clinically useful for evaluating liver fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to compare plasma proteins in patients with early nonalcoholic steatohepatitis (NASH) (F0-F1) versus NASH with significant/advanced fibrosis (F2–F4) to determine whether candidate proteins could be used as potential noninvasive biomarkers. Nineteen biopsy-proven NAFLD patients including ten early NASH patients and nine NASH patients with significant/advanced fibrosis were enrolled in the present study. High-resolution proteomics screening of plasma was performed with the SCIEX TripleTOF 5600 System. Proteins were quantified using two different software platforms, Progenesis Qi and Scaffold Q+, respectively. Progenesis Qi analysis resulted in the discovery of 277 proteins compared with 235 proteins in Scaffold Q+. Five consensus proteins (i.e. Complement component C7; α-2-macroglobulin; Complement component C8 γ chain; Fibulin-1; α-1-antichymotrypsin) were identified. Complement component C7 was three-fold higher in the NASH group with significant/advanced fibrosis (F2–F4) compared with the early NASH (F0-F1) group (q-value = 3.6E-6). Complement component C7 and Fibulin-1 are positively correlated with liver stiffness (P=0.000, P=0.002, respectively); whereas, Complement component C8 γ chain is negatively correlated (P=0.009). High levels of Complement C7 are associated with NASH with significant/advanced fibrosis and Complement C7 is a perfect classifier of patients included in this pilot study. Further studies will be needed in a larger validation cohort to confirm the utility of complement proteins as biomarkers or mechanistic determinants of NASH with significant/advanced fibrosis.
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45
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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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Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Yoneda M, Imajo K, Takahashi H, Eguchi Y, Ono M, Nozaki Y, Hyogo H, Koseki M, Yoshida Y, Kawaguchi T, Kamada Y, Okanoue T, Nakajima A, Japan Study Group of NAFLD (JSG-NAFLD). FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic. Life (Basel) 2021; 11:143. [PMID: 33672864 PMCID: PMC7917687 DOI: 10.3390/life11020143] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 12/16/2022] Open
Abstract
The prevalence of obesity or metabolic syndrome is increasing worldwide (globally metabodemic). Approximately 25% of the adult general population is suffering from nonalcoholic fatty liver disease (NAFLD), which has become a serious health problem. In 2020, global experts suggested that the nomenclature of NAFLD should be updated to metabolic-dysfunction-associated fatty liver disease (MAFLD). Hepatic fibrosis is the most significant determinant of all cause- and liver -related mortality in MAFLD. The non-invasive test (NIT) is urgently required to evaluate hepatic fibrosis in MAFLD. The fibrosis-4 (FIB-4) index is the first triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness, especially for general physicians or endocrinologists, although the FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration-controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the second step after triaging by the FIB-4 index. The leading cause of mortality in MAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. MAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation. The FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocellular carcinoma, but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, the FIB-4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of the FIB-4 index in the management of MAFLD.
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Affiliation(s)
- Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
| | - Masashi Yoneda
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
| | - Katsutoshi Tokushige
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan;
| | - Miwa Kawanaka
- Department of General Internal Medicine2, Kawasaki Medical School, Okayama 700-8505, Japan;
| | - Hideki Fujii
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 558-8585, Japan;
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
| | - Kento Imajo
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
| | - Hirokazu Takahashi
- Department of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 840-8502, Japan;
| | | | - Masafumi Ono
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo 116-8567, Japan;
| | - Yuichi Nozaki
- Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan;
| | - Hideyuki Hyogo
- Department of Gastroenterology, JA Hiroshima General Hospital, Hiroshima 738-8503, Japan;
| | - Masahiro Koseki
- Division of Cardiovascular Medicine, Department of Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan;
| | - Yuichi Yoshida
- Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka 564-8567, Japan;
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan;
| | - Yoshihiro Kamada
- Department of Advanced Gastroenterology & Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan;
| | - Takeshi Okanoue
- Hepatology Center, Saiseikai Suita Hospital, Osaka 564-0013, Japan;
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
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Yoshio S, Kanto T. Macrophages as a source of fibrosis biomarkers for non-alcoholic fatty liver disease. Immunol Med 2021; 44:175-186. [PMID: 33444517 DOI: 10.1080/25785826.2020.1868664] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) are becoming major liver diseases worldwide. Liver fibrosis and cirrhosis are among the most significant risk factors of hepatocellular carcinoma (HCC) and associated with the long-term prognosis of NAFLD patients. To stratify the risk of HCC in NAFLD patients clinically, the discovery of non-invasive fibrosis markers is needed urgently. Liver macrophages play critical roles in the regulation of inflammation and fibrosis by interacting with hepatic stellate cells (HSCs) and other immune cells. Thus, it is rational to explore feasible biomarkers for liver fibrosis by focusing on macrophage-related factors. We examined serum factors comprehensively in multiple cohorts of NAFLD/NASH patients to determine whether they were correlated with the biopsy-proven fibrosis stage. We found that the serum levels of interleukin (IL)-34, YKL-40 and soluble Siglec-7 (sSiglec7) were closely associated with liver fibrosis and served as diagnostic biomarkers in patients with NAFLD/NASH. In the NAFLD liver, IL-34 was produced by activated fibroblasts, and YKL-40 and sSiglec-7 were secreted from macrophages. The sensitivity and specificity of these markers to detect advanced liver fibrosis varied, supporting the notion that the combination of these markers with other modalities is an option for clinical application.
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Affiliation(s)
- Sachiyo Yoshio
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Tatsuya Kanto
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan
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Tamaki N, Kurosaki M, Takahashi Y, Itakura Y, Kirino S, Inada K, Yamashita K, Sekiguchi S, Hayakawa Y, Osawa L, Higuchi M, Takaura K, Maeyashiki C, Kaneko S, Yasui Y, Tsuchiya K, Nakanishi H, Itakura J, Loomba R, Izumi N. Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein as a Screening Tool for Significant Liver Fibrosis in Health Checkup. Int J Mol Sci 2020; 22:ijms22010040. [PMID: 33375190 PMCID: PMC7793131 DOI: 10.3390/ijms22010040] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/09/2020] [Accepted: 12/17/2020] [Indexed: 02/08/2023] Open
Abstract
Chronic liver disease is generally widespread, and a test for screening fibrotic subjects in a large population is needed. The ability of Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) to detect significant fibrosis was investigated in health checkup subjects in this research. Of 2021 health checkup subjects enrolled in this prospective cross-sectional study, those with WFA+-M2BP ≥ 1.0 were defined as high risk. Liver fibrosis was evaluated using magnetic resonance elastography (MRE) in subjects with high risk. The primary outcome was the positive predictive value (PPV) of WFA+-M2BP for significant fibrosis (liver stiffness ≥ 2.97 kPa by MRE). This trial was registered with the UMIN clinical trial registry, UMIN000036175. WFA+-M2BP ≥ 1.0 was observed in 5.3% of the 2021 subjects. The PPV for significant fibrosis with the threshold of WFA+-M2BP at ≥1.0, ≥1.1, ≥1.2, ≥1.3, ≥1.4, and ≥1.5 was 29.2%, 36.4%, 43.5%, 42.9%, 62.5%, and 71.4%, respectively. A WFA+-M2BP of 1.2 was selected as the optimal threshold for significant fibrosis among high-risk subjects, and the PPV, negative predictive value, sensitivity, and specificity for significant fibrosis were 43.5%, 84.0%, 71.4%, and 61.8%, respectively. WFA+-M2BP ≥ 1.2 was significantly associated with significant fibrosis, with an odds ratio (OR) of 4.04 (95% confidence interval (CI): 1.1–16, p = 0.04), but not FIB-4 ≥ 2.67 (OR: 2.40, 95%CI: 0.7–8.6, p-value = 0.2). In conclusion, WFA+-M2BP is associated with significant fibrosis and could narrow down potential subjects with liver fibrosis. The strategy of narrowing down fibrosis subjects using WFA+-M2BP may be used to screen for fibrotic subjects in a large population.
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Affiliation(s)
- Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
- Department of Medicine, Division of Gastroenterology and Hepatology, NAFLD Research Center, University of California San Diego, La Jolla, CA 92093, USA;
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Yuka Takahashi
- Medical Examination Center, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (Y.T.); (Y.I.)
| | - Yoshie Itakura
- Medical Examination Center, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (Y.T.); (Y.I.)
| | - Sakura Kirino
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Kento Inada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Koji Yamashita
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Shuhei Sekiguchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Yuka Hayakawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Leona Osawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Kenta Takaura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Chiaki Maeyashiki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Shun Kaneko
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
| | - Rohit Loomba
- Department of Medicine, Division of Gastroenterology and Hepatology, NAFLD Research Center, University of California San Diego, La Jolla, CA 92093, USA;
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (N.T.); (M.K.); (S.K.); (K.I.); (K.Y.); (S.S.); (Y.H.); (L.O.); (M.H.); (K.T.); (C.M.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.)
- Correspondence: ; Tel.: +81-422-32-3111; Fax: +81-422-32-9551
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Sasaki R, Miyaaki H, Narita S, Fukushima M, Haraguchi M, Miuma S, Hidaka M, Eguchi S, Okudaira S, Abe K, Nakao K. Serum Mac-2 binding protein glycosylation isomer as a biomarker of fibrosis in living donor liver transplant graft. Clin Transplant 2020; 35:e14175. [PMID: 33247961 DOI: 10.1111/ctr.14175] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 11/16/2020] [Accepted: 11/21/2020] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Non-invasive assessment of graft fibrosis is important in liver transplantation. Mac-2 binding protein glycosylation isomer (M2BPGi) has been reported as a diagnostic marker for this purpose, and thus, this predictive ability of M2BPGi was assessed in this study. PATIENTS AND METHODS In this retrospective study, 236 patients who received living donor liver transplantation (LDLT) from August 1997 to March 2017 were enrolled. Among them, 94 biopsy patients were analyzed. Further, the predictive ability of fibrotic biopsy using M2BPGi, Fibroscan, and Fib-4 index was compared. RESULTS Of 94 LDLT patients (53 men, 41 women), the median ages of recipients and donors were 57.5 and 33.0 years, respectively. The median M2BPGi values in patients with F0 (n = 11), F1 (n = 38), F2 (n = 35), and F3/4 (n = 10) were 0.680, 0.760, 1.240, and 4.110 COI, respectively. There were significant correlations between the fibrotic stage and M2BPGi levels (Kruskal-Wallis test, P < .0001). The area under the ROC curve for the diagnosis of F ≥ 2 in M2BPGi was 0.778, which was superior to Fibroscan (0.701) and Fib-4 index (0.639). CONCLUSION M2BPGi is an accurate, non-invasive detection method for significant fibrosis after LDLT.
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Affiliation(s)
- Ryu Sasaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Shohei Narita
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masanori Fukushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masafumi Haraguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Sadayuki Okudaira
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kuniko Abe
- Department of Pathology, Nagasaki University Hospital, Nagasaki, Japan.,Pathology Department, Japanese Red Cross Nagasaki Genbaku (Atomic Bomb) Hospital, Nagasaki, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Takamura M, Sakamaki A, Arao Y, Setsu T, Kamimura H, Yokoo T, Kamimura K, Tsuchiya A, Terai S. Daily Monitoring of Serum Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein Is Useful for Predicting Therapeutic Effect of Tolvaptan in Cirrhotic Ascites. TOHOKU J EXP MED 2020; 252:287-296. [PMID: 33208569 DOI: 10.1620/tjem.252.287] [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: 11/18/2022]
Abstract
Wisteria floribunda agglutinin (WFA) is a lectin that binds to the sugar chain of Mac-2 binding protein (M2BP), and WFA-positive M2BP (WFA+-M2BP) has been reported as a useful marker for assessing liver fibrosis in chronic liver disease. Tolvaptan (TLV), a selective vasopressin V2 receptor antagonist, is used for cirrhotic ascites in Japan, but good predictors of treatment efficacy remain to be established. Our aim was to investigate whether WFA+-M2BP monitoring before and after TLV administration can predict treatment efficacy in patients with cirrhotic ascites. Twenty patients (10 men), with a median age of 72 years, were enrolled. Cirrhosis was caused by hepatitis B virus (n = 3), hepatitis C virus (n = 4), alcohol (n = 8), and others (n = 5). Responders were defined as having a body weight loss of ≥ 1.5 kg/week after TLV administration. Serum WFA+-M2BP levels were measured at baseline and days 1, 3, and 7 after TLV treatment. Twelve patients (60%) were responders. Baseline WFA+-M2BP levels were correlated with serum albumin levels (r = -0.544, P = 0.013). The baseline furosemide dose was lower and platelet count was higher in responders than in non-responders (P < 0.05). The ratio of WFA+-M2BP levels on day 1 after TLV administration to baseline was lower in responders than in non-responders (P < 0.05). The decrease in the ratio discriminated responders from non-responders (AUC = 0.844, P < 0.05). In conclusion, monitoring serum WFA+-M2BP is helpful for predicting the efficacy of TLV treatment in patients with cirrhotic ascites.
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Affiliation(s)
- Masaaki Takamura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences
| | - Yoshihisa Arao
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences
| | - Toru Setsu
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences
| | - Takeshi Yokoo
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences
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